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18794493
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12553350
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40577675
|
T2 relaxometry and fMRI of the brain in late-onset restless legs syndrome.
|
Proteoglycan depletion-induced changes in transverse relaxation maps of cartilage: comparison of T2 and T1rho.
|
Gestational Age at Birth and Clinical Manifestations of Spinal Muscular Atrophy.
|
To assess in patients with late-onset idiopathic restless legs syndrome (RLS) the brain iron content with magnetic resonance relaxometry, and brain activation during dorsiflexion and plantar flexion of both feet, using fMRI.</AbstractText The study was approved by the institutional review board, and informed consent was obtained. Twenty-five RLS patients (14 women, 11 men; age range 55-82 years; mean 66.5 +/- 8.9 years; disease duration 6.5 +/- 4.5 years) and 12 sex- and age-matched controls were studied. A T1-weighted high-resolution three-dimensional spoiled gradient echo sequence was used for structural imaging, a multislice spin echo Tau2-weighted sequence was used for T2 relaxometry, and a single-shot multislice gradient echo planar sequence was used for fMRI. The motor paradigm consisted of alternating periods of rest and movement, each 40 seconds in duration. Region of interest analysis was used on the T2 relaxometry maps. Statistical parametric mapping software was used for analysis of the functional data.</AbstractText T2 relaxation time was significantly higher in patients than in controls in the substantia nigra pars compacta. Within-group analysis showed that both patients and controls activated the primary motor cortex, the primary somatosensory cortex, the somatosensory association cortex, and the middle cerebellar peduncles. Patients also activated the thalamus, putamen, middle frontal gyrus, and cingulate gyrus. Between-group analysis showed that patients had higher activation of the dorsolateral prefrontal cortex.</AbstractText Late-onset restless legs syndrome is associated with low iron content of the basal ganglia and increased activity of the dorsolateral prefrontal cortex.</AbstractText
|
The authors performed this study to (a) measure changes in T2 relaxation rates, signal-to-noise ratio (SNR), and contrast with sequential depletion of proteoglycan in cartilage; (b) determine whether there is a relationship between the T2 relaxation rate and proteoglycan in cartilage; and (c) compare the T2 mapping method with the spin-lattice relaxation time in the rotating frame (T1rho) mapping method in the quantification of proteoglycan-induced changes.</AbstractText T2- and T1rho-weighted magnetic resonance (MR) images were obtained in five bovine patellae. All images were obtained with a 4-T whole-body MR unit and a 10-cm-diameter transmit-receive quadrature birdcage coil tuned to 170 MHz. T2 and T1rho maps were computed.</AbstractText The SNR and contrast on the T2-weighted images were, on average, about 43% lower than those on the corresponding T1rho-weighted images. The T2 relaxation rates varied randomly without any particular trend, which yielded a poor correlation with sequential depletion of proteoglycan (R2 = 0.008, P < .70). There was excellent linear correlation between the percentage of proteoglycan in the tissue and the T1rho relaxation rate (R2 = 0.85, P < .0001).</AbstractText T2-weighted imaging neither yields quantitative information about the changes in proteoglycan distribution in cartilage nor can be used for longitudinal studies to quantify proteoglycan-induced changes. T1rho-weighted imaging, however, is sensitive to sequential depletion of proteoglycan in bovine cartilage and can be used to quantify proteoglycan-induced changes.</AbstractText
|
Enhanced efficacy with spinal muscular atrophy (SMA) treatments is demonstrated with earlier initiation, ideally before the onset of symptoms. High-quality pregnancy and postnatal care for mother-baby dyads with SMA are important to ensure optimal outcomes. The aim of this study was to investigate obstetric and postnatal factors that could modify clinical outcomes of mother-baby dyads with SMA.</AbstractText This is an Australian dual-center prospective cohort study of 42 consecutive mother-baby dyads with SMA (≤4 survival motor neuron 2 [<i Forty-two mother-baby dyads participated (n = 1 with 1 <i Early detection and timely administration of treatments are imperative in managing the rapid and severe loss of motor function that can occur in neonates with SMA. A personalized obstetric health care approach, prenatal testing, and planning the timing of delivery and initiation of treatment for newborns with genetically diagnosed SMA may improve outcomes.</AbstractText
|
T2 relaxometry and fMRI of the brain in late-onset restless legs syndrome. To assess in patients with late-onset idiopathic restless legs syndrome (RLS) the brain iron content with magnetic resonance relaxometry, and brain activation during dorsiflexion and plantar flexion of both feet, using fMRI.</AbstractText The study was approved by the institutional review board, and informed consent was obtained. Twenty-five RLS patients (14 women, 11 men; age range 55-82 years; mean 66.5 +/- 8.9 years; disease duration 6.5 +/- 4.5 years) and 12 sex- and age-matched controls were studied. A T1-weighted high-resolution three-dimensional spoiled gradient echo sequence was used for structural imaging, a multislice spin echo Tau2-weighted sequence was used for T2 relaxometry, and a single-shot multislice gradient echo planar sequence was used for fMRI. The motor paradigm consisted of alternating periods of rest and movement, each 40 seconds in duration. Region of interest analysis was used on the T2 relaxometry maps. Statistical parametric mapping software was used for analysis of the functional data.</AbstractText T2 relaxation time was significantly higher in patients than in controls in the substantia nigra pars compacta. Within-group analysis showed that both patients and controls activated the primary motor cortex, the primary somatosensory cortex, the somatosensory association cortex, and the middle cerebellar peduncles. Patients also activated the thalamus, putamen, middle frontal gyrus, and cingulate gyrus. Between-group analysis showed that patients had higher activation of the dorsolateral prefrontal cortex.</AbstractText Late-onset restless legs syndrome is associated with low iron content of the basal ganglia and increased activity of the dorsolateral prefrontal cortex.</AbstractText
|
Proteoglycan depletion-induced changes in transverse relaxation maps of cartilage: comparison of T2 and T1rho. The authors performed this study to (a) measure changes in T2 relaxation rates, signal-to-noise ratio (SNR), and contrast with sequential depletion of proteoglycan in cartilage; (b) determine whether there is a relationship between the T2 relaxation rate and proteoglycan in cartilage; and (c) compare the T2 mapping method with the spin-lattice relaxation time in the rotating frame (T1rho) mapping method in the quantification of proteoglycan-induced changes.</AbstractText T2- and T1rho-weighted magnetic resonance (MR) images were obtained in five bovine patellae. All images were obtained with a 4-T whole-body MR unit and a 10-cm-diameter transmit-receive quadrature birdcage coil tuned to 170 MHz. T2 and T1rho maps were computed.</AbstractText The SNR and contrast on the T2-weighted images were, on average, about 43% lower than those on the corresponding T1rho-weighted images. The T2 relaxation rates varied randomly without any particular trend, which yielded a poor correlation with sequential depletion of proteoglycan (R2 = 0.008, P < .70). There was excellent linear correlation between the percentage of proteoglycan in the tissue and the T1rho relaxation rate (R2 = 0.85, P < .0001).</AbstractText T2-weighted imaging neither yields quantitative information about the changes in proteoglycan distribution in cartilage nor can be used for longitudinal studies to quantify proteoglycan-induced changes. T1rho-weighted imaging, however, is sensitive to sequential depletion of proteoglycan in bovine cartilage and can be used to quantify proteoglycan-induced changes.</AbstractText
|
Gestational Age at Birth and Clinical Manifestations of Spinal Muscular Atrophy. Enhanced efficacy with spinal muscular atrophy (SMA) treatments is demonstrated with earlier initiation, ideally before the onset of symptoms. High-quality pregnancy and postnatal care for mother-baby dyads with SMA are important to ensure optimal outcomes. The aim of this study was to investigate obstetric and postnatal factors that could modify clinical outcomes of mother-baby dyads with SMA.</AbstractText This is an Australian dual-center prospective cohort study of 42 consecutive mother-baby dyads with SMA (≤4 survival motor neuron 2 [<i Forty-two mother-baby dyads participated (n = 1 with 1 <i Early detection and timely administration of treatments are imperative in managing the rapid and severe loss of motor function that can occur in neonates with SMA. A personalized obstetric health care approach, prenatal testing, and planning the timing of delivery and initiation of treatment for newborns with genetically diagnosed SMA may improve outcomes.</AbstractText
|
38017977
|
37664580
|
37421714
|
Improving optical sectioning with spinning disk structured illumination microscopy.
|
Stress-mediated dysregulation of the Rap1 small GTPase impairs hippocampal structure and function.
|
Arousal deregulation in the co-shaping of neuropsychological dysfunction in frontal and mesial temporal lobe epilepsy.
|
A new fluorescence microscopy technique for optical sectioning was investigated. This technique combined Spinning Disk microscopy (SD) with Structured Illumination Microscopy (SIM), resulting in more background removal than either method. Spinning Disk Structured Illumination Microscopy (SD-SIM) resulted in higher signal-to-background ratios. The method detected and quantified a dendritic spine neck that was impossible to detect with either SIM or SD alone.</AbstractText
|
The effects of repeated stress on cognitive impairment are thought to be mediated, at least in part, by reductions in the stability of dendritic spines in brain regions critical for proper learning and memory, including the hippocampus. Small GTPases are particularly potent regulators of dendritic spine formation, stability, and morphology in hippocampal neurons. Through the use of small GTPase protein profiling in mice, we identify increased levels of synaptic Rap1 in the hippocampal CA3 region in response to escalating, intermittent stress. We then demonstrate that increased Rap1 in the CA3 is sufficient in and of itself to produce stress-relevant dendritic spine and cognitive phenotypes. Further, using super-resolution imaging, we investigate how the pattern of Rap1 trafficking to synapses likely underlies its effects on the stability of select dendritic spine subtypes. These findings illuminate the involvement of aberrant Rap1 regulation in the hippocampus in contributing to the psychobiological effects of stress.</AbstractText
|
Our work aims to investigate the role of physiological arousal in the expression of neuropsychological deficits in frontal lobe epilepsy (FLE) and mesial temporal lobe epilepsy (mTLE), by drawing on the Lurian theory of brain function.</AbstractText For this study a total of 43 patients with focal onset epilepsy has been taken; twenty-four patients with FLE, 19 patients with mTLE and 26 healthy controls, all matched for age and education. Participants underwent a comprehensive neuropsychological assessment including various cognitive domains, such as attention, episodic memory, speed of information processing, response inhibition and mental flexibility, working memory, verbal fluency (phonological & semantic).</AbstractText There were no significant differences between FLE and mTLE patients in terms of neuropsychological performance. However, both FLE and mTLE patients showed significantly worse performance in several cognitive domains than HCs. The results seem to support our hypothesis that aberrant physiological arousal, as reflected in patients' worse performance in vigilance and attention, response inhibition, and processing speed, along with other disease-specific variables, may co-determine neuropsychological dysfunction and/or impairment in both FLE and mTLE.</AbstractText Identifying a differential arousal-related neuropsychological affection in FLE and mTLE, among the known deleterious effects of the functional deficit zone and other disease-related variables, may further our understanding of the underlying cognitive-pathophysiological mechanisms in focal epilepsy syndromes.</AbstractText
|
Improving optical sectioning with spinning disk structured illumination microscopy. A new fluorescence microscopy technique for optical sectioning was investigated. This technique combined Spinning Disk microscopy (SD) with Structured Illumination Microscopy (SIM), resulting in more background removal than either method. Spinning Disk Structured Illumination Microscopy (SD-SIM) resulted in higher signal-to-background ratios. The method detected and quantified a dendritic spine neck that was impossible to detect with either SIM or SD alone.</AbstractText
|
Stress-mediated dysregulation of the Rap1 small GTPase impairs hippocampal structure and function. The effects of repeated stress on cognitive impairment are thought to be mediated, at least in part, by reductions in the stability of dendritic spines in brain regions critical for proper learning and memory, including the hippocampus. Small GTPases are particularly potent regulators of dendritic spine formation, stability, and morphology in hippocampal neurons. Through the use of small GTPase protein profiling in mice, we identify increased levels of synaptic Rap1 in the hippocampal CA3 region in response to escalating, intermittent stress. We then demonstrate that increased Rap1 in the CA3 is sufficient in and of itself to produce stress-relevant dendritic spine and cognitive phenotypes. Further, using super-resolution imaging, we investigate how the pattern of Rap1 trafficking to synapses likely underlies its effects on the stability of select dendritic spine subtypes. These findings illuminate the involvement of aberrant Rap1 regulation in the hippocampus in contributing to the psychobiological effects of stress.</AbstractText
|
Arousal deregulation in the co-shaping of neuropsychological dysfunction in frontal and mesial temporal lobe epilepsy. Our work aims to investigate the role of physiological arousal in the expression of neuropsychological deficits in frontal lobe epilepsy (FLE) and mesial temporal lobe epilepsy (mTLE), by drawing on the Lurian theory of brain function.</AbstractText For this study a total of 43 patients with focal onset epilepsy has been taken; twenty-four patients with FLE, 19 patients with mTLE and 26 healthy controls, all matched for age and education. Participants underwent a comprehensive neuropsychological assessment including various cognitive domains, such as attention, episodic memory, speed of information processing, response inhibition and mental flexibility, working memory, verbal fluency (phonological & semantic).</AbstractText There were no significant differences between FLE and mTLE patients in terms of neuropsychological performance. However, both FLE and mTLE patients showed significantly worse performance in several cognitive domains than HCs. The results seem to support our hypothesis that aberrant physiological arousal, as reflected in patients' worse performance in vigilance and attention, response inhibition, and processing speed, along with other disease-specific variables, may co-determine neuropsychological dysfunction and/or impairment in both FLE and mTLE.</AbstractText Identifying a differential arousal-related neuropsychological affection in FLE and mTLE, among the known deleterious effects of the functional deficit zone and other disease-related variables, may further our understanding of the underlying cognitive-pathophysiological mechanisms in focal epilepsy syndromes.</AbstractText
|
39347234
|
35414446
|
37847449
|
Anti-GABAB Receptor Autoimmune Encephalitis: A Report of a Rare Case in Central America.
|
Paroxysmal limb dystonias associated with GABBR2 pathogenic variant: A case-based literature review.
|
Combining Physician Expertise and Women's Lived Experience to Educate Health Professionals about Preventing Fetal Alcohol Spectrum Disorders.
|
Autoimmune encephalitis (AE) is a rare disease. There have been very few reports of anti-GABAB receptor encephalitis, and no case of this subtype has ever been reported in Central America. We present a case of a 21-year-old male patient with an unremarkable previous medical history who was hospitalized because of a new onset of seizures and status epilepticus. Central nervous system infections, neoplastic disorders, cerebrovascular disease, septic and metabolic encephalopathy, and drug toxicity were ruled out. Cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis and oligoclonal bands. Initial head computed tomography (CT) scans with and without contrast were normal, and brain magnetic resonance imaging (MRI) showed no abnormalities. An electroencephalogram showed slow waves and spike waves in the frontal and temporal areas. During hospitalization, encephalopathy progressed, along with seizures and altered mental status requiring mechanical ventilation and admission to the intensive care unit. Intravenous valproic acid and phenytoin for seizure control were given. The unexplained seizures, persisting altered mental status despite the reduction of sedatives, CSF pleocytosis, and oligoclonal bands, along with reasonable exclusion of alternative disorders, suggested AE. The diagnosis was confirmed with positive anti-GABAB1-B2 receptor antibody titers in serum and CSF. A whole-body CT scan showed increased pancreatic head size, but endoscopic ultrasonography ruled out malignancy, and a normal IgG4 range excluded IgG4 disease. The patient received treatment with methylprednisolone, plasmapheresis, and immunoglobulin therapy, with excellent response. The patient has been followed up for seven months, taking immunomodulation with mycophenolate. He is seizure-free with valproic acid and levetiracetam treatment and is receiving cognitive rehabilitation after mild cognitive decline was noted in the psychometric analysis.</AbstractText
|
De novo mutations in the GABBR2 (Gamma-Aminobutyric acid Type B Receptor Subunit 2) gene have recently been reported to be associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM# 617904), as well as a Rett syndrome (RTT)-like disorder defined as a neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM# 617903).</AbstractText We describe a pediatric case carrying a de novo GABBR2 pathogenic variant and showing a phenotype encompassing RTT, epilepsy, generalized hypotonia with a paroxysmal limb dystonia.</AbstractText A 11-year-old girl, born to non-consanguineous parents after an uneventful pregnancy, had developmental delay and generalized hypotonia. At age 3.5 months she presented with infantile spasms with an electroencephalographic pattern of hypsarrhythmia. After treatment with clonazepam and prednisolone, she became seizure-free with a slow background electrical activity. Brain magnetic resonance imaging was normal. Paroxysmal dystonic posturing of the extremities, especially the upper limbs, have been observed since the age of 3 years. Motor stereotypies, non-epileptic episodes of hyperventilation and breath-holding were also reported. The girl suffered from feeding difficulties requiring gastrostomy at the age of 8. Exome sequencing (ES) revealed a de novo GABBR2 pathogenic variant (NM_005458:c.G2077T:p.G693W).</AbstractText Paroxysmal limb dystonias, especially in the context of neurodevelopmental disorder featuring epilepsy, generalized hypotonia and RTT-like features should lead to the suspect of GABBR2 mutations.</AbstractText
|
Physician Champions from the American College of Obstetricians and Gynecologists (ACOG) and trained women Speakers from FASD United, who have given birth to a child with a fetal alcohol spectrum disorder (FASD), co-present to healthcare providers (HCPs) in medical residency programs as part of an educational intervention. They present FASDs as a biological and social problem surrounded by stigma that prevent pregnant women from talking openly to their HCPs about their alcohol use or alcohol use disorder (AUD) and getting the medical help they need.</AbstractText Semi-structured interviews were conducted with 10 ACOG Champions and nine FASD United Speakers and a thematic analysis assessed how the co-presentations can enhance HCPs' understanding about FASDs and address stigma associated with alcohol use during pregnancy.</AbstractText Interview findings indicated that both Champions and Speakers emphasized the need for HCPs to be nonjudgmental and create a safe space for open dialogue. They reported that residents were moved by mothers' personal stories, wanted to understand AUD better, and asked about the type of help HCPs can offer women.</AbstractText Combining physicians' expertise with mothers' personal stories of lived experiences of FASDs directed at residents, who are more reflective and open at this phase of their careers, moved them from a fact-based to an empathy-based approach to learning that is critical to address the stigma surrounding women who may be using alcohol or struggling with an AUD during pregnancy. Collaboration between national organizations allowed this intervention to be widely implemented across the country.</AbstractText
|
Anti-GABAB Receptor Autoimmune Encephalitis: A Report of a Rare Case in Central America. Autoimmune encephalitis (AE) is a rare disease. There have been very few reports of anti-GABAB receptor encephalitis, and no case of this subtype has ever been reported in Central America. We present a case of a 21-year-old male patient with an unremarkable previous medical history who was hospitalized because of a new onset of seizures and status epilepticus. Central nervous system infections, neoplastic disorders, cerebrovascular disease, septic and metabolic encephalopathy, and drug toxicity were ruled out. Cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis and oligoclonal bands. Initial head computed tomography (CT) scans with and without contrast were normal, and brain magnetic resonance imaging (MRI) showed no abnormalities. An electroencephalogram showed slow waves and spike waves in the frontal and temporal areas. During hospitalization, encephalopathy progressed, along with seizures and altered mental status requiring mechanical ventilation and admission to the intensive care unit. Intravenous valproic acid and phenytoin for seizure control were given. The unexplained seizures, persisting altered mental status despite the reduction of sedatives, CSF pleocytosis, and oligoclonal bands, along with reasonable exclusion of alternative disorders, suggested AE. The diagnosis was confirmed with positive anti-GABAB1-B2 receptor antibody titers in serum and CSF. A whole-body CT scan showed increased pancreatic head size, but endoscopic ultrasonography ruled out malignancy, and a normal IgG4 range excluded IgG4 disease. The patient received treatment with methylprednisolone, plasmapheresis, and immunoglobulin therapy, with excellent response. The patient has been followed up for seven months, taking immunomodulation with mycophenolate. He is seizure-free with valproic acid and levetiracetam treatment and is receiving cognitive rehabilitation after mild cognitive decline was noted in the psychometric analysis.</AbstractText
|
Paroxysmal limb dystonias associated with GABBR2 pathogenic variant: A case-based literature review. De novo mutations in the GABBR2 (Gamma-Aminobutyric acid Type B Receptor Subunit 2) gene have recently been reported to be associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM# 617904), as well as a Rett syndrome (RTT)-like disorder defined as a neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM# 617903).</AbstractText We describe a pediatric case carrying a de novo GABBR2 pathogenic variant and showing a phenotype encompassing RTT, epilepsy, generalized hypotonia with a paroxysmal limb dystonia.</AbstractText A 11-year-old girl, born to non-consanguineous parents after an uneventful pregnancy, had developmental delay and generalized hypotonia. At age 3.5 months she presented with infantile spasms with an electroencephalographic pattern of hypsarrhythmia. After treatment with clonazepam and prednisolone, she became seizure-free with a slow background electrical activity. Brain magnetic resonance imaging was normal. Paroxysmal dystonic posturing of the extremities, especially the upper limbs, have been observed since the age of 3 years. Motor stereotypies, non-epileptic episodes of hyperventilation and breath-holding were also reported. The girl suffered from feeding difficulties requiring gastrostomy at the age of 8. Exome sequencing (ES) revealed a de novo GABBR2 pathogenic variant (NM_005458:c.G2077T:p.G693W).</AbstractText Paroxysmal limb dystonias, especially in the context of neurodevelopmental disorder featuring epilepsy, generalized hypotonia and RTT-like features should lead to the suspect of GABBR2 mutations.</AbstractText
|
Combining Physician Expertise and Women's Lived Experience to Educate Health Professionals about Preventing Fetal Alcohol Spectrum Disorders. Physician Champions from the American College of Obstetricians and Gynecologists (ACOG) and trained women Speakers from FASD United, who have given birth to a child with a fetal alcohol spectrum disorder (FASD), co-present to healthcare providers (HCPs) in medical residency programs as part of an educational intervention. They present FASDs as a biological and social problem surrounded by stigma that prevent pregnant women from talking openly to their HCPs about their alcohol use or alcohol use disorder (AUD) and getting the medical help they need.</AbstractText Semi-structured interviews were conducted with 10 ACOG Champions and nine FASD United Speakers and a thematic analysis assessed how the co-presentations can enhance HCPs' understanding about FASDs and address stigma associated with alcohol use during pregnancy.</AbstractText Interview findings indicated that both Champions and Speakers emphasized the need for HCPs to be nonjudgmental and create a safe space for open dialogue. They reported that residents were moved by mothers' personal stories, wanted to understand AUD better, and asked about the type of help HCPs can offer women.</AbstractText Combining physicians' expertise with mothers' personal stories of lived experiences of FASDs directed at residents, who are more reflective and open at this phase of their careers, moved them from a fact-based to an empathy-based approach to learning that is critical to address the stigma surrounding women who may be using alcohol or struggling with an AUD during pregnancy. Collaboration between national organizations allowed this intervention to be widely implemented across the country.</AbstractText
|
24553576
|
18328507
|
24680837
|
Attenuation by baclofen of nicotine rewarding properties and nicotine withdrawal manifestations.
|
Evaluation of the anxiolytic-like profile of the GABAB receptor positive modulator CGP7930 in rodents.
|
The error processing system in major depressive disorder: cortical phenotypal marker hypothesis.
|
Nicotine is a major active ingredient in tobacco and plays a major role in tobacco addiction. In rodents, repeated nicotine administration produces behavioral responses related to its addictive properties, such as reinforcing effects and physical dependence.</AbstractText The aim of the present study was to evaluate the possible role of GABAB receptor in responses induced by repeated nicotine administration in Swiss Webster mice.</AbstractText Nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.) administration induced rewarding properties in the conditioning place preference test. The GABAB receptor agonist, baclofen (3 mg/kg, i.p.) abolished the rewarding properties induced by nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.). In addition, naloxone-precipitated nicotine withdrawal induced somatic manifestations, anxiety-like effects in the elevated plus maze test and dysphoric manifestations in the conditioned place aversion paradigm. Baclofen (2 and 3 mg/kg, i.p.) prevented the somatic manifestations and the anxiety-like effects associated with naloxone-precipitated nicotine withdrawal but not the dysphoric manifestations.</AbstractText These results showed that nicotine rewarding properties and negative aspects of nicotine withdrawal, such as anxiety-like effects and somatic manifestations, can be modulated by the GABAB receptor activity. This study now reveals a novel possible application of baclofen to develop new therapeutic strategies to achieve smoking cessation.</AbstractText
|
There is a growing body of data to support the notion that GABA(B) receptors may be a therapeutic target for anxiety disorders. However, the application of GABA(B) receptor agonists in anxiety research and psychiatry is hampered by side effects that include motor in-coordination and hypothermia. Recently the GABA(B) receptor positive modulator GS39783 was shown to be anxiolytic in rodent models, but was devoid of accompanying side effects characteristic of full agonists. However, it is important to test whether such anxiolytic effects generalise to another chemical class of GABA(B) receptor positive modulators. We therefore aimed to investigate the anxiolytic and side-effect profile of CGP7930, the first-reported GABA(B) receptor positive modulator, in rodent models of anxiety, motor coordination and hypothermia. CGP7930 (3-300 mg/kg) showed a modest, compared to the benzodiazepine chlordiazepoxide (10mg/kg), dose-dependent anxiolytic profile in the mouse stress-induced hyperthermia (100mg/kg), staircase (100 and 300 mg/kg) and elevated zero maze tests (3-100mg/kg), but did not have any anxiolytic effects in the rat elevated plus maze. Similar to GS39783, CGP7930 also demonstrated a greatly reduced side-effect profile in comparison to the GABA(B) receptor full agonist baclofen in the mouse rotarod and traction wire tests and did not induce hypothermia. Although the effects of CGP7930 were modest, these results represent a second, structurally distinct, class of GABA(B) positive modulators showing anxiolytic activity. As such, these data support the premise that GABA(B) receptor positive modulation represents a novel therapeutic strategy for the development of anxiolytic drugs with a superior side-effect profile. The generation of more potent compounds is now warranted.</AbstractText
|
Major depressive disorder (MDD) ensues reduced goal-directed cognition and behaviour. Cognitive and emotional flexibility to disengage and adapt future responses was examined in the error processing system (error-related negativity/ERN, error-positivity/Pe event-related potentials) of 58 depressed patients (21 current, 37 remitted) vs. 27 controls undergoing cognitive and affective Go/NoGo paradigms. ERN was equivalent between patient and controls for the cognitive task, albeit amplitude attenuated in patients during the affective task. Blunted ERN amplitudes were evident between patients and controls in males compared to females, plausibly underpinned by disparities in dopaminergic pathways. Patients displayed enhanced Pe amplitudes for both cognitive and affective tasks. Abberations in cortical error processing in MDD appear specific to affective systems for the pre-attentive ERN, opposed to cognitive and affective processing for the consciously-integrated Pe. Heightened Pe, observed in both current and remitted patients, advocates the possibility of the Pe waveform as a candidate intermediate phenotype of depression.</AbstractText
|
Attenuation by baclofen of nicotine rewarding properties and nicotine withdrawal manifestations. Nicotine is a major active ingredient in tobacco and plays a major role in tobacco addiction. In rodents, repeated nicotine administration produces behavioral responses related to its addictive properties, such as reinforcing effects and physical dependence.</AbstractText The aim of the present study was to evaluate the possible role of GABAB receptor in responses induced by repeated nicotine administration in Swiss Webster mice.</AbstractText Nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.) administration induced rewarding properties in the conditioning place preference test. The GABAB receptor agonist, baclofen (3 mg/kg, i.p.) abolished the rewarding properties induced by nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.). In addition, naloxone-precipitated nicotine withdrawal induced somatic manifestations, anxiety-like effects in the elevated plus maze test and dysphoric manifestations in the conditioned place aversion paradigm. Baclofen (2 and 3 mg/kg, i.p.) prevented the somatic manifestations and the anxiety-like effects associated with naloxone-precipitated nicotine withdrawal but not the dysphoric manifestations.</AbstractText These results showed that nicotine rewarding properties and negative aspects of nicotine withdrawal, such as anxiety-like effects and somatic manifestations, can be modulated by the GABAB receptor activity. This study now reveals a novel possible application of baclofen to develop new therapeutic strategies to achieve smoking cessation.</AbstractText
|
Evaluation of the anxiolytic-like profile of the GABAB receptor positive modulator CGP7930 in rodents. There is a growing body of data to support the notion that GABA(B) receptors may be a therapeutic target for anxiety disorders. However, the application of GABA(B) receptor agonists in anxiety research and psychiatry is hampered by side effects that include motor in-coordination and hypothermia. Recently the GABA(B) receptor positive modulator GS39783 was shown to be anxiolytic in rodent models, but was devoid of accompanying side effects characteristic of full agonists. However, it is important to test whether such anxiolytic effects generalise to another chemical class of GABA(B) receptor positive modulators. We therefore aimed to investigate the anxiolytic and side-effect profile of CGP7930, the first-reported GABA(B) receptor positive modulator, in rodent models of anxiety, motor coordination and hypothermia. CGP7930 (3-300 mg/kg) showed a modest, compared to the benzodiazepine chlordiazepoxide (10mg/kg), dose-dependent anxiolytic profile in the mouse stress-induced hyperthermia (100mg/kg), staircase (100 and 300 mg/kg) and elevated zero maze tests (3-100mg/kg), but did not have any anxiolytic effects in the rat elevated plus maze. Similar to GS39783, CGP7930 also demonstrated a greatly reduced side-effect profile in comparison to the GABA(B) receptor full agonist baclofen in the mouse rotarod and traction wire tests and did not induce hypothermia. Although the effects of CGP7930 were modest, these results represent a second, structurally distinct, class of GABA(B) positive modulators showing anxiolytic activity. As such, these data support the premise that GABA(B) receptor positive modulation represents a novel therapeutic strategy for the development of anxiolytic drugs with a superior side-effect profile. The generation of more potent compounds is now warranted.</AbstractText
|
The error processing system in major depressive disorder: cortical phenotypal marker hypothesis. Major depressive disorder (MDD) ensues reduced goal-directed cognition and behaviour. Cognitive and emotional flexibility to disengage and adapt future responses was examined in the error processing system (error-related negativity/ERN, error-positivity/Pe event-related potentials) of 58 depressed patients (21 current, 37 remitted) vs. 27 controls undergoing cognitive and affective Go/NoGo paradigms. ERN was equivalent between patient and controls for the cognitive task, albeit amplitude attenuated in patients during the affective task. Blunted ERN amplitudes were evident between patients and controls in males compared to females, plausibly underpinned by disparities in dopaminergic pathways. Patients displayed enhanced Pe amplitudes for both cognitive and affective tasks. Abberations in cortical error processing in MDD appear specific to affective systems for the pre-attentive ERN, opposed to cognitive and affective processing for the consciously-integrated Pe. Heightened Pe, observed in both current and remitted patients, advocates the possibility of the Pe waveform as a candidate intermediate phenotype of depression.</AbstractText
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32208153
|
23813661
|
32812615
|
Social Neuroscience: Rats Can Be Considerate to Others.
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Perceiving nonverbal behavior: neural correlates of processing movement fluency and contingency in dyadic interactions.
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Synergistic regulation of longitudinal and transverse relaxivity of extremely small iron oxide nanoparticles (ESIONPs) using pH-responsive nanoassemblies.
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Are rats willing to avoid causing suffering in other rats? A new study shows that rats might change their behaviour if it is harmful to others.</AbstractText
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Despite the fact that nonverbal dyadic social interactions are abundant in the environment, the neural mechanisms underlying their processing are not yet fully understood. Research in the field of social neuroscience has suggested that two neural networks appear to be involved in social understanding: (1) the action observation network (AON) and (2) the social neural network (SNN). The aim of this study was to determine the differential contributions of the AON and the SNN to the processing of nonverbal behavior as observed in dyadic social interactions. To this end, we used short computer animation sequences displaying dyadic social interactions between two virtual characters and systematically manipulated two key features of movement activity, which are known to influence the perception of meaning in nonverbal stimuli: (1) movement fluency and (2) contingency of movement patterns. A group of 21 male participants rated the "naturalness" of the observed scenes on a four-point scale while undergoing fMRI. Behavioral results showed that both fluency and contingency significantly influenced the "naturalness" experience of the presented animations. Neurally, the AON was preferentially engaged when processing contingent movement patterns, but did not discriminate between different degrees of movement fluency. In contrast, regions of the SNN were engaged more strongly when observing dyads with disturbed movement fluency. In conclusion, while the AON is involved in the general processing of contingent social actions, irrespective of their kinematic properties, the SNN is preferentially recruited when atypical kinematic properties prompt inferences about the agents' intentions.</AbstractText
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Extremely small iron oxide nanoparticles (ESIONPs), as a kind of the special T1 magnetic resonance imaging (MRI) contrast agent that can provide T1 contrasting enhancement since their magnetically disordered shells are dominant compared to their magnetic cores and have powerful potential for constructing stimuli-responsive contrast agents (CAs) to realize precise the tumor diagnosis with high specificity and sensitivity. The stimuli-responsive function of ESIONPs-based CAs can be directly endowed through the synergistic regulation of the longitudinal and transverse relaxivity (r1 and r2) of ESIONPs. However, the systematical investigation for the synergistic regulation of r1 and r2 of ESIONPs is quite lacking. Herein, based on the relaxivity theories, three kinds of ESIONPs-based nanoassemblies with pH-responsiveness were designed and constructed to explore the possibility of various synergistic regulations on r1 and r2. When three kinds of ESIONPs-based nanoassemblies were converted to dissociated ones under a weak acid environment, ESIONPs micelle could realize a synergistic regulation of the single r2 decrease along with the stable r1, while gold nanoparticles-ESIONPs (AuNPs-ESIONPs) vesicle could provide a synergistic regulation comprising the single r1 increase along with the stable r2, and ESIONPs vesicle could offer a synergistic regulation involving the r2 decrease together with the r1 increase. Moreover, all the synergistic regulations on r1 and r2 were efficient strategies to fabricate ESIONPs-based CAs with the stimuli-responsive function. These systematic and feasible synergistic regulations of r1 and r2 may guide and promote the development of ESIONPs-based stimuli-responsive CAs for the highly sensitive and specific tumor diagnosis.</AbstractText
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Social Neuroscience: Rats Can Be Considerate to Others. Are rats willing to avoid causing suffering in other rats? A new study shows that rats might change their behaviour if it is harmful to others.</AbstractText
|
Perceiving nonverbal behavior: neural correlates of processing movement fluency and contingency in dyadic interactions. Despite the fact that nonverbal dyadic social interactions are abundant in the environment, the neural mechanisms underlying their processing are not yet fully understood. Research in the field of social neuroscience has suggested that two neural networks appear to be involved in social understanding: (1) the action observation network (AON) and (2) the social neural network (SNN). The aim of this study was to determine the differential contributions of the AON and the SNN to the processing of nonverbal behavior as observed in dyadic social interactions. To this end, we used short computer animation sequences displaying dyadic social interactions between two virtual characters and systematically manipulated two key features of movement activity, which are known to influence the perception of meaning in nonverbal stimuli: (1) movement fluency and (2) contingency of movement patterns. A group of 21 male participants rated the "naturalness" of the observed scenes on a four-point scale while undergoing fMRI. Behavioral results showed that both fluency and contingency significantly influenced the "naturalness" experience of the presented animations. Neurally, the AON was preferentially engaged when processing contingent movement patterns, but did not discriminate between different degrees of movement fluency. In contrast, regions of the SNN were engaged more strongly when observing dyads with disturbed movement fluency. In conclusion, while the AON is involved in the general processing of contingent social actions, irrespective of their kinematic properties, the SNN is preferentially recruited when atypical kinematic properties prompt inferences about the agents' intentions.</AbstractText
|
Synergistic regulation of longitudinal and transverse relaxivity of extremely small iron oxide nanoparticles (ESIONPs) using pH-responsive nanoassemblies. Extremely small iron oxide nanoparticles (ESIONPs), as a kind of the special T1 magnetic resonance imaging (MRI) contrast agent that can provide T1 contrasting enhancement since their magnetically disordered shells are dominant compared to their magnetic cores and have powerful potential for constructing stimuli-responsive contrast agents (CAs) to realize precise the tumor diagnosis with high specificity and sensitivity. The stimuli-responsive function of ESIONPs-based CAs can be directly endowed through the synergistic regulation of the longitudinal and transverse relaxivity (r1 and r2) of ESIONPs. However, the systematical investigation for the synergistic regulation of r1 and r2 of ESIONPs is quite lacking. Herein, based on the relaxivity theories, three kinds of ESIONPs-based nanoassemblies with pH-responsiveness were designed and constructed to explore the possibility of various synergistic regulations on r1 and r2. When three kinds of ESIONPs-based nanoassemblies were converted to dissociated ones under a weak acid environment, ESIONPs micelle could realize a synergistic regulation of the single r2 decrease along with the stable r1, while gold nanoparticles-ESIONPs (AuNPs-ESIONPs) vesicle could provide a synergistic regulation comprising the single r1 increase along with the stable r2, and ESIONPs vesicle could offer a synergistic regulation involving the r2 decrease together with the r1 increase. Moreover, all the synergistic regulations on r1 and r2 were efficient strategies to fabricate ESIONPs-based CAs with the stimuli-responsive function. These systematic and feasible synergistic regulations of r1 and r2 may guide and promote the development of ESIONPs-based stimuli-responsive CAs for the highly sensitive and specific tumor diagnosis.</AbstractText
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37201892
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31641052
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37346949
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Sensory gating functions of the auditory thalamus: Adaptation and modulations through noise-exposure and high-frequency stimulation in rats.
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Alpha Oscillations in the Human Brain Implement Distractor Suppression Independent of Target Selection.
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Investigation of the structure, phase transitions, molecular dynamics, and ferroelasticity of organic-inorganic hybrid NH(CH(3))(3)CdCl(3) crystals.
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The medial geniculate body (MGB) of the thalamus is an obligatory relay for auditory processing. A breakdown of adaptive filtering and sensory gating at this level may lead to multiple auditory dysfunctions, while high-frequency stimulation (HFS) of the MGB might mitigate aberrant sensory gating. To further investigate the sensory gating functions of the MGB, this study (i) recorded electrophysiological evoked potentials in response to continuous auditory stimulation, and (ii) assessed the effect of MGB HFS on these responses in noise-exposed and control animals. Pure-tone sequences were presented to assess differential sensory gating functions associated with stimulus pitch, grouping (pairing), and temporal regularity. Evoked potentials were recorded from the MGB and acquired before and after HFS (100 Hz). All animals (unexposed and noise-exposed, pre- and post-HFS) showed gating for pitch and grouping. Unexposed animals also showed gating for temporal regularity not found in noise-exposed animals. Moreover, only noise-exposed animals showed restoration comparable to the typical EP amplitude suppression following MGB HFS. The current findings confirm adaptive thalamic sensory gating based on different sound characteristics and provide evidence that temporal regularity affects MGB auditory signaling.</AbstractText
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In principle, selective attention is the net result of target selection and distractor suppression. The way in which both mechanisms are implemented neurally has remained contested. Neural oscillatory power in the alpha frequency band (∼10 Hz) has been implicated in the selection of to-be-attended targets, but there is lack of empirical evidence for its involvement in the suppression of to-be-ignored distractors. Here, we use electroencephalography recordings of <i
|
Understanding the physical and chemical properties of the organic-inorganic hybrid NH(CH<sub
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Sensory gating functions of the auditory thalamus: Adaptation and modulations through noise-exposure and high-frequency stimulation in rats. The medial geniculate body (MGB) of the thalamus is an obligatory relay for auditory processing. A breakdown of adaptive filtering and sensory gating at this level may lead to multiple auditory dysfunctions, while high-frequency stimulation (HFS) of the MGB might mitigate aberrant sensory gating. To further investigate the sensory gating functions of the MGB, this study (i) recorded electrophysiological evoked potentials in response to continuous auditory stimulation, and (ii) assessed the effect of MGB HFS on these responses in noise-exposed and control animals. Pure-tone sequences were presented to assess differential sensory gating functions associated with stimulus pitch, grouping (pairing), and temporal regularity. Evoked potentials were recorded from the MGB and acquired before and after HFS (100 Hz). All animals (unexposed and noise-exposed, pre- and post-HFS) showed gating for pitch and grouping. Unexposed animals also showed gating for temporal regularity not found in noise-exposed animals. Moreover, only noise-exposed animals showed restoration comparable to the typical EP amplitude suppression following MGB HFS. The current findings confirm adaptive thalamic sensory gating based on different sound characteristics and provide evidence that temporal regularity affects MGB auditory signaling.</AbstractText
|
Alpha Oscillations in the Human Brain Implement Distractor Suppression Independent of Target Selection. In principle, selective attention is the net result of target selection and distractor suppression. The way in which both mechanisms are implemented neurally has remained contested. Neural oscillatory power in the alpha frequency band (∼10 Hz) has been implicated in the selection of to-be-attended targets, but there is lack of empirical evidence for its involvement in the suppression of to-be-ignored distractors. Here, we use electroencephalography recordings of <i
|
Investigation of the structure, phase transitions, molecular dynamics, and ferroelasticity of organic-inorganic hybrid NH(CH(3))(3)CdCl(3) crystals. Understanding the physical and chemical properties of the organic-inorganic hybrid NH(CH<sub
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38755252
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35915381
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36645725
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Multi-scale coupled attention for visual object detection.
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Microsaccades as a long-term oculomotor correlate in visual perceptual learning.
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Are Mindfulness and Mind-Wandering Opposite Constructs? It Depends on How Mindfulness is Conceptualised.
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The application of deep neural network has achieved remarkable success in object detection. However, the network structures should be still evolved consistently and tuned finely to acquire better performance. This gears to the continuous demands on high performance in those complex scenes, where multi-scale objects to be detected are located here and there. To this end, this paper proposes a network structure called Multi-Scale Coupled Attention (MSCA) under the framework of self-attention learning with methodologies of importance assessment. Architecturally, it consists of a Multi-Scale Coupled Channel Attention (MSCCA) module, and a Multi-Scale Coupled Spatial Attention (MSCSA) module. Specifically, the MSCCA module is developed to achieve the goal of self-attention learning linearly on the multi-scale channels. In parallel, the MSCSA module is constructed to achieve this goal nonlinearly on the multi-scale spatial grids. The MSCCA and MSSCA modules can be connected together into a sequence, which can be used as a plugin to develop end-to-end learning models for object detection. Finally, our proposed network is compared on two public datasets with 13 classical or state-of-the-art models, including the Faster R-CNN, Cascade R-CNN, RetinaNet, SSD, PP-YOLO, YOLO v3, YOLO v5, YOLO v7, YOLOX, DETR, conditional DETR, UP-DETR and FP-DETR. Comparative experimental results with numerical scores, the ablation study, and the performance behaviour all demonstrate the effectiveness of our proposed model.</AbstractText
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Human perceptual learning, experience-induced gains in sensory discrimination, typically yields long-term performance improvements. Recent research revealed long-lasting transfer at the untrained location enabled by feature-based attention (FBA), reminiscent of its global effect (Hung & Carrasco, Scientific Reports, 11(1), 13914, (2021)). Visual Perceptual Learning (VPL) is typically studied while observers maintain fixation, but the role of fixational eye movements is unknown. Microsaccades - the largest of fixational eye movements - provide a continuous, online, physiological measure from the oculomotor system that reveals dynamic processing, which is unavailable from behavioral measures alone. We investigated whether and how microsaccades change after training in an orientation discrimination task. For human observers trained with or without FBA, microsaccade rates were significantly reduced during the response window in both trained and untrained locations and orientations. Critically, consistent with long-term training benefits, this microsaccade-rate reduction persisted over a year. Furthermore, microsaccades were biased toward the target location prior to stimulus onset and were more suppressed for incorrect than correct trials after observers' responses. These findings reveal that fixational eye movements and VPL are tightly coupled and that learning-induced microsaccade changes are long lasting. Thus, microsaccades reflect functional dynamics of the oculomotor system during information encoding, maintenance and readout, and may serve as a reliable long-term physiological correlate in VPL.</AbstractText
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This study investigated if trait mindfulness and its components, mindful attention, acceptance, and non-judging correlate negatively with self-reported and indirect markers of mind-wandering. The 552 participants of the study completed an anonymous online questionnaire consisting of trait mindfulness and mind-wandering scales. They also completed the computer-based Sustained Attention to Response Task (SART), an objective measure of mind-wandering. The total mindfulness score and acceptance and non-judging subscale scores were strongly negatively correlated with both self-reported trait mind-wandering (TMW) and SART indices of mind-wandering. In contrast, attention was significantly positively correlated with both. These findings suggest that trait mindfulness conceptualised as a multi-component construct, but not a uni-component one, is probably an opposing construct to trait mind-wandering. Furthermore, mindfulness and its components, acceptance and non-judging, are associated with a reduction in the more common form of SART errors. However, only the acceptance component made a unique contribution to the variance in TMW and SART performance. Therefore, it is advisable for researchers to specify whether they investigated mindfulness as a uni-component or multi-component construct. Furthermore, it would be beneficial if future research investigates the relationship of mindfulness and its components with mind-wandering further by also incorporating a measure of state mindfulness.</AbstractText
|
Multi-scale coupled attention for visual object detection. The application of deep neural network has achieved remarkable success in object detection. However, the network structures should be still evolved consistently and tuned finely to acquire better performance. This gears to the continuous demands on high performance in those complex scenes, where multi-scale objects to be detected are located here and there. To this end, this paper proposes a network structure called Multi-Scale Coupled Attention (MSCA) under the framework of self-attention learning with methodologies of importance assessment. Architecturally, it consists of a Multi-Scale Coupled Channel Attention (MSCCA) module, and a Multi-Scale Coupled Spatial Attention (MSCSA) module. Specifically, the MSCCA module is developed to achieve the goal of self-attention learning linearly on the multi-scale channels. In parallel, the MSCSA module is constructed to achieve this goal nonlinearly on the multi-scale spatial grids. The MSCCA and MSSCA modules can be connected together into a sequence, which can be used as a plugin to develop end-to-end learning models for object detection. Finally, our proposed network is compared on two public datasets with 13 classical or state-of-the-art models, including the Faster R-CNN, Cascade R-CNN, RetinaNet, SSD, PP-YOLO, YOLO v3, YOLO v5, YOLO v7, YOLOX, DETR, conditional DETR, UP-DETR and FP-DETR. Comparative experimental results with numerical scores, the ablation study, and the performance behaviour all demonstrate the effectiveness of our proposed model.</AbstractText
|
Microsaccades as a long-term oculomotor correlate in visual perceptual learning. Human perceptual learning, experience-induced gains in sensory discrimination, typically yields long-term performance improvements. Recent research revealed long-lasting transfer at the untrained location enabled by feature-based attention (FBA), reminiscent of its global effect (Hung & Carrasco, Scientific Reports, 11(1), 13914, (2021)). Visual Perceptual Learning (VPL) is typically studied while observers maintain fixation, but the role of fixational eye movements is unknown. Microsaccades - the largest of fixational eye movements - provide a continuous, online, physiological measure from the oculomotor system that reveals dynamic processing, which is unavailable from behavioral measures alone. We investigated whether and how microsaccades change after training in an orientation discrimination task. For human observers trained with or without FBA, microsaccade rates were significantly reduced during the response window in both trained and untrained locations and orientations. Critically, consistent with long-term training benefits, this microsaccade-rate reduction persisted over a year. Furthermore, microsaccades were biased toward the target location prior to stimulus onset and were more suppressed for incorrect than correct trials after observers' responses. These findings reveal that fixational eye movements and VPL are tightly coupled and that learning-induced microsaccade changes are long lasting. Thus, microsaccades reflect functional dynamics of the oculomotor system during information encoding, maintenance and readout, and may serve as a reliable long-term physiological correlate in VPL.</AbstractText
|
Are Mindfulness and Mind-Wandering Opposite Constructs? It Depends on How Mindfulness is Conceptualised. This study investigated if trait mindfulness and its components, mindful attention, acceptance, and non-judging correlate negatively with self-reported and indirect markers of mind-wandering. The 552 participants of the study completed an anonymous online questionnaire consisting of trait mindfulness and mind-wandering scales. They also completed the computer-based Sustained Attention to Response Task (SART), an objective measure of mind-wandering. The total mindfulness score and acceptance and non-judging subscale scores were strongly negatively correlated with both self-reported trait mind-wandering (TMW) and SART indices of mind-wandering. In contrast, attention was significantly positively correlated with both. These findings suggest that trait mindfulness conceptualised as a multi-component construct, but not a uni-component one, is probably an opposing construct to trait mind-wandering. Furthermore, mindfulness and its components, acceptance and non-judging, are associated with a reduction in the more common form of SART errors. However, only the acceptance component made a unique contribution to the variance in TMW and SART performance. Therefore, it is advisable for researchers to specify whether they investigated mindfulness as a uni-component or multi-component construct. Furthermore, it would be beneficial if future research investigates the relationship of mindfulness and its components with mind-wandering further by also incorporating a measure of state mindfulness.</AbstractText
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31998179
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29528683
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31841538
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Persistent Effects of Musical Training on Mathematical Skills of Children With Developmental Dyscalculia.
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Conceptual size in developmental dyscalculia and dyslexia.
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Radiocarbon, Bayesian chronological modeling and early European metal circulation in the sixteenth-century AD Mohawk River Valley, USA.
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Musical training (MT) is perceived as a multi-sensory program that simultaneously integrates visual, aural, oral, and kinesthetic senses. Furthermore, MT stimulates cognitive functions in a ludic way instead of tapping straight into the traditional context of school learning, including mathematics. Nevertheless, the efficacy of MT over mathematics remains understudied, especially concerning longstanding effects. For this reason, this longitudinal study explored the impact of MT on numerical cognition and abstract visual reasoning using a double-blind and quasi-experimental design. We assessed two groups of children from primary schools, namely one with developmental dyscalculia [DD; <i
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People suffering from developmental dyscalculia (DD) are known to have impairment in numerical abilities and have been found to have weaker processing of countable magnitudes. However, not much research was done on their abilities to process noncountable magnitudes. An example of noncountable magnitude is conceptual size (e.g., mouse is small and elephant is big). Recently, we found that adults process conceptual size automatically. The current study examined automatic processing of conceptual size in students with DD and developmental dyslexia.</AbstractText Conceptual and physical sizes were manipulated orthogonally to create congruent (e.g., a physically small apple compared to a physically large violin) and incongruent (e.g., a physically large apple compared to a physically small violin) conditions. Participants were presented with 2 objects and had to choose the larger one. Each trial began with an instruction to respond to the physical or to the conceptual dimension.</AbstractText Control and the dyslexic groups presented automatic processing of both conceptual and physical sizes. The dyscalculic group presented automatic processing of physical size but not automaticity of processing conceptual size.</AbstractText Our results fit with previous findings of weaker magnitude representation in those with DD, specifically regarding noncountable magnitudes, and support theories of a shared neurocognitive substrate for different types of magnitudes. (PsycINFO Database Record</AbstractText
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European metal artifacts in assemblages from sites predating the physical presence of Europeans in Northern Iroquoia in present-day New York, USA and southern Ontario, Canada have been used as chronological markers for the mid-sixteenth century AD. In the Mohawk River Valley of New York, European metal artifacts at sites pre-dating the physical presence of Europeans have been used by archaeologists as a terminus post quem (TPQ) of 1525 to 1550 in regional chronologies. This has been done under the assumption that these metals did not begin to circulate until after sustained European presence on the northern Atlantic coast beginning in 1517. Here we use Bayesian chronological modeling of a large set of radiocarbon dates to refine our understanding of early European metal circulation in the Mohawk River Valley. Our results indicate that European iron and cuprous metals arrived earlier than previously thought, by the beginning of the sixteenth century, and cannot be used as TPQs. Together with recent Bayesian chronological analyses of radiocarbon dates from several sites in southern Ontario, these results add to our evolving understanding of intra-regional variation in Northern Iroquoia of sixteenth-century AD circulation and adoption of European goods.</AbstractText
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Persistent Effects of Musical Training on Mathematical Skills of Children With Developmental Dyscalculia. Musical training (MT) is perceived as a multi-sensory program that simultaneously integrates visual, aural, oral, and kinesthetic senses. Furthermore, MT stimulates cognitive functions in a ludic way instead of tapping straight into the traditional context of school learning, including mathematics. Nevertheless, the efficacy of MT over mathematics remains understudied, especially concerning longstanding effects. For this reason, this longitudinal study explored the impact of MT on numerical cognition and abstract visual reasoning using a double-blind and quasi-experimental design. We assessed two groups of children from primary schools, namely one with developmental dyscalculia [DD; <i
|
Conceptual size in developmental dyscalculia and dyslexia. People suffering from developmental dyscalculia (DD) are known to have impairment in numerical abilities and have been found to have weaker processing of countable magnitudes. However, not much research was done on their abilities to process noncountable magnitudes. An example of noncountable magnitude is conceptual size (e.g., mouse is small and elephant is big). Recently, we found that adults process conceptual size automatically. The current study examined automatic processing of conceptual size in students with DD and developmental dyslexia.</AbstractText Conceptual and physical sizes were manipulated orthogonally to create congruent (e.g., a physically small apple compared to a physically large violin) and incongruent (e.g., a physically large apple compared to a physically small violin) conditions. Participants were presented with 2 objects and had to choose the larger one. Each trial began with an instruction to respond to the physical or to the conceptual dimension.</AbstractText Control and the dyslexic groups presented automatic processing of both conceptual and physical sizes. The dyscalculic group presented automatic processing of physical size but not automaticity of processing conceptual size.</AbstractText Our results fit with previous findings of weaker magnitude representation in those with DD, specifically regarding noncountable magnitudes, and support theories of a shared neurocognitive substrate for different types of magnitudes. (PsycINFO Database Record</AbstractText
|
Radiocarbon, Bayesian chronological modeling and early European metal circulation in the sixteenth-century AD Mohawk River Valley, USA. European metal artifacts in assemblages from sites predating the physical presence of Europeans in Northern Iroquoia in present-day New York, USA and southern Ontario, Canada have been used as chronological markers for the mid-sixteenth century AD. In the Mohawk River Valley of New York, European metal artifacts at sites pre-dating the physical presence of Europeans have been used by archaeologists as a terminus post quem (TPQ) of 1525 to 1550 in regional chronologies. This has been done under the assumption that these metals did not begin to circulate until after sustained European presence on the northern Atlantic coast beginning in 1517. Here we use Bayesian chronological modeling of a large set of radiocarbon dates to refine our understanding of early European metal circulation in the Mohawk River Valley. Our results indicate that European iron and cuprous metals arrived earlier than previously thought, by the beginning of the sixteenth century, and cannot be used as TPQs. Together with recent Bayesian chronological analyses of radiocarbon dates from several sites in southern Ontario, these results add to our evolving understanding of intra-regional variation in Northern Iroquoia of sixteenth-century AD circulation and adoption of European goods.</AbstractText
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36186848
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20920478
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35911886
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Aptamer engineering exosomes loaded on biomimetic periosteum to promote angiogenesis and bone regeneration by targeting injured nerves via JNK3 MAPK pathway.
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Differentiation of neural stem cells into Schwann-like cells in vitro.
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Movement Disorders Associated With Cerebral Artery Stenosis: A Nationwide Study.
|
Repairing critical bone defects is a complex problem in the clinic. The periosteum rich in nerve plays a vital role in initiating and regulating bone regeneration. However, current studies have paid little attention to repairing nerves in the periosteum to promote bone regeneration. Thus, it is essential to construct bionic periosteum with the targeted injured nerves in the periosteum. We coupled phosphatidylserine (PS) targeted aptamers with repair Schwann cell exosomes to construct exosome@aptamer (EA). Then through PEI, EA was successfully built on the surface of the electrospun fiber, which was PCL@PEI@exosome@aptamer (PPEA). Through SEM, TEM, and other technologies, PPEA was characterized. Experiments prove in vivo and in vitro that it has an excellent repair effect on damaged nerves and regeneration of vascular and bones. In vivo, we confirmed that biomimetic periosteum has an apparent ability to promote nerve and bone regeneration by using Microcomputer tomography, hematoxylin-eosin, Masson, and Immunofluorescence. In vitro, we used Immunofluorescence, Real-Time Quantitative PCR, Alkaline phosphatase staining, and other tests to confirm that it has central nerve, blood vessel, and bone regeneration ability. The PPEA biomimetic periosteum has apparent neurogenic, angiogenic, and osteogenic effects. The PPEA biomimetic periosteum will provide a promising method for treating bone defects.</AbstractText
|
Neural stem cells (NSCs) are multipotent stem cells that have the potential to differentiate into different cells of the neural lineage like neurons, astrocytes and oligodendrocytes. In the current work, we explored whether NSCs could be differentiated into functional Schwann-like cells, which has not been investigated up to date. NSCs were harvested from the hippocampus of rats and identified by single cell cloning and immunofluorescence staining. Then NSCs were treated with DMEM/F12 supplemented with forskolin, heregulin, bFGF, PDGF-AA and retinoic acid (RA). Differentiated NSCs (dNSCs) exhibited a spindle-like morphology similar to Schwann cells and expressed the glial markers p75 and S100. We also found that dNSCs could enhance neurite outgrowth when co-cultured with NG108-15 cells. These results indicated that NSCs, derived from hippocampus of rats, could differentiate into Schwann-like cells with morphological, phenotypic and functional similarities.</AbstractText
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Studies of secondary movement disorder (MD) caused by cerebrovascular diseases have primarily focused on post-stroke MD. However, MD can also result from cerebral artery stenosis (CAS) without clinical manifestations of stroke. In this study, we aimed to investigate the clinical characteristics of MD associated with CAS.</AbstractText A nationwide multicenter retrospective analysis was performed based on the data from patients with CAS-associated MDs from 16 MD specialized clinics in South Korea, available between January 1999 and September 2019. CAS was defined as the >50% luminal stenosis of the major cerebral arteries. The association between MD and CAS was determined by MD specialists using pre-defined clinical criteria. The collected clinical information included baseline demographics, features of MD, characteristics of CAS, treatment, and MD outcomes. Statistical analyses were performed to identify factors associated with the MD outcomes.</AbstractText The data from a total of 81 patients with CAS-associated MD were analyzed. The mean age of MD onset was 60.5 ± 19.7 years. Chorea was the most common MD (57%), followed by tremor/limb-shaking, myoclonus, and dystonia. Atherosclerosis was the most common etiology of CAS (78%), with the remaining cases attributed to moyamoya disease (MMD). Relative to patients with atherosclerosis, those with MMD developed MD at a younger age (<i This study highlights the spectrum of CAS-associated with MD across the country. A progressive, age-dependent functional neuronal modulation in the basal ganglia due to CAS may underlie this condition.</AbstractText
|
Aptamer engineering exosomes loaded on biomimetic periosteum to promote angiogenesis and bone regeneration by targeting injured nerves via JNK3 MAPK pathway. Repairing critical bone defects is a complex problem in the clinic. The periosteum rich in nerve plays a vital role in initiating and regulating bone regeneration. However, current studies have paid little attention to repairing nerves in the periosteum to promote bone regeneration. Thus, it is essential to construct bionic periosteum with the targeted injured nerves in the periosteum. We coupled phosphatidylserine (PS) targeted aptamers with repair Schwann cell exosomes to construct exosome@aptamer (EA). Then through PEI, EA was successfully built on the surface of the electrospun fiber, which was PCL@PEI@exosome@aptamer (PPEA). Through SEM, TEM, and other technologies, PPEA was characterized. Experiments prove in vivo and in vitro that it has an excellent repair effect on damaged nerves and regeneration of vascular and bones. In vivo, we confirmed that biomimetic periosteum has an apparent ability to promote nerve and bone regeneration by using Microcomputer tomography, hematoxylin-eosin, Masson, and Immunofluorescence. In vitro, we used Immunofluorescence, Real-Time Quantitative PCR, Alkaline phosphatase staining, and other tests to confirm that it has central nerve, blood vessel, and bone regeneration ability. The PPEA biomimetic periosteum has apparent neurogenic, angiogenic, and osteogenic effects. The PPEA biomimetic periosteum will provide a promising method for treating bone defects.</AbstractText
|
Differentiation of neural stem cells into Schwann-like cells in vitro. Neural stem cells (NSCs) are multipotent stem cells that have the potential to differentiate into different cells of the neural lineage like neurons, astrocytes and oligodendrocytes. In the current work, we explored whether NSCs could be differentiated into functional Schwann-like cells, which has not been investigated up to date. NSCs were harvested from the hippocampus of rats and identified by single cell cloning and immunofluorescence staining. Then NSCs were treated with DMEM/F12 supplemented with forskolin, heregulin, bFGF, PDGF-AA and retinoic acid (RA). Differentiated NSCs (dNSCs) exhibited a spindle-like morphology similar to Schwann cells and expressed the glial markers p75 and S100. We also found that dNSCs could enhance neurite outgrowth when co-cultured with NG108-15 cells. These results indicated that NSCs, derived from hippocampus of rats, could differentiate into Schwann-like cells with morphological, phenotypic and functional similarities.</AbstractText
|
Movement Disorders Associated With Cerebral Artery Stenosis: A Nationwide Study. Studies of secondary movement disorder (MD) caused by cerebrovascular diseases have primarily focused on post-stroke MD. However, MD can also result from cerebral artery stenosis (CAS) without clinical manifestations of stroke. In this study, we aimed to investigate the clinical characteristics of MD associated with CAS.</AbstractText A nationwide multicenter retrospective analysis was performed based on the data from patients with CAS-associated MDs from 16 MD specialized clinics in South Korea, available between January 1999 and September 2019. CAS was defined as the >50% luminal stenosis of the major cerebral arteries. The association between MD and CAS was determined by MD specialists using pre-defined clinical criteria. The collected clinical information included baseline demographics, features of MD, characteristics of CAS, treatment, and MD outcomes. Statistical analyses were performed to identify factors associated with the MD outcomes.</AbstractText The data from a total of 81 patients with CAS-associated MD were analyzed. The mean age of MD onset was 60.5 ± 19.7 years. Chorea was the most common MD (57%), followed by tremor/limb-shaking, myoclonus, and dystonia. Atherosclerosis was the most common etiology of CAS (78%), with the remaining cases attributed to moyamoya disease (MMD). Relative to patients with atherosclerosis, those with MMD developed MD at a younger age (<i This study highlights the spectrum of CAS-associated with MD across the country. A progressive, age-dependent functional neuronal modulation in the basal ganglia due to CAS may underlie this condition.</AbstractText
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40769196
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35787839
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40358729
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α-Synuclein Drives SNARE-Dependent Tubular Remodeling of Vesicles.
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Functional and Pathological Effects of α-Synuclein on Synaptic SNARE Complexes.
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Sleep disorders and psychological comorbidities in women with polycystic ovary syndrome - a cross-sectional study.
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α-Synuclein (α-syn) disrupts synaptic vesicle architecture in Parkinson's disease (PD), yet the underlying mechanisms remain unclear. Here, we identify a previously unrecognized phenomenon in which α-syn (≥20 μM) rapidly induces SNARE-dependent tubular protrusions on highly curved small unilamellar vesicles (∼45 nm in diameter). This process requires functional v- and t-SNAREs, as neither v-SNARE nor t-SNARE alone, nor predocked SNARE complexes or CDV-treated SNARE liposomes, support tubulation. Notably, the familial PD-associated mutations A30P and E46K enhance tubule formation, whereas A53T exhibits minimal activity. Disrupting the α-syn-VAMP2 interaction abolishes tubulation, directly linking this interface to vesicle remodeling. Tubule formation increases with α-syn concentration, impairs SNARE-mediated membrane fusion, and significantly modulates α-syn liquid-liquid phase separation (LLPS), underscoring its pathological relevance. These findings reveal a novel mechanism by which α-syn remodels vesicle architecture, providing deeper insights into synaptic dysfunction in PD.</AbstractText
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α-Synuclein is an abundant protein at the neuronal synapse that has been implicated in Parkinson's disease for over 25 years and characterizes the hallmark pathology of a group of neurodegenerative diseases now known as the synucleinopathies. Physiologically, α-synuclein exists in an equilibrium between a synaptic vesicle membrane-bound α-helical multimer and a cytosolic largely unstructured monomer. Through its membrane-bound state, α-synuclein functions in neurotransmitter release by modulating several steps in the synaptic vesicle cycle, including synaptic vesicle clustering and docking, SNARE complex assembly, and homeostasis of synaptic vesicle pools. These functions have been ascribed to α-synuclein's interactions with the synaptic vesicle SNARE protein VAMP2/synaptobrevin-2, the synaptic vesicle-attached synapsins, and the synaptic vesicle membrane itself. How α-synuclein affects these processes, and whether disease is due to loss-of-function or gain-of-toxic-function of α-synuclein remains unclear. In this review, we provide an in-depth summary of the existing literature, discuss possible reasons for the discrepancies in the field, and propose a working model that reconciles the findings in the literature.</AbstractText
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Polycystic ovary syndrome (PCOS) is a metabolic and hormonal disorder that affects physical and emotional well-being. The aim of this cross-sectional study was to assess associated factors like sleep disturbance, obstructive sleep apnea (OSA), anxiety and depression in a German-speaking population with PCOS.</AbstractText We designed an anonymous online survey with items from validated questionnaires, including the Hospital Anxiety and Depression Scale (HADS), the Generalized Anxiety Disorder (GAD-7), the Pittsburgh Sleep Quality Index (PSQI) and the STOP-Bang questionnaire to screen for OSA. The survey was mainly distributed via social media in Austria, Germany and Switzerland. Data from 587 questionnaires were analyzed.</AbstractText Based on the STOP Bang questionnaire, 19.5% of women had a high probability for OSA. BMI and insulin resistance were identified as independent associated factors with OSA (both p < 0.001). Overall, the median anxiety score (GAD-7) was in the moderate range (Median 10.0, Interquartile range (IQR) 8.0). According to the HADS, association with moderate to severe anxiety (HADS-A) was 52.0% and with moderate to severe depression (HADS-D) 27.8%. There was a significant positive correlation between HADS-A/ HADS-D and BMI (r = 0.122, (HADS-A)/ r = 0.223 (HADS-D), both p < 0.01). According to the PSQI, 60.5% had mild sleep disturbance and 29.7% had chronic sleep disturbance. Chronic sleep disturbance was associated with anxiety disorders and depression, as well as a high probability of OSA (p < 0.001) after adjustment for age.</AbstractText Our study highlights the probability of depression, anxiety and sleep disorders, including OSA, in women with PCOS and their association with BMI and insulin resistance.</AbstractText
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α-Synuclein Drives SNARE-Dependent Tubular Remodeling of Vesicles. α-Synuclein (α-syn) disrupts synaptic vesicle architecture in Parkinson's disease (PD), yet the underlying mechanisms remain unclear. Here, we identify a previously unrecognized phenomenon in which α-syn (≥20 μM) rapidly induces SNARE-dependent tubular protrusions on highly curved small unilamellar vesicles (∼45 nm in diameter). This process requires functional v- and t-SNAREs, as neither v-SNARE nor t-SNARE alone, nor predocked SNARE complexes or CDV-treated SNARE liposomes, support tubulation. Notably, the familial PD-associated mutations A30P and E46K enhance tubule formation, whereas A53T exhibits minimal activity. Disrupting the α-syn-VAMP2 interaction abolishes tubulation, directly linking this interface to vesicle remodeling. Tubule formation increases with α-syn concentration, impairs SNARE-mediated membrane fusion, and significantly modulates α-syn liquid-liquid phase separation (LLPS), underscoring its pathological relevance. These findings reveal a novel mechanism by which α-syn remodels vesicle architecture, providing deeper insights into synaptic dysfunction in PD.</AbstractText
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Functional and Pathological Effects of α-Synuclein on Synaptic SNARE Complexes. α-Synuclein is an abundant protein at the neuronal synapse that has been implicated in Parkinson's disease for over 25 years and characterizes the hallmark pathology of a group of neurodegenerative diseases now known as the synucleinopathies. Physiologically, α-synuclein exists in an equilibrium between a synaptic vesicle membrane-bound α-helical multimer and a cytosolic largely unstructured monomer. Through its membrane-bound state, α-synuclein functions in neurotransmitter release by modulating several steps in the synaptic vesicle cycle, including synaptic vesicle clustering and docking, SNARE complex assembly, and homeostasis of synaptic vesicle pools. These functions have been ascribed to α-synuclein's interactions with the synaptic vesicle SNARE protein VAMP2/synaptobrevin-2, the synaptic vesicle-attached synapsins, and the synaptic vesicle membrane itself. How α-synuclein affects these processes, and whether disease is due to loss-of-function or gain-of-toxic-function of α-synuclein remains unclear. In this review, we provide an in-depth summary of the existing literature, discuss possible reasons for the discrepancies in the field, and propose a working model that reconciles the findings in the literature.</AbstractText
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Sleep disorders and psychological comorbidities in women with polycystic ovary syndrome - a cross-sectional study. Polycystic ovary syndrome (PCOS) is a metabolic and hormonal disorder that affects physical and emotional well-being. The aim of this cross-sectional study was to assess associated factors like sleep disturbance, obstructive sleep apnea (OSA), anxiety and depression in a German-speaking population with PCOS.</AbstractText We designed an anonymous online survey with items from validated questionnaires, including the Hospital Anxiety and Depression Scale (HADS), the Generalized Anxiety Disorder (GAD-7), the Pittsburgh Sleep Quality Index (PSQI) and the STOP-Bang questionnaire to screen for OSA. The survey was mainly distributed via social media in Austria, Germany and Switzerland. Data from 587 questionnaires were analyzed.</AbstractText Based on the STOP Bang questionnaire, 19.5% of women had a high probability for OSA. BMI and insulin resistance were identified as independent associated factors with OSA (both p < 0.001). Overall, the median anxiety score (GAD-7) was in the moderate range (Median 10.0, Interquartile range (IQR) 8.0). According to the HADS, association with moderate to severe anxiety (HADS-A) was 52.0% and with moderate to severe depression (HADS-D) 27.8%. There was a significant positive correlation between HADS-A/ HADS-D and BMI (r = 0.122, (HADS-A)/ r = 0.223 (HADS-D), both p < 0.01). According to the PSQI, 60.5% had mild sleep disturbance and 29.7% had chronic sleep disturbance. Chronic sleep disturbance was associated with anxiety disorders and depression, as well as a high probability of OSA (p < 0.001) after adjustment for age.</AbstractText Our study highlights the probability of depression, anxiety and sleep disorders, including OSA, in women with PCOS and their association with BMI and insulin resistance.</AbstractText
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36293431
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32348981
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36274444
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Dysregulated Hemostasis and Immunothrombosis in Cerebral Cavernous Malformations.
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Cavernous Malformation Hemorrhagic Presentation at Diagnosis Associated with Low 25-Hydroxy-Vitamin D Level.
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The role of the basal ganglia and cerebellum in adaptation to others' speech rate and rhythm: A study of patients with Parkinson's disease and cerebellar degeneration.
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Cerebral cavernous malformation (CCM) is a neurovascular disease that affects 0.5% of the general population. For a long time, CCM research focused on genetic mutations, endothelial junctions and proliferation, but recently, transcriptome and proteome studies have revealed that the hemostatic system and neuroinflammation play a crucial role in the development and severity of cavernomas, with some of these publications coming from our group. The aim of this review is to give an overview of the latest molecular insights into the interaction between CCM-deficient endothelial cells with blood components and the neurovascular unit. Specifically, we underscore how endothelial dysfunction can result in dysregulated hemostasis, bleeding, hypoxia and neurological symptoms. We conducted a thorough review of the literature and found a field that is increasingly poised to regard CCM as a hemostatic disease, which may have implications for therapy.</AbstractText
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Cavernous malformations (CM) are angiographically occult vascular malformations that may be incidental or present with intracerebral or spinal hemorrhage, seizures, or nonhemorrhagic focal neurologic deficit (FND). Recently in vitro data have suggested vitamin D may play a role in stabilizing CCM2 endothelial cells. Little is known about the effect of vitamin D in human CM disease.</AbstractText Beginning in 2015, consecutive patients at our institution with radiologically confirmed CM were recruited to participate in a prospective clinical registry as well as 25-hydroxy-vitamin D study. A structured interview, survey, and examination were performed at baseline. Medical records and magnetic resonance imaging studies were reviewed and data collected included comorbid conditions, medication use, and location of CM. Standard definition of clinical hemorrhage, FND, and seizures was used. Univariate and multivariate logistic regression models were used, and OR, 95% CIs, and likelihood-ratio p values were calculated to determine the influence of the 25-hydroxy-vitamin D level on clinical presentation with hemorrhage.</AbstractText Of 213 patients enrolled in the clinical registry between January 2015 and October 2018, 70 participated in the vitamin D study (median age: 38.3 years; 51.4% female). Of the 70 participants, 30 (42.9%) presented with hemorrhage. 25-Hydroxy-vitamin D levels were performed within 1 year of symptoms in 64.1% of patients. Patients presenting with hemorrhage had a lower 25-hydroxy-vitamin D level compared to those presenting with seizure without hemorrhage, FND, or as an incidental finding (median 25.5 ng/mL; range 11-59 hemorrhage vs. median 31.0; range 14-60, no hemorrhage; p = 0.04). After adjusting for age, month of blood draw, and body mass index, 25-hydroxy-vitamin D remained a significant predictor of hemorrhagic presentation. Brainstem location also predicted hemorrhage at presentation.</AbstractText Low 25-hydroxy-vitamin D level was more common in patients with CM presenting with hemorrhage. This study supports the potential role of modifiable factor in the initial clinical presentation of CM. Further study is needed to determine the role of vitamin D on prospective hemorrhage risk and whether supplementation may be beneficial.</AbstractText
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Spoken language is constantly undergoing change: Speakers within and across social and regional groups influence each other's speech, leading to the emergence and drifts of accents in a language. These processes are driven by mutual unintentional imitation of the phonetic details of others' speech in conversational interactions, suggesting that continuous auditory-motor adaptation takes place in interactive language use and plasticity of auditory-motor representations of speech persists across the lifespan. The brain mechanisms underlying this large-scale social-linguistic behavior are still poorly understood.</AbstractText To investigate the role of cerebellar and basal ganglia dysfunctions in unintended adaptation to the speech rhythm and articulation rate of a second speaker.</AbstractText Twelve patients with spinocerebellar ataxia type 6 (SCA6), 15 patients with Parkinson's disease (PD), and 27 neurologically healthy controls (CTRL) participated in two interactive speech tasks, i.e., sentence repetition and "turn-taking" (i.e., dyadic interaction with sentences produced by a model speaker). Production of scripted sentences was used as a control task. Two types of sentence rhythm were distinguished, i.e., regular and irregular, and model speech rate was manipulated in 12 steps between 2.9 and 4.0 syllables per second. Acoustic analyses of the participants' utterances were performed to determine the extent to which participants adapted their speech rate and rhythm to the model.</AbstractText Neurologically healthy speakers showed significant adaptation of rate in all conditions, and of rhythm in the repetition task and partly also the turn-taking task. Patients with PD showed a stronger propensity to adapt than the controls. In contrast, the patients with cerebellar degeneration were largely insensitive to the model speaker's rate and rhythm. Contrary to expectations, sentences with an irregular speech rhythm exerted a stronger adaptive attraction than regular sentences in the two patient groups.</AbstractText Cerebellar degeneration inhibits the propensity to covertly adapt to others' speech. Striatal dysfunction in Parkinson's disease spares or even promotes the tendency to accommodate to other speakers' speech rate and rhythm.</AbstractText
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Dysregulated Hemostasis and Immunothrombosis in Cerebral Cavernous Malformations. Cerebral cavernous malformation (CCM) is a neurovascular disease that affects 0.5% of the general population. For a long time, CCM research focused on genetic mutations, endothelial junctions and proliferation, but recently, transcriptome and proteome studies have revealed that the hemostatic system and neuroinflammation play a crucial role in the development and severity of cavernomas, with some of these publications coming from our group. The aim of this review is to give an overview of the latest molecular insights into the interaction between CCM-deficient endothelial cells with blood components and the neurovascular unit. Specifically, we underscore how endothelial dysfunction can result in dysregulated hemostasis, bleeding, hypoxia and neurological symptoms. We conducted a thorough review of the literature and found a field that is increasingly poised to regard CCM as a hemostatic disease, which may have implications for therapy.</AbstractText
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Cavernous Malformation Hemorrhagic Presentation at Diagnosis Associated with Low 25-Hydroxy-Vitamin D Level. Cavernous malformations (CM) are angiographically occult vascular malformations that may be incidental or present with intracerebral or spinal hemorrhage, seizures, or nonhemorrhagic focal neurologic deficit (FND). Recently in vitro data have suggested vitamin D may play a role in stabilizing CCM2 endothelial cells. Little is known about the effect of vitamin D in human CM disease.</AbstractText Beginning in 2015, consecutive patients at our institution with radiologically confirmed CM were recruited to participate in a prospective clinical registry as well as 25-hydroxy-vitamin D study. A structured interview, survey, and examination were performed at baseline. Medical records and magnetic resonance imaging studies were reviewed and data collected included comorbid conditions, medication use, and location of CM. Standard definition of clinical hemorrhage, FND, and seizures was used. Univariate and multivariate logistic regression models were used, and OR, 95% CIs, and likelihood-ratio p values were calculated to determine the influence of the 25-hydroxy-vitamin D level on clinical presentation with hemorrhage.</AbstractText Of 213 patients enrolled in the clinical registry between January 2015 and October 2018, 70 participated in the vitamin D study (median age: 38.3 years; 51.4% female). Of the 70 participants, 30 (42.9%) presented with hemorrhage. 25-Hydroxy-vitamin D levels were performed within 1 year of symptoms in 64.1% of patients. Patients presenting with hemorrhage had a lower 25-hydroxy-vitamin D level compared to those presenting with seizure without hemorrhage, FND, or as an incidental finding (median 25.5 ng/mL; range 11-59 hemorrhage vs. median 31.0; range 14-60, no hemorrhage; p = 0.04). After adjusting for age, month of blood draw, and body mass index, 25-hydroxy-vitamin D remained a significant predictor of hemorrhagic presentation. Brainstem location also predicted hemorrhage at presentation.</AbstractText Low 25-hydroxy-vitamin D level was more common in patients with CM presenting with hemorrhage. This study supports the potential role of modifiable factor in the initial clinical presentation of CM. Further study is needed to determine the role of vitamin D on prospective hemorrhage risk and whether supplementation may be beneficial.</AbstractText
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The role of the basal ganglia and cerebellum in adaptation to others' speech rate and rhythm: A study of patients with Parkinson's disease and cerebellar degeneration. Spoken language is constantly undergoing change: Speakers within and across social and regional groups influence each other's speech, leading to the emergence and drifts of accents in a language. These processes are driven by mutual unintentional imitation of the phonetic details of others' speech in conversational interactions, suggesting that continuous auditory-motor adaptation takes place in interactive language use and plasticity of auditory-motor representations of speech persists across the lifespan. The brain mechanisms underlying this large-scale social-linguistic behavior are still poorly understood.</AbstractText To investigate the role of cerebellar and basal ganglia dysfunctions in unintended adaptation to the speech rhythm and articulation rate of a second speaker.</AbstractText Twelve patients with spinocerebellar ataxia type 6 (SCA6), 15 patients with Parkinson's disease (PD), and 27 neurologically healthy controls (CTRL) participated in two interactive speech tasks, i.e., sentence repetition and "turn-taking" (i.e., dyadic interaction with sentences produced by a model speaker). Production of scripted sentences was used as a control task. Two types of sentence rhythm were distinguished, i.e., regular and irregular, and model speech rate was manipulated in 12 steps between 2.9 and 4.0 syllables per second. Acoustic analyses of the participants' utterances were performed to determine the extent to which participants adapted their speech rate and rhythm to the model.</AbstractText Neurologically healthy speakers showed significant adaptation of rate in all conditions, and of rhythm in the repetition task and partly also the turn-taking task. Patients with PD showed a stronger propensity to adapt than the controls. In contrast, the patients with cerebellar degeneration were largely insensitive to the model speaker's rate and rhythm. Contrary to expectations, sentences with an irregular speech rhythm exerted a stronger adaptive attraction than regular sentences in the two patient groups.</AbstractText Cerebellar degeneration inhibits the propensity to covertly adapt to others' speech. Striatal dysfunction in Parkinson's disease spares or even promotes the tendency to accommodate to other speakers' speech rate and rhythm.</AbstractText
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40516005
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39414359
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40599865
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From neurotoxicity to neuroprotection: Rethinking GABA(A)R-targeting anesthetics.
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Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain.
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Case Report: Somatic malignancy classified as Wilms tumor arising within an immature teratoma.
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The brain growth spurt (BGS) represents a pivotal window in neurodevelopment, defined by rapid neurogenesis, heightened synaptogenesis, and the dynamic establishment of neural networks. During this phase, heightened brain plasticity significantly enhances learning and memory abilities, while also increasing the brain's susceptibility to disruptions. Anesthetics, particularly those targeting γ-aminobutyric acid type A receptors (GABA<sub
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Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spatial transcriptomics and multiplexed fluorescent in situ hybridization.</AbstractText We computationally examined the spatial expression of various canonical neurogenesis markers in postmortem dentate gyrus (DG) sections from young and middle-aged sudden-death males. We conducted in situ assessment of markers expressed in neural stem cells, proliferative cells, and immature granule neurons in postmortem DG sections from infant, adolescent, and middle-aged males.</AbstractText We examined frozen DG tissue from infant (<i The study was limited by small sample sizes and included samples only from males.</AbstractText Our findings indicate very low levels of hippocampal neurogenesis throughout life and the existence of a local reserve of plasticity in the adult human hippocampus. Overall, our study provides important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus.</AbstractText
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Nongeminomatous germ cell tumors (NGGCTs) are aggressive malignancies known for their rapid metastatic potential. Teratomas, a subtype of NGGCTs, can be classified as either mature (benign) or immature (malignant). Immature teratomas carry a higher metastatic risk than mature teratomas due to their embryonic-like tissue composition. Intracranial teratomas are rare in nature and can develop secondary malignancies, such as Wilms tumors. We report the case of a 70-year-old man with a history of prostate cancer who presented with neurological symptoms and was diagnosed with a Wilms tumor arising from an immature teratoma. A heterogenous morphology, including squamous, cartilaginous, and neural differentiation, was revealed upon surgical resection. Despite interventions, the patient experienced rapid disease progression and eventually passed away in hospice care 7 months after the initial diagnosis. This case highlights the complexity of diagnosing and managing NGGCTs, particularly when secondary malignancies arise. Ultimately, it underscores the need for careful diagnosis and precise therapeutic strategies to manage these tumors.</AbstractText
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From neurotoxicity to neuroprotection: Rethinking GABA(A)R-targeting anesthetics. The brain growth spurt (BGS) represents a pivotal window in neurodevelopment, defined by rapid neurogenesis, heightened synaptogenesis, and the dynamic establishment of neural networks. During this phase, heightened brain plasticity significantly enhances learning and memory abilities, while also increasing the brain's susceptibility to disruptions. Anesthetics, particularly those targeting γ-aminobutyric acid type A receptors (GABA<sub
|
Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain. Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spatial transcriptomics and multiplexed fluorescent in situ hybridization.</AbstractText We computationally examined the spatial expression of various canonical neurogenesis markers in postmortem dentate gyrus (DG) sections from young and middle-aged sudden-death males. We conducted in situ assessment of markers expressed in neural stem cells, proliferative cells, and immature granule neurons in postmortem DG sections from infant, adolescent, and middle-aged males.</AbstractText We examined frozen DG tissue from infant (<i The study was limited by small sample sizes and included samples only from males.</AbstractText Our findings indicate very low levels of hippocampal neurogenesis throughout life and the existence of a local reserve of plasticity in the adult human hippocampus. Overall, our study provides important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus.</AbstractText
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Case Report: Somatic malignancy classified as Wilms tumor arising within an immature teratoma. Nongeminomatous germ cell tumors (NGGCTs) are aggressive malignancies known for their rapid metastatic potential. Teratomas, a subtype of NGGCTs, can be classified as either mature (benign) or immature (malignant). Immature teratomas carry a higher metastatic risk than mature teratomas due to their embryonic-like tissue composition. Intracranial teratomas are rare in nature and can develop secondary malignancies, such as Wilms tumors. We report the case of a 70-year-old man with a history of prostate cancer who presented with neurological symptoms and was diagnosed with a Wilms tumor arising from an immature teratoma. A heterogenous morphology, including squamous, cartilaginous, and neural differentiation, was revealed upon surgical resection. Despite interventions, the patient experienced rapid disease progression and eventually passed away in hospice care 7 months after the initial diagnosis. This case highlights the complexity of diagnosing and managing NGGCTs, particularly when secondary malignancies arise. Ultimately, it underscores the need for careful diagnosis and precise therapeutic strategies to manage these tumors.</AbstractText
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38330968
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39276808
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38876917
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Biomarkers of Cartilage Composition.
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POSE: POSition Encoding for accelerated quantitative MRI.
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Radiomics and Clinical Data for the Diagnosis of Incidental Pulmonary Nodules and Lung Cancer Screening: Radiolung Integrative Predictive Model.
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Magnetic resonance imaging (MRI) has significantly advanced the understanding of osteoarthritis (OA) because it enables visualization of noncalcified tissues. Cartilage is avascular and nurtured by diffusion, so it has a very low turnover and limited capabilities of repair. Consequently, prevention of structural and detection of premorphological damage is key in maintaining cartilage health. The integrity of cartilage composition and ultrastructure determines its mechanical properties but is not accessible to morphological imaging. Therefore, various techniques of compositional MRI with and without use of intravenous contrast medium have been developed. Spin-spin relaxation time (T2) and spin-lattice relaxation time constant in rotating frame (T1rho) mapping, the most studied cartilage biomarkers, were included in the recent standardization effort by the Quantitative Imaging Biomarkers Alliance (QIBA) that aims to make compositional MRI of cartilage clinically feasible and comparable. Additional techniques that are less frequently used include ultrashort echo time with T2*, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), glycosaminoglycan concentration by chemical exchange-dependent saturation transfer (gagCEST), sodium imaging, and diffusion-weighted MRI.</AbstractText
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Quantitative MRI utilizes multiple acquisitions with varying sequence parameters to sufficiently characterize a biophysical model of interest, resulting in undesirable scan times. Here we propose, validate and demonstrate a new general strategy for accelerating MRI using subvoxel shifting as a source of encoding called POSition Encoding (POSE). The POSE framework applies unique subvoxel shifts along the acquisition parameter dimension, thereby creating an extra source of encoding. Combining with a biophysical signal model of interest, accelerated and enhanced resolution maps of biophysical parameters are obtained. This has been validated and demonstrated through numerical Bloch equation simulations, phantom experiments and in vivo experiments using the variable flip angle signal model in 3D acquisitions as an application example. Monte Carlo simulations were performed using in vivo data to investigate our method's noise performance. POSE quantification results from numerical Bloch equation simulations of both a numerical phantom and realistic digital brain phantom concur well with the reference method, validating our method both theoretically and for realistic situations. NIST phantom experiment results show excellent overall agreement with the reference method, confirming our method's applicability for a wide range of T<sub
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Early diagnosis of lung cancer (LC) is crucial to improve survival rates. Radiomics models hold promise for enhancing LC diagnosis. This study assesses the impact of integrating a clinical and a radiomic model based on deep learning to predict the malignancy of pulmonary nodules (PN).</AbstractText Prospective cross-sectional study of 97 PNs from 93 patients. Clinical data included epidemiological risk factors and pulmonary function tests. The region of interest of each chest CT containing the PN was analysed. The radiomic model employed a pre-trained convolutional network to extract visual features. From these features, 500 with a positive standard deviation were chosen as inputs for an optimised neural network. The clinical model was estimated by a logistic regression model using clinical data. The malignancy probability from the clinical model was used as the best estimate of the pre-test probability of disease to update the malignancy probability of the radiomic model using a nomogram for Bayes' theorem.</AbstractText The radiomic model had a positive predictive value (PPV) of 86%, an accuracy of 79% and an AUC of 0.67. The clinical model identified DLCO, obstruction index and smoking status as the most consistent clinical predictors associated with outcome. Integrating the clinical features into the deep-learning radiomic model achieves a PPV of 94%, an accuracy of 76% and an AUC of 0.80.</AbstractText Incorporating clinical data into a deep-learning radiomic model improved PN malignancy assessment, boosting predictive performance. This study supports the potential of combined image-based and clinical features to improve LC diagnosis.</AbstractText
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Biomarkers of Cartilage Composition. Magnetic resonance imaging (MRI) has significantly advanced the understanding of osteoarthritis (OA) because it enables visualization of noncalcified tissues. Cartilage is avascular and nurtured by diffusion, so it has a very low turnover and limited capabilities of repair. Consequently, prevention of structural and detection of premorphological damage is key in maintaining cartilage health. The integrity of cartilage composition and ultrastructure determines its mechanical properties but is not accessible to morphological imaging. Therefore, various techniques of compositional MRI with and without use of intravenous contrast medium have been developed. Spin-spin relaxation time (T2) and spin-lattice relaxation time constant in rotating frame (T1rho) mapping, the most studied cartilage biomarkers, were included in the recent standardization effort by the Quantitative Imaging Biomarkers Alliance (QIBA) that aims to make compositional MRI of cartilage clinically feasible and comparable. Additional techniques that are less frequently used include ultrashort echo time with T2*, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), glycosaminoglycan concentration by chemical exchange-dependent saturation transfer (gagCEST), sodium imaging, and diffusion-weighted MRI.</AbstractText
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POSE: POSition Encoding for accelerated quantitative MRI. Quantitative MRI utilizes multiple acquisitions with varying sequence parameters to sufficiently characterize a biophysical model of interest, resulting in undesirable scan times. Here we propose, validate and demonstrate a new general strategy for accelerating MRI using subvoxel shifting as a source of encoding called POSition Encoding (POSE). The POSE framework applies unique subvoxel shifts along the acquisition parameter dimension, thereby creating an extra source of encoding. Combining with a biophysical signal model of interest, accelerated and enhanced resolution maps of biophysical parameters are obtained. This has been validated and demonstrated through numerical Bloch equation simulations, phantom experiments and in vivo experiments using the variable flip angle signal model in 3D acquisitions as an application example. Monte Carlo simulations were performed using in vivo data to investigate our method's noise performance. POSE quantification results from numerical Bloch equation simulations of both a numerical phantom and realistic digital brain phantom concur well with the reference method, validating our method both theoretically and for realistic situations. NIST phantom experiment results show excellent overall agreement with the reference method, confirming our method's applicability for a wide range of T<sub
|
Radiomics and Clinical Data for the Diagnosis of Incidental Pulmonary Nodules and Lung Cancer Screening: Radiolung Integrative Predictive Model. Early diagnosis of lung cancer (LC) is crucial to improve survival rates. Radiomics models hold promise for enhancing LC diagnosis. This study assesses the impact of integrating a clinical and a radiomic model based on deep learning to predict the malignancy of pulmonary nodules (PN).</AbstractText Prospective cross-sectional study of 97 PNs from 93 patients. Clinical data included epidemiological risk factors and pulmonary function tests. The region of interest of each chest CT containing the PN was analysed. The radiomic model employed a pre-trained convolutional network to extract visual features. From these features, 500 with a positive standard deviation were chosen as inputs for an optimised neural network. The clinical model was estimated by a logistic regression model using clinical data. The malignancy probability from the clinical model was used as the best estimate of the pre-test probability of disease to update the malignancy probability of the radiomic model using a nomogram for Bayes' theorem.</AbstractText The radiomic model had a positive predictive value (PPV) of 86%, an accuracy of 79% and an AUC of 0.67. The clinical model identified DLCO, obstruction index and smoking status as the most consistent clinical predictors associated with outcome. Integrating the clinical features into the deep-learning radiomic model achieves a PPV of 94%, an accuracy of 76% and an AUC of 0.80.</AbstractText Incorporating clinical data into a deep-learning radiomic model improved PN malignancy assessment, boosting predictive performance. This study supports the potential of combined image-based and clinical features to improve LC diagnosis.</AbstractText
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39172288
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32446162
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39472760
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Profile of miRNA expression in the hippocampus of epileptic mice and the prediction of potential therapeutic targets.
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Influence of stiripentol on perampanel serum levels.
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QualityNet: A multi-stream fusion framework with spatial and channel attention for blind image quality assessment.
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Epilepsy is a common neurological disease. Increasing evidence has highlighted the role of miRNAs in the molecular mechanisms underlying the development of neurological diseases such as epilepsy. In this study, we established a lithium chloride-pilocarpine epilepsy mouse model, performed miRNA sequencing of hippocampal tissue samples, and compared the obtained miRNA expression profile with that of normal control mice to determine differences in expression levels. We found that 55 miRNAs were differentially expressed in status epilepticus mice compared with normal control mice, with 38 upregulated and 17 downregulated miRNAs. Through subsequent analysis of the five downregulated miRNAs (mmu-let-7a-1-3p, mmu-let-7a-2-3p, mmu-let-7c-5p, mmu-let-7d-5p, and mmu-let-7e-5p) with the most significant differences in expression, the key pathways involved included the MAPK signaling pathway and focal adhesion, among others. Therefore, we believe that let-7 family miRNAs may be potential therapeutic targets for epilepsy.</AbstractText
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Stiripentol is an orphan drug successfully used in combination with valproate and clobazam in the treatment of Dravet syndrome. Perampanel has also been added by experts. In this retrospective study, we investigated the influence of stiripentol on perampanel serum levels by using the doses and corresponding perampanel serum levels of 10 patients. The impact of stiripentol on the perampanel serum levels was significant as shown in a linear regression analysis, with perampanel serum levels increasing linearly with the stiripentol doses. We conclude that dose adjustments of stiripentol and perampanel when administered together, should be done carefully to avoid side effects or even severe intoxication. Hence, perampanel serum level monitoring seems advisable.</AbstractText
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This study introduces a novel Blind Image Quality Assessment (BIQA) approach leveraging a multi-stream spatial and channel attention model. Our method addresses challenges posed by diverse image content and distortions by integrating feature maps from two distinct backbones. Through spatial and channel attention mechanisms, our algorithm prioritizes regions of interest, enhancing its ability to capture crucial image details. Extensive evaluations on four benchmark datasets demonstrate superior performance compared to existing methods, closely aligning with human perceptual assessment. Our approach exhibits exceptional generalization capabilities on both authentic and synthetic distortion databases. Moreover, it demonstrates a distinctive focus on perceptual foreground information, enhancing its practical applicability. Thorough quantitative analyses underscore the algorithm's superior performance, establishing its dominance over existing methods.</AbstractText
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Profile of miRNA expression in the hippocampus of epileptic mice and the prediction of potential therapeutic targets. Epilepsy is a common neurological disease. Increasing evidence has highlighted the role of miRNAs in the molecular mechanisms underlying the development of neurological diseases such as epilepsy. In this study, we established a lithium chloride-pilocarpine epilepsy mouse model, performed miRNA sequencing of hippocampal tissue samples, and compared the obtained miRNA expression profile with that of normal control mice to determine differences in expression levels. We found that 55 miRNAs were differentially expressed in status epilepticus mice compared with normal control mice, with 38 upregulated and 17 downregulated miRNAs. Through subsequent analysis of the five downregulated miRNAs (mmu-let-7a-1-3p, mmu-let-7a-2-3p, mmu-let-7c-5p, mmu-let-7d-5p, and mmu-let-7e-5p) with the most significant differences in expression, the key pathways involved included the MAPK signaling pathway and focal adhesion, among others. Therefore, we believe that let-7 family miRNAs may be potential therapeutic targets for epilepsy.</AbstractText
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Influence of stiripentol on perampanel serum levels. Stiripentol is an orphan drug successfully used in combination with valproate and clobazam in the treatment of Dravet syndrome. Perampanel has also been added by experts. In this retrospective study, we investigated the influence of stiripentol on perampanel serum levels by using the doses and corresponding perampanel serum levels of 10 patients. The impact of stiripentol on the perampanel serum levels was significant as shown in a linear regression analysis, with perampanel serum levels increasing linearly with the stiripentol doses. We conclude that dose adjustments of stiripentol and perampanel when administered together, should be done carefully to avoid side effects or even severe intoxication. Hence, perampanel serum level monitoring seems advisable.</AbstractText
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QualityNet: A multi-stream fusion framework with spatial and channel attention for blind image quality assessment. This study introduces a novel Blind Image Quality Assessment (BIQA) approach leveraging a multi-stream spatial and channel attention model. Our method addresses challenges posed by diverse image content and distortions by integrating feature maps from two distinct backbones. Through spatial and channel attention mechanisms, our algorithm prioritizes regions of interest, enhancing its ability to capture crucial image details. Extensive evaluations on four benchmark datasets demonstrate superior performance compared to existing methods, closely aligning with human perceptual assessment. Our approach exhibits exceptional generalization capabilities on both authentic and synthetic distortion databases. Moreover, it demonstrates a distinctive focus on perceptual foreground information, enhancing its practical applicability. Thorough quantitative analyses underscore the algorithm's superior performance, establishing its dominance over existing methods.</AbstractText
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23489778
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26530395
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23932402
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The effects of working memory training on functional brain network efficiency.
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Aberrant topological patterns of brain structural network in temporal lobe epilepsy.
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Dauer-specific dendrite arborization in C. elegans is regulated by KPC-1/Furin.
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The human brain is a highly interconnected network. Recent studies have shown that the functional and anatomical features of this network are organized in an efficient small-world manner that confers high efficiency of information processing at relatively low connection cost. However, it has been unclear how the architecture of functional brain networks is related to performance in working memory (WM) tasks and if these networks can be modified by WM training. Therefore, we conducted a double-blind training study enrolling 66 young adults. Half of the subjects practiced three WM tasks and were compared to an active control group practicing three tasks with low WM demand. High-density resting-state electroencephalography (EEG) was recorded before and after training to analyze graph-theoretical functional network characteristics at an intracortical level. WM performance was uniquely correlated with power in the theta frequency, and theta power was increased by WM training. Moreover, the better a person's WM performance, the more their network exhibited small-world topology. WM training shifted network characteristics in the direction of high performers, showing increased small-worldness within a distributed fronto-parietal network. Taken together, this is the first longitudinal study that provides evidence for the plasticity of the functional brain network underlying WM.</AbstractText
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Although altered large-scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as cortical thickness, these studies, have not included critical subcortical structures (such as hippocampus and amygdala) and have had relatively small sample sizes. Here, we investigated differences in topological organization of the brain volumetric networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy.</AbstractText We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches.</AbstractText We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased global efficiency and increased local efficiency and clustering coefficient. LTLE also displayed a more pronounced network disruption. Contrary to controls, hub nodes in both TLE groups were not distributed across whole brain, but rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE.</AbstractText These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology.</AbstractText
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Dendrites often display remarkably complex and diverse morphologies that are influenced by developmental and environmental cues. Neuroplasticity in response to adverse environmental conditions entails both hypertrophy and resorption of dendrites. How dendrites rapidly alter morphology in response to unfavorable environmental conditions is unclear. The nematode Caenorhabditis elegans enters into a stress-resistant dauer larval stage in response to an adverse environment.</AbstractText Here we show that the IL2 bipolar sensory neurons undergo dendrite arborization and axon remodeling during dauer development. When dauer larvae are returned to favorable environmental conditions, animals resume reproductive development and IL2 dendritic branches retract, leaving behind remnant branches in postdauer L4 and adult animals. The C. elegans furin homolog KPC-1 is required for dauer IL2 dendritic arborization and dauer-specific nictation behavior. KPC-1 is also necessary for dendritic arborization of PVD and FLP sensory neurons. In mammals, furin is essential, ubiquitously expressed, and associated with numerous pathologies, including neurodegenerative diseases. While broadly expressed in C. elegans neurons and epithelia, KPC-1 acts cell autonomously in IL2 neurons to regulate dauer-specific dendritic arborization and nictation.</AbstractText Neuroplasticity of the C. elegans IL2 sensory neurons provides a paradigm to study stress-induced and reversible dendritic branching, and the role of environmental and developmental cues in this process. The newly discovered role of KPC-1 in dendrite morphogenesis provides insight into the function of proprotein convertases in nervous system development.</AbstractText
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The effects of working memory training on functional brain network efficiency. The human brain is a highly interconnected network. Recent studies have shown that the functional and anatomical features of this network are organized in an efficient small-world manner that confers high efficiency of information processing at relatively low connection cost. However, it has been unclear how the architecture of functional brain networks is related to performance in working memory (WM) tasks and if these networks can be modified by WM training. Therefore, we conducted a double-blind training study enrolling 66 young adults. Half of the subjects practiced three WM tasks and were compared to an active control group practicing three tasks with low WM demand. High-density resting-state electroencephalography (EEG) was recorded before and after training to analyze graph-theoretical functional network characteristics at an intracortical level. WM performance was uniquely correlated with power in the theta frequency, and theta power was increased by WM training. Moreover, the better a person's WM performance, the more their network exhibited small-world topology. WM training shifted network characteristics in the direction of high performers, showing increased small-worldness within a distributed fronto-parietal network. Taken together, this is the first longitudinal study that provides evidence for the plasticity of the functional brain network underlying WM.</AbstractText
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Aberrant topological patterns of brain structural network in temporal lobe epilepsy. Although altered large-scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as cortical thickness, these studies, have not included critical subcortical structures (such as hippocampus and amygdala) and have had relatively small sample sizes. Here, we investigated differences in topological organization of the brain volumetric networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy.</AbstractText We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches.</AbstractText We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased global efficiency and increased local efficiency and clustering coefficient. LTLE also displayed a more pronounced network disruption. Contrary to controls, hub nodes in both TLE groups were not distributed across whole brain, but rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE.</AbstractText These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology.</AbstractText
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Dauer-specific dendrite arborization in C. elegans is regulated by KPC-1/Furin. Dendrites often display remarkably complex and diverse morphologies that are influenced by developmental and environmental cues. Neuroplasticity in response to adverse environmental conditions entails both hypertrophy and resorption of dendrites. How dendrites rapidly alter morphology in response to unfavorable environmental conditions is unclear. The nematode Caenorhabditis elegans enters into a stress-resistant dauer larval stage in response to an adverse environment.</AbstractText Here we show that the IL2 bipolar sensory neurons undergo dendrite arborization and axon remodeling during dauer development. When dauer larvae are returned to favorable environmental conditions, animals resume reproductive development and IL2 dendritic branches retract, leaving behind remnant branches in postdauer L4 and adult animals. The C. elegans furin homolog KPC-1 is required for dauer IL2 dendritic arborization and dauer-specific nictation behavior. KPC-1 is also necessary for dendritic arborization of PVD and FLP sensory neurons. In mammals, furin is essential, ubiquitously expressed, and associated with numerous pathologies, including neurodegenerative diseases. While broadly expressed in C. elegans neurons and epithelia, KPC-1 acts cell autonomously in IL2 neurons to regulate dauer-specific dendritic arborization and nictation.</AbstractText Neuroplasticity of the C. elegans IL2 sensory neurons provides a paradigm to study stress-induced and reversible dendritic branching, and the role of environmental and developmental cues in this process. The newly discovered role of KPC-1 in dendrite morphogenesis provides insight into the function of proprotein convertases in nervous system development.</AbstractText
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40586788
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33389036
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40202304
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Radiation Dose Reduction and Image Quality Improvement of UHR CT of the Neck by Novel Deep-learning Image Reconstruction.
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Diagnostic value of deep learning reconstruction for radiation dose reduction at abdominal ultra-high-resolution CT.
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Early identification of taboo words reveals a prominent role of semantic information in visual word recognition.
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We evaluated a dedicated dose-reduced UHR-CT for head and neck imaging, combined with a novel deep learning reconstruction algorithm to assess its impact on image quality and radiation exposure.</AbstractText Retrospective analysis of ninety-eight consecutive patients examined using a new body weight-adapted protocol. Images were reconstructed using adaptive iterative dose reduction and advanced intelligent Clear-IQ engine with an already established (DL-1) and a newly implemented reconstruction algorithm (DL-2). Additional thirty patients were scanned without body-weight-adapted dose reduction (DL-1-SD). Three readers evaluated subjective image quality regarding image quality and assessment of several anatomic regions. For objective image quality, signal-to-noise ratio and contrast-to-noise ratio were calculated for temporalis and masseteric muscle and the floor of the mouth. Radiation dose was evaluated by comparing the computed tomography dose index (CTDIvol) values.</AbstractText Deep learning-based reconstruction algorithms significantly improved subjective image quality (diagnostic acceptability: DL‑1 vs AIDR OR of 25.16 [6.30;38.85], p < 0.001 and DL‑2 vs AIDR 720.15 [410.14;> 999.99], p < 0.001). Although higher doses (DL-1-SD) resulted in significantly enhanced image quality, DL‑2 demonstrated significant superiority over all other techniques across all defined parameters (p < 0.001). Similar results were demonstrated for objective image quality, e.g. image noise (DL‑1 vs AIDR OR of 19.0 [11.56;31.24], p < 0.001 and DL‑2 vs AIDR > 999.9 [825.81;> 999.99], p < 0.001). Using weight-adapted kV reduction, very low radiation doses could be achieved (CTDIvol: 7.4 ± 4.2 mGy).</AbstractText AI-based reconstruction algorithms in ultra-high resolution head and neck imaging provide excellent image quality while achieving very low radiation exposure.</AbstractText
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We evaluated lower dose (LD) hepatic dynamic ultra-high-resolution computed tomography (U-HRCT) images reconstructed with deep learning reconstruction (DLR), hybrid iterative reconstruction (hybrid-IR), or model-based IR (MBIR) in comparison with standard-dose (SD) U-HRCT images reconstructed with hybrid-IR as the reference standard to identify the method that allowed for the greatest radiation dose reduction while preserving the diagnostic value.</AbstractText Evaluated were 72 patients who had undergone hepatic dynamic U-HRCT; 36 were scanned with the standard radiation dose (SD group) and 36 with 70% of the SD (lower dose [LD] group). Hepatic arterial and equilibrium phase (HAP, EP) images were reconstructed with hybrid-IR in the SD group, and with hybrid-IR, MBIR, and DLR in the LD group. One radiologist recorded the standard deviation of attenuation in the paraspinal muscle as the image noise. The overall image quality was assessed by 3 other radiologists; they used a 5-point confidence scale ranging from 1 (unacceptable) to 5 (excellent). Superiority and equivalence with prespecified margins were assessed.</AbstractText With respect to the image noise, in the HAP and EP, LD DLR and LD MBIR images were superior to SD hybrid-IR images; LD hybrid-IR images were neither superior nor equivalent to SD hybrid-IR images. With respect to the quality scores, only LD DLR images were superior to SD hybrid-IR images.</AbstractText DLR preserved the quality of abdominal U-HRCT images even when scanned with a reduced radiation dose.</AbstractText • Lower dose DLR images were superior to the standard-dose hybrid-IR images quantitatively and qualitatively at abdominal U-HRCT. • Neither hybrid-IR nor MBIR may allow for a radiation dose reduction at abdominal U-HRCT without compromising the image quality. • Because DLR allows for a reduction in the radiation dose and maintains the image quality even at the thinnest slice section, DLR should be applied to abdominal U-HRCT scans.</AbstractText
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This research used the progressive demasking paradigm to investigate whether perceptual word identification is facilitated by semantic information. Experiment 1 revealed faster identification for taboo than neutral words. Experiment 2 revealed faster identification for taboo than emotionally-comparable non-taboo words, whereas the difference with respect to neutral words was possibly mitigated by list-wise factors related to list composition. Moreover, the facilitation for taboo words was impervious to habituation. The taboo connotation advantage seemingly originates from the attentional capture triggered by tabooness, a socio-culturally determined semantic feature that, under appropriate contextual conditions, modulates perceptual word identification. Our results suggest that (a) semantic processing is a pervasive component of any task involving word processing, and (b) when semantic information does not hinder the main task, it may influence even the earliest stages of word perceptual identification.</AbstractText
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Radiation Dose Reduction and Image Quality Improvement of UHR CT of the Neck by Novel Deep-learning Image Reconstruction. We evaluated a dedicated dose-reduced UHR-CT for head and neck imaging, combined with a novel deep learning reconstruction algorithm to assess its impact on image quality and radiation exposure.</AbstractText Retrospective analysis of ninety-eight consecutive patients examined using a new body weight-adapted protocol. Images were reconstructed using adaptive iterative dose reduction and advanced intelligent Clear-IQ engine with an already established (DL-1) and a newly implemented reconstruction algorithm (DL-2). Additional thirty patients were scanned without body-weight-adapted dose reduction (DL-1-SD). Three readers evaluated subjective image quality regarding image quality and assessment of several anatomic regions. For objective image quality, signal-to-noise ratio and contrast-to-noise ratio were calculated for temporalis and masseteric muscle and the floor of the mouth. Radiation dose was evaluated by comparing the computed tomography dose index (CTDIvol) values.</AbstractText Deep learning-based reconstruction algorithms significantly improved subjective image quality (diagnostic acceptability: DL‑1 vs AIDR OR of 25.16 [6.30;38.85], p < 0.001 and DL‑2 vs AIDR 720.15 [410.14;> 999.99], p < 0.001). Although higher doses (DL-1-SD) resulted in significantly enhanced image quality, DL‑2 demonstrated significant superiority over all other techniques across all defined parameters (p < 0.001). Similar results were demonstrated for objective image quality, e.g. image noise (DL‑1 vs AIDR OR of 19.0 [11.56;31.24], p < 0.001 and DL‑2 vs AIDR > 999.9 [825.81;> 999.99], p < 0.001). Using weight-adapted kV reduction, very low radiation doses could be achieved (CTDIvol: 7.4 ± 4.2 mGy).</AbstractText AI-based reconstruction algorithms in ultra-high resolution head and neck imaging provide excellent image quality while achieving very low radiation exposure.</AbstractText
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Diagnostic value of deep learning reconstruction for radiation dose reduction at abdominal ultra-high-resolution CT. We evaluated lower dose (LD) hepatic dynamic ultra-high-resolution computed tomography (U-HRCT) images reconstructed with deep learning reconstruction (DLR), hybrid iterative reconstruction (hybrid-IR), or model-based IR (MBIR) in comparison with standard-dose (SD) U-HRCT images reconstructed with hybrid-IR as the reference standard to identify the method that allowed for the greatest radiation dose reduction while preserving the diagnostic value.</AbstractText Evaluated were 72 patients who had undergone hepatic dynamic U-HRCT; 36 were scanned with the standard radiation dose (SD group) and 36 with 70% of the SD (lower dose [LD] group). Hepatic arterial and equilibrium phase (HAP, EP) images were reconstructed with hybrid-IR in the SD group, and with hybrid-IR, MBIR, and DLR in the LD group. One radiologist recorded the standard deviation of attenuation in the paraspinal muscle as the image noise. The overall image quality was assessed by 3 other radiologists; they used a 5-point confidence scale ranging from 1 (unacceptable) to 5 (excellent). Superiority and equivalence with prespecified margins were assessed.</AbstractText With respect to the image noise, in the HAP and EP, LD DLR and LD MBIR images were superior to SD hybrid-IR images; LD hybrid-IR images were neither superior nor equivalent to SD hybrid-IR images. With respect to the quality scores, only LD DLR images were superior to SD hybrid-IR images.</AbstractText DLR preserved the quality of abdominal U-HRCT images even when scanned with a reduced radiation dose.</AbstractText • Lower dose DLR images were superior to the standard-dose hybrid-IR images quantitatively and qualitatively at abdominal U-HRCT. • Neither hybrid-IR nor MBIR may allow for a radiation dose reduction at abdominal U-HRCT without compromising the image quality. • Because DLR allows for a reduction in the radiation dose and maintains the image quality even at the thinnest slice section, DLR should be applied to abdominal U-HRCT scans.</AbstractText
|
Early identification of taboo words reveals a prominent role of semantic information in visual word recognition. This research used the progressive demasking paradigm to investigate whether perceptual word identification is facilitated by semantic information. Experiment 1 revealed faster identification for taboo than neutral words. Experiment 2 revealed faster identification for taboo than emotionally-comparable non-taboo words, whereas the difference with respect to neutral words was possibly mitigated by list-wise factors related to list composition. Moreover, the facilitation for taboo words was impervious to habituation. The taboo connotation advantage seemingly originates from the attentional capture triggered by tabooness, a socio-culturally determined semantic feature that, under appropriate contextual conditions, modulates perceptual word identification. Our results suggest that (a) semantic processing is a pervasive component of any task involving word processing, and (b) when semantic information does not hinder the main task, it may influence even the earliest stages of word perceptual identification.</AbstractText
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32145250
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17924656
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32678182
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Regulation of autophagy by inhibitory CSPG interactions with receptor PTPσ and its impact on plasticity and regeneration after spinal cord injury.
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BMP-3 and BMP-6 structures illuminate the nature of binding specificity with receptors.
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Mitigation of B(1)(+) inhomogeneity for ultra-high-field magnetic resonance imaging: hybrid mode shaping with auxiliary EM potential.
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Chondroitin sulfate proteoglycans (CSPGs), extracellular matrix molecules that increase dramatically following a variety of CNS injuries or diseases, have long been known for their potent capacity to curtail cell migrations as well as axon regeneration and sprouting. The inhibition can be conferred through binding to their major cognate receptor, Protein Tyrosine Phosphatase Sigma (PTPσ). However, the precise mechanisms downstream of receptor binding that mediate growth inhibition have remained elusive. Recently, CSPGs/PTPσ interactions were found to regulate autophagic flux at the axon growth cone by dampening the autophagosome-lysosomal fusion step. Because of the intense interest in autophagic phenomena in the regulation of a wide variety of critical cellular functions, we summarize here what is currently known about dysregulation of autophagy following spinal cord injury, and highlight this critical new mechanism underlying axon regeneration failure. Furthermore, we review how CSPGs/PTPσ interactions influence plasticity through autophagic regulation and how PTPσ serves as a switch to execute either axon outgrowth or synaptogenesis. This has exciting implications for the role CSPGs play not only in axon regeneration failure after spinal cord injury, but also in neurodegenerative diseases where, again, inhibitory CSPGs are upregulated.</AbstractText
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Bone morphogenetic proteins (BMPs) are extracellular messenger ligands involved in controlling a wide array of developmental and intercellular signaling processes. To initiate their specific intracellular signaling pathways, the ligands recognize and bind two structurally related serine/threonine kinase receptors, termed type I and type II, on the cell surface. Here, we present the crystal structures of BMP-3 and BMP-6, of which BMP-3 has remained poorly understood with respect to its receptor identity, affinity, and specificity. Using surface plasmon resonance (BIAcore) we show that BMP-3 binds Activin Receptor type II (ActRII) with Kd approximately 1.8 microM but ActRIIb with 30-fold higher affinity at Kd approximately 53 nM. This low affinity for ActRII may involve Ser-28 and Asp-33 of BMP-3, which are found only in BMP-3's type II receptor-binding interfaces. Point mutations of either residue to alanine results in up to 20-fold higher affinity to either receptor. We further demonstrate by Smad-based whole cell luciferase assays that the increased affinity of BMP-3S28A to ActRII enables the ligand's signaling ability to a level comparable to that of BMP-6. Focusing on BMP-3's preference for ActRIIb, we find that Lys-76 of ActRII and the structurally equivalent Glu-76 of ActRIIb are distinct between the two receptors. We demonstrate that ActRIIbE76K and ActRII bind BMP-3 with similar affinity, indicating BMP-3 receptor specificity is controlled by the interaction of Lys-30 of BMP-3 with Glu-76 of ActRIIb. These studies illustrate how a single amino acid can regulate the specificity of ligand-receptor binding and potentially alter biological signaling and function in vivo.</AbstractText
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The notion of mode shaping based on evanescent coupling has been successfully applied in various fields of optics, such as in the dispersion engineering of optical waveguides. Here, we show that the same concept provides an opportunity for the seemingly different field of ultra-high-field MRI, addressing transmit RF magnetic field (B<sub
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Regulation of autophagy by inhibitory CSPG interactions with receptor PTPσ and its impact on plasticity and regeneration after spinal cord injury. Chondroitin sulfate proteoglycans (CSPGs), extracellular matrix molecules that increase dramatically following a variety of CNS injuries or diseases, have long been known for their potent capacity to curtail cell migrations as well as axon regeneration and sprouting. The inhibition can be conferred through binding to their major cognate receptor, Protein Tyrosine Phosphatase Sigma (PTPσ). However, the precise mechanisms downstream of receptor binding that mediate growth inhibition have remained elusive. Recently, CSPGs/PTPσ interactions were found to regulate autophagic flux at the axon growth cone by dampening the autophagosome-lysosomal fusion step. Because of the intense interest in autophagic phenomena in the regulation of a wide variety of critical cellular functions, we summarize here what is currently known about dysregulation of autophagy following spinal cord injury, and highlight this critical new mechanism underlying axon regeneration failure. Furthermore, we review how CSPGs/PTPσ interactions influence plasticity through autophagic regulation and how PTPσ serves as a switch to execute either axon outgrowth or synaptogenesis. This has exciting implications for the role CSPGs play not only in axon regeneration failure after spinal cord injury, but also in neurodegenerative diseases where, again, inhibitory CSPGs are upregulated.</AbstractText
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BMP-3 and BMP-6 structures illuminate the nature of binding specificity with receptors. Bone morphogenetic proteins (BMPs) are extracellular messenger ligands involved in controlling a wide array of developmental and intercellular signaling processes. To initiate their specific intracellular signaling pathways, the ligands recognize and bind two structurally related serine/threonine kinase receptors, termed type I and type II, on the cell surface. Here, we present the crystal structures of BMP-3 and BMP-6, of which BMP-3 has remained poorly understood with respect to its receptor identity, affinity, and specificity. Using surface plasmon resonance (BIAcore) we show that BMP-3 binds Activin Receptor type II (ActRII) with Kd approximately 1.8 microM but ActRIIb with 30-fold higher affinity at Kd approximately 53 nM. This low affinity for ActRII may involve Ser-28 and Asp-33 of BMP-3, which are found only in BMP-3's type II receptor-binding interfaces. Point mutations of either residue to alanine results in up to 20-fold higher affinity to either receptor. We further demonstrate by Smad-based whole cell luciferase assays that the increased affinity of BMP-3S28A to ActRII enables the ligand's signaling ability to a level comparable to that of BMP-6. Focusing on BMP-3's preference for ActRIIb, we find that Lys-76 of ActRII and the structurally equivalent Glu-76 of ActRIIb are distinct between the two receptors. We demonstrate that ActRIIbE76K and ActRII bind BMP-3 with similar affinity, indicating BMP-3 receptor specificity is controlled by the interaction of Lys-30 of BMP-3 with Glu-76 of ActRIIb. These studies illustrate how a single amino acid can regulate the specificity of ligand-receptor binding and potentially alter biological signaling and function in vivo.</AbstractText
|
Mitigation of B(1)(+) inhomogeneity for ultra-high-field magnetic resonance imaging: hybrid mode shaping with auxiliary EM potential. The notion of mode shaping based on evanescent coupling has been successfully applied in various fields of optics, such as in the dispersion engineering of optical waveguides. Here, we show that the same concept provides an opportunity for the seemingly different field of ultra-high-field MRI, addressing transmit RF magnetic field (B<sub
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36911523
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10878102
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37901633
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Binding of RPR260243 at the intracellular side of the hERG1 channel pore domain slows closure of the helix bundle crossing gate.
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Hyperpolarization-activated currents in presynaptic terminals of mouse cerebellar basket cells.
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Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
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The opening and closing of voltage-dependent potassium channels is dependent on a tight coupling between movement of the voltage sensing S4 segments and the activation gate. A specific interaction between intracellular amino- and carboxyl-termini is required for the characteristically slow rate of channel closure (deactivation) of hERG1 channels. Compounds that increase hERG1 channel currents represent a novel approach for prevention of arrhythmia associated with prolonged ventricular repolarization. RPR260243 (RPR), a quinoline oxo-propyl piperidine derivative, inhibits inactivation and dramatically slows the rate of hERG1 channel deactivation. Here we report that similar to its effect on wild-type channels, RPR greatly slows the deactivation rate of hERG1 channels missing their amino-termini, or of split channels lacking a covalent link between the voltage sensor domain and the pore domain. By contrast, RPR did not slow deactivation of C-terminal truncated hERG1 channels or D540K hERG1 mutant channels activated by hyperpolarization. Together, these findings indicate that ability of RPR to slow deactivation requires an intact C-terminus, does not slow deactivation by stabilizing an interaction involving the amino-terminus or require a covalent link between the voltage sensor and pore domains. All-atom molecular dynamics simulations using the cryo-EM structure of the hERG1 channel revealed that RPR binds to a pocket located at the intracellular ends of helices S5 and S6 of a single subunit. The slowing of channel deactivation by RPR may be mediated by disruption of normal S5-S6 interactions.</AbstractText
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Using patch-clamp techniques, a hyperpolarization-activated current (I(h)) was recorded from synaptic terminals of mouse cerebellar basket cells. Ih was blocked quickly and reversibly by 2 mM Cs(+), and subtraction revealed a rapidly activating and deactivating I(h) current. Similar gating and block of presynaptic I(h) were also seen with the more selective inhibitor ZD 7288 (10 microM). The time constant of activation (tau (a))of presynaptic I(h) current became faster with membrane hyperpolarization, being approximately 74 ms at -130 mV, changing e-fold for a 33 mV change in membrane potential. Whole-cell recordings from basket cell somata also revealed an I(h) current, which was similarly sensitive to block by ZD 7288. Inhibition of I(h) by 10 microM ZD 7288 reduced the frequency ( approximately 34 %) and amplitude ( approximately 26 %) of spontaneous IPSCs (sIPSCs) recorded in Purkinje cells, one of the principal synaptic targets of basket neurones. This is the first report of an I(h) current in mammalian inhibitory presynaptic terminals, which may be an important target for neuromodulation in the cerebellum. Comparing the biophysical properties and distribution of cloned hyperpolarization-activated cation channels, we also suggest a molecular candidate underlying I(h) at these synapses.</AbstractText
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A 28-year-old woman presented to eye casualty with signs and symptoms suggestive of optic neuritis following a recent COVID-19 vaccination (the Moderna mRNA-1273 vaccine). The best corrected visual acuity was 6/15 in the right eye and 6/6 in the left eye with a relative afferent pupillary defect in the right eye. Following examination and investigation, she was found to fit the McDonald criteria for multiple sclerosis and was commenced on disease-modifying therapy. Demyelinating events have been identified to occur following COVID-19 vaccinations. In this case, we have found that the Moderna mRNA-1273 vaccine could have contributed to the development of optic neuritis following a second dose of the vaccine.</AbstractText
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Binding of RPR260243 at the intracellular side of the hERG1 channel pore domain slows closure of the helix bundle crossing gate. The opening and closing of voltage-dependent potassium channels is dependent on a tight coupling between movement of the voltage sensing S4 segments and the activation gate. A specific interaction between intracellular amino- and carboxyl-termini is required for the characteristically slow rate of channel closure (deactivation) of hERG1 channels. Compounds that increase hERG1 channel currents represent a novel approach for prevention of arrhythmia associated with prolonged ventricular repolarization. RPR260243 (RPR), a quinoline oxo-propyl piperidine derivative, inhibits inactivation and dramatically slows the rate of hERG1 channel deactivation. Here we report that similar to its effect on wild-type channels, RPR greatly slows the deactivation rate of hERG1 channels missing their amino-termini, or of split channels lacking a covalent link between the voltage sensor domain and the pore domain. By contrast, RPR did not slow deactivation of C-terminal truncated hERG1 channels or D540K hERG1 mutant channels activated by hyperpolarization. Together, these findings indicate that ability of RPR to slow deactivation requires an intact C-terminus, does not slow deactivation by stabilizing an interaction involving the amino-terminus or require a covalent link between the voltage sensor and pore domains. All-atom molecular dynamics simulations using the cryo-EM structure of the hERG1 channel revealed that RPR binds to a pocket located at the intracellular ends of helices S5 and S6 of a single subunit. The slowing of channel deactivation by RPR may be mediated by disruption of normal S5-S6 interactions.</AbstractText
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Hyperpolarization-activated currents in presynaptic terminals of mouse cerebellar basket cells. Using patch-clamp techniques, a hyperpolarization-activated current (I(h)) was recorded from synaptic terminals of mouse cerebellar basket cells. Ih was blocked quickly and reversibly by 2 mM Cs(+), and subtraction revealed a rapidly activating and deactivating I(h) current. Similar gating and block of presynaptic I(h) were also seen with the more selective inhibitor ZD 7288 (10 microM). The time constant of activation (tau (a))of presynaptic I(h) current became faster with membrane hyperpolarization, being approximately 74 ms at -130 mV, changing e-fold for a 33 mV change in membrane potential. Whole-cell recordings from basket cell somata also revealed an I(h) current, which was similarly sensitive to block by ZD 7288. Inhibition of I(h) by 10 microM ZD 7288 reduced the frequency ( approximately 34 %) and amplitude ( approximately 26 %) of spontaneous IPSCs (sIPSCs) recorded in Purkinje cells, one of the principal synaptic targets of basket neurones. This is the first report of an I(h) current in mammalian inhibitory presynaptic terminals, which may be an important target for neuromodulation in the cerebellum. Comparing the biophysical properties and distribution of cloned hyperpolarization-activated cation channels, we also suggest a molecular candidate underlying I(h) at these synapses.</AbstractText
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Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report. A 28-year-old woman presented to eye casualty with signs and symptoms suggestive of optic neuritis following a recent COVID-19 vaccination (the Moderna mRNA-1273 vaccine). The best corrected visual acuity was 6/15 in the right eye and 6/6 in the left eye with a relative afferent pupillary defect in the right eye. Following examination and investigation, she was found to fit the McDonald criteria for multiple sclerosis and was commenced on disease-modifying therapy. Demyelinating events have been identified to occur following COVID-19 vaccinations. In this case, we have found that the Moderna mRNA-1273 vaccine could have contributed to the development of optic neuritis following a second dose of the vaccine.</AbstractText
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40359377
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39560415
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40781387
|
Neuroanatomy and lesion networks of central poststroke pain.
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The concept of nociplastic pain-where to from here?
|
Feasibility and Efficacy of Decision Aids to Improve Decision-Making for Contralateral Prophylactic Mastectomy: A Systematic Review.
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Identifying lesion sites associated with central poststroke pain (CPSP) may facilitate targeted screening for early symptoms, possibly even paving the way for preventive measures and earlier treatment initiation. Here, we test the hypothesis that damage to a nociceptive pathway extending from the brainstem to the cerebral cortex, and including white matter tracts, is associated with CPSP. We investigated the lesion locations of 72 patients with CPSP relative to poststroke comparison subjects without pain (n = 123), divided into a discovery and independent validation data set. The study included three main analyses: (1) we compared lesion intersection with our a priori region of interest (ROI) between groups with and without CPSP, (2) we performed lesion-symptom mapping to evaluate whether lesions associated with CPSP localize to the a priori ROI, and (3) we used lesion network mapping to infer the broader structural and functional connectivity patterns associated with CPSP lesions. CPSP lesions overlapped the nociceptive pathway ROI to a greater extent than comparison lesions. Lesion-symptom mapping identified a CPSP-associated region overlapping with the ventrocaudal thalamus and adjacent white matter, which was located mostly within the a priori ROI. Lesion network mapping demonstrated that lesions associated with CPSP disrupt nodes and tracts of the nociceptive pathway ROI. Interestingly, the CPSP lesion network results demonstrated connectivity to intereffector nodes of the primary motor cortex, providing a novel link between CPSP and the somato-cognitive action network. Together, these findings indicate that CPSP can be conceptualized as a lesion-associated network disruption of the nociceptive pathway and somato-cognitive action network.</AbstractText
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Nociplastic pain, a third mechanistic pain descriptor in addition to nociceptive and neuropathic pain, was adopted in 2017 by the International Association for the Study of Pain (IASP). It is defined as "pain that arises from altered nociception" not fully explained by nociceptive or neuropathic pain mechanisms. Peripheral and/or central sensitization, manifesting as allodynia and hyperalgesia, is typically present, although not specific for nociplastic pain. Criteria for possible nociplastic pain manifesting in the musculoskeletal system define a minimum of 4 conditions: (1) pain duration of more than 3 months; (2) regional, multifocal or widespread rather than discrete distribution of pain; (3) pain cannot entirely be explained by nociceptive or neuropathic mechanisms; and (4) clinical signs of pain hypersensitivity present in the region of pain. Educational endeavors and field testing of criteria are needed. Pharmacological treatment guidelines, based on the three pain types, need to be developed. Currently pharmacological treatments of nociplastic pain resemble those of neuropathic; however, opioids should be avoided. A major challenge is to unravel pathophysiological mechanisms driving altered nociception in patients suffering from nociplastic pain. Examples from fibromyalgia would include pathophysiology of the peripheral as well as central nervous system, such as autoreactive antibodies acting at the level of the dorsal root ganglia and aberrant cerebral pain processing, including altered brain network architecture. Understanding pathophysiological mechanisms and their interactions is a prerequisite for the development of diagnostic tests allowing for individualized treatments and development of new strategies for prevention and treatment.</AbstractText
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Rates of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer have increased significantly. Decision aids (DAs) can support the shared decision-making process. This study systematically reviewed the literature to understand the feasibility and efficacy of using DAs to improve decision outcomes about CPM.</AbstractText Six databases were searched through April 2024. Included studies reported on patient DAs about CPM after diagnosis of unilateral breast cancer for average- or low-risk patients. Two investigators reviewed 6186 abstracts and 155 full-text articles, extracting data for studies that met the criteria. Data quality assessment was performed using GRADE.</AbstractText The review included six studies published from 2017 to 2021. Four (66.7%) studies reported solely on patient acceptance of the DAs, whereas two (33.3%) studies included clinicians. Three (50%) DAs were formatted for online delivery, whereas two (33.3%) were formatted for paper delivery, and one (16.7%) was formatted for unknown delivery. Two (33.3%) research teams used a multi-disciplinary group to develop their DA. Overall, patient satisfaction with the DAs was high, and knowledge scores increased, but little consensus existed on when to introduce the DA. Important DA characteristics measured were use with or without a clinician, literacy considerations, and the order and balance of information.</AbstractText More research should be conducted to develop and test DAs for CPM decisions, with attention to the balance of information, type of content, format, timing, and optimal delivery of such DAs. Future research in larger, multi-institutional populations using standardized, validated measures for satisfaction, values, decisional conflict, and health literacy could assess the impact of DAs for CPM.</AbstractText
|
Neuroanatomy and lesion networks of central poststroke pain. Identifying lesion sites associated with central poststroke pain (CPSP) may facilitate targeted screening for early symptoms, possibly even paving the way for preventive measures and earlier treatment initiation. Here, we test the hypothesis that damage to a nociceptive pathway extending from the brainstem to the cerebral cortex, and including white matter tracts, is associated with CPSP. We investigated the lesion locations of 72 patients with CPSP relative to poststroke comparison subjects without pain (n = 123), divided into a discovery and independent validation data set. The study included three main analyses: (1) we compared lesion intersection with our a priori region of interest (ROI) between groups with and without CPSP, (2) we performed lesion-symptom mapping to evaluate whether lesions associated with CPSP localize to the a priori ROI, and (3) we used lesion network mapping to infer the broader structural and functional connectivity patterns associated with CPSP lesions. CPSP lesions overlapped the nociceptive pathway ROI to a greater extent than comparison lesions. Lesion-symptom mapping identified a CPSP-associated region overlapping with the ventrocaudal thalamus and adjacent white matter, which was located mostly within the a priori ROI. Lesion network mapping demonstrated that lesions associated with CPSP disrupt nodes and tracts of the nociceptive pathway ROI. Interestingly, the CPSP lesion network results demonstrated connectivity to intereffector nodes of the primary motor cortex, providing a novel link between CPSP and the somato-cognitive action network. Together, these findings indicate that CPSP can be conceptualized as a lesion-associated network disruption of the nociceptive pathway and somato-cognitive action network.</AbstractText
|
The concept of nociplastic pain-where to from here? Nociplastic pain, a third mechanistic pain descriptor in addition to nociceptive and neuropathic pain, was adopted in 2017 by the International Association for the Study of Pain (IASP). It is defined as "pain that arises from altered nociception" not fully explained by nociceptive or neuropathic pain mechanisms. Peripheral and/or central sensitization, manifesting as allodynia and hyperalgesia, is typically present, although not specific for nociplastic pain. Criteria for possible nociplastic pain manifesting in the musculoskeletal system define a minimum of 4 conditions: (1) pain duration of more than 3 months; (2) regional, multifocal or widespread rather than discrete distribution of pain; (3) pain cannot entirely be explained by nociceptive or neuropathic mechanisms; and (4) clinical signs of pain hypersensitivity present in the region of pain. Educational endeavors and field testing of criteria are needed. Pharmacological treatment guidelines, based on the three pain types, need to be developed. Currently pharmacological treatments of nociplastic pain resemble those of neuropathic; however, opioids should be avoided. A major challenge is to unravel pathophysiological mechanisms driving altered nociception in patients suffering from nociplastic pain. Examples from fibromyalgia would include pathophysiology of the peripheral as well as central nervous system, such as autoreactive antibodies acting at the level of the dorsal root ganglia and aberrant cerebral pain processing, including altered brain network architecture. Understanding pathophysiological mechanisms and their interactions is a prerequisite for the development of diagnostic tests allowing for individualized treatments and development of new strategies for prevention and treatment.</AbstractText
|
Feasibility and Efficacy of Decision Aids to Improve Decision-Making for Contralateral Prophylactic Mastectomy: A Systematic Review. Rates of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer have increased significantly. Decision aids (DAs) can support the shared decision-making process. This study systematically reviewed the literature to understand the feasibility and efficacy of using DAs to improve decision outcomes about CPM.</AbstractText Six databases were searched through April 2024. Included studies reported on patient DAs about CPM after diagnosis of unilateral breast cancer for average- or low-risk patients. Two investigators reviewed 6186 abstracts and 155 full-text articles, extracting data for studies that met the criteria. Data quality assessment was performed using GRADE.</AbstractText The review included six studies published from 2017 to 2021. Four (66.7%) studies reported solely on patient acceptance of the DAs, whereas two (33.3%) studies included clinicians. Three (50%) DAs were formatted for online delivery, whereas two (33.3%) were formatted for paper delivery, and one (16.7%) was formatted for unknown delivery. Two (33.3%) research teams used a multi-disciplinary group to develop their DA. Overall, patient satisfaction with the DAs was high, and knowledge scores increased, but little consensus existed on when to introduce the DA. Important DA characteristics measured were use with or without a clinician, literacy considerations, and the order and balance of information.</AbstractText More research should be conducted to develop and test DAs for CPM decisions, with attention to the balance of information, type of content, format, timing, and optimal delivery of such DAs. Future research in larger, multi-institutional populations using standardized, validated measures for satisfaction, values, decisional conflict, and health literacy could assess the impact of DAs for CPM.</AbstractText
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27121044
|
22933737
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27193360
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Approach to the Management of Pediatric-Onset Anti-N-Methyl-d-Aspartate (Anti-NMDA) Receptor Encephalitis: A Case Series.
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Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis.
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Some Unusual Neuropsychological Syndromes: Somatoparaphrenia, Akinetopsia, Reduplicative Paramnesia, Autotopagnosia.
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Anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis is a treatable cause of autoimmune encephalitis. It remains unclear if the natural history of this disease is altered by choice of acute therapy or the employment of chronic immunotherapy. Chart review was undertaken for pediatric patients diagnosed with anti-NMDA receptor encephalitis. Data obtained included patient demographics, disease manifestations, treatment course, and clinical outcomes. Ten patients with anti-NMDA receptor encephalitis were identified. All patients were treated with immunotherapy in the acute period, and all patients experienced good recovery. Neurologic relapse did not occur in any patient. All patients received varied forms of chronic immunosuppression to prevent relapses. Complications of chronic immunotherapy occurred in 50% of patients. The benefits of chronic immunotherapy and the duration of use should be carefully weighed against the risks. Complications from immunotherapy are not uncommon and can be serious. Clinical trials assessing the benefit of long-term immunotherapy in this population are needed.</AbstractText
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To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder.</AbstractText We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers.</AbstractText Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1-123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2-200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named "extreme delta brush" because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089).</AbstractText Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.</AbstractText
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Some unusual neuropsychological syndromes are rarely reported in the neuropsychological literature. This paper presents a review of four of these unusual clinical syndromes: (1) somatoparaphrenia (delusional belief in which a patient states that the limb contralateral to a brain pathology, does not belong to him/her); (2) akinetopsia (cortical syndrome in which patient losses the ability to perceive visual motion); (3) reduplicative paramnesia (believe that a familiar place, person, object, or body part has been duplicated); and (4) autotopagnosia (disturbance of body schema involving the loss of ability to localize, recognize, or identify the specific parts of one's body). It is concluded that regardless of their rarity, it is fundamental to take them into consideration in order to understand how the brain organizes cognition; their understanding is also crucial in the clinical analysis of patients with brain pathologies.</AbstractText
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Approach to the Management of Pediatric-Onset Anti-N-Methyl-d-Aspartate (Anti-NMDA) Receptor Encephalitis: A Case Series. Anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis is a treatable cause of autoimmune encephalitis. It remains unclear if the natural history of this disease is altered by choice of acute therapy or the employment of chronic immunotherapy. Chart review was undertaken for pediatric patients diagnosed with anti-NMDA receptor encephalitis. Data obtained included patient demographics, disease manifestations, treatment course, and clinical outcomes. Ten patients with anti-NMDA receptor encephalitis were identified. All patients were treated with immunotherapy in the acute period, and all patients experienced good recovery. Neurologic relapse did not occur in any patient. All patients received varied forms of chronic immunosuppression to prevent relapses. Complications of chronic immunotherapy occurred in 50% of patients. The benefits of chronic immunotherapy and the duration of use should be carefully weighed against the risks. Complications from immunotherapy are not uncommon and can be serious. Clinical trials assessing the benefit of long-term immunotherapy in this population are needed.</AbstractText
|
Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder.</AbstractText We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers.</AbstractText Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1-123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2-200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named "extreme delta brush" because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089).</AbstractText Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.</AbstractText
|
Some Unusual Neuropsychological Syndromes: Somatoparaphrenia, Akinetopsia, Reduplicative Paramnesia, Autotopagnosia. Some unusual neuropsychological syndromes are rarely reported in the neuropsychological literature. This paper presents a review of four of these unusual clinical syndromes: (1) somatoparaphrenia (delusional belief in which a patient states that the limb contralateral to a brain pathology, does not belong to him/her); (2) akinetopsia (cortical syndrome in which patient losses the ability to perceive visual motion); (3) reduplicative paramnesia (believe that a familiar place, person, object, or body part has been duplicated); and (4) autotopagnosia (disturbance of body schema involving the loss of ability to localize, recognize, or identify the specific parts of one's body). It is concluded that regardless of their rarity, it is fundamental to take them into consideration in order to understand how the brain organizes cognition; their understanding is also crucial in the clinical analysis of patients with brain pathologies.</AbstractText
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40653400
|
35172019
|
39889529
|
Employment is associated with manual ability in adults with cerebral palsy - a population-based study.
|
Parent-recorded videos of infant spontaneous movement: Comparisons at 3-4 months and relationships with 2-year developmental outcomes in extremely preterm, extremely low birthweight and term-born infants.
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The role of nonlinear axonal membrane capacitance in modulating ion channel cooperativity in action potential dynamics: Studies on Hodgkin-Huxley's model.
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Employment rates are lower in adults with cerebral palsy (CP). Even though reduced manual ability is associated with limitations in daily activities, it is unclear whether employment rates are associated with manual ability in adults with CP.</AbstractText To analyze regular employment and employment rates (hours/week) in adults with CP and estimate their associations with manual ability relative to age and sex.</AbstractText This was a cross-sectional study of adults with CP, aged 20-64 years, from the combined Swedish CP follow-up program and registry. Manual ability was classified as levels I-V using the Manual Ability Classification System (MACS). Logistic regression analysis was used.</AbstractText The study included 2304 adults with CP (1271 men; median age 28 years, interquartile range 20-64 years). Fewer than one in five (19 %) were employed, and about half (52 %) of these worked full time. The probability of employment in adults with MACS level II was almost half that of those with level I (OR 0.44; 95 % CI 0.34-0.57) and decreased with each MACS level to OR 0.01 (95 % CI 0.00-0.03) for MACS V. Limited manual ability was associated with a lower probability of working full time: ORs of 0.46 (95 % CI 0.30-0.72) for MACS II and 0.29 (95 % CI 0.16-0.56) for MACS III-V.</AbstractText Limited manual ability in adults with CP impacts both their likelihood of employment and employment rate. Greater manual ability is associated with a higher probability of regular employment and working full time.</AbstractText
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Infants born extremely preterm (EP, <28-week gestational age) or extremely low birthweight (ELBW, <1000 g) are at risk of developmental delay and cerebral palsy (CP). The General Movements Assessment (GMA) and its extension, the Motor Optimality Score, revised (MOS-R) (assesses movement patterns and posture), may help to identify early delays.</AbstractText To compare differences in the MOS-R scored from parent-recorded videos between infants born EP/ELBW and term-born infants, to determine relationships between the MOS-R and 2-year cognitive, language and motor outcomes and if any relationships differ between birth groups and the association of the GMA (fidgety) with CP.</AbstractText A geographical cohort (EP/ELBW and term-control infants) was assessed using the MOS-R inclusive of the GMA at 3- to 4-month corrected age (CA), and the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at 2-year CA. Differences in mean total MOS-R between groups, relationships between MOS-R and 2-year outcomes and relationships between GMA (fidgety) and CP in infants born EP/ELBW were estimated using linear/logistic regression.</AbstractText Three hundred and twelve infants (147 EP/ELBW; 165 term) had complete MOS-R and Bayley-III assessments. Mean MOS-R was lower in infants born EP/ELBW than controls (mean difference -3.2, 95% confidence interval [CI] -4.2, -2.3). MOS-R was positively related to cognitive (β [regression coefficient] = 0.71, 95% CI 0.27, 1.15), language (β = 0.96, 95% CI 0.38, 1.54) and motor outcomes (β = .89, 95% CI 0.45, 1.34). There was little evidence for interaction effects between birth groups for any outcome. Absent/abnormal fidgety movements were related to CP in children born EP/ELBW (risk ratio 5.91, 95% CI 1.48, 23.7).</AbstractText Infants born EP/ELBW have lower MOS-R than infants born at term. A higher MOS-R is related to better outcomes for 2-year development, with similar relationships in both birth groups. Absent/abnormal fidgety movements are related to CP in EP/ELBW survivors.</AbstractText
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Hodgkin-Huxley's (HH) model of action potential (AP) has been modified in view of the nonlinear membrane capacitance of the axon of a neuron as well as the cooperation among the participating ion channels in the axon. Previous studies of action potential behavior based on computational analysis of modified HH models with either nonlinear axonal membrane capacitance or ion channel cooperativity show significant changes in action potential dynamics, e.g. AP peak, hyperpolarization amplitude, spike threshold, rapid onset, etc. As shown in the present paper, the combined effect of the nonlinear capacitance and ion channel cooperativity displays qualitatively similar results that are quantitatively different. For example, the nonlinear membrane capacitance leads to a reduction in the ion channel cooperativity effect on the action potential dynamics. The reason for this combined effect is thought to be axonal membrane distortion and depolarization caused by the varying membrane potential.</AbstractText
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Employment is associated with manual ability in adults with cerebral palsy - a population-based study. Employment rates are lower in adults with cerebral palsy (CP). Even though reduced manual ability is associated with limitations in daily activities, it is unclear whether employment rates are associated with manual ability in adults with CP.</AbstractText To analyze regular employment and employment rates (hours/week) in adults with CP and estimate their associations with manual ability relative to age and sex.</AbstractText This was a cross-sectional study of adults with CP, aged 20-64 years, from the combined Swedish CP follow-up program and registry. Manual ability was classified as levels I-V using the Manual Ability Classification System (MACS). Logistic regression analysis was used.</AbstractText The study included 2304 adults with CP (1271 men; median age 28 years, interquartile range 20-64 years). Fewer than one in five (19 %) were employed, and about half (52 %) of these worked full time. The probability of employment in adults with MACS level II was almost half that of those with level I (OR 0.44; 95 % CI 0.34-0.57) and decreased with each MACS level to OR 0.01 (95 % CI 0.00-0.03) for MACS V. Limited manual ability was associated with a lower probability of working full time: ORs of 0.46 (95 % CI 0.30-0.72) for MACS II and 0.29 (95 % CI 0.16-0.56) for MACS III-V.</AbstractText Limited manual ability in adults with CP impacts both their likelihood of employment and employment rate. Greater manual ability is associated with a higher probability of regular employment and working full time.</AbstractText
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Parent-recorded videos of infant spontaneous movement: Comparisons at 3-4 months and relationships with 2-year developmental outcomes in extremely preterm, extremely low birthweight and term-born infants. Infants born extremely preterm (EP, <28-week gestational age) or extremely low birthweight (ELBW, <1000 g) are at risk of developmental delay and cerebral palsy (CP). The General Movements Assessment (GMA) and its extension, the Motor Optimality Score, revised (MOS-R) (assesses movement patterns and posture), may help to identify early delays.</AbstractText To compare differences in the MOS-R scored from parent-recorded videos between infants born EP/ELBW and term-born infants, to determine relationships between the MOS-R and 2-year cognitive, language and motor outcomes and if any relationships differ between birth groups and the association of the GMA (fidgety) with CP.</AbstractText A geographical cohort (EP/ELBW and term-control infants) was assessed using the MOS-R inclusive of the GMA at 3- to 4-month corrected age (CA), and the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at 2-year CA. Differences in mean total MOS-R between groups, relationships between MOS-R and 2-year outcomes and relationships between GMA (fidgety) and CP in infants born EP/ELBW were estimated using linear/logistic regression.</AbstractText Three hundred and twelve infants (147 EP/ELBW; 165 term) had complete MOS-R and Bayley-III assessments. Mean MOS-R was lower in infants born EP/ELBW than controls (mean difference -3.2, 95% confidence interval [CI] -4.2, -2.3). MOS-R was positively related to cognitive (β [regression coefficient] = 0.71, 95% CI 0.27, 1.15), language (β = 0.96, 95% CI 0.38, 1.54) and motor outcomes (β = .89, 95% CI 0.45, 1.34). There was little evidence for interaction effects between birth groups for any outcome. Absent/abnormal fidgety movements were related to CP in children born EP/ELBW (risk ratio 5.91, 95% CI 1.48, 23.7).</AbstractText Infants born EP/ELBW have lower MOS-R than infants born at term. A higher MOS-R is related to better outcomes for 2-year development, with similar relationships in both birth groups. Absent/abnormal fidgety movements are related to CP in EP/ELBW survivors.</AbstractText
|
The role of nonlinear axonal membrane capacitance in modulating ion channel cooperativity in action potential dynamics: Studies on Hodgkin-Huxley's model. Hodgkin-Huxley's (HH) model of action potential (AP) has been modified in view of the nonlinear membrane capacitance of the axon of a neuron as well as the cooperation among the participating ion channels in the axon. Previous studies of action potential behavior based on computational analysis of modified HH models with either nonlinear axonal membrane capacitance or ion channel cooperativity show significant changes in action potential dynamics, e.g. AP peak, hyperpolarization amplitude, spike threshold, rapid onset, etc. As shown in the present paper, the combined effect of the nonlinear capacitance and ion channel cooperativity displays qualitatively similar results that are quantitatively different. For example, the nonlinear membrane capacitance leads to a reduction in the ion channel cooperativity effect on the action potential dynamics. The reason for this combined effect is thought to be axonal membrane distortion and depolarization caused by the varying membrane potential.</AbstractText
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40490260
|
36577183
|
40733487
|
Perspectives on Analgesia for Craniotomy: A Survey of Anesthetic Practices.
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Radiomics-based evaluation and possible characterization of dynamic contrast enhanced (DCE) perfusion derived different sub-regions of Glioblastoma.
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Evidence of Transmission Capability in UK Culex pipiens for Japanese Encephalitis Virus (JEV) Genotype I and Potential Impact of Climate Change.
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This study aimed to compare analgesic practices for patients undergoing craniotomy in high-income countries (HICs) and low-income and middle-income countries (LMICs), focusing on variations in medication use and techniques.</AbstractText An English-language and Spanish-language electronic survey was sent to over 300 anesthesiologists in 35 countries from March 22 to May 19, 2024, to gather data on analgesia for craniotomy patients. Anonymous responses through REDCap were analyzed as a whole and by income category (HICs and LMICs).</AbstractText We received 328 responses (105 HICs, 221 LMICs, and 2 missing locations). Acetaminophen was used by 78% of respondents (HIC: 82%, LMIC: 76%), with low nonavailability in both groups (0.95% HICs, 4.98% LMICs). Fentanyl boluses were used in 57% of cases (HIC: 60%, LMIC: 55%). Incisional local anesthesia was administered in 51% (HIC: 52%, LMIC: 50%), with minimal nonavailability (1.9% HIC, 1.4% LMIC). The use of a remifentanil infusion was more common in HICs (64%) than LMICs (31%), where nonavailability was significantly higher (43.89% vs. 7.62% HICs). Scalp blocks were used by 15% of HICs and 43% of LMICs. Craniotomy indication influenced the choice of analgesia for 61% of respondents.</AbstractText Analgesic practices for craniotomy vary significantly between HICs and LMICs, primarily due to medication availability. Global guidelines should consider resource differences to improve postoperative pain management.</AbstractText
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Glioblastoma (GB) is among the most devastative brain tumors, which usually comprises sub-regions like enhancing tumor (ET), non-enhancing tumor (NET), edema (ED), and necrosis (NEC) as described on MRI. Semi-automated algorithms to extract these tumor subpart volumes and boundaries have been demonstrated using dynamic contrast-enhanced (DCE) perfusion imaging. We aim to characterize these sub-regions derived from DCE perfusion MRI using routine 3D post-contrast-T1 (T1GD) and FLAIR images with the aid of Radiomics analysis. We also explored the possibility of separating edema from tumor sub-regions by extracting the most influential radiomics features.</AbstractText A total of 89 patients with histopathological confirmed IDH wild type GB were considered, who underwent the MR imaging with DCE perfusion-MRI. Perfusion and kinetic indices were computed and further used to segment tumor sub-regions. Radiomics features were extracted from FLAIR and T1GD images with PyRadiomics tool. Statistical analysis of the features was carried out using two approaches as well as machine learning (ML) models were constructed separately, i) within different tumor sub-regions and ii) ED as one category and the remaining sub-regions combined as another category. ML based predictive feature maps was also constructed.</AbstractText Seven features found to be statistically significant to differentiate tumor sub-regions in FLAIR and T1GD images, with p-value < 0.05 and AUC values in the range of 0.72 to 0.93. However, the edema features stood out in the analysis. In the second approach, the ML model was able to categorize the ED from the rest of the tumor sub-regions in FLAIR and T1GD images with AUC of 0.95 and 0.89 respectively.</AbstractText Radiomics-based specific feature values and maps help to characterize different tumor sub-regions. However, the GLDM_DependenceNonUniformity feature appears to be most specific for separating edema from the remaining tumor sub-regions using conventional FLAIR images. This may be of value in the segmentation of edema from tumors using conventional MRI in the future.</AbstractText
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Japanese encephalitis virus (JEV) is a mosquito-borne orthoflavivirus and a major cause of human encephalitis throughout Asia, although it is currently not reported in Europe. To assess the potential impact of climate change, such as increased temperatures, and the potential for native <i
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Perspectives on Analgesia for Craniotomy: A Survey of Anesthetic Practices. This study aimed to compare analgesic practices for patients undergoing craniotomy in high-income countries (HICs) and low-income and middle-income countries (LMICs), focusing on variations in medication use and techniques.</AbstractText An English-language and Spanish-language electronic survey was sent to over 300 anesthesiologists in 35 countries from March 22 to May 19, 2024, to gather data on analgesia for craniotomy patients. Anonymous responses through REDCap were analyzed as a whole and by income category (HICs and LMICs).</AbstractText We received 328 responses (105 HICs, 221 LMICs, and 2 missing locations). Acetaminophen was used by 78% of respondents (HIC: 82%, LMIC: 76%), with low nonavailability in both groups (0.95% HICs, 4.98% LMICs). Fentanyl boluses were used in 57% of cases (HIC: 60%, LMIC: 55%). Incisional local anesthesia was administered in 51% (HIC: 52%, LMIC: 50%), with minimal nonavailability (1.9% HIC, 1.4% LMIC). The use of a remifentanil infusion was more common in HICs (64%) than LMICs (31%), where nonavailability was significantly higher (43.89% vs. 7.62% HICs). Scalp blocks were used by 15% of HICs and 43% of LMICs. Craniotomy indication influenced the choice of analgesia for 61% of respondents.</AbstractText Analgesic practices for craniotomy vary significantly between HICs and LMICs, primarily due to medication availability. Global guidelines should consider resource differences to improve postoperative pain management.</AbstractText
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Radiomics-based evaluation and possible characterization of dynamic contrast enhanced (DCE) perfusion derived different sub-regions of Glioblastoma. Glioblastoma (GB) is among the most devastative brain tumors, which usually comprises sub-regions like enhancing tumor (ET), non-enhancing tumor (NET), edema (ED), and necrosis (NEC) as described on MRI. Semi-automated algorithms to extract these tumor subpart volumes and boundaries have been demonstrated using dynamic contrast-enhanced (DCE) perfusion imaging. We aim to characterize these sub-regions derived from DCE perfusion MRI using routine 3D post-contrast-T1 (T1GD) and FLAIR images with the aid of Radiomics analysis. We also explored the possibility of separating edema from tumor sub-regions by extracting the most influential radiomics features.</AbstractText A total of 89 patients with histopathological confirmed IDH wild type GB were considered, who underwent the MR imaging with DCE perfusion-MRI. Perfusion and kinetic indices were computed and further used to segment tumor sub-regions. Radiomics features were extracted from FLAIR and T1GD images with PyRadiomics tool. Statistical analysis of the features was carried out using two approaches as well as machine learning (ML) models were constructed separately, i) within different tumor sub-regions and ii) ED as one category and the remaining sub-regions combined as another category. ML based predictive feature maps was also constructed.</AbstractText Seven features found to be statistically significant to differentiate tumor sub-regions in FLAIR and T1GD images, with p-value < 0.05 and AUC values in the range of 0.72 to 0.93. However, the edema features stood out in the analysis. In the second approach, the ML model was able to categorize the ED from the rest of the tumor sub-regions in FLAIR and T1GD images with AUC of 0.95 and 0.89 respectively.</AbstractText Radiomics-based specific feature values and maps help to characterize different tumor sub-regions. However, the GLDM_DependenceNonUniformity feature appears to be most specific for separating edema from the remaining tumor sub-regions using conventional FLAIR images. This may be of value in the segmentation of edema from tumors using conventional MRI in the future.</AbstractText
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Evidence of Transmission Capability in UK Culex pipiens for Japanese Encephalitis Virus (JEV) Genotype I and Potential Impact of Climate Change. Japanese encephalitis virus (JEV) is a mosquito-borne orthoflavivirus and a major cause of human encephalitis throughout Asia, although it is currently not reported in Europe. To assess the potential impact of climate change, such as increased temperatures, and the potential for native <i
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26669509
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24333831
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27980478
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Parallel Spectral Acquisition with an Ion Cyclotron Resonance Cell Array.
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Dynamic nuclear polarization using frequency modulation at 3.34 T.
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The Woman Born Without a Cerebellum: A Real-Life Case Adapted for Use in an Undergraduate Developmental and Systems Neuroscience Course.
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Mass measurement accuracy is a critical analytical figure-of-merit in most areas of mass spectrometry application. However, the time required for acquisition of high-resolution, high mass accuracy data limits many applications and is an aspect under continual pressure for development. Current efforts target implementation of higher electrostatic and magnetic fields because ion oscillatory frequencies increase linearly with field strength. As such, the time required for spectral acquisition of a given resolving power and mass accuracy decreases linearly with increasing fields. Mass spectrometer developments to include multiple high-resolution detectors that can be operated in parallel could further decrease the acquisition time by a factor of n, the number of detectors. Efforts described here resulted in development of an instrument with a set of Fourier transform ion cyclotron resonance (ICR) cells as detectors that constitute the first MS array capable of parallel high-resolution spectral acquisition. ICR cell array systems consisting of three or five cells were constructed with printed circuit boards and installed within a single superconducting magnet and vacuum system. Independent ion populations were injected and trapped within each cell in the array. Upon filling the array, all ions in all cells were simultaneously excited and ICR signals from each cell were independently amplified and recorded in parallel. Presented here are the initial results of successful parallel spectral acquisition, parallel mass spectrometry (MS) and MS/MS measurements, and parallel high-resolution acquisition with the MS array system.</AbstractText
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During dynamic nuclear polarization (DNP) experiments polarization is transferred from unpaired electrons to their neighboring nuclear spins, resulting in dramatic enhancement of the NMR signals. While in most cases this is achieved by continuous wave (cw) irradiation applied to samples in fixed external magnetic fields, here we show that DNP enhancement of static samples can improve by modulating the microwave (MW) frequency at a constant field of 3.34 T. The efficiency of triangular shaped modulation is explored by monitoring the (1)H signal enhancement in frozen solutions containing different TEMPOL radical concentrations at different temperatures. The optimal modulation parameters are examined experimentally and under the most favorable conditions a threefold enhancement is obtained with respect to constant frequency DNP in samples with low radical concentrations. The results are interpreted using numerical simulations on small spin systems. In particular, it is shown experimentally and explained theoretically that: (i) The optimal modulation frequency is higher than the electron spin-lattice relaxation rate. (ii) The optimal modulation amplitude must be smaller than the nuclear Larmor frequency and the EPR line-width, as expected. (iii) The MW frequencies corresponding to the enhancement maxima and minima are shifted away from one another when using frequency modulation, relative to the constant frequency experiments.</AbstractText
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In 2014, the case of a 24-year-old woman who had just discovered she was born without a cerebellum made headlines around the world. The details of this case were combined with other published cases of cerebellar agenesis to create an active learning exercise for an undergraduate developmental and systems neuroscience course. By reading an intriguing narrative and answering questions in stages, students work together to apply and extend their knowledge of brain development and cerebellar function. The case can be used to introduce new information in a "flipped classroom" setting or as an interactive exam review.</AbstractText
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Parallel Spectral Acquisition with an Ion Cyclotron Resonance Cell Array. Mass measurement accuracy is a critical analytical figure-of-merit in most areas of mass spectrometry application. However, the time required for acquisition of high-resolution, high mass accuracy data limits many applications and is an aspect under continual pressure for development. Current efforts target implementation of higher electrostatic and magnetic fields because ion oscillatory frequencies increase linearly with field strength. As such, the time required for spectral acquisition of a given resolving power and mass accuracy decreases linearly with increasing fields. Mass spectrometer developments to include multiple high-resolution detectors that can be operated in parallel could further decrease the acquisition time by a factor of n, the number of detectors. Efforts described here resulted in development of an instrument with a set of Fourier transform ion cyclotron resonance (ICR) cells as detectors that constitute the first MS array capable of parallel high-resolution spectral acquisition. ICR cell array systems consisting of three or five cells were constructed with printed circuit boards and installed within a single superconducting magnet and vacuum system. Independent ion populations were injected and trapped within each cell in the array. Upon filling the array, all ions in all cells were simultaneously excited and ICR signals from each cell were independently amplified and recorded in parallel. Presented here are the initial results of successful parallel spectral acquisition, parallel mass spectrometry (MS) and MS/MS measurements, and parallel high-resolution acquisition with the MS array system.</AbstractText
|
Dynamic nuclear polarization using frequency modulation at 3.34 T. During dynamic nuclear polarization (DNP) experiments polarization is transferred from unpaired electrons to their neighboring nuclear spins, resulting in dramatic enhancement of the NMR signals. While in most cases this is achieved by continuous wave (cw) irradiation applied to samples in fixed external magnetic fields, here we show that DNP enhancement of static samples can improve by modulating the microwave (MW) frequency at a constant field of 3.34 T. The efficiency of triangular shaped modulation is explored by monitoring the (1)H signal enhancement in frozen solutions containing different TEMPOL radical concentrations at different temperatures. The optimal modulation parameters are examined experimentally and under the most favorable conditions a threefold enhancement is obtained with respect to constant frequency DNP in samples with low radical concentrations. The results are interpreted using numerical simulations on small spin systems. In particular, it is shown experimentally and explained theoretically that: (i) The optimal modulation frequency is higher than the electron spin-lattice relaxation rate. (ii) The optimal modulation amplitude must be smaller than the nuclear Larmor frequency and the EPR line-width, as expected. (iii) The MW frequencies corresponding to the enhancement maxima and minima are shifted away from one another when using frequency modulation, relative to the constant frequency experiments.</AbstractText
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The Woman Born Without a Cerebellum: A Real-Life Case Adapted for Use in an Undergraduate Developmental and Systems Neuroscience Course. In 2014, the case of a 24-year-old woman who had just discovered she was born without a cerebellum made headlines around the world. The details of this case were combined with other published cases of cerebellar agenesis to create an active learning exercise for an undergraduate developmental and systems neuroscience course. By reading an intriguing narrative and answering questions in stages, students work together to apply and extend their knowledge of brain development and cerebellar function. The case can be used to introduce new information in a "flipped classroom" setting or as an interactive exam review.</AbstractText
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33113068
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23419190
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34179842
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Impairment of right ventricular strain evaluated by cardiovascular magnetic resonance feature tracking in patients with interstitial lung disease.
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Brain and neck tumors among physicians performing interventional procedures.
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Building a best-in-class automated de-identification tool for electronic health records through ensemble learning.
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The aims of this study were to investigate the relationship between pulmonary hypertension (PH) and right ventricular (RV) strain, and to evaluate the prognostic value of RV strain by cardiac magnetic resonance (CMR) feature tracking for patients with interstitial lung disease (ILD).</AbstractText A total of seventy ILD patients (mean age: 71 ± 8 years, 39 [56%] males) who underwent CMR and right heart catheterization (RHC) were studied. Using a 1.5T magnetic resonance (MR) scanner, steady-state free precession cine MR images encompassing the RV were acquired in all patients and 20 control subjects. RV longitudinal strain were calculated with a feature tracking algorithm. PH was defined as a mean pulmonary artery pressure of more than 20 mmHg at rest and a pulmonary vascular resistance ≥3 Woods unit.</AbstractText The RV longitudinal strain was significantly impaired in the ILD patients with PH (n=18) than ILD patients without PH (n=52) (-13.3 ± 5.4% vs. -16.9±5.4%, p=0.048). The RV longitudinal strain differed significantly between the ILD patients without PH and the controls (n=20) (-16.9 ± 5.4% vs. -20.8 ± 6.2%, p=0.002). Five of 70 (7%) patients died within one-year after CMR scan. Area under receiver operating characteristics curve for predicting death was 0.900 (95%CI: 0.800 to 1.000) for RV strain, 0.643 (95%CI: 0.454 to 0.832) for RVEF.</AbstractText Presence of PH was associated with impairment of RV strain, and RV strain could predict short-term mortality in patients with ILD. RV strain by feature tracking might be useful as a non-invasive prognostic marker for patients with ILD.</AbstractText
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Physicians performing interventional procedures are chronically exposed to ionizing radiation, which is known to pose increased cancer risks. We recently reported 9 cases of brain cancer in interventional cardiologists. Subsequently, we received 22 additional cases from around the world, comprising an expanded 31 case cohort. Data were transmitted to us during the past few months. For all cases, where possible, we endeavored to obtain the baseline data, including age, gender, tumor type, and side involved, specialty (cardiologist vs radiologist), and number of years in practice. These data were obtained from the medical records, interviews with patients, when possible, or with family members and/or colleagues. The present report documented brain and neck tumors occurring in 31 physicians: 23 interventional cardiologists, 2 electrophysiologists, and 6 interventional radiologists. All physicians had worked for prolonged periods (latency period 12 to 32 years, mean 23.5 ± 5.9) in active interventional practice with exposure to ionizing radiation in the catheterization laboratory. The tumors included 17 cases (55%) of glioblastoma multiforme (GBM), 2 astrocytomas (7%), and 5 meningiomas (16%). In 26 of 31 cases, data were available regarding the side of the brain involved. The malignancy was left sided in 22 (85%), midline in 1, and right sided in 3 operators. In conclusion, these results raise additional concerns regarding brain cancer developing in physicians performing interventional procedures. Given that the brain is relatively unprotected and the left side of the head is known to be more exposed to radiation than the right, these findings of disproportionate reports of left-sided tumors suggest the possibility of a causal relation to occupational radiation exposure.</AbstractText
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The presence of personally identifiable information (PII) in natural language portions of electronic health records (EHRs) constrains their broad reuse. Despite continuous improvements in automated detection of PII, residual identifiers require manual validation and correction. Here, we describe an automated de-identification system that employs an ensemble architecture, incorporating attention-based deep-learning models and rule-based methods, supported by heuristics for detecting PII in EHR data. Detected identifiers are then transformed into plausible, though fictional, surrogates to further obfuscate any leaked identifier. Our approach outperforms existing tools, with a recall of 0.992 and precision of 0.979 on the i2b2 2014 dataset and a recall of 0.994 and precision of 0.967 on a dataset of 10,000 notes from the Mayo Clinic. The de-identification system presented here enables the generation of de-identified patient data at the scale required for modern machine-learning applications to help accelerate medical discoveries.</AbstractText
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Impairment of right ventricular strain evaluated by cardiovascular magnetic resonance feature tracking in patients with interstitial lung disease. The aims of this study were to investigate the relationship between pulmonary hypertension (PH) and right ventricular (RV) strain, and to evaluate the prognostic value of RV strain by cardiac magnetic resonance (CMR) feature tracking for patients with interstitial lung disease (ILD).</AbstractText A total of seventy ILD patients (mean age: 71 ± 8 years, 39 [56%] males) who underwent CMR and right heart catheterization (RHC) were studied. Using a 1.5T magnetic resonance (MR) scanner, steady-state free precession cine MR images encompassing the RV were acquired in all patients and 20 control subjects. RV longitudinal strain were calculated with a feature tracking algorithm. PH was defined as a mean pulmonary artery pressure of more than 20 mmHg at rest and a pulmonary vascular resistance ≥3 Woods unit.</AbstractText The RV longitudinal strain was significantly impaired in the ILD patients with PH (n=18) than ILD patients without PH (n=52) (-13.3 ± 5.4% vs. -16.9±5.4%, p=0.048). The RV longitudinal strain differed significantly between the ILD patients without PH and the controls (n=20) (-16.9 ± 5.4% vs. -20.8 ± 6.2%, p=0.002). Five of 70 (7%) patients died within one-year after CMR scan. Area under receiver operating characteristics curve for predicting death was 0.900 (95%CI: 0.800 to 1.000) for RV strain, 0.643 (95%CI: 0.454 to 0.832) for RVEF.</AbstractText Presence of PH was associated with impairment of RV strain, and RV strain could predict short-term mortality in patients with ILD. RV strain by feature tracking might be useful as a non-invasive prognostic marker for patients with ILD.</AbstractText
|
Brain and neck tumors among physicians performing interventional procedures. Physicians performing interventional procedures are chronically exposed to ionizing radiation, which is known to pose increased cancer risks. We recently reported 9 cases of brain cancer in interventional cardiologists. Subsequently, we received 22 additional cases from around the world, comprising an expanded 31 case cohort. Data were transmitted to us during the past few months. For all cases, where possible, we endeavored to obtain the baseline data, including age, gender, tumor type, and side involved, specialty (cardiologist vs radiologist), and number of years in practice. These data were obtained from the medical records, interviews with patients, when possible, or with family members and/or colleagues. The present report documented brain and neck tumors occurring in 31 physicians: 23 interventional cardiologists, 2 electrophysiologists, and 6 interventional radiologists. All physicians had worked for prolonged periods (latency period 12 to 32 years, mean 23.5 ± 5.9) in active interventional practice with exposure to ionizing radiation in the catheterization laboratory. The tumors included 17 cases (55%) of glioblastoma multiforme (GBM), 2 astrocytomas (7%), and 5 meningiomas (16%). In 26 of 31 cases, data were available regarding the side of the brain involved. The malignancy was left sided in 22 (85%), midline in 1, and right sided in 3 operators. In conclusion, these results raise additional concerns regarding brain cancer developing in physicians performing interventional procedures. Given that the brain is relatively unprotected and the left side of the head is known to be more exposed to radiation than the right, these findings of disproportionate reports of left-sided tumors suggest the possibility of a causal relation to occupational radiation exposure.</AbstractText
|
Building a best-in-class automated de-identification tool for electronic health records through ensemble learning. The presence of personally identifiable information (PII) in natural language portions of electronic health records (EHRs) constrains their broad reuse. Despite continuous improvements in automated detection of PII, residual identifiers require manual validation and correction. Here, we describe an automated de-identification system that employs an ensemble architecture, incorporating attention-based deep-learning models and rule-based methods, supported by heuristics for detecting PII in EHR data. Detected identifiers are then transformed into plausible, though fictional, surrogates to further obfuscate any leaked identifier. Our approach outperforms existing tools, with a recall of 0.992 and precision of 0.979 on the i2b2 2014 dataset and a recall of 0.994 and precision of 0.967 on a dataset of 10,000 notes from the Mayo Clinic. The de-identification system presented here enables the generation of de-identified patient data at the scale required for modern machine-learning applications to help accelerate medical discoveries.</AbstractText
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38507796
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38733576
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39049950
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Robust residual-guided iterative reconstruction for sparse-view CT in small animal imaging.
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Improved stent sharpness evaluation with super-resolution deep learning reconstruction in coronary CT angiography.
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Subjective cognitive decline in healthy older adults is associated with altered processing of negative versus positive feedback in a probabilistic learning task.
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<i
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This study aimed to assess the impact of super-resolution deep learning reconstruction (SR-DLR) on coronary CT angiography (CCTA) image quality and blooming artifacts from coronary artery stents in comparison to conventional methods, including hybrid iterative reconstruction (HIR) and deep learning-based reconstruction (DLR).</AbstractText A retrospective analysis included 66 CCTA patients from July to November 2022. Major coronary arteries were evaluated for image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Stent sharpness was quantified using 10%-90% edge rise slope (ERS) and 10%-90% edge rise distance (ERD). Qualitative analysis employed a 5-point scoring system to assess overall image quality, image noise, vessel wall, and stent structure.</AbstractText SR-DLR demonstrated significantly lower image noise compared to HIR and DLR. SNR and CNR were notably higher in SR-DLR. Stent ERS was significantly improved in SR-DLR, with mean ERD values of 0.70 ± 0.20 mm for SR-DLR, 1.13 ± 0.28 mm for HIR, and 0.85 ± 0.26 mm for DLR. Qualitatively, SR-DLR scored higher in all categories.</AbstractText SR-DLR produces images with lower image noise, leading to improved overall image quality, compared with HIR and DLR. SR-DLR is a valuable image reconstruction algorithm for enhancing the spatial resolution and sharpness of coronary artery stents without being constrained by hardware limitations.</AbstractText The overall image quality was significantly higher in SR-DLR, resulting in sharper coronary artery stents compared to HIR and DLR.</AbstractText
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Older adults who worry about their own cognitive capabilities declining, but who do not show evidence of actual cognitive decline in neuropsychological tests, are at an increased risk of being diagnosed with dementia at a later time. Since neural markers may be more sensitive to early stages of cognitive decline, in the present study we examined whether event-related potential responses of feedback processing, elicited in a probabilistic learning task, differ between healthy older adults recruited from the community, who either did (subjective cognitive decline/SCD-group) or did not report (No-SCD group) worry about their own cognition declining beyond the normal age-related development. In the absence of group differences in learning from emotionally charged feedback in the probabilistic learning task, the amplitude of the feedback-related negativity (FRN) varied with feedback valence differently in the two groups: In the No-SCD group, the FRN was larger for positive than negative feedback, while in the SCD group, FRN amplitude did not differ between positive and negative feedback. The P3b was enhanced for negative feedback in both groups, and group differences in P3b amplitude were not significant. Altered sensitivity in neural processing of negative versus positive feedback may be a marker of SCD.</AbstractText
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Robust residual-guided iterative reconstruction for sparse-view CT in small animal imaging. <i
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Improved stent sharpness evaluation with super-resolution deep learning reconstruction in coronary CT angiography. This study aimed to assess the impact of super-resolution deep learning reconstruction (SR-DLR) on coronary CT angiography (CCTA) image quality and blooming artifacts from coronary artery stents in comparison to conventional methods, including hybrid iterative reconstruction (HIR) and deep learning-based reconstruction (DLR).</AbstractText A retrospective analysis included 66 CCTA patients from July to November 2022. Major coronary arteries were evaluated for image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Stent sharpness was quantified using 10%-90% edge rise slope (ERS) and 10%-90% edge rise distance (ERD). Qualitative analysis employed a 5-point scoring system to assess overall image quality, image noise, vessel wall, and stent structure.</AbstractText SR-DLR demonstrated significantly lower image noise compared to HIR and DLR. SNR and CNR were notably higher in SR-DLR. Stent ERS was significantly improved in SR-DLR, with mean ERD values of 0.70 ± 0.20 mm for SR-DLR, 1.13 ± 0.28 mm for HIR, and 0.85 ± 0.26 mm for DLR. Qualitatively, SR-DLR scored higher in all categories.</AbstractText SR-DLR produces images with lower image noise, leading to improved overall image quality, compared with HIR and DLR. SR-DLR is a valuable image reconstruction algorithm for enhancing the spatial resolution and sharpness of coronary artery stents without being constrained by hardware limitations.</AbstractText The overall image quality was significantly higher in SR-DLR, resulting in sharper coronary artery stents compared to HIR and DLR.</AbstractText
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Subjective cognitive decline in healthy older adults is associated with altered processing of negative versus positive feedback in a probabilistic learning task. Older adults who worry about their own cognitive capabilities declining, but who do not show evidence of actual cognitive decline in neuropsychological tests, are at an increased risk of being diagnosed with dementia at a later time. Since neural markers may be more sensitive to early stages of cognitive decline, in the present study we examined whether event-related potential responses of feedback processing, elicited in a probabilistic learning task, differ between healthy older adults recruited from the community, who either did (subjective cognitive decline/SCD-group) or did not report (No-SCD group) worry about their own cognition declining beyond the normal age-related development. In the absence of group differences in learning from emotionally charged feedback in the probabilistic learning task, the amplitude of the feedback-related negativity (FRN) varied with feedback valence differently in the two groups: In the No-SCD group, the FRN was larger for positive than negative feedback, while in the SCD group, FRN amplitude did not differ between positive and negative feedback. The P3b was enhanced for negative feedback in both groups, and group differences in P3b amplitude were not significant. Altered sensitivity in neural processing of negative versus positive feedback may be a marker of SCD.</AbstractText
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39322491
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34536341
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38638086
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Antibodies in immune-mediated peripheral neuropathies. Where are we in 2024?
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Central neuroinflammation in Covid-19: a systematic review of 182 cases with encephalitis, acute disseminated encephalomyelitis, and necrotizing encephalopathies.
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Grey matter alterations in generalized anxiety disorder: A voxel-wise meta-analysis of voxel-based morphometry studies.
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Over the past 30 years, about 20 antibodies have been identified in immune-mediated neuropathies, recognizing membrane or intracellular proteins or glycolipids of neuron and Schwann cells. This article reviews the different methods used for their detection, what we know about their pathogenic role, how they have helped identify several disorders, and how they are essential for diagnosis. Despite sustained efforts, some immune-mediated disorders still lack identified autoantibodies, notably the classical form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. The reasons for this are discussed. The article also tries to determine potential future developments in antibody research, particularly the use of omic approaches and the search for other types of biomarkers beyond diagnostic ones, such as those that can identify patients who will respond to a given treatment.</AbstractText
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Growing evidence demonstrates the association of encephalitis, meningoencephalitis or encephalomyelitis, with SARS-CoV-2 infection. This study aims to determine the profile and possible mechanisms behind CNS inflammatory diseases in the context of Covid-19. We conducted a systematic review of case reports on Covid-19-related encephalitis, meningoencephalitis, acute necrotizing encephalitis, and acute disseminated encephalomyelitis in adults, published before January 2021. A total of 182 cases (encephalitis = 109, meningoencephalitis = 26, acute disseminated encephalomyelitis = 35, acute necrotizing (hemorrhagic) encephalitis = 12) were included. While cerebrospinal fluid (CSF) pleocytosis and increased protein level was present in less than 50%, magnetic resonance imaging (MRI) and electroencephalogram (EEG) were abnormal in 78 and 93.2% of all cases, respectively. Viral particles were detected in cerebrospinal fluid of only 13 patients and autoantibodies were present in seven patients. All patients presented with altered mental status, either in the form of impaired consciousness or psychological/cognitive decline. Seizure, cranial nerve signs, motor, and reflex abnormalities were among associated symptoms. Covid-19-associated encephalitis presents with a distinctive profile requiring thorough diagnosis and thereby a comprehensive knowledge of the disease. The clinical profile of brain inflammation in Covid-19 exhibits majority of abnormal imaging and electroencephalography findings with mild/moderate pleocytosis or proteinorrhachia as prevalent as normal cerebrospinal fluid (CSF). Oligoclonal bands and autoantibody assessments are useful in further evaluating neuro-covid patients, as supported by our pooled evidence. Despite the possibility that direct viral invasion cannot be easily estimated, it is still more likely that immune-mediated or autoimmune reactions play a more important role in SARS-CoV-2 neuroinflammation.</AbstractText
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Grey matter, a crucial component of the brain, has been found altered in generalized anxiety disorder (GAD) of several voxel-based morphometry studies. The conclusive and consistent grey matter alterations in GAD have not been confirmed.</AbstractText Eleven voxel-based morphometry studies of GAD patients were included in the current systematic review and meta-analysis. The linear model of anxiety severity scores was applied to explore the relationship of grey matter alterations and anxiety severity. The subgroup analysis of adult GAD and adolescent GAD was also performed.</AbstractText Significantly modest grey matter alterations in the left superior temporal gyrus of patients with GAD were found. The anxiety severity score was significantly correlated with grey matter alterations in the right insula, lenticular nucleus, putamen and striatum. The subgroup analysis of adult GAD and adolescent GAD all failed to show significant grey matter alterations. However, in the adult GAD subgroup, anxiety severity score was significantly correlated with grey matter alterations in the right insula.</AbstractText GAD might have the modest grey matter alterations in the left superior temporal gyrus. Anxiety severity might be related to the grey matter alterations in the limbic regions, such as the right insula, lenticular nucleus, putamen and striatum. This kind of correlation might be related to the effects of adult GAD. Future studies with adequate sample sizes and sophisticated GAD categories will be needed.</AbstractText
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Antibodies in immune-mediated peripheral neuropathies. Where are we in 2024? Over the past 30 years, about 20 antibodies have been identified in immune-mediated neuropathies, recognizing membrane or intracellular proteins or glycolipids of neuron and Schwann cells. This article reviews the different methods used for their detection, what we know about their pathogenic role, how they have helped identify several disorders, and how they are essential for diagnosis. Despite sustained efforts, some immune-mediated disorders still lack identified autoantibodies, notably the classical form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. The reasons for this are discussed. The article also tries to determine potential future developments in antibody research, particularly the use of omic approaches and the search for other types of biomarkers beyond diagnostic ones, such as those that can identify patients who will respond to a given treatment.</AbstractText
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Central neuroinflammation in Covid-19: a systematic review of 182 cases with encephalitis, acute disseminated encephalomyelitis, and necrotizing encephalopathies. Growing evidence demonstrates the association of encephalitis, meningoencephalitis or encephalomyelitis, with SARS-CoV-2 infection. This study aims to determine the profile and possible mechanisms behind CNS inflammatory diseases in the context of Covid-19. We conducted a systematic review of case reports on Covid-19-related encephalitis, meningoencephalitis, acute necrotizing encephalitis, and acute disseminated encephalomyelitis in adults, published before January 2021. A total of 182 cases (encephalitis = 109, meningoencephalitis = 26, acute disseminated encephalomyelitis = 35, acute necrotizing (hemorrhagic) encephalitis = 12) were included. While cerebrospinal fluid (CSF) pleocytosis and increased protein level was present in less than 50%, magnetic resonance imaging (MRI) and electroencephalogram (EEG) were abnormal in 78 and 93.2% of all cases, respectively. Viral particles were detected in cerebrospinal fluid of only 13 patients and autoantibodies were present in seven patients. All patients presented with altered mental status, either in the form of impaired consciousness or psychological/cognitive decline. Seizure, cranial nerve signs, motor, and reflex abnormalities were among associated symptoms. Covid-19-associated encephalitis presents with a distinctive profile requiring thorough diagnosis and thereby a comprehensive knowledge of the disease. The clinical profile of brain inflammation in Covid-19 exhibits majority of abnormal imaging and electroencephalography findings with mild/moderate pleocytosis or proteinorrhachia as prevalent as normal cerebrospinal fluid (CSF). Oligoclonal bands and autoantibody assessments are useful in further evaluating neuro-covid patients, as supported by our pooled evidence. Despite the possibility that direct viral invasion cannot be easily estimated, it is still more likely that immune-mediated or autoimmune reactions play a more important role in SARS-CoV-2 neuroinflammation.</AbstractText
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Grey matter alterations in generalized anxiety disorder: A voxel-wise meta-analysis of voxel-based morphometry studies. Grey matter, a crucial component of the brain, has been found altered in generalized anxiety disorder (GAD) of several voxel-based morphometry studies. The conclusive and consistent grey matter alterations in GAD have not been confirmed.</AbstractText Eleven voxel-based morphometry studies of GAD patients were included in the current systematic review and meta-analysis. The linear model of anxiety severity scores was applied to explore the relationship of grey matter alterations and anxiety severity. The subgroup analysis of adult GAD and adolescent GAD was also performed.</AbstractText Significantly modest grey matter alterations in the left superior temporal gyrus of patients with GAD were found. The anxiety severity score was significantly correlated with grey matter alterations in the right insula, lenticular nucleus, putamen and striatum. The subgroup analysis of adult GAD and adolescent GAD all failed to show significant grey matter alterations. However, in the adult GAD subgroup, anxiety severity score was significantly correlated with grey matter alterations in the right insula.</AbstractText GAD might have the modest grey matter alterations in the left superior temporal gyrus. Anxiety severity might be related to the grey matter alterations in the limbic regions, such as the right insula, lenticular nucleus, putamen and striatum. This kind of correlation might be related to the effects of adult GAD. Future studies with adequate sample sizes and sophisticated GAD categories will be needed.</AbstractText
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35752467
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29935317
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35796591
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Chiari Type 1 malformation: CSF flow dynamics and morphology in the posterior fossa and craniocervical junction and correlation of these findings with syrinx formation.
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Racial Differences in the Anatomy of the Posterior Fossa: Neurosurgical Considerations.
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Vanishing Bile Duct Syndrome Secondary to Hodgkin Lymphoma in a Child.
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Chiari type 1 malformation (CMI) is a disorder in which cerebellar tonsils descend below the foramen magnum. Although syringomyelia associated with CMI thought to be caused by hypoplastic posterior fossa and stenosis at the craniocervical junction; it has characteristic neurological and radiological features and the exact mechanism of syringomyelia remains unknown.</AbstractText The purposes of this study were to gain insight into morphological changes in posterior fossa and to find whether there is a difference in aqueductal stroke volume (ASV) between CMI with syrinx and without syrinx which may be an underlying mechanism of syrinx development.</AbstractText We consecutively evaluated 85 patients with Chiari malformation between January 2017 and December 2019 who had undergone phase-contrast MRI examination for CSF flow and between 18-60-years-old. We divided patients into two groups as subjects with syrinx (n=19) and without syrinx (n=66). After evaluating morphological changes, peak and average velocity (cm/s), forward and reverse flow volume (μl), net forward flow volume (μl), ASV (aqueductal stroke volume) (μl), aqueductus Sylvi (AS) area (mm<sup The forward and reverse volumes were statistically significantly higher in patients with syrinx (P=0.021, P=0.005 respectively). ASV was significantly increased in patients with syringomyelia (P=0.014). The PPC/AS was significantly lower in patients with syrinx compared to those without (P <0.001). AS area was significantly larger in those with syrinx. (P=0.022). The diameter of foramen magnum was significantly lower in patients with syrinx than those without (P <0.0001). The diameter of the herniated tonsilla at the foramen magnum level was found to be significantly lower in those with syrinx (P=0.011).</AbstractText Foramen magnum diameter, ASV, diameter of herniated tonsil, and PPC/AS ratio are important factors in syrinx development.</AbstractText
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Racial differences in anatomy of the cranium exist but have not been specifically considered in neurosurgical access planning. We sought to find differences in the anatomy of the posterior fossa in a cohort study consisting of Asian, African American, and Caucasian patients.</AbstractText Magnetic resonance imaging data of 60 Asian, 57 African American, and 70 Caucasian individuals were obtained from the Human Connectome Project. Measurements were done in axial, coronal, and sagittal planes in T2-weighted thin-sliced images. P values were calculated using 2-tailed Student t test. P < 0.05 was considered significant.</AbstractText We measured distance in millimeters from the z values (craniocaudal axis) from the internal acoustic meatus to the transition of the transverse sinus into the sigmoid sinus. We discovered significant differences across all races. Our results show that the junction of the transverse to sigmoid sinus is lowest in Caucasians followed by Asians and African Americans.</AbstractText Significant differences in anatomy have practical implications in the retrosigmoid approach to the cerebellopontine angle. Based on our findings, the junction of the transverse sinus with the sigmoid sinus can differ up to 0.5 cm in the craniocaudal axis depending on race. As neuronavigation is not standard to the approach to the cerebellopontine angle, the study aimed to provide the neurosurgeon operating in the retrosigmoid area additional knowledge to avoid sinus injury with subsequent complications, such as blood loss, sinus occlusion, or air embolism.</AbstractText
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Vanishing bile duct syndrome (VBDS) is a condition resulting from progressive destruction and loss of intrahepatic bile ducts leading to cholestasis, biliary cirrhosis, and liver failure. It occurs secondary to various pathologic conditions like autoimmune diseases, graft versus host disease, drug reactions, and as a paraneoplastic syndrome in malignancies. We here described a 9-year-old girl who presented with cervical lymphadenopathy and jaundice. This child was diagnosed as a case of Hodgkin lymphoma. All other causes of cholestasis were ruled out by appropriate investigations (particularly autoimmune, metabolic, infections, and drug-induced possibilities). On liver biopsy, her diagnosis was established as VBDS. In view of hepatic dysfunction, alternative chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP) was given, and she was started on hepatoprotective measures with ursodeoxycholic acid. Hepatic function gradually improved after the initiation of chemotherapy. VBDS is considered a dismal paraneoplastic syndrome with a high-case fatality. This case report highlights the importance of early recognition and initiation of appropriate full-dose chemotherapy as the only way to achieve complete resolution of VBDS.</AbstractText
|
Chiari Type 1 malformation: CSF flow dynamics and morphology in the posterior fossa and craniocervical junction and correlation of these findings with syrinx formation. Chiari type 1 malformation (CMI) is a disorder in which cerebellar tonsils descend below the foramen magnum. Although syringomyelia associated with CMI thought to be caused by hypoplastic posterior fossa and stenosis at the craniocervical junction; it has characteristic neurological and radiological features and the exact mechanism of syringomyelia remains unknown.</AbstractText The purposes of this study were to gain insight into morphological changes in posterior fossa and to find whether there is a difference in aqueductal stroke volume (ASV) between CMI with syrinx and without syrinx which may be an underlying mechanism of syrinx development.</AbstractText We consecutively evaluated 85 patients with Chiari malformation between January 2017 and December 2019 who had undergone phase-contrast MRI examination for CSF flow and between 18-60-years-old. We divided patients into two groups as subjects with syrinx (n=19) and without syrinx (n=66). After evaluating morphological changes, peak and average velocity (cm/s), forward and reverse flow volume (μl), net forward flow volume (μl), ASV (aqueductal stroke volume) (μl), aqueductus Sylvi (AS) area (mm<sup The forward and reverse volumes were statistically significantly higher in patients with syrinx (P=0.021, P=0.005 respectively). ASV was significantly increased in patients with syringomyelia (P=0.014). The PPC/AS was significantly lower in patients with syrinx compared to those without (P <0.001). AS area was significantly larger in those with syrinx. (P=0.022). The diameter of foramen magnum was significantly lower in patients with syrinx than those without (P <0.0001). The diameter of the herniated tonsilla at the foramen magnum level was found to be significantly lower in those with syrinx (P=0.011).</AbstractText Foramen magnum diameter, ASV, diameter of herniated tonsil, and PPC/AS ratio are important factors in syrinx development.</AbstractText
|
Racial Differences in the Anatomy of the Posterior Fossa: Neurosurgical Considerations. Racial differences in anatomy of the cranium exist but have not been specifically considered in neurosurgical access planning. We sought to find differences in the anatomy of the posterior fossa in a cohort study consisting of Asian, African American, and Caucasian patients.</AbstractText Magnetic resonance imaging data of 60 Asian, 57 African American, and 70 Caucasian individuals were obtained from the Human Connectome Project. Measurements were done in axial, coronal, and sagittal planes in T2-weighted thin-sliced images. P values were calculated using 2-tailed Student t test. P < 0.05 was considered significant.</AbstractText We measured distance in millimeters from the z values (craniocaudal axis) from the internal acoustic meatus to the transition of the transverse sinus into the sigmoid sinus. We discovered significant differences across all races. Our results show that the junction of the transverse to sigmoid sinus is lowest in Caucasians followed by Asians and African Americans.</AbstractText Significant differences in anatomy have practical implications in the retrosigmoid approach to the cerebellopontine angle. Based on our findings, the junction of the transverse sinus with the sigmoid sinus can differ up to 0.5 cm in the craniocaudal axis depending on race. As neuronavigation is not standard to the approach to the cerebellopontine angle, the study aimed to provide the neurosurgeon operating in the retrosigmoid area additional knowledge to avoid sinus injury with subsequent complications, such as blood loss, sinus occlusion, or air embolism.</AbstractText
|
Vanishing Bile Duct Syndrome Secondary to Hodgkin Lymphoma in a Child. Vanishing bile duct syndrome (VBDS) is a condition resulting from progressive destruction and loss of intrahepatic bile ducts leading to cholestasis, biliary cirrhosis, and liver failure. It occurs secondary to various pathologic conditions like autoimmune diseases, graft versus host disease, drug reactions, and as a paraneoplastic syndrome in malignancies. We here described a 9-year-old girl who presented with cervical lymphadenopathy and jaundice. This child was diagnosed as a case of Hodgkin lymphoma. All other causes of cholestasis were ruled out by appropriate investigations (particularly autoimmune, metabolic, infections, and drug-induced possibilities). On liver biopsy, her diagnosis was established as VBDS. In view of hepatic dysfunction, alternative chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP) was given, and she was started on hepatoprotective measures with ursodeoxycholic acid. Hepatic function gradually improved after the initiation of chemotherapy. VBDS is considered a dismal paraneoplastic syndrome with a high-case fatality. This case report highlights the importance of early recognition and initiation of appropriate full-dose chemotherapy as the only way to achieve complete resolution of VBDS.</AbstractText
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29253324
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18219673
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30618874
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Layered metal(IV) phosphonate materials: Solid-state (1) H, (13) C, (31) P NMR spectra and NMR relaxation.
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MR thermometry.
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Substance Dependence Among Bipolar, Unipolar Depression and Psychotic Homeless: A Canadian National Study.
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Multinuclear solid-state NMR and powder X-ray diffraction data collected for phosphonate materials Zr(O<sub
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Minimally invasive thermal therapy as local treatment of benign and malignant diseases has received increasing interest in recent years. Safety and efficacy of the treatment require accurate temperature measurement throughout the thermal procedure. Noninvasive temperature monitoring is feasible with magnetic resonance (MR) imaging based on temperature-sensitive MR parameters such as the proton resonance frequency (PRF), the diffusion coefficient (D), T1 and T2 relaxation times, magnetization transfer, the proton density, as well as temperature-sensitive contrast agents. In this article the principles of temperature measurements with these methods are reviewed and their usefulness for monitoring in vivo procedures is discussed. Whereas most measurements give a temperature change relative to a baseline condition, temperature-sensitive contrast agents and spectroscopic imaging can provide absolute temperature measurements. The excellent linearity and temperature dependence of the PRF and its near independence of tissue type have made PRF-based phase mapping methods the preferred choice for many in vivo applications. Accelerated MRI imaging techniques for real-time monitoring with the PRF method are discussed. Special attention is paid to acquisition and reconstruction methods for reducing temperature measurement artifacts introduced by tissue motion, which is often unavoidable during in vivo applications.</AbstractText
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<b
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Layered metal(IV) phosphonate materials: Solid-state (1) H, (13) C, (31) P NMR spectra and NMR relaxation. Multinuclear solid-state NMR and powder X-ray diffraction data collected for phosphonate materials Zr(O<sub
|
MR thermometry. Minimally invasive thermal therapy as local treatment of benign and malignant diseases has received increasing interest in recent years. Safety and efficacy of the treatment require accurate temperature measurement throughout the thermal procedure. Noninvasive temperature monitoring is feasible with magnetic resonance (MR) imaging based on temperature-sensitive MR parameters such as the proton resonance frequency (PRF), the diffusion coefficient (D), T1 and T2 relaxation times, magnetization transfer, the proton density, as well as temperature-sensitive contrast agents. In this article the principles of temperature measurements with these methods are reviewed and their usefulness for monitoring in vivo procedures is discussed. Whereas most measurements give a temperature change relative to a baseline condition, temperature-sensitive contrast agents and spectroscopic imaging can provide absolute temperature measurements. The excellent linearity and temperature dependence of the PRF and its near independence of tissue type have made PRF-based phase mapping methods the preferred choice for many in vivo applications. Accelerated MRI imaging techniques for real-time monitoring with the PRF method are discussed. Special attention is paid to acquisition and reconstruction methods for reducing temperature measurement artifacts introduced by tissue motion, which is often unavoidable during in vivo applications.</AbstractText
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Substance Dependence Among Bipolar, Unipolar Depression and Psychotic Homeless: A Canadian National Study. <b
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39794140
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35017509
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39801332
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Ultrastructural Localization of Glutamate Delta Receptor 1 in the Rodent and Primate Lateral Habenula.
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Determinants of synapse diversity revealed by super-resolution quantal transmission and active zone imaging.
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Epidemiological analysis and potential factors affecting the 2022-23 Crimean-Congo hemorrhagic fever outbreak in Iraq.
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Glutamate delta receptor 1 (GluD1) is a unique synaptogenic molecule expressed at excitatory and inhibitory synapses. The lateral habenula (LHb), a subcortical structure that regulates negative reward prediction error and major monoaminergic systems, is enriched in GluD1. LHb dysfunction has been implicated in psychiatric disorders such as depression and schizophrenia, both of which are associated with GRID1, the gene that encodes GluD1. Thus, disruption in GluD1 synaptic signaling may contribute to LHb dysfunction and the pathophysiology of LHb-associated disorders. Despite its strong cellular expression, little is known about the subsynaptic and subcellular localization of GluD1 in LHb neurons. Given that GluD1 is involved in the development and/or regulation of glutamatergic and GABAergic synapses in various brain regions, a detailed map of GluD1 synaptic localization is essential to elucidate its role in the LHb. To address this issue, we used immunoelectron microscopy methods in rodents and monkeys. In both species, GluD1 immunoreactivity was primarily expressed in dendritic profiles, with lower expression in somata, spines, and glial elements. Pre- and post-embedding immunogold experiments revealed strong GluD1 expression in the core of symmetric GABAergic synapses. Albeit less frequent, GluD1 was also found at the edges (i.e., perisynaptic) of asymmetric, putative glutamatergic synapses. Through the combination of anterograde tracing with immunogold labeling in rats, we showed that axon terminals from the entopeduncular nucleus and the lateral hypothalamus express postsynaptic GluD1 immunolabeling in the LHb. Our findings suggest that GluD1 may play a critical role in modulating GABAergic transmission in the rodent and primate LHb.</AbstractText
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Neural circuit function depends on the pattern of synaptic connections between neurons and the strength of those connections. Synaptic strength is determined by both postsynaptic sensitivity to neurotransmitter and the presynaptic probability of action potential evoked transmitter release (P<sub
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Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne disease with a case fatality rate of up to 40% in humans, posing a significant health threat. This study investigates the 2022-23 CCHF outbreaks in Iraq, the highest recorded to date, and analyzes potential factors at the human-animal-environmental interface. Data from the Iraqi government, the World Health Organization, and the World Bank were used to analyze CCHF trends and affecting factors. This included epidemiological reports, clinical data, tick infestation and seroprevalence studies, and climate data. Descriptive and statistical analyses examined case trends, geographic and demographic characteristics, clinical manifestations, risk factors, seasonal patterns, and influencing factors. A sudden rise in CCHF cases began in southern Iraq in April 2022 and expanded across all governorates, with a shift toward urban areas. Higher incidence was observed among males, aged 25-44, and those involved in slaughtering. The most common clinical manifestation was fever (97%), followed by hemorrhagic symptoms (54%). Bleeding from the gums or mouth and subcutaneous bleeding were more frequent in patients with fatal outcomes. Seasonal patterns showed peaks during spring and fall, correlating with tick activity and potentially exacerbated by climate change. Tick infestation and seroprevalence studies indicated a high prevalence of Hyalomma ticks and CCHF seropositivity among domestic animals in southern Iraq (60%), consistent with the distribution of CCHF human cases. Iraq's ongoing CCHF outbreak demands multidisciplinary One Health strategies. The Iraqi government has adopted such a control strategy, contributing to regional and global efforts to enhance pandemic preparedness.</AbstractText
|
Ultrastructural Localization of Glutamate Delta Receptor 1 in the Rodent and Primate Lateral Habenula. Glutamate delta receptor 1 (GluD1) is a unique synaptogenic molecule expressed at excitatory and inhibitory synapses. The lateral habenula (LHb), a subcortical structure that regulates negative reward prediction error and major monoaminergic systems, is enriched in GluD1. LHb dysfunction has been implicated in psychiatric disorders such as depression and schizophrenia, both of which are associated with GRID1, the gene that encodes GluD1. Thus, disruption in GluD1 synaptic signaling may contribute to LHb dysfunction and the pathophysiology of LHb-associated disorders. Despite its strong cellular expression, little is known about the subsynaptic and subcellular localization of GluD1 in LHb neurons. Given that GluD1 is involved in the development and/or regulation of glutamatergic and GABAergic synapses in various brain regions, a detailed map of GluD1 synaptic localization is essential to elucidate its role in the LHb. To address this issue, we used immunoelectron microscopy methods in rodents and monkeys. In both species, GluD1 immunoreactivity was primarily expressed in dendritic profiles, with lower expression in somata, spines, and glial elements. Pre- and post-embedding immunogold experiments revealed strong GluD1 expression in the core of symmetric GABAergic synapses. Albeit less frequent, GluD1 was also found at the edges (i.e., perisynaptic) of asymmetric, putative glutamatergic synapses. Through the combination of anterograde tracing with immunogold labeling in rats, we showed that axon terminals from the entopeduncular nucleus and the lateral hypothalamus express postsynaptic GluD1 immunolabeling in the LHb. Our findings suggest that GluD1 may play a critical role in modulating GABAergic transmission in the rodent and primate LHb.</AbstractText
|
Determinants of synapse diversity revealed by super-resolution quantal transmission and active zone imaging. Neural circuit function depends on the pattern of synaptic connections between neurons and the strength of those connections. Synaptic strength is determined by both postsynaptic sensitivity to neurotransmitter and the presynaptic probability of action potential evoked transmitter release (P<sub
|
Epidemiological analysis and potential factors affecting the 2022-23 Crimean-Congo hemorrhagic fever outbreak in Iraq. Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne disease with a case fatality rate of up to 40% in humans, posing a significant health threat. This study investigates the 2022-23 CCHF outbreaks in Iraq, the highest recorded to date, and analyzes potential factors at the human-animal-environmental interface. Data from the Iraqi government, the World Health Organization, and the World Bank were used to analyze CCHF trends and affecting factors. This included epidemiological reports, clinical data, tick infestation and seroprevalence studies, and climate data. Descriptive and statistical analyses examined case trends, geographic and demographic characteristics, clinical manifestations, risk factors, seasonal patterns, and influencing factors. A sudden rise in CCHF cases began in southern Iraq in April 2022 and expanded across all governorates, with a shift toward urban areas. Higher incidence was observed among males, aged 25-44, and those involved in slaughtering. The most common clinical manifestation was fever (97%), followed by hemorrhagic symptoms (54%). Bleeding from the gums or mouth and subcutaneous bleeding were more frequent in patients with fatal outcomes. Seasonal patterns showed peaks during spring and fall, correlating with tick activity and potentially exacerbated by climate change. Tick infestation and seroprevalence studies indicated a high prevalence of Hyalomma ticks and CCHF seropositivity among domestic animals in southern Iraq (60%), consistent with the distribution of CCHF human cases. Iraq's ongoing CCHF outbreak demands multidisciplinary One Health strategies. The Iraqi government has adopted such a control strategy, contributing to regional and global efforts to enhance pandemic preparedness.</AbstractText
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36030210
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31350442
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36060580
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EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism.
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Structural connectivity and weight loss in children with obesity: a study of the "connectobese".
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Ferumoxytol-enhanced 4D multiphase, steady-state imaging with magnetic resonance in congenital heart disease: ventricular volume and function across 2D and 3D software platforms.
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Autism spectrum disorder (ASD) is associated with atypical neural activity in resting state. Most of the studies have focused on abnormalities in alpha frequency as a marker of ASD dysfunctions. However, few have explored alpha synchronization within a specific interest in resting-state networks, namely the default mode network (DMN), the sensorimotor network (SMN), and the dorsal attention network (DAN). These functional connectivity analyses provide relevant insight into the neurophysiological correlates of multimodal integration in ASD.</AbstractText Using high temporal resolution EEG, the present study investigates the functional connectivity in the alpha band within and between the DMN, SMN, and the DAN. We examined eyes-closed EEG alpha lagged phase synchronization, using standardized low-resolution brain electromagnetic tomography (sLORETA) in 29 participants with ASD and 38 developing (TD) controls (age, sex, and IQ matched).</AbstractText We observed reduced functional connectivity in the ASD group relative to TD controls, within and between the DMN, the SMN, and the DAN. We identified three hubs of dysconnectivity in ASD: the posterior cingulate cortex, the precuneus, and the medial frontal gyrus. These three regions also presented decreased current source density in the alpha band.</AbstractText These results shed light on possible multimodal integration impairments affecting the communication between bottom-up and top-down information. The observed hypoconnectivity between the DMN, SMN, and DAN could also be related to difficulties in switching between externally oriented attention and internally oriented thoughts.</AbstractText
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Previous studies suggest that obesity (OB) is associated with disrupted brain network organization; however, it remains unclear whether these differences already exist during childhood. Moreover, it should be investigated whether deviant network organization may be susceptible to treatment.</AbstractText Here, we compared the structural connectomes of children with OB with age-matched healthy weight (HW) controls (aged 7-11 years). In addition, we examined the effect of a multidisciplinary treatment program, consisting of diet restriction, cognitive behavioral therapy, and physical activity for children with OB on brain network organization. After stringent quality assessment criteria, 40 (18 OB, 22 HW) data sets of the total sample of 51 participants (25 OB, 26 HW) were included in further analyses. For all participants, anthropometric measurements were administered twice, with a 5-month interval between pre- and post tests. Pre- and post T1- and diffusion-weighted imaging scans were also acquired and analyzed using a graph-theoretical approach and network-based statistics.</AbstractText Global network analyses revealed a significantly increased normalized clustering coefficient and small-worldness in children with OB compared with HW controls. In addition, regional analyses revealed increased betweenness centrality, reduced clustering coefficient, and increased structural network strength in children with OB, mainly in the motor cortex and reward network. Importantly, children with OB lost a considerable amount of their body mass after the treatment; however, no changes were observed in the organization of their brain networks.</AbstractText This is the first study showing disrupted structural connectomes of children with OB, especially in the motor and reward network. These results provide new insights into the pathophysiology underlying childhood obesity. The treatment did result in a significant weight loss, which was however not associated with alterations in the brain networks. These findings call for larger samples to examine the impact of short-term and long-term weight loss (treatment) on children's brain network organization.</AbstractText
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Quantitative ventricular volumetry and function are important in the management of congenital heart disease (CHD). Ferumoxytol-enhanced (FE) 4D multiphase, steady state imaging with contrast enhancement (MUSIC) enables high-resolution, 3D cardiac phase-resolved magnetic resonance imaging (MRI) of the beating heart and extracardiac vessels in a single acquisition and without concerns about renal impairment. We aim to evaluate the semi-automatic quantification of ventricular volumetry and function of 4D MUSIC MRI using 2D and 3D software platforms.</AbstractText This HIPAA-compliant and IRB-approved study prospectively recruited 50 children with CHD (3 days to 18 years) who underwent 4D MUSIC MRI at 3.0T between 2013-2017 for clinical indications. Each patient was either intubated in the neonatal intensive care unit (NICU) or underwent general anesthesia at MRI suite. For 2D analysis, we reformatted MUSIC images in Digital Imaging and Communications in Medicine (DICOM) format into ventricular short-axis slices with zero interslice gap. For 3D analysis, we imported DICOMs into a commercially available 3D software platform. Using semi-automatic thresholding, we quantified biventricular volume and ejection fraction (EF). We assessed the bias between MUSIC-derived 2D <i There was a high degree of correlation between MUSIC-derived volumetric and functional measurements using 2D <i Accurate and reliable ventricular volumetry and function can be derived from FE 4D MUSIC MRI studies using commercially available 2D and 3D software platforms. If fully validated in multicenter studies, the FE 4D-MUSIC pulse sequence may supercede conventional multislice 2D cine cardiovascular MRI acquisition protocols for functional evaluation of children with complex CHD.</AbstractText
|
EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism. Autism spectrum disorder (ASD) is associated with atypical neural activity in resting state. Most of the studies have focused on abnormalities in alpha frequency as a marker of ASD dysfunctions. However, few have explored alpha synchronization within a specific interest in resting-state networks, namely the default mode network (DMN), the sensorimotor network (SMN), and the dorsal attention network (DAN). These functional connectivity analyses provide relevant insight into the neurophysiological correlates of multimodal integration in ASD.</AbstractText Using high temporal resolution EEG, the present study investigates the functional connectivity in the alpha band within and between the DMN, SMN, and the DAN. We examined eyes-closed EEG alpha lagged phase synchronization, using standardized low-resolution brain electromagnetic tomography (sLORETA) in 29 participants with ASD and 38 developing (TD) controls (age, sex, and IQ matched).</AbstractText We observed reduced functional connectivity in the ASD group relative to TD controls, within and between the DMN, the SMN, and the DAN. We identified three hubs of dysconnectivity in ASD: the posterior cingulate cortex, the precuneus, and the medial frontal gyrus. These three regions also presented decreased current source density in the alpha band.</AbstractText These results shed light on possible multimodal integration impairments affecting the communication between bottom-up and top-down information. The observed hypoconnectivity between the DMN, SMN, and DAN could also be related to difficulties in switching between externally oriented attention and internally oriented thoughts.</AbstractText
|
Structural connectivity and weight loss in children with obesity: a study of the "connectobese". Previous studies suggest that obesity (OB) is associated with disrupted brain network organization; however, it remains unclear whether these differences already exist during childhood. Moreover, it should be investigated whether deviant network organization may be susceptible to treatment.</AbstractText Here, we compared the structural connectomes of children with OB with age-matched healthy weight (HW) controls (aged 7-11 years). In addition, we examined the effect of a multidisciplinary treatment program, consisting of diet restriction, cognitive behavioral therapy, and physical activity for children with OB on brain network organization. After stringent quality assessment criteria, 40 (18 OB, 22 HW) data sets of the total sample of 51 participants (25 OB, 26 HW) were included in further analyses. For all participants, anthropometric measurements were administered twice, with a 5-month interval between pre- and post tests. Pre- and post T1- and diffusion-weighted imaging scans were also acquired and analyzed using a graph-theoretical approach and network-based statistics.</AbstractText Global network analyses revealed a significantly increased normalized clustering coefficient and small-worldness in children with OB compared with HW controls. In addition, regional analyses revealed increased betweenness centrality, reduced clustering coefficient, and increased structural network strength in children with OB, mainly in the motor cortex and reward network. Importantly, children with OB lost a considerable amount of their body mass after the treatment; however, no changes were observed in the organization of their brain networks.</AbstractText This is the first study showing disrupted structural connectomes of children with OB, especially in the motor and reward network. These results provide new insights into the pathophysiology underlying childhood obesity. The treatment did result in a significant weight loss, which was however not associated with alterations in the brain networks. These findings call for larger samples to examine the impact of short-term and long-term weight loss (treatment) on children's brain network organization.</AbstractText
|
Ferumoxytol-enhanced 4D multiphase, steady-state imaging with magnetic resonance in congenital heart disease: ventricular volume and function across 2D and 3D software platforms. Quantitative ventricular volumetry and function are important in the management of congenital heart disease (CHD). Ferumoxytol-enhanced (FE) 4D multiphase, steady state imaging with contrast enhancement (MUSIC) enables high-resolution, 3D cardiac phase-resolved magnetic resonance imaging (MRI) of the beating heart and extracardiac vessels in a single acquisition and without concerns about renal impairment. We aim to evaluate the semi-automatic quantification of ventricular volumetry and function of 4D MUSIC MRI using 2D and 3D software platforms.</AbstractText This HIPAA-compliant and IRB-approved study prospectively recruited 50 children with CHD (3 days to 18 years) who underwent 4D MUSIC MRI at 3.0T between 2013-2017 for clinical indications. Each patient was either intubated in the neonatal intensive care unit (NICU) or underwent general anesthesia at MRI suite. For 2D analysis, we reformatted MUSIC images in Digital Imaging and Communications in Medicine (DICOM) format into ventricular short-axis slices with zero interslice gap. For 3D analysis, we imported DICOMs into a commercially available 3D software platform. Using semi-automatic thresholding, we quantified biventricular volume and ejection fraction (EF). We assessed the bias between MUSIC-derived 2D <i There was a high degree of correlation between MUSIC-derived volumetric and functional measurements using 2D <i Accurate and reliable ventricular volumetry and function can be derived from FE 4D MUSIC MRI studies using commercially available 2D and 3D software platforms. If fully validated in multicenter studies, the FE 4D-MUSIC pulse sequence may supercede conventional multislice 2D cine cardiovascular MRI acquisition protocols for functional evaluation of children with complex CHD.</AbstractText
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21478988
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23850758
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21327978
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Digital broadband linearization technique and its application to photonic time-stretch analog-to-digital converter.
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A 10-b 50-MS/s 820- μW SAR ADC With On-Chip Digital Calibration.
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Direct application of MR images to computer-assisted bone tumor surgery.
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Suppression of distortion induced by nonlinearity in a dynamical system (such as an analog optical link) is very challenging, particularly for a wide-bandwidth signal. Conventional compensation techniques are computationally intensive, significantly limiting their realization in real-time applications. Here, we propose and demonstrate an efficient digital postprocessing technique to suppress distortions added to a wideband signal by a nonlinear system with memory effect. Experimentally, digital broadband linearization of the photonic time-stretch analog-to-digital converter (TSADC) is demonstrated. In case of TSADC, a dynamic range improvement of >15 dB compared to conventional memory-less correction method is achieved.</AbstractText
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This 10-b 50-MSamples/s SAR analog-to-digital converter (ADC) features on-chip digital calibration techniques, comparator offset cancellation, a capacitor digital-to-analog converter (CDAC) linearity calibration, and internal clock control to compensate for PVT variations. A split-CDAC reduces the exponential increase in the number of unit capacitors needed and enables the input load capacitance to be as small as the kT/C noise restriction. The prototype fabricated in 65 nm 1P7M complementary metal-oxide semiconductor with MIM capacitor achieves 56.6 dB SNDR at 50-MSamples/s, 25-MHz input frequency and consumes 820 μW from a 1.0-V supply, including the digital calibration circuits. The figure of merit was 29.7 fJ/conversion-step under the Nyquist condition. The ADC occupied an active area of 0.039 mm(2) .</AbstractText
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We describe a method for the direct application of MR images to navigation-assisted bone tumor surgery as an alternative to CT-MRI fusion.</AbstractText Six patients with an orthopedic malignancy were employed for this method during navigation-assisted tumor resection. Tumor types included osteosarcoma (4), high-grade chondrosarcoma (1), and adamantinoma (1). Mean patient age was 25.3 years (range 18-52 years). Mean duration of follow-up was 25.8 months (range 18-32 months). Resorbable pin placement and rapid 3-dimensional spoiled gradient echo sequences made the direct application of MR images to computer-assisted bone tumor surgery without CT-MR image fusion possible. A paired-point registration technique was employed for patient-image registration in all patients.</AbstractText It took 20 min on average to set up the navigation (range 15-25 min). The mean registration error was 0.98 mm (range 0.4-1.7 mm). On histologic examination, distances from tumors to resection margins were in accord with preoperative plans. No patient had a local recurrence or distant metastasis at the last follow-up.</AbstractText Direct patient-to-MRI registration is a very useful method for bone tumor surgery, permitting the application of MR images to intraoperative visualization without any additional costs or exposure of the patient to radiation from the preoperative CT scan.</AbstractText
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Digital broadband linearization technique and its application to photonic time-stretch analog-to-digital converter. Suppression of distortion induced by nonlinearity in a dynamical system (such as an analog optical link) is very challenging, particularly for a wide-bandwidth signal. Conventional compensation techniques are computationally intensive, significantly limiting their realization in real-time applications. Here, we propose and demonstrate an efficient digital postprocessing technique to suppress distortions added to a wideband signal by a nonlinear system with memory effect. Experimentally, digital broadband linearization of the photonic time-stretch analog-to-digital converter (TSADC) is demonstrated. In case of TSADC, a dynamic range improvement of >15 dB compared to conventional memory-less correction method is achieved.</AbstractText
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A 10-b 50-MS/s 820- μW SAR ADC With On-Chip Digital Calibration. This 10-b 50-MSamples/s SAR analog-to-digital converter (ADC) features on-chip digital calibration techniques, comparator offset cancellation, a capacitor digital-to-analog converter (CDAC) linearity calibration, and internal clock control to compensate for PVT variations. A split-CDAC reduces the exponential increase in the number of unit capacitors needed and enables the input load capacitance to be as small as the kT/C noise restriction. The prototype fabricated in 65 nm 1P7M complementary metal-oxide semiconductor with MIM capacitor achieves 56.6 dB SNDR at 50-MSamples/s, 25-MHz input frequency and consumes 820 μW from a 1.0-V supply, including the digital calibration circuits. The figure of merit was 29.7 fJ/conversion-step under the Nyquist condition. The ADC occupied an active area of 0.039 mm(2) .</AbstractText
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Direct application of MR images to computer-assisted bone tumor surgery. We describe a method for the direct application of MR images to navigation-assisted bone tumor surgery as an alternative to CT-MRI fusion.</AbstractText Six patients with an orthopedic malignancy were employed for this method during navigation-assisted tumor resection. Tumor types included osteosarcoma (4), high-grade chondrosarcoma (1), and adamantinoma (1). Mean patient age was 25.3 years (range 18-52 years). Mean duration of follow-up was 25.8 months (range 18-32 months). Resorbable pin placement and rapid 3-dimensional spoiled gradient echo sequences made the direct application of MR images to computer-assisted bone tumor surgery without CT-MR image fusion possible. A paired-point registration technique was employed for patient-image registration in all patients.</AbstractText It took 20 min on average to set up the navigation (range 15-25 min). The mean registration error was 0.98 mm (range 0.4-1.7 mm). On histologic examination, distances from tumors to resection margins were in accord with preoperative plans. No patient had a local recurrence or distant metastasis at the last follow-up.</AbstractText Direct patient-to-MRI registration is a very useful method for bone tumor surgery, permitting the application of MR images to intraoperative visualization without any additional costs or exposure of the patient to radiation from the preoperative CT scan.</AbstractText
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40664359
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31725590
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40690096
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Development and Effectiveness of Tinnitus Activities Treatment-Online, a Self-Paced Remote Counseling Program.
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Validation of the Hearing Handicap Inventory for Adults Scale for Spanish-Speaking Patients.
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C20orf27 promotes hepatocellular carcinoma progression via NT5E.
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For many people with bothersome tinnitus, accessing in-person intervention is difficult. We developed a remote counseling program, Tinnitus Activities Treatment-Online (TAT-Online), to provide for patients' tinnitus education and coping strategies. We aimed to test the effectiveness and acceptability of the remote counseling program in adults with tinnitus.</AbstractText We included adults with chronic tinnitus who had access to a smartphone, tablet, or computer. In total, 59 adult participants completed all study procedures out of 243 adults who were initially enrolled. Participants completed weekly modules that included viewing narrated videos, practicing strategies using homework, and completing quizzes at the end of each session to assess learning. Participants completed the sessions in a self-paced manner over 6 weeks: Week 1: Questionnaires and Introduction; Week 2: Thoughts and Emotions; Week 3: Sleep; Week 4: Hearing; Week 5: Concentration; and Week 6: Relaxation Techniques and Sound Therapy. Participants completed four outcome measures before the remote counseling began in Week 1 and after the remote counseling concluded in Week 6. Statistical analysis was conducted using a doubly multivariate analysis of variance approach. Acceptability of TAT-Online was determined based on an exit survey and compliance in completing the activities.</AbstractText Comparing pre- to posttest scores, there was a significant improvement on all tinnitus measures and significantly lower ratings of tinnitus loudness and annoyance. There was no significant change in Meaning of Life ratings. Mean ratings of effectiveness for the TAT-Online videos were rated at 9 out of 10. The self-paced format of TAT-Online was acceptable and easy to follow and effective for patients' learning to cope with tinnitus.</AbstractText Self-paced remote tinnitus counseling, which included asynchronous educational videos, reflection exercises, and helpful strategies, was effective for learning how to cope with tinnitus. In future studies, we plan to conduct a randomized control trial to further investigate the effectiveness of TAT-Online in combination with hearing or tinnitus devices.</AbstractText
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To perform translation, cross-cultural adaptation, and validation of the hearing handicap inventory for adults scale (HHIA) to the Spanish language.</AbstractText Prospective study.</AbstractText Tertiary neurotologic referral center.</AbstractText The study included 104 hearing impaired persons. Inclusion criteria were adults with untreated hearing loss, diagnosed in the past 12 months. A control group of 30 normal hearing subjects was also recruited.</AbstractText HHIA was translated and translated back, and a pretest trial was performed. Feasibility, internal consistency, test-retest reliability, construct validity, and ceiling and floor effects were assessed for the present study.</AbstractText The mean overall score of the HHIA was 31.9 (0-100 scale, lowest to highest handicap). Cronbach's α was 0.95. Intraclass correlation coefficient was performed for each item, with an overall score of 0.95. The k coefficient scores ranged between moderate and almost perfect in all patients. The emotional score of the HHIA was correlated with the mental component of the SF-12.</AbstractText Feasibility, internal consistency, reliability, and construct validity outcomes in the current study support the validity of the Spanish version of the HHIA.</AbstractText
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Liver cancer is one of the most lethal human malignancies in the world. Although great efforts have been made to develop novel therapeutic targets, effective drug targeting remains limited. C20orf27, located on human chromosome 20, is a gene whose function has not been fully elucidated. In this study, we identified C20orf27 as a critical gene that facilitates liver cancer progression. We detected that C20orf27 was upregulated in liver cancer samples. Gain- and loss-of-function experiments demonstrated that C20orf27 enhanced liver cancer cell proliferation and migration by regulating cyclin-related proteins, including MDM2, PCNA, Cyclin E1, CDK2, and p-Rb. RNA sequencing and bioinformatics analyses revealed that NT5E, ACE, and TTR were potential downstream targets of C20orf27. Immunohistochemistry analysis of tissue microarrays suggested that NT5E expression was significantly associated with C20orf27 levels. Moreover, the combination of C20orf27 and NT5E predicted the prognosis of liver cancer patients, as higher levels of both were associated with poorer overall survival and disease-free survival after surgery. Our findings are the first to report the functional role of the C20orf27/NT5E axis in promoting hepatocellular carcinoma progression, highlighting its potential as a novel therapeutic target and biomarker for HCC.</AbstractText
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Development and Effectiveness of Tinnitus Activities Treatment-Online, a Self-Paced Remote Counseling Program. For many people with bothersome tinnitus, accessing in-person intervention is difficult. We developed a remote counseling program, Tinnitus Activities Treatment-Online (TAT-Online), to provide for patients' tinnitus education and coping strategies. We aimed to test the effectiveness and acceptability of the remote counseling program in adults with tinnitus.</AbstractText We included adults with chronic tinnitus who had access to a smartphone, tablet, or computer. In total, 59 adult participants completed all study procedures out of 243 adults who were initially enrolled. Participants completed weekly modules that included viewing narrated videos, practicing strategies using homework, and completing quizzes at the end of each session to assess learning. Participants completed the sessions in a self-paced manner over 6 weeks: Week 1: Questionnaires and Introduction; Week 2: Thoughts and Emotions; Week 3: Sleep; Week 4: Hearing; Week 5: Concentration; and Week 6: Relaxation Techniques and Sound Therapy. Participants completed four outcome measures before the remote counseling began in Week 1 and after the remote counseling concluded in Week 6. Statistical analysis was conducted using a doubly multivariate analysis of variance approach. Acceptability of TAT-Online was determined based on an exit survey and compliance in completing the activities.</AbstractText Comparing pre- to posttest scores, there was a significant improvement on all tinnitus measures and significantly lower ratings of tinnitus loudness and annoyance. There was no significant change in Meaning of Life ratings. Mean ratings of effectiveness for the TAT-Online videos were rated at 9 out of 10. The self-paced format of TAT-Online was acceptable and easy to follow and effective for patients' learning to cope with tinnitus.</AbstractText Self-paced remote tinnitus counseling, which included asynchronous educational videos, reflection exercises, and helpful strategies, was effective for learning how to cope with tinnitus. In future studies, we plan to conduct a randomized control trial to further investigate the effectiveness of TAT-Online in combination with hearing or tinnitus devices.</AbstractText
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Validation of the Hearing Handicap Inventory for Adults Scale for Spanish-Speaking Patients. To perform translation, cross-cultural adaptation, and validation of the hearing handicap inventory for adults scale (HHIA) to the Spanish language.</AbstractText Prospective study.</AbstractText Tertiary neurotologic referral center.</AbstractText The study included 104 hearing impaired persons. Inclusion criteria were adults with untreated hearing loss, diagnosed in the past 12 months. A control group of 30 normal hearing subjects was also recruited.</AbstractText HHIA was translated and translated back, and a pretest trial was performed. Feasibility, internal consistency, test-retest reliability, construct validity, and ceiling and floor effects were assessed for the present study.</AbstractText The mean overall score of the HHIA was 31.9 (0-100 scale, lowest to highest handicap). Cronbach's α was 0.95. Intraclass correlation coefficient was performed for each item, with an overall score of 0.95. The k coefficient scores ranged between moderate and almost perfect in all patients. The emotional score of the HHIA was correlated with the mental component of the SF-12.</AbstractText Feasibility, internal consistency, reliability, and construct validity outcomes in the current study support the validity of the Spanish version of the HHIA.</AbstractText
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C20orf27 promotes hepatocellular carcinoma progression via NT5E. Liver cancer is one of the most lethal human malignancies in the world. Although great efforts have been made to develop novel therapeutic targets, effective drug targeting remains limited. C20orf27, located on human chromosome 20, is a gene whose function has not been fully elucidated. In this study, we identified C20orf27 as a critical gene that facilitates liver cancer progression. We detected that C20orf27 was upregulated in liver cancer samples. Gain- and loss-of-function experiments demonstrated that C20orf27 enhanced liver cancer cell proliferation and migration by regulating cyclin-related proteins, including MDM2, PCNA, Cyclin E1, CDK2, and p-Rb. RNA sequencing and bioinformatics analyses revealed that NT5E, ACE, and TTR were potential downstream targets of C20orf27. Immunohistochemistry analysis of tissue microarrays suggested that NT5E expression was significantly associated with C20orf27 levels. Moreover, the combination of C20orf27 and NT5E predicted the prognosis of liver cancer patients, as higher levels of both were associated with poorer overall survival and disease-free survival after surgery. Our findings are the first to report the functional role of the C20orf27/NT5E axis in promoting hepatocellular carcinoma progression, highlighting its potential as a novel therapeutic target and biomarker for HCC.</AbstractText
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39119951
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2547398
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38397882
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Acute Sympathetic Blockade Improves Insulin-Mediated Microvascular Blood Flow in the Forearm of Adult Human Subjects With Obesity.
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Facilitatory effects of ouabain and digitalis-like substance on adrenergic transmission in hypertension.
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Impaired Mitochondrial Network Morphology and Reactive Oxygen Species Production in Fibroblasts from Parkinson's Disease Patients.
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Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity.</AbstractText In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, <i We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.</AbstractText
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The purpose of the present study was to examine the role of Na+,K+-ATPase activity in vascular adrenergic transmission of hypertension. In isolated perfused mesenteric vasculatures of spontaneously hypertensive rats (SHR, Okamoto and Aoki strain, seven- to ten-weeks-old) and age-matched Wistar Kyoto rats (WKY), the effects of ouabain, a potent Na+,K+-ATPase inhibitor, or partially purified plasma obtained from salt-induced hypertension on pressor responses and norepinephrine overflow were investigated. Pressor responses and norepinephrine overflow during electrical nerve stimulation were significantly greater in SHR than in WKY. Ouabain increased the stimulation-evoked pressor responses and norepinephrine overflow. This facilitation was more prominent in SHR than in WKY. Partially purified plasma obtained from reduced renal mass-salt hypertensive rats, which had a crossimmunoreactivity with digoxin, also increased the pressor responses and norepinephrine overflow during electrical nerve stimulation, and the effects were greater in SHR than in WKY. These results suggest that Na+,K+-ATPase on vascular adrenergic neurons has an important role in the regulation of neurotransmitter release, and that its activity might be enhanced in SHR.</AbstractText
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The mitochondrial network (MN) is a dynamic structure undergoing constant remodeling in the cell. It is assumed that perturbations to the MN may be associated with various pathologies, including Parkinson's disease (PD). Using automatic image analysis and super-resolution microscopy, we have assessed the MN parameters in fibroblasts from patients with established hereditary PD mutations (associated with PINK1, LRRK2, and α-synuclein, as well as PINK1 and Parkin proteins simultaneously) under normal conditions and after hydrogen peroxide-induced stress. Fibroblasts with the Pink1/Parkin mutation are most different in morphology to fibroblasts obtained from conditionally healthy donors: the MN is larger, and it contains longer mitochondria and accumulated individual mitochondria. In addition to MN, we evaluated other cellular parameters, such as cytosolic and mitochondrial ROS production and mitochondrial membrane potential. It has been shown that mitochondria of fibroblasts with mutations in genes encoding PINK1, α-synuclein, and Pink/Parkin tend towards hyperpolarization and cytosolic ROS overproduction, while mitochondrial ROS production was higher only in fibroblasts with PINK1 and α-synuclein mutations.</AbstractText
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Acute Sympathetic Blockade Improves Insulin-Mediated Microvascular Blood Flow in the Forearm of Adult Human Subjects With Obesity. Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity.</AbstractText In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, <i We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.</AbstractText
|
Facilitatory effects of ouabain and digitalis-like substance on adrenergic transmission in hypertension. The purpose of the present study was to examine the role of Na+,K+-ATPase activity in vascular adrenergic transmission of hypertension. In isolated perfused mesenteric vasculatures of spontaneously hypertensive rats (SHR, Okamoto and Aoki strain, seven- to ten-weeks-old) and age-matched Wistar Kyoto rats (WKY), the effects of ouabain, a potent Na+,K+-ATPase inhibitor, or partially purified plasma obtained from salt-induced hypertension on pressor responses and norepinephrine overflow were investigated. Pressor responses and norepinephrine overflow during electrical nerve stimulation were significantly greater in SHR than in WKY. Ouabain increased the stimulation-evoked pressor responses and norepinephrine overflow. This facilitation was more prominent in SHR than in WKY. Partially purified plasma obtained from reduced renal mass-salt hypertensive rats, which had a crossimmunoreactivity with digoxin, also increased the pressor responses and norepinephrine overflow during electrical nerve stimulation, and the effects were greater in SHR than in WKY. These results suggest that Na+,K+-ATPase on vascular adrenergic neurons has an important role in the regulation of neurotransmitter release, and that its activity might be enhanced in SHR.</AbstractText
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Impaired Mitochondrial Network Morphology and Reactive Oxygen Species Production in Fibroblasts from Parkinson's Disease Patients. The mitochondrial network (MN) is a dynamic structure undergoing constant remodeling in the cell. It is assumed that perturbations to the MN may be associated with various pathologies, including Parkinson's disease (PD). Using automatic image analysis and super-resolution microscopy, we have assessed the MN parameters in fibroblasts from patients with established hereditary PD mutations (associated with PINK1, LRRK2, and α-synuclein, as well as PINK1 and Parkin proteins simultaneously) under normal conditions and after hydrogen peroxide-induced stress. Fibroblasts with the Pink1/Parkin mutation are most different in morphology to fibroblasts obtained from conditionally healthy donors: the MN is larger, and it contains longer mitochondria and accumulated individual mitochondria. In addition to MN, we evaluated other cellular parameters, such as cytosolic and mitochondrial ROS production and mitochondrial membrane potential. It has been shown that mitochondria of fibroblasts with mutations in genes encoding PINK1, α-synuclein, and Pink/Parkin tend towards hyperpolarization and cytosolic ROS overproduction, while mitochondrial ROS production was higher only in fibroblasts with PINK1 and α-synuclein mutations.</AbstractText
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31461371
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17557297
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31639929
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High-definition tDCS to the right temporoparietal junction modulates slow-wave resting state power and coherence in healthy adults.
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The extended language network: a meta-analysis of neuroimaging studies on text comprehension.
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Emergence of an optimal temperature in action-potential propagation through myelinated axons.
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The right temporoparietal junction (rTPJ) is a multisensory integration hub that is increasingly utilized as a target of stimulation studies exploring its rich functional network roles and potential clinical applications. While transcranial direct current stimulation (tDCS) is frequently employed in such studies, there is still relatively little known regarding its local and network neurophysiological effects, particularly at important nonmotor sites such as the rTPJ. The current study applied either anodal, cathodal, or sham high-definition tDCS to the rTPJ of 53 healthy participants and used offline EEG to assess the impacts of stimulation on resting state (eyes open and eyes closed) band power and coherence. Temporoparietal and central region delta power was increased after anodal stimulation (the latter trend only), whereas cathodal stimulation increased frontal region delta and theta power. Increased coherence between right and left temporoparietal regions was also observed after anodal stimulation. All significant effects occurred in the eyes open condition. These findings are discussed with reference to domain general and mechanistic theories of rTPJ function. Low-frequency oscillatory activity may exert long-range inhibitory network influences that enable switching between and integration of endogenous/exogenous processing streams.<b
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Language processing in context requires more than merely comprehending words and sentences. Important subprocesses are inferences for bridging successive utterances, the use of background knowledge and discourse context, and pragmatic interpretations. The functional neuroanatomy of these text comprehension processes has only recently been investigated. Although there is evidence for right-hemisphere contributions, reviews have implicated the left lateral prefrontal cortex, left temporal regions beyond Wernicke's area, and the left dorso-medial prefrontal cortex (dmPFC) for text comprehension. To objectively confirm this extended language network and to evaluate the respective contribution of right hemisphere regions, meta-analyses of 23 neuroimaging studies are reported here. The analyses used replicator dynamics based on activation likelihood estimates. Independent of the baseline, the anterior temporal lobes (aTL) were active bilaterally. In addition, processing of coherent compared with incoherent text engaged the dmPFC and the posterior cingulate cortex. Right hemisphere activations were seen most notably in the analysis of contrasts testing specific subprocesses, such as metaphor comprehension. These results suggest task dependent contributions for the lateral PFC and the right hemisphere. Most importantly, they confirm the role of the aTL and the fronto-medial cortex for language processing in context.</AbstractText
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In biological organisms, an optimal temperature exists at which the system functioning is maximized or is most effective. To obtain a general and quantitative understanding of the emergence of the optimal temperature is a challenging task. We aim to gain insights into this significant problem in biological physics by addressing the problem of propagation of action potential in myelinated axons. In particular, we construct a Hodgkin-Huxley type of cortical, compartmental model to describe the nodes of Ranvier with coupling between a pair of neighboring compartments characterized by internodal conductance and investigate the effect of temperature on the propagation of the action potential. We conduct direct numerical simulations and develop a physical analysis by taking advantage of the spatially continuous approximation. We find that increasing the temperature requires a larger value of the critical internodal conductance for successful propagation. The striking finding is the spontaneous emergence of an optimal temperature in the sense that, for the propagation of a single action potential at a fixed value of the internodal conductance, the minimum average passage time for one node of Ranvier occurs at this temperature value. A remarkable phenomenon is that the value of the optimal temperature is similar to those of living biological systems observed in experiments.</AbstractText
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High-definition tDCS to the right temporoparietal junction modulates slow-wave resting state power and coherence in healthy adults. The right temporoparietal junction (rTPJ) is a multisensory integration hub that is increasingly utilized as a target of stimulation studies exploring its rich functional network roles and potential clinical applications. While transcranial direct current stimulation (tDCS) is frequently employed in such studies, there is still relatively little known regarding its local and network neurophysiological effects, particularly at important nonmotor sites such as the rTPJ. The current study applied either anodal, cathodal, or sham high-definition tDCS to the rTPJ of 53 healthy participants and used offline EEG to assess the impacts of stimulation on resting state (eyes open and eyes closed) band power and coherence. Temporoparietal and central region delta power was increased after anodal stimulation (the latter trend only), whereas cathodal stimulation increased frontal region delta and theta power. Increased coherence between right and left temporoparietal regions was also observed after anodal stimulation. All significant effects occurred in the eyes open condition. These findings are discussed with reference to domain general and mechanistic theories of rTPJ function. Low-frequency oscillatory activity may exert long-range inhibitory network influences that enable switching between and integration of endogenous/exogenous processing streams.<b
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The extended language network: a meta-analysis of neuroimaging studies on text comprehension. Language processing in context requires more than merely comprehending words and sentences. Important subprocesses are inferences for bridging successive utterances, the use of background knowledge and discourse context, and pragmatic interpretations. The functional neuroanatomy of these text comprehension processes has only recently been investigated. Although there is evidence for right-hemisphere contributions, reviews have implicated the left lateral prefrontal cortex, left temporal regions beyond Wernicke's area, and the left dorso-medial prefrontal cortex (dmPFC) for text comprehension. To objectively confirm this extended language network and to evaluate the respective contribution of right hemisphere regions, meta-analyses of 23 neuroimaging studies are reported here. The analyses used replicator dynamics based on activation likelihood estimates. Independent of the baseline, the anterior temporal lobes (aTL) were active bilaterally. In addition, processing of coherent compared with incoherent text engaged the dmPFC and the posterior cingulate cortex. Right hemisphere activations were seen most notably in the analysis of contrasts testing specific subprocesses, such as metaphor comprehension. These results suggest task dependent contributions for the lateral PFC and the right hemisphere. Most importantly, they confirm the role of the aTL and the fronto-medial cortex for language processing in context.</AbstractText
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Emergence of an optimal temperature in action-potential propagation through myelinated axons. In biological organisms, an optimal temperature exists at which the system functioning is maximized or is most effective. To obtain a general and quantitative understanding of the emergence of the optimal temperature is a challenging task. We aim to gain insights into this significant problem in biological physics by addressing the problem of propagation of action potential in myelinated axons. In particular, we construct a Hodgkin-Huxley type of cortical, compartmental model to describe the nodes of Ranvier with coupling between a pair of neighboring compartments characterized by internodal conductance and investigate the effect of temperature on the propagation of the action potential. We conduct direct numerical simulations and develop a physical analysis by taking advantage of the spatially continuous approximation. We find that increasing the temperature requires a larger value of the critical internodal conductance for successful propagation. The striking finding is the spontaneous emergence of an optimal temperature in the sense that, for the propagation of a single action potential at a fixed value of the internodal conductance, the minimum average passage time for one node of Ranvier occurs at this temperature value. A remarkable phenomenon is that the value of the optimal temperature is similar to those of living biological systems observed in experiments.</AbstractText
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40585996
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36167468
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40595290
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Overcoming barriers in glioblastoma: The potential of CAR T cell immunotherapy.
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GD2-targeting CAR-T cells enhanced by transgenic IL-15 expression are an effective and clinically feasible therapy for glioblastoma.
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Reprogramming of human urine cells into cardiomyocytes via a small molecule cocktail in xeno-free conditions.
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Glioblastoma (GBM), the most aggressive and lethal primary brain tumor, is characterized by its high rate of growth, high genetic diversity, and resistance to conventional therapies. Chimeric antigen receptor (CAR) T cell immunotherapy has emerged as a promising treatment option for a variety of cancers, including GBM. However, CAR T therapy use in GBM is very challenging due to the unique challenges posed by the brain tumor microenvironment, including immune suppression, antigen heterogeneity, poor CAR T cell trafficking, and the blood-brain barrier (BBB). Advances in CAR T cell engineering, antigen screening, targeted administration, image-guided CAR-T therapy and combination therapies are transforming immunotherapy for GBM.AI-driven CAR T immunotherapy optimizes GBM treatment by enhancing target identification, therapy customization, and efficacy monitoring. This review aims to highlight the challenges hindering the success of CAR T cell therapy in glioblastoma and explore innovative strategies to enhance its efficacy, ultimately paving the way for more effective and durable treatment options for glioblastoma. We hope this review will stimulate interest among researchers and expedite the clinic translation of CAR T therapy of glioblastoma.</AbstractText
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Aggressive primary brain tumors such as glioblastoma are uniquely challenging to treat. The intracranial location poses barriers to therapy, and the potential for severe toxicity. Effective treatments for primary brain tumors are limited, and 5-year survival rates remain poor. Immune checkpoint inhibitor therapy has transformed treatment of some other cancers but has yet to significantly benefit patients with glioblastoma. Early phase trials of chimeric antigen receptor (CAR) T-cell therapy in patients with glioblastoma have demonstrated that this approach is safe and feasible, but with limited evidence of its effectiveness. The choices of appropriate target antigens for CAR-T-cell therapy also remain limited.</AbstractText We profiled an extensive biobank of patients' biopsy tissues and patient-derived early passage glioma neural stem cell lines for GD2 expression using immunomicroscopy and flow cytometry. We then employed an approved clinical manufacturing process to make CAR- T cells from patients with peripheral blood of glioblastoma and diffuse midline glioma and characterized their phenotype and function in vitro. Finally, we tested intravenously administered CAR-T cells in an aggressive intracranial xenograft model of glioblastoma and used multicolor flow cytometry, multicolor whole-tissue immunofluorescence and next-generation RNA sequencing to uncover markers associated with effective tumor control.</AbstractText Here we show that the tumor-associated antigen GD2 is highly and consistently expressed in primary glioblastoma tissue removed at surgery. Moreover, despite patients with glioblastoma having perturbations in their immune system, highly functional GD2-specific CAR-T cells can be produced from their peripheral T cells using an approved clinical manufacturing process. Finally, after intravenous administration, GD2-CAR-T cells effectively infiltrated the brain and controlled tumor growth in an aggressive orthotopic xenograft model of glioblastoma. Tumor control was further improved using CAR-T cells manufactured with a clinical retroviral vector encoding an interleukin-15 transgene alongside the GD2-specific CAR. These CAR-T cells achieved a striking 50% complete response rate by bioluminescence imaging in established intracranial tumors.</AbstractText Targeting GD2 using a clinically deployed CAR-T-cell therapy has a sound scientific and clinical rationale as a treatment for glioblastoma and other aggressive primary brain tumors.</AbstractText
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Cell therapy, particularly using cardiomyocytes, shows significant promise for treating heart failure. Direct reprogramming of somatic cells into cardiomyocytes using small molecules is advantageous due to its efficiency and cost-effectiveness.</AbstractText Human urine-derived cells (hUCs) were transdifferentiated into functional cardiomyocyte-like cells (hCiCMs) using a cocktail of 15 small molecules under xeno-free conditions. Various Characterizations were performed, including immunofluorescence, transmission electron microscopy (TEM), qPCR, single-cell RNA sequencing, patch-clamp recordings, and intracellular Ca²<sup Reprogramming efficiency achieves 15.08% on day 30, with purity reaching 96.67% on day 60. hCiCMs display cardiomyocyte markers, sarcomeric structures, and abundant mitochondria. Electrophysiological analysis confirms ventricular-like action potentials and regular calcium transients. Single-cell RNA sequencing reveals cardiomyocyte subpopulations resembling 13-week embryonic human heart cells, with gene ontology analysis indicating successful maturation. In the MI model, hCiCM transplantation improves cardiac function, increasing ejection fraction and fractional shortening while reducing fibrosis.</AbstractText This study demonstrates the successful reprogramming of hUCs into functional hCiCMs using small molecules under xeno-free conditions, offering a scalable, autologous cell source for cardiac repair with significant potential for regenerative therapies.</AbstractText Cardiomyocytes are the muscle cells within the heart that enable the heart to contract and pump blood. We aimed to develop a method to generate cardiomyocytes from cells derived from human urine. We used a combination of 15 small molecules to transform human urine-derived cells into cardiomyocyte-like cells. The cells were tested in mouse and porcine models of heart damage, where they were found to enhance heart function. This approach could be further developed as a possible safe, efficient, and scalable solution for producing heart cells that could be transplanted into people with heart disease as a treatment.</AbstractText
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Overcoming barriers in glioblastoma: The potential of CAR T cell immunotherapy. Glioblastoma (GBM), the most aggressive and lethal primary brain tumor, is characterized by its high rate of growth, high genetic diversity, and resistance to conventional therapies. Chimeric antigen receptor (CAR) T cell immunotherapy has emerged as a promising treatment option for a variety of cancers, including GBM. However, CAR T therapy use in GBM is very challenging due to the unique challenges posed by the brain tumor microenvironment, including immune suppression, antigen heterogeneity, poor CAR T cell trafficking, and the blood-brain barrier (BBB). Advances in CAR T cell engineering, antigen screening, targeted administration, image-guided CAR-T therapy and combination therapies are transforming immunotherapy for GBM.AI-driven CAR T immunotherapy optimizes GBM treatment by enhancing target identification, therapy customization, and efficacy monitoring. This review aims to highlight the challenges hindering the success of CAR T cell therapy in glioblastoma and explore innovative strategies to enhance its efficacy, ultimately paving the way for more effective and durable treatment options for glioblastoma. We hope this review will stimulate interest among researchers and expedite the clinic translation of CAR T therapy of glioblastoma.</AbstractText
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GD2-targeting CAR-T cells enhanced by transgenic IL-15 expression are an effective and clinically feasible therapy for glioblastoma. Aggressive primary brain tumors such as glioblastoma are uniquely challenging to treat. The intracranial location poses barriers to therapy, and the potential for severe toxicity. Effective treatments for primary brain tumors are limited, and 5-year survival rates remain poor. Immune checkpoint inhibitor therapy has transformed treatment of some other cancers but has yet to significantly benefit patients with glioblastoma. Early phase trials of chimeric antigen receptor (CAR) T-cell therapy in patients with glioblastoma have demonstrated that this approach is safe and feasible, but with limited evidence of its effectiveness. The choices of appropriate target antigens for CAR-T-cell therapy also remain limited.</AbstractText We profiled an extensive biobank of patients' biopsy tissues and patient-derived early passage glioma neural stem cell lines for GD2 expression using immunomicroscopy and flow cytometry. We then employed an approved clinical manufacturing process to make CAR- T cells from patients with peripheral blood of glioblastoma and diffuse midline glioma and characterized their phenotype and function in vitro. Finally, we tested intravenously administered CAR-T cells in an aggressive intracranial xenograft model of glioblastoma and used multicolor flow cytometry, multicolor whole-tissue immunofluorescence and next-generation RNA sequencing to uncover markers associated with effective tumor control.</AbstractText Here we show that the tumor-associated antigen GD2 is highly and consistently expressed in primary glioblastoma tissue removed at surgery. Moreover, despite patients with glioblastoma having perturbations in their immune system, highly functional GD2-specific CAR-T cells can be produced from their peripheral T cells using an approved clinical manufacturing process. Finally, after intravenous administration, GD2-CAR-T cells effectively infiltrated the brain and controlled tumor growth in an aggressive orthotopic xenograft model of glioblastoma. Tumor control was further improved using CAR-T cells manufactured with a clinical retroviral vector encoding an interleukin-15 transgene alongside the GD2-specific CAR. These CAR-T cells achieved a striking 50% complete response rate by bioluminescence imaging in established intracranial tumors.</AbstractText Targeting GD2 using a clinically deployed CAR-T-cell therapy has a sound scientific and clinical rationale as a treatment for glioblastoma and other aggressive primary brain tumors.</AbstractText
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Reprogramming of human urine cells into cardiomyocytes via a small molecule cocktail in xeno-free conditions. Cell therapy, particularly using cardiomyocytes, shows significant promise for treating heart failure. Direct reprogramming of somatic cells into cardiomyocytes using small molecules is advantageous due to its efficiency and cost-effectiveness.</AbstractText Human urine-derived cells (hUCs) were transdifferentiated into functional cardiomyocyte-like cells (hCiCMs) using a cocktail of 15 small molecules under xeno-free conditions. Various Characterizations were performed, including immunofluorescence, transmission electron microscopy (TEM), qPCR, single-cell RNA sequencing, patch-clamp recordings, and intracellular Ca²<sup Reprogramming efficiency achieves 15.08% on day 30, with purity reaching 96.67% on day 60. hCiCMs display cardiomyocyte markers, sarcomeric structures, and abundant mitochondria. Electrophysiological analysis confirms ventricular-like action potentials and regular calcium transients. Single-cell RNA sequencing reveals cardiomyocyte subpopulations resembling 13-week embryonic human heart cells, with gene ontology analysis indicating successful maturation. In the MI model, hCiCM transplantation improves cardiac function, increasing ejection fraction and fractional shortening while reducing fibrosis.</AbstractText This study demonstrates the successful reprogramming of hUCs into functional hCiCMs using small molecules under xeno-free conditions, offering a scalable, autologous cell source for cardiac repair with significant potential for regenerative therapies.</AbstractText Cardiomyocytes are the muscle cells within the heart that enable the heart to contract and pump blood. We aimed to develop a method to generate cardiomyocytes from cells derived from human urine. We used a combination of 15 small molecules to transform human urine-derived cells into cardiomyocyte-like cells. The cells were tested in mouse and porcine models of heart damage, where they were found to enhance heart function. This approach could be further developed as a possible safe, efficient, and scalable solution for producing heart cells that could be transplanted into people with heart disease as a treatment.</AbstractText
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15721240
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9030628
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15574799
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Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity.
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Dendritic and postsynaptic localizations of glycine receptor alpha subunit mRNAs.
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Time course of changes in brain activity and functional connectivity associated with long-term adaptation to a rotational transformation.
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Little is known about the molecular mechanisms underlying differences in the ligand binding properties of AMPA, kainate, and NMDA subtype glutamate receptors. Crystal structures of the GluR5 and GluR6 kainate receptor ligand binding cores in complexes with glutamate, 2S,4R-4-methylglutamate, kainate, and quisqualate have now been solved. The structures reveal that the ligand binding cavities are 40% (GluR5) and 16% (GluR6) larger than for GluR2. The binding of AMPA- and GluR5-selective agonists to GluR6 is prevented by steric occlusion, which also interferes with the high-affinity binding of 2S,4R-4-methylglutamate to AMPA receptors. Strikingly, the extent of domain closure produced by the GluR6 partial agonist kainate is only 3 degrees less than for glutamate and 11 degrees greater than for the GluR2 kainate complex. This, together with extensive interdomain contacts between domains 1 and 2 of GluR5 and GluR6, absent from AMPA receptors, likely contributes to the high stability of GluR5 and GluR6 kainate complexes.</AbstractText
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Some synaptic neurotransmitter receptors, such as those for glycine, have somato-dendritic distributions. Although the machinery for protein synthesis and several mRNAs are present in dendrites and close to synapses in central neurons, so far the mRNAs for neurotransmitter receptors have not been found unequivocally in dendrites. The glycine receptor (GlyR), a ligand-gated channel mediating a chloride-dependent inhibition, is composed of transmembrane alpha and beta subunits. GlyRs are only present at glycinergic postsynaptic differentiation, where they are stabilized by the associated protein gephyrin. With light nonradioactive in situ hybridization (ISH), we observe that GlyR alpha subunit mRNAs are present in both somata and dendrites of most neurons of the ventral horn of rat spinal cord, whereas the beta subunit and gephyrin mRNAs are predominantly in somata. Interestingly, within dendrites GlyR alpha subunit mRNAs form aggregates that are mostly localized peripherally to the dendritic axial core. Electron microscopic ISH shows that GlyR alpha subunit mRNAs are associated with postsynaptic differentiations. At these sites, the GlyR alpha subunit mRNAs are detected in close association with subsynaptic cisternae. This targeting of alpha subunit mRNAs to postsynaptic domains could provide a means of dynamically modulating synaptic efficacy by changing the composition and the density of receptors at glycinergic synapses.</AbstractText
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The purpose of this study was to examine the time course of changes in cerebral activity and functional connectivity during long-term adaptation to a visuomotor transformation. Positron emission tomography was used to measure changes in brain activity as subjects tracked a target under the influence of a rotational transformation that distorted visual feedback. The experiment was 1 week long and consisted of two scanning sessions (obtained on days 2 and 7), aimed at examining early and late stages of learning. On average, visuomotor adaptation was achieved within 3 days. During early stages of adaptation, better performance was associated with greater activity in brain areas related to attention including bilateral dorso- and ventrolateral prefrontal cortices, frontal eye fields, and the human homologue of area MT. However, as adaptation proceeded, improvements in performance were associated with greater activity in motor regions such as the left (contralateral) sensorimotor cortex, bilateral anterior cerebellum, left cingulate motor area, right putamen, and a nonmotor region within the middle temporal gyrus. This learning-specific shift in brain activity was associated with a progressive change in the functional connectivity of these regions toward the end of the first session. Interestingly, only the functional connections between the anterior cerebellum, left middle temporal gyrus, and left sensorimotor cortex remained strong once visuomotor adaptation was achieved. Our findings suggest that visuomotor adaptation is not only reflected in persistent changes in activity in motor-related regions, but also in the strengthening and maintenance of specific functional connections.</AbstractText
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Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity. Little is known about the molecular mechanisms underlying differences in the ligand binding properties of AMPA, kainate, and NMDA subtype glutamate receptors. Crystal structures of the GluR5 and GluR6 kainate receptor ligand binding cores in complexes with glutamate, 2S,4R-4-methylglutamate, kainate, and quisqualate have now been solved. The structures reveal that the ligand binding cavities are 40% (GluR5) and 16% (GluR6) larger than for GluR2. The binding of AMPA- and GluR5-selective agonists to GluR6 is prevented by steric occlusion, which also interferes with the high-affinity binding of 2S,4R-4-methylglutamate to AMPA receptors. Strikingly, the extent of domain closure produced by the GluR6 partial agonist kainate is only 3 degrees less than for glutamate and 11 degrees greater than for the GluR2 kainate complex. This, together with extensive interdomain contacts between domains 1 and 2 of GluR5 and GluR6, absent from AMPA receptors, likely contributes to the high stability of GluR5 and GluR6 kainate complexes.</AbstractText
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Dendritic and postsynaptic localizations of glycine receptor alpha subunit mRNAs. Some synaptic neurotransmitter receptors, such as those for glycine, have somato-dendritic distributions. Although the machinery for protein synthesis and several mRNAs are present in dendrites and close to synapses in central neurons, so far the mRNAs for neurotransmitter receptors have not been found unequivocally in dendrites. The glycine receptor (GlyR), a ligand-gated channel mediating a chloride-dependent inhibition, is composed of transmembrane alpha and beta subunits. GlyRs are only present at glycinergic postsynaptic differentiation, where they are stabilized by the associated protein gephyrin. With light nonradioactive in situ hybridization (ISH), we observe that GlyR alpha subunit mRNAs are present in both somata and dendrites of most neurons of the ventral horn of rat spinal cord, whereas the beta subunit and gephyrin mRNAs are predominantly in somata. Interestingly, within dendrites GlyR alpha subunit mRNAs form aggregates that are mostly localized peripherally to the dendritic axial core. Electron microscopic ISH shows that GlyR alpha subunit mRNAs are associated with postsynaptic differentiations. At these sites, the GlyR alpha subunit mRNAs are detected in close association with subsynaptic cisternae. This targeting of alpha subunit mRNAs to postsynaptic domains could provide a means of dynamically modulating synaptic efficacy by changing the composition and the density of receptors at glycinergic synapses.</AbstractText
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Time course of changes in brain activity and functional connectivity associated with long-term adaptation to a rotational transformation. The purpose of this study was to examine the time course of changes in cerebral activity and functional connectivity during long-term adaptation to a visuomotor transformation. Positron emission tomography was used to measure changes in brain activity as subjects tracked a target under the influence of a rotational transformation that distorted visual feedback. The experiment was 1 week long and consisted of two scanning sessions (obtained on days 2 and 7), aimed at examining early and late stages of learning. On average, visuomotor adaptation was achieved within 3 days. During early stages of adaptation, better performance was associated with greater activity in brain areas related to attention including bilateral dorso- and ventrolateral prefrontal cortices, frontal eye fields, and the human homologue of area MT. However, as adaptation proceeded, improvements in performance were associated with greater activity in motor regions such as the left (contralateral) sensorimotor cortex, bilateral anterior cerebellum, left cingulate motor area, right putamen, and a nonmotor region within the middle temporal gyrus. This learning-specific shift in brain activity was associated with a progressive change in the functional connectivity of these regions toward the end of the first session. Interestingly, only the functional connections between the anterior cerebellum, left middle temporal gyrus, and left sensorimotor cortex remained strong once visuomotor adaptation was achieved. Our findings suggest that visuomotor adaptation is not only reflected in persistent changes in activity in motor-related regions, but also in the strengthening and maintenance of specific functional connections.</AbstractText
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31269243
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17215723
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30069785
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Neuropathy associated with immunoglobulin M monoclonal gammopathy: A combined sonographic and nerve conduction study.
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Vasculitic neuropathies: an update.
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Histogram analysis of quantitative pharmacokinetic parameters on DCE-MRI: correlations with prognostic factors and molecular subtypes in breast cancer.
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We assessed the specific sonographic pattern of structural nerve abnormalities in immunoglobulin M (IgM) neuropathy and disease controls.</AbstractText We enrolled 106 incident patients-32 patients with IgM neuropathy, 42 treatment-naive patients with chronic inflammatory demyelinating polyneuropathy, and 32 patients with axonal neuropathies. All patients underwent standardized ancillary testing in addition to standardized sonography of the brachial plexus and the large arm and leg nerves bilaterally.</AbstractText We found widespread nerve enlargement in IgM neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP), with specific enlargement of brachial plexus and proximal segments of median nerve but not in axonal disease controls (P < .001). Sonographic nerve hypertrophy in IgM neuropathy was not associated with nerve conduction, clinical, or laboratory characteristics.</AbstractText Immunoglobulin M neuropathy is characterized by widespread nerve enlargement indistinguishable from CIDP. Our data provide evidence to confirm that the disease process is not confined to the more distal parts of nerves in either classical demyelinating or axonal variants of neuropathy with associated IgM.</AbstractText
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Systemic vasculitis has been classically categorized as a primary disorder, such as polyarteritis nodosa, Churg-Strauss syndrome, and Wegener granulomatous, or as a secondary process, representing a complication from a connective tissue disorder (eg, rheumatoid vasculitis), infection, medication, or malignancy. Peripheral neuropathy is a well-recognized consequence of systemic vasculitis due to peripheral nerve infarction with Wallerian degeneration. Rarely, neuropathy is the sole manifestation of vasculitis, referred to as nonsystemic vasculitic neuropathy (NSVN). These conditions are defined pathologically by tissue biopsy demonstrating disruption or destruction of the vessel wall with inflammatory cell infiltrates.</AbstractText The diagnosis of vasculitic neuropathy is straightforward in patients with an established diagnosis of systemic vasculitis and classic features of mononeuritis multiplex. Most patients have clinical features of a subacute, progressive, generalized but asymmetric, painful, sensorimotor polyneuropathy. Laboratory tests often indicate features of systemic inflammation, such as an elevated sedimentation rate or positive anti-neutrophil cytoplasmic antibody, and electrodiagnostic evaluation shows multiple mononeuropathies or a confluent, asymmetric axonal neuropathy. Nerve biopsy is necessary to establish the diagnosis in most cases, particularly in patients with NSVN. This review summarizes the current treatment of vasculitic neuropathy.</AbstractText Long-term immunosuppressive therapy is required in most cases. High-dose prednisone combined with intravenous pulse or oral daily cyclophosphamide is standard initial therapy. In those with NSVN, cyclophosphamide also should be used if prednisone monotherapy is ineffective or the patient relapses with tapering. Other agents, such as azathioprine, methotrexate, intravenous immunoglobulin, mycophenolate mofetil, plasma exchange, and rituximab can be offered to patients who are intolerant or have a contraindication to cyclophosphamide. However, evidence for the benefit of these agents is limited to case reports and small case series.</AbstractText
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Breast cancer heterogeneity influences poor prognoses thorough therapy resistance. This study quantitatively evaluated intratumoral heterogeneity through a histogram analysis of dynamic contrast-enhanced MRI (DCE-MRI) pharmacokinetic parameters, and determined correlations with prognostic factors and molecular subtypes.</AbstractText We retrospectively investigated 101 invasive ductal breast cancers from 99 women who underwent preoperative DCE-MRI between July 2012 and November 2014. Pharmacokinetic parameters (K<sup The mean of v<sub Various v<sub
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Neuropathy associated with immunoglobulin M monoclonal gammopathy: A combined sonographic and nerve conduction study. We assessed the specific sonographic pattern of structural nerve abnormalities in immunoglobulin M (IgM) neuropathy and disease controls.</AbstractText We enrolled 106 incident patients-32 patients with IgM neuropathy, 42 treatment-naive patients with chronic inflammatory demyelinating polyneuropathy, and 32 patients with axonal neuropathies. All patients underwent standardized ancillary testing in addition to standardized sonography of the brachial plexus and the large arm and leg nerves bilaterally.</AbstractText We found widespread nerve enlargement in IgM neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP), with specific enlargement of brachial plexus and proximal segments of median nerve but not in axonal disease controls (P < .001). Sonographic nerve hypertrophy in IgM neuropathy was not associated with nerve conduction, clinical, or laboratory characteristics.</AbstractText Immunoglobulin M neuropathy is characterized by widespread nerve enlargement indistinguishable from CIDP. Our data provide evidence to confirm that the disease process is not confined to the more distal parts of nerves in either classical demyelinating or axonal variants of neuropathy with associated IgM.</AbstractText
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Vasculitic neuropathies: an update. Systemic vasculitis has been classically categorized as a primary disorder, such as polyarteritis nodosa, Churg-Strauss syndrome, and Wegener granulomatous, or as a secondary process, representing a complication from a connective tissue disorder (eg, rheumatoid vasculitis), infection, medication, or malignancy. Peripheral neuropathy is a well-recognized consequence of systemic vasculitis due to peripheral nerve infarction with Wallerian degeneration. Rarely, neuropathy is the sole manifestation of vasculitis, referred to as nonsystemic vasculitic neuropathy (NSVN). These conditions are defined pathologically by tissue biopsy demonstrating disruption or destruction of the vessel wall with inflammatory cell infiltrates.</AbstractText The diagnosis of vasculitic neuropathy is straightforward in patients with an established diagnosis of systemic vasculitis and classic features of mononeuritis multiplex. Most patients have clinical features of a subacute, progressive, generalized but asymmetric, painful, sensorimotor polyneuropathy. Laboratory tests often indicate features of systemic inflammation, such as an elevated sedimentation rate or positive anti-neutrophil cytoplasmic antibody, and electrodiagnostic evaluation shows multiple mononeuropathies or a confluent, asymmetric axonal neuropathy. Nerve biopsy is necessary to establish the diagnosis in most cases, particularly in patients with NSVN. This review summarizes the current treatment of vasculitic neuropathy.</AbstractText Long-term immunosuppressive therapy is required in most cases. High-dose prednisone combined with intravenous pulse or oral daily cyclophosphamide is standard initial therapy. In those with NSVN, cyclophosphamide also should be used if prednisone monotherapy is ineffective or the patient relapses with tapering. Other agents, such as azathioprine, methotrexate, intravenous immunoglobulin, mycophenolate mofetil, plasma exchange, and rituximab can be offered to patients who are intolerant or have a contraindication to cyclophosphamide. However, evidence for the benefit of these agents is limited to case reports and small case series.</AbstractText
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Histogram analysis of quantitative pharmacokinetic parameters on DCE-MRI: correlations with prognostic factors and molecular subtypes in breast cancer. Breast cancer heterogeneity influences poor prognoses thorough therapy resistance. This study quantitatively evaluated intratumoral heterogeneity through a histogram analysis of dynamic contrast-enhanced MRI (DCE-MRI) pharmacokinetic parameters, and determined correlations with prognostic factors and molecular subtypes.</AbstractText We retrospectively investigated 101 invasive ductal breast cancers from 99 women who underwent preoperative DCE-MRI between July 2012 and November 2014. Pharmacokinetic parameters (K<sup The mean of v<sub Various v<sub
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32096051
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29513146
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31509206
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Experimental Models of Tauopathy - From Mechanisms to Therapies.
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The Biology of Regeneration Failure and Success After Spinal Cord Injury.
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Magnetic Resonance Imaging-Guided Confirmatory Biopsy for Initiating Active Surveillance of Prostate Cancer.
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Animal models have been instrumental in reproducing key aspects of human tauopathy. In pursuing these efforts, the mouse continues to have a prominent role. In this chapter, we focus on models that overexpress wild-type or mutant forms of tau, the latter being based on mutations found in familial cases of frontotemporal dementia. We review some of these models in more detail and discuss what they have revealed about the underlying pathomechanisms, as well as highlighting new developments that exploit gene editing tools such as TALEN and CRISPR. Interestingly, when investigating the role of tau in impairing cellular functions, common themes emerge. Because tau is a scaffolding protein that aggregates in the somatodendritic domain under pathological conditions, it traps proteins such as parkin and JIP1, preventing them from executing their normal function in mitophagy and axonal transport, respectively. Another aspect is the emerging role of tau in the translational machinery and the finding that the somatodendritic accumulation of tau in Alzheimer's disease may in part be due to the induction of the de novo synthesis of tau by amyloid-β via the Fyn/ERK/S6 pathway. We further discuss treatment strategies such as tau-based vaccinations and therapeutic ultrasound and conclude by discussing whether there is a future for animal models of tauopathies.</AbstractText
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Since no approved therapies to restore mobility and sensation following spinal cord injury (SCI) currently exist, a better understanding of the cellular and molecular mechanisms following SCI that compromise regeneration or neuroplasticity is needed to develop new strategies to promote axonal regrowth and restore function. Physical trauma to the spinal cord results in vascular disruption that, in turn, causes blood-spinal cord barrier rupture leading to hemorrhage and ischemia, followed by rampant local cell death. As subsequent edema and inflammation occur, neuronal and glial necrosis and apoptosis spread well beyond the initial site of impact, ultimately resolving into a cavity surrounded by glial/fibrotic scarring. The glial scar, which stabilizes the spread of secondary injury, also acts as a chronic, physical, and chemo-entrapping barrier that prevents axonal regeneration. Understanding the formative events in glial scarring helps guide strategies towards the development of potential therapies to enhance axon regeneration and functional recovery at both acute and chronic stages following SCI. This review will also discuss the perineuronal net and how chondroitin sulfate proteoglycans (CSPGs) deposited in both the glial scar and net impede axonal outgrowth at the level of the growth cone. We will end the review with a summary of current CSPG-targeting strategies that help to foster axonal regeneration, neuroplasticity/sprouting, and functional recovery following SCI.</AbstractText
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Transrectal, ultrasonography-guided prostate biopsy often fails to disclose the severity of underlying pathologic findings for prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy may improve the characterization of prostate pathologic results, but few studies have examined its use for the decision to enter active surveillance.</AbstractText To evaluate whether confirmatory biopsy findings by MRI guidance are associated with the risk of pathologic disease upgrading among patients with prostate cancer during active surveillance.</AbstractText This retrospective cohort study used prospectively obtained registry data from 332 men with prostate cancer of Gleason grade group (GG) 2 or lower who were referred for active surveillance at a large academic medical center from January 1, 2009, through December 31, 2017.</AbstractText All confirmatory and follow-up biopsies were performed using MRI guidance with an MRI-ultrasonography fusion device. Patients underwent repeated MRI-guided biopsies every 12 to 24 months. At follow-up sessions, in addition to obtaining systematic samples, lesions seen on MRI were targeted and foci of low-grade prostate cancer were obtained again using tracking technology. Active surveillance was terminated with detection of at least GG3 disease or receipt of treatment.</AbstractText The primary outcome was upgrading to at least GG3 disease during active surveillance. Secondary outcomes were the associations of MRI lesion grade, prostate-specific antigen (PSA) level, PSA density, and biopsy method (targeted, systematic, or tracked) with the primary outcome.</AbstractText Of 332 patients (mean [SD] age, 62.8 [7.6] years), 39 (11.7%) upgraded to at least GG3 disease during follow-up. The incidence of upgrading was 7.9% (9 of 114) when the confirmatory biopsy finding was normal, 11.4% (20 of 175) when the finding showed GG1 disease, and 23.3% (10 of 43) when the finding was GG2 disease (P = .03). Men with GG2 disease were almost 8 times more likely to upgrade during surveillance compared with those with normal findings but only among those with low PSA density (hazard ratio [HR], 7.82; 95% CI, 2.29-26.68). A PSA density of at least 0.15 ng/mL/mL was associated with increased risk of upgrading among patients with normal findings (HR, 7.21; 95% CI, 1.98-26.24) or GG1 disease (HR, 2.86; 95% CI, 1.16 to 7.03) on confirmatory biopsy. A total of 46% of pathologic disease upgrades would have been missed if only the targeted biopsy was performed and 65% of disease upgrades were detected only with tracked biopsy.</AbstractText The findings suggest that confirmatory biopsy with MRI guidance is significantly associated with future disease upgrading of prostate cancer, especially when combined with PSA density, and should be considered as an appropriate entry point for active surveillance. Systematic and targeted biopsies were additive in detection of clinically significant cancers. Repeated biopsy at sites at which findings were previously abnormal (tracking biopsy) facilitated detection of cancers not suitable for continued active surveillance.</AbstractText
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Experimental Models of Tauopathy - From Mechanisms to Therapies. Animal models have been instrumental in reproducing key aspects of human tauopathy. In pursuing these efforts, the mouse continues to have a prominent role. In this chapter, we focus on models that overexpress wild-type or mutant forms of tau, the latter being based on mutations found in familial cases of frontotemporal dementia. We review some of these models in more detail and discuss what they have revealed about the underlying pathomechanisms, as well as highlighting new developments that exploit gene editing tools such as TALEN and CRISPR. Interestingly, when investigating the role of tau in impairing cellular functions, common themes emerge. Because tau is a scaffolding protein that aggregates in the somatodendritic domain under pathological conditions, it traps proteins such as parkin and JIP1, preventing them from executing their normal function in mitophagy and axonal transport, respectively. Another aspect is the emerging role of tau in the translational machinery and the finding that the somatodendritic accumulation of tau in Alzheimer's disease may in part be due to the induction of the de novo synthesis of tau by amyloid-β via the Fyn/ERK/S6 pathway. We further discuss treatment strategies such as tau-based vaccinations and therapeutic ultrasound and conclude by discussing whether there is a future for animal models of tauopathies.</AbstractText
|
The Biology of Regeneration Failure and Success After Spinal Cord Injury. Since no approved therapies to restore mobility and sensation following spinal cord injury (SCI) currently exist, a better understanding of the cellular and molecular mechanisms following SCI that compromise regeneration or neuroplasticity is needed to develop new strategies to promote axonal regrowth and restore function. Physical trauma to the spinal cord results in vascular disruption that, in turn, causes blood-spinal cord barrier rupture leading to hemorrhage and ischemia, followed by rampant local cell death. As subsequent edema and inflammation occur, neuronal and glial necrosis and apoptosis spread well beyond the initial site of impact, ultimately resolving into a cavity surrounded by glial/fibrotic scarring. The glial scar, which stabilizes the spread of secondary injury, also acts as a chronic, physical, and chemo-entrapping barrier that prevents axonal regeneration. Understanding the formative events in glial scarring helps guide strategies towards the development of potential therapies to enhance axon regeneration and functional recovery at both acute and chronic stages following SCI. This review will also discuss the perineuronal net and how chondroitin sulfate proteoglycans (CSPGs) deposited in both the glial scar and net impede axonal outgrowth at the level of the growth cone. We will end the review with a summary of current CSPG-targeting strategies that help to foster axonal regeneration, neuroplasticity/sprouting, and functional recovery following SCI.</AbstractText
|
Magnetic Resonance Imaging-Guided Confirmatory Biopsy for Initiating Active Surveillance of Prostate Cancer. Transrectal, ultrasonography-guided prostate biopsy often fails to disclose the severity of underlying pathologic findings for prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy may improve the characterization of prostate pathologic results, but few studies have examined its use for the decision to enter active surveillance.</AbstractText To evaluate whether confirmatory biopsy findings by MRI guidance are associated with the risk of pathologic disease upgrading among patients with prostate cancer during active surveillance.</AbstractText This retrospective cohort study used prospectively obtained registry data from 332 men with prostate cancer of Gleason grade group (GG) 2 or lower who were referred for active surveillance at a large academic medical center from January 1, 2009, through December 31, 2017.</AbstractText All confirmatory and follow-up biopsies were performed using MRI guidance with an MRI-ultrasonography fusion device. Patients underwent repeated MRI-guided biopsies every 12 to 24 months. At follow-up sessions, in addition to obtaining systematic samples, lesions seen on MRI were targeted and foci of low-grade prostate cancer were obtained again using tracking technology. Active surveillance was terminated with detection of at least GG3 disease or receipt of treatment.</AbstractText The primary outcome was upgrading to at least GG3 disease during active surveillance. Secondary outcomes were the associations of MRI lesion grade, prostate-specific antigen (PSA) level, PSA density, and biopsy method (targeted, systematic, or tracked) with the primary outcome.</AbstractText Of 332 patients (mean [SD] age, 62.8 [7.6] years), 39 (11.7%) upgraded to at least GG3 disease during follow-up. The incidence of upgrading was 7.9% (9 of 114) when the confirmatory biopsy finding was normal, 11.4% (20 of 175) when the finding showed GG1 disease, and 23.3% (10 of 43) when the finding was GG2 disease (P = .03). Men with GG2 disease were almost 8 times more likely to upgrade during surveillance compared with those with normal findings but only among those with low PSA density (hazard ratio [HR], 7.82; 95% CI, 2.29-26.68). A PSA density of at least 0.15 ng/mL/mL was associated with increased risk of upgrading among patients with normal findings (HR, 7.21; 95% CI, 1.98-26.24) or GG1 disease (HR, 2.86; 95% CI, 1.16 to 7.03) on confirmatory biopsy. A total of 46% of pathologic disease upgrades would have been missed if only the targeted biopsy was performed and 65% of disease upgrades were detected only with tracked biopsy.</AbstractText The findings suggest that confirmatory biopsy with MRI guidance is significantly associated with future disease upgrading of prostate cancer, especially when combined with PSA density, and should be considered as an appropriate entry point for active surveillance. Systematic and targeted biopsies were additive in detection of clinically significant cancers. Repeated biopsy at sites at which findings were previously abnormal (tracking biopsy) facilitated detection of cancers not suitable for continued active surveillance.</AbstractText
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32219701
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24825730
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32281216
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The Misdiagnosis of CIDP: A Review.
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Diagnostic value of MR imaging in the Lewis-Sumner syndrome: a case series.
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Comparison of the transcriptional profile in the decidua of early-onset and late-onset pre-eclampsia.
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There is a growing realization that many patients are incorrectly diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), with at least half of patients that carry a diagnosis of CIDP in the USA possibly having a different explanation for their neuropathy or having no neuropathy at all. Many misdiagnosed patients go on to receive costly and potentially harmful treatments for a disease that they do not have, while at the same time missing an opportunity to treat their true ailment. The cost of misdiagnosis on patients and society is not trivial. Many factors contribute to misdiagnosis. Particular points of vulnerability include the evaluation of "atypical" CIDP, interpretation of equivocal nerve conduction studies, over-reliance on elevations in cerebrospinal fluid protein concentration in indeterminate ranges, and placing excessive diagnostic weight on subjective changes following the initiation of immunotherapy. In addition to heighted awareness of the challenges, adherence to CIDP diagnostic guidelines, utilization of objective metrics to document clinical change, and referrals to CIDP centers of excellence are strategies that may improve diagnostic accuracy.</AbstractText
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Lewis-Sumner syndrome (LSS) is considered a variant of chronic inflammatory demyelinating polyneuropathy (CIDP), which is more frequently described with exclusive upper limb involvement. The diagnosis of LSS is clinical and electrophysiological. However, these are not always obvious and in view of its rarity, the diagnosis may be missed and patients denied effective immunomodulatory therapy. We herein describe the magnetic resonance imaging (MRI) findings in a series of five consecutive patients with a clinical diagnosis of LSS, using T2 STIR (Short Tau Inversion recovery) images without contrast. We demonstrated hyperintensity with or without hypertrophy of cervical roots and/or brachial plexus on the affected side and/or controlaterally which aided diagnostic confirmation. This helped therapeutic decision making regarding immunotherapy in all cases. MR imaging of the cervical spine/brachial plexus with T2 STIR may be helpful in suspected cases of LSS as it represents a very useful additional diagnostic tool.</AbstractText
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To compare early-onset pre-eclampsia (EOPE) and late-onset pre-eclampsia (LOPE) and provide insight into the pathophysiology of pre-eclampsia (PE).</AbstractText Our recent work compared the transcriptomics in decidua of EOPE, LOPE and normal pregnancies (NP).</AbstractText We found there are a significant number of genes uniquely expressed in the decidua of EOPE and LOPE comparing with NP. Moreover, EOPE and LOPE have their distinct profiles. Unique EOPE-associated genes were mainly involved in apoptosis related pathways such as 'apoptosis' and 'Ras signaling pathway'. PIK3CB and BCL-2 are the core regulatory genes in EOPE decidua, their abnormal expression caused decidual abnormal apoptosis which is relevant to the pathogenesis of EOPE. Whereas, LOPE is a more complicated entity which has more special LOPE-associated genes involved in decidua differentiation, especially in 'gap junction pathway', 'vascular smooth muscle contraction' and 'long-term depression'. PIK3CB, FLT1, CBLC and ITGA7 are the core regulatory genes differentially expressed in EOPE decidua comparing with LOPE.</AbstractText In brief, the different decidual transcriptomics of EOPE and LOPE may correlate with their different etiology. These findings highlight the complex pathophysiology of PE and provide potential targets for a new treatment strategy in patients with PE.</AbstractText
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The Misdiagnosis of CIDP: A Review. There is a growing realization that many patients are incorrectly diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), with at least half of patients that carry a diagnosis of CIDP in the USA possibly having a different explanation for their neuropathy or having no neuropathy at all. Many misdiagnosed patients go on to receive costly and potentially harmful treatments for a disease that they do not have, while at the same time missing an opportunity to treat their true ailment. The cost of misdiagnosis on patients and society is not trivial. Many factors contribute to misdiagnosis. Particular points of vulnerability include the evaluation of "atypical" CIDP, interpretation of equivocal nerve conduction studies, over-reliance on elevations in cerebrospinal fluid protein concentration in indeterminate ranges, and placing excessive diagnostic weight on subjective changes following the initiation of immunotherapy. In addition to heighted awareness of the challenges, adherence to CIDP diagnostic guidelines, utilization of objective metrics to document clinical change, and referrals to CIDP centers of excellence are strategies that may improve diagnostic accuracy.</AbstractText
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Diagnostic value of MR imaging in the Lewis-Sumner syndrome: a case series. Lewis-Sumner syndrome (LSS) is considered a variant of chronic inflammatory demyelinating polyneuropathy (CIDP), which is more frequently described with exclusive upper limb involvement. The diagnosis of LSS is clinical and electrophysiological. However, these are not always obvious and in view of its rarity, the diagnosis may be missed and patients denied effective immunomodulatory therapy. We herein describe the magnetic resonance imaging (MRI) findings in a series of five consecutive patients with a clinical diagnosis of LSS, using T2 STIR (Short Tau Inversion recovery) images without contrast. We demonstrated hyperintensity with or without hypertrophy of cervical roots and/or brachial plexus on the affected side and/or controlaterally which aided diagnostic confirmation. This helped therapeutic decision making regarding immunotherapy in all cases. MR imaging of the cervical spine/brachial plexus with T2 STIR may be helpful in suspected cases of LSS as it represents a very useful additional diagnostic tool.</AbstractText
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Comparison of the transcriptional profile in the decidua of early-onset and late-onset pre-eclampsia. To compare early-onset pre-eclampsia (EOPE) and late-onset pre-eclampsia (LOPE) and provide insight into the pathophysiology of pre-eclampsia (PE).</AbstractText Our recent work compared the transcriptomics in decidua of EOPE, LOPE and normal pregnancies (NP).</AbstractText We found there are a significant number of genes uniquely expressed in the decidua of EOPE and LOPE comparing with NP. Moreover, EOPE and LOPE have their distinct profiles. Unique EOPE-associated genes were mainly involved in apoptosis related pathways such as 'apoptosis' and 'Ras signaling pathway'. PIK3CB and BCL-2 are the core regulatory genes in EOPE decidua, their abnormal expression caused decidual abnormal apoptosis which is relevant to the pathogenesis of EOPE. Whereas, LOPE is a more complicated entity which has more special LOPE-associated genes involved in decidua differentiation, especially in 'gap junction pathway', 'vascular smooth muscle contraction' and 'long-term depression'. PIK3CB, FLT1, CBLC and ITGA7 are the core regulatory genes differentially expressed in EOPE decidua comparing with LOPE.</AbstractText In brief, the different decidual transcriptomics of EOPE and LOPE may correlate with their different etiology. These findings highlight the complex pathophysiology of PE and provide potential targets for a new treatment strategy in patients with PE.</AbstractText
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38262413
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35085492
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39090065
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Neuronal ensembles: Building blocks of neural circuits.
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Orthogonal representations for robust context-dependent task performance in brains and neural networks.
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[The clinical characteristics of 497 children with congenital pseudarthrosis of the tibia].
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Neuronal ensembles, defined as groups of neurons displaying recurring patterns of coordinated activity, represent an intermediate functional level between individual neurons and brain areas. Novel methods to measure and optically manipulate the activity of neuronal populations have provided evidence of ensembles in the neocortex and hippocampus. Ensembles can be activated intrinsically or in response to sensory stimuli and play a causal role in perception and behavior. Here we review ensemble phenomenology, developmental origin, biophysical and synaptic mechanisms, and potential functional roles across different brain areas and species, including humans. As modular units of neural circuits, ensembles could provide a mechanistic underpinning of fundamental brain processes, including neural coding, motor planning, decision-making, learning, and adaptability.</AbstractText
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How do neural populations code for multiple, potentially conflicting tasks? Here we used computational simulations involving neural networks to define "lazy" and "rich" coding solutions to this context-dependent decision-making problem, which trade off learning speed for robustness. During lazy learning the input dimensionality is expanded by random projections to the network hidden layer, whereas in rich learning hidden units acquire structured representations that privilege relevant over irrelevant features. For context-dependent decision-making, one rich solution is to project task representations onto low-dimensional and orthogonal manifolds. Using behavioral testing and neuroimaging in humans and analysis of neural signals from macaque prefrontal cortex, we report evidence for neural coding patterns in biological brains whose dimensionality and neural geometry are consistent with the rich learning regime.</AbstractText
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<b <b
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Neuronal ensembles: Building blocks of neural circuits. Neuronal ensembles, defined as groups of neurons displaying recurring patterns of coordinated activity, represent an intermediate functional level between individual neurons and brain areas. Novel methods to measure and optically manipulate the activity of neuronal populations have provided evidence of ensembles in the neocortex and hippocampus. Ensembles can be activated intrinsically or in response to sensory stimuli and play a causal role in perception and behavior. Here we review ensemble phenomenology, developmental origin, biophysical and synaptic mechanisms, and potential functional roles across different brain areas and species, including humans. As modular units of neural circuits, ensembles could provide a mechanistic underpinning of fundamental brain processes, including neural coding, motor planning, decision-making, learning, and adaptability.</AbstractText
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Orthogonal representations for robust context-dependent task performance in brains and neural networks. How do neural populations code for multiple, potentially conflicting tasks? Here we used computational simulations involving neural networks to define "lazy" and "rich" coding solutions to this context-dependent decision-making problem, which trade off learning speed for robustness. During lazy learning the input dimensionality is expanded by random projections to the network hidden layer, whereas in rich learning hidden units acquire structured representations that privilege relevant over irrelevant features. For context-dependent decision-making, one rich solution is to project task representations onto low-dimensional and orthogonal manifolds. Using behavioral testing and neuroimaging in humans and analysis of neural signals from macaque prefrontal cortex, we report evidence for neural coding patterns in biological brains whose dimensionality and neural geometry are consistent with the rich learning regime.</AbstractText
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[The clinical characteristics of 497 children with congenital pseudarthrosis of the tibia]. <b <b
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40546338
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10810996
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40739156
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Bitemporal Oedema in a Child: A Rare Manifestation of Epstein-Barr Virus Infection.
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Enterococcus hirae enteropathy with ascending cholangitis and pancreatitis in a kitten.
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A closed loop fully automated wireless vagus nerve stimulation system.
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Primary infection by the Epstein-Barr virus (EBV) is common in children, can affect multiple organs and be associated with a wide variety of clinical manifestations. We present the case of a 7-year-old female patient assessed in the emergency department for bitemporal swelling with a one-day evolution, following self-limiting odynophagia and fever 1 week earlier. Physical examination revealed a soft, bitemporal swelling, more evident on the right, painful on palpation, with no other inflammatory signs. The soft tissue ultrasound showed no alterations, and the CT scan showed thickening of the right parietotemporal epicranial soft tissues, of an imprecise nature. At a 2-week follow-up consultation, swelling had completely resolved. The serological study revealed previous contact with cytomegalovirus and positive EBV IgG and IgM with negative EBNA IgG and EA IgG, indicative of acute EBV infection. Bitemporal oedema is a very atypical and rare presentation of primary EBV infection, with very few cases previously reported. The aim of this clinical case is to draw attention to the importance of considering EBV infection in the differential diagnosis of situations like the one described.</AbstractText
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A 2-month-old female Persian cat that had been showing episodes of anorexia and diarrhea for the previous 4 weeks was presented in shock and died 2 days later. Numerous Gram-positive cocci were located along the brush border of small intestinal villi, without significant inflammatory infiltration. Similar bacteria were present within hepatic bile ducts and pancreatic ducts and were associated with suppurative inflammation and exfoliation of epithelial cells. Culture of the liver and lung yielded bacteria identified as Enterococcus hirae. Fecal culture from an asymptomatic adult female from the same cattery also yielded large numbers of E. hirae. To our knowledge, this is the first report of E. hirae enteropathy in a cat and the first report of ascending cholangitis and ductal pancreatitis caused by an Enterococcus spp.</AbstractText
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Vagus nerve stimulation (VNS) has been explored as a treatment for a range of conditions, including epilepsy, cardiovascular disorders, drug-resistant depression, chronic pain, and obesity. Conventionally, VNS is administered using an open-loop approach, in which trained personnel adjust stimulation parameters. Medical supervision is necessary to minimize adverse effects, such as severe bradycardia, which can significantly interfere with daily activities. This requirement limits the feasibility of VNS in unsupervised settings and highlights the need for an automated control system. To address this limitation, we introduce the fully automated wireless VNS (FAW-VNS) system, which dynamically adjusts stimulation parameters to maintain steady-state operation while minimizing bradycardia. The FAW-VNS system operates in real-time and consists of a biocompatible, miniaturized, wirelessly powered implant equipped with cuff electrodes; a handheld device for power delivery and stimulation protocol communication; a sensing patch to collect and transmit heart rate (HR) data; and a central control unit (CCU) that updates stimulation protocols based on the acquired physiological signals. In-vivo studies were conducted on four anesthetized pigs to validate the system's ability to reach a steady-state response, achieving a controlled HR reduction within 2-4% of baseline during stimulation. This work lays the foundation for developing closed-loop, wireless implants for point-of-care applications.</AbstractText
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Bitemporal Oedema in a Child: A Rare Manifestation of Epstein-Barr Virus Infection. Primary infection by the Epstein-Barr virus (EBV) is common in children, can affect multiple organs and be associated with a wide variety of clinical manifestations. We present the case of a 7-year-old female patient assessed in the emergency department for bitemporal swelling with a one-day evolution, following self-limiting odynophagia and fever 1 week earlier. Physical examination revealed a soft, bitemporal swelling, more evident on the right, painful on palpation, with no other inflammatory signs. The soft tissue ultrasound showed no alterations, and the CT scan showed thickening of the right parietotemporal epicranial soft tissues, of an imprecise nature. At a 2-week follow-up consultation, swelling had completely resolved. The serological study revealed previous contact with cytomegalovirus and positive EBV IgG and IgM with negative EBNA IgG and EA IgG, indicative of acute EBV infection. Bitemporal oedema is a very atypical and rare presentation of primary EBV infection, with very few cases previously reported. The aim of this clinical case is to draw attention to the importance of considering EBV infection in the differential diagnosis of situations like the one described.</AbstractText
|
Enterococcus hirae enteropathy with ascending cholangitis and pancreatitis in a kitten. A 2-month-old female Persian cat that had been showing episodes of anorexia and diarrhea for the previous 4 weeks was presented in shock and died 2 days later. Numerous Gram-positive cocci were located along the brush border of small intestinal villi, without significant inflammatory infiltration. Similar bacteria were present within hepatic bile ducts and pancreatic ducts and were associated with suppurative inflammation and exfoliation of epithelial cells. Culture of the liver and lung yielded bacteria identified as Enterococcus hirae. Fecal culture from an asymptomatic adult female from the same cattery also yielded large numbers of E. hirae. To our knowledge, this is the first report of E. hirae enteropathy in a cat and the first report of ascending cholangitis and ductal pancreatitis caused by an Enterococcus spp.</AbstractText
|
A closed loop fully automated wireless vagus nerve stimulation system. Vagus nerve stimulation (VNS) has been explored as a treatment for a range of conditions, including epilepsy, cardiovascular disorders, drug-resistant depression, chronic pain, and obesity. Conventionally, VNS is administered using an open-loop approach, in which trained personnel adjust stimulation parameters. Medical supervision is necessary to minimize adverse effects, such as severe bradycardia, which can significantly interfere with daily activities. This requirement limits the feasibility of VNS in unsupervised settings and highlights the need for an automated control system. To address this limitation, we introduce the fully automated wireless VNS (FAW-VNS) system, which dynamically adjusts stimulation parameters to maintain steady-state operation while minimizing bradycardia. The FAW-VNS system operates in real-time and consists of a biocompatible, miniaturized, wirelessly powered implant equipped with cuff electrodes; a handheld device for power delivery and stimulation protocol communication; a sensing patch to collect and transmit heart rate (HR) data; and a central control unit (CCU) that updates stimulation protocols based on the acquired physiological signals. In-vivo studies were conducted on four anesthetized pigs to validate the system's ability to reach a steady-state response, achieving a controlled HR reduction within 2-4% of baseline during stimulation. This work lays the foundation for developing closed-loop, wireless implants for point-of-care applications.</AbstractText
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39402595
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37181360
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38946527
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Impact of contrast-enhanced CT in the dosimetry of SBRT for liver metastases treated with MR-Linac.
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Functional lung imaging using novel and emerging MRI techniques.
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Exploring the effect of wound related pain on psychological stress, inflammatory response, and wound healing.
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To investigate the impact of using contrast-enhanced computed tomography (CHCT) in the dosimetry of stereotactic body radiation therapy (SBRT) for liver metastases treated with MR-Linac.</AbstractText A retrospective study was conducted on 21 liver cancer patients treated with SBRT (50 Gy in 5 fractions) using a 1.5 Tesla Unity MR-Linac. The clinical treatment plans optimised on plain computed tomography (pCT) were used as reference. The electronic density (ED) of regions of interest (ROIs) including the liver, duodenum, esophagus, spinal cord, heart, ribs, and lungs, from pCT and CHCT, was analysed. The average ED of each ROI from CHCT was used to generate synthetic CT (sCT) images by assigning the average ED value from the CHCT to the pCT. Clinical plans were recalculated on sCT images. Dosimetric comparisons between the original treatment plan (TP<sub Significant ED differences (p < 0.05) were observed in the liver, great vessels, heart, lungs, and spinal cord between CHCT and pCT, with the lungs showing the largest differences (average deviation of 11.73% and 12.15% for the left and right lung, respectively). The target volume covered by the prescribed dose (V<sub The findings suggest that the use of CHCT in the SBRT workflow for liver metastases may result in minor target volume overdosage, indicating its potential for adoption in clinical settings. However, its use should be further explored in a broader context and tied to personalized treatment approaches.</AbstractText
|
Respiratory diseases are leading causes of death and disability in the world. While early diagnosis is key, this has proven difficult due to the lack of sensitive and non-invasive tools. Computed tomography is regarded as the gold standard for structural lung imaging but lacks functional information and involves significant radiation exposure. Lung magnetic resonance imaging (MRI) has historically been challenging due to its short T2 and low proton density. Hyperpolarised gas MRI is an emerging technique that is able to overcome these difficulties, permitting the functional and microstructural evaluation of the lung. Other novel imaging techniques such as fluorinated gas MRI, oxygen-enhanced MRI, Fourier decomposition MRI and phase-resolved functional lung imaging can also be used to interrogate lung function though they are currently at varying stages of development. This article provides a clinically focused review of these contrast and non-contrast MR imaging techniques and their current applications in lung disease.</AbstractText
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The relationship between pain and poor healing is intricate, potentially mediated by psychological stress and aberrations in inflammatory response. The purpose of this study was to examine the biopsychosocial model of pain by assessing the relationships between pain, stress, inflammation and healing in people with chronic wounds.</AbstractText This was a 4-week prospective observational study to explore the relationship of pain, stress, inflammation and wound healing in a convenience sample of patients with chronic wounds in a chronic care hospital in Canada.</AbstractText Only subjects over 18 with chronic wounds were recruited into the study. Chronic wounds were defined by the duration of wounds for more than 4 weeks of various aetiologies including wounds caused by pressure injuries, venous disease, arterial insufficiency, surgery or trauma and diabetic neuropathy. Participants were evaluated for pain by responding to the Brief Pain Inventory-Short Form, the McGill Pain Questionnaire-Short Form and the Leeds Assessment of Neuropathic Symptoms and Signs scale. Stress was measured by the Perceived Stress Scale (PSS). All wounds were assessed with the Pressure Ulcer Scale for Healing tool. The levels of matrix metalloproteinases were analysis by obtaining wound fluid from all participants.</AbstractText A total of 32 individuals with chronic wounds participated in the study. Correlation analysis indicated pain severity was positively and significantly related to pain interference, McGill Pain Questionnaire scores, neuropathic pain and matrix metalloproteinase levels. Logistic regression was used to determine the predictors for high or low perceived stress. The only significant variable that contributed to the stress levels was BPI-I. Results suggested that participants who experienced higher levels of pain interference also had an increased odds to report high level of stress by 1.6 times controlling for all other factor in the model.</AbstractText Pain is a complex biopsychosocial phenomenon affecting quality of life in people with chronic wounds. Results of this study identified a significant relationship between pain, stress and wound healing.</AbstractText
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Impact of contrast-enhanced CT in the dosimetry of SBRT for liver metastases treated with MR-Linac. To investigate the impact of using contrast-enhanced computed tomography (CHCT) in the dosimetry of stereotactic body radiation therapy (SBRT) for liver metastases treated with MR-Linac.</AbstractText A retrospective study was conducted on 21 liver cancer patients treated with SBRT (50 Gy in 5 fractions) using a 1.5 Tesla Unity MR-Linac. The clinical treatment plans optimised on plain computed tomography (pCT) were used as reference. The electronic density (ED) of regions of interest (ROIs) including the liver, duodenum, esophagus, spinal cord, heart, ribs, and lungs, from pCT and CHCT, was analysed. The average ED of each ROI from CHCT was used to generate synthetic CT (sCT) images by assigning the average ED value from the CHCT to the pCT. Clinical plans were recalculated on sCT images. Dosimetric comparisons between the original treatment plan (TP<sub Significant ED differences (p < 0.05) were observed in the liver, great vessels, heart, lungs, and spinal cord between CHCT and pCT, with the lungs showing the largest differences (average deviation of 11.73% and 12.15% for the left and right lung, respectively). The target volume covered by the prescribed dose (V<sub The findings suggest that the use of CHCT in the SBRT workflow for liver metastases may result in minor target volume overdosage, indicating its potential for adoption in clinical settings. However, its use should be further explored in a broader context and tied to personalized treatment approaches.</AbstractText
|
Functional lung imaging using novel and emerging MRI techniques. Respiratory diseases are leading causes of death and disability in the world. While early diagnosis is key, this has proven difficult due to the lack of sensitive and non-invasive tools. Computed tomography is regarded as the gold standard for structural lung imaging but lacks functional information and involves significant radiation exposure. Lung magnetic resonance imaging (MRI) has historically been challenging due to its short T2 and low proton density. Hyperpolarised gas MRI is an emerging technique that is able to overcome these difficulties, permitting the functional and microstructural evaluation of the lung. Other novel imaging techniques such as fluorinated gas MRI, oxygen-enhanced MRI, Fourier decomposition MRI and phase-resolved functional lung imaging can also be used to interrogate lung function though they are currently at varying stages of development. This article provides a clinically focused review of these contrast and non-contrast MR imaging techniques and their current applications in lung disease.</AbstractText
|
Exploring the effect of wound related pain on psychological stress, inflammatory response, and wound healing. The relationship between pain and poor healing is intricate, potentially mediated by psychological stress and aberrations in inflammatory response. The purpose of this study was to examine the biopsychosocial model of pain by assessing the relationships between pain, stress, inflammation and healing in people with chronic wounds.</AbstractText This was a 4-week prospective observational study to explore the relationship of pain, stress, inflammation and wound healing in a convenience sample of patients with chronic wounds in a chronic care hospital in Canada.</AbstractText Only subjects over 18 with chronic wounds were recruited into the study. Chronic wounds were defined by the duration of wounds for more than 4 weeks of various aetiologies including wounds caused by pressure injuries, venous disease, arterial insufficiency, surgery or trauma and diabetic neuropathy. Participants were evaluated for pain by responding to the Brief Pain Inventory-Short Form, the McGill Pain Questionnaire-Short Form and the Leeds Assessment of Neuropathic Symptoms and Signs scale. Stress was measured by the Perceived Stress Scale (PSS). All wounds were assessed with the Pressure Ulcer Scale for Healing tool. The levels of matrix metalloproteinases were analysis by obtaining wound fluid from all participants.</AbstractText A total of 32 individuals with chronic wounds participated in the study. Correlation analysis indicated pain severity was positively and significantly related to pain interference, McGill Pain Questionnaire scores, neuropathic pain and matrix metalloproteinase levels. Logistic regression was used to determine the predictors for high or low perceived stress. The only significant variable that contributed to the stress levels was BPI-I. Results suggested that participants who experienced higher levels of pain interference also had an increased odds to report high level of stress by 1.6 times controlling for all other factor in the model.</AbstractText Pain is a complex biopsychosocial phenomenon affecting quality of life in people with chronic wounds. Results of this study identified a significant relationship between pain, stress and wound healing.</AbstractText
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40120474
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30978232
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38954650
|
Diagnostic performance of abbreviated non-contrast MRI for liver metastases in patients with newly diagnosed breast cancer.
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Reduction of procedure times in routine clinical practice with Compressed SENSE magnetic resonance imaging technique.
|
Kinked Again! From Congenital Brachial Plexus Palsy to Adult Neurogenic Thoracic Outlet Syndrome: A Case Report.
|
To compare the diagnostic performance of non-contrast abbreviated liver MRI (abMRI) and standard MRI (sMRI) with gadoxetic acid enhancement in the detection of liver metastasis during the initial workup for patients with breast cancer.</AbstractText Of 7621 patients diagnosed with breast cancer who underwent abdominopelvic CT for their initial staging, 222 underwent sMRI between January 2016 and June 2019 to evaluate and/or characterize CT-indeterminate liver lesions. The abMRI protocol included diffusion-weighted images, apparent diffusion coefficient maps, and T2-weighted fat-suppression images, while the reference standard was histopathology or composite imaging follow-up. Two radiologists utilized a five-point scale to determine the probability of malignancy for each lesion. The per-patient diagnostic parameters were compared using generalized estimating equation and chi-square test.</AbstractText A total of 222 female patients (age, 49.8 ± 10.4 years) including 17 with metastases (7.7 %) were included in the present analysis. When defining scores ≥4 as metastasis, there were no significant differences in the per-patient sensitivities (82.4 % vs. 82.4 %; p > 0.99), specificities (97.6 % vs. 98.1 %; p = 0.61), positive predictive values (73.7 % vs. 77.8 %; p = 0.63), negative predictive values (98.5 % vs. 98.5 %; p = 0.99), or accuracies (96.4 % vs. 96.9 %; p = 0.99) between the abMRI and sMRI groups, respectively. Additionally, there were no significant differences in the subgroups of patients with subcentimetre and stage II or higher disease.</AbstractText During the patients' initial workup, the diagnostic performance of non-contrast abMRI was comparable to that of sMRI with gadoxetic acid for CT-indeterminate liver lesions.</AbstractText
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Acceleration of MR sequences beyond current parallel imaging techniques is possible with the Compressed SENSE technique that has recently become available for 1.5 and 3 Tesla scanners, for nearly all image contrasts and for 2D and 3D sequences. The impact of this technique on examination timing parameters and MR protocols in a clinical setting was investigated in this retrospective study.</AbstractText A numerical analysis of the examination timing parameters (scan time, exam time, procedure time, interscan delay time, changeover time, nonscan time) based on the MR protocols of 6 different body regions (brain, knee, lumbar spine, breast, shoulder) using MR log files was performed and the total number of examinations acquired from January to April both in 2017 and 2018 on a 1.5 T MR scanner was registered. Percentages, box plots and unpaired two-sided t tests were obtained for statistical evaluation.</AbstractText All examination timing parameters of the six anatomical regions analysed were significantly shortened after implementation of Compressed SENSE. On average, scan times were accelerated by 20.2% (p<0.0001) while procedure times were shortened by 16% (p<0.0001). Considering all anatomical regions and all MR protocols, 27% more examinations were performed over the same 4 month period in 2018 compared to 2017.</AbstractText Compressed SENSE allows for a significant acceleration of MR examinations and a considerable increase in the total number of MR examinations is possible.</AbstractText
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Neurogenic thoracic outlet syndrome is a chronic, focal lesion of the lower trunk of the brachial plexus or of the T1 and C8 anterior primary rami, often arising due to distortion of neural structures by a fibrous congenital band extending from a C7 transverse process or cervical rib. Accordingly, patients present with chronic weakness or atrophy of the hand, most prominently of the thenar eminence, which receives most innervation from the T1 root. We present clinical, electrophysiologic, and imaging findings in a case of neurogenic thoracic outlet syndrome presenting in an adult with a history most suggestive of congenital brachial plexus palsy, another pathology sharing the mechanism of nerve compression or injury within the supracostoclavicular space. The patient had new right thenar eminence atrophy and a lifelong history of medial forearm sensory deficit and she improved after first rib resection. The convergence of two disorders in the same patient arising in different phases of life illustrates how anatomic or structural variation in this space can predispose to lower brachial plexus injury.</AbstractText
|
Diagnostic performance of abbreviated non-contrast MRI for liver metastases in patients with newly diagnosed breast cancer. To compare the diagnostic performance of non-contrast abbreviated liver MRI (abMRI) and standard MRI (sMRI) with gadoxetic acid enhancement in the detection of liver metastasis during the initial workup for patients with breast cancer.</AbstractText Of 7621 patients diagnosed with breast cancer who underwent abdominopelvic CT for their initial staging, 222 underwent sMRI between January 2016 and June 2019 to evaluate and/or characterize CT-indeterminate liver lesions. The abMRI protocol included diffusion-weighted images, apparent diffusion coefficient maps, and T2-weighted fat-suppression images, while the reference standard was histopathology or composite imaging follow-up. Two radiologists utilized a five-point scale to determine the probability of malignancy for each lesion. The per-patient diagnostic parameters were compared using generalized estimating equation and chi-square test.</AbstractText A total of 222 female patients (age, 49.8 ± 10.4 years) including 17 with metastases (7.7 %) were included in the present analysis. When defining scores ≥4 as metastasis, there were no significant differences in the per-patient sensitivities (82.4 % vs. 82.4 %; p > 0.99), specificities (97.6 % vs. 98.1 %; p = 0.61), positive predictive values (73.7 % vs. 77.8 %; p = 0.63), negative predictive values (98.5 % vs. 98.5 %; p = 0.99), or accuracies (96.4 % vs. 96.9 %; p = 0.99) between the abMRI and sMRI groups, respectively. Additionally, there were no significant differences in the subgroups of patients with subcentimetre and stage II or higher disease.</AbstractText During the patients' initial workup, the diagnostic performance of non-contrast abMRI was comparable to that of sMRI with gadoxetic acid for CT-indeterminate liver lesions.</AbstractText
|
Reduction of procedure times in routine clinical practice with Compressed SENSE magnetic resonance imaging technique. Acceleration of MR sequences beyond current parallel imaging techniques is possible with the Compressed SENSE technique that has recently become available for 1.5 and 3 Tesla scanners, for nearly all image contrasts and for 2D and 3D sequences. The impact of this technique on examination timing parameters and MR protocols in a clinical setting was investigated in this retrospective study.</AbstractText A numerical analysis of the examination timing parameters (scan time, exam time, procedure time, interscan delay time, changeover time, nonscan time) based on the MR protocols of 6 different body regions (brain, knee, lumbar spine, breast, shoulder) using MR log files was performed and the total number of examinations acquired from January to April both in 2017 and 2018 on a 1.5 T MR scanner was registered. Percentages, box plots and unpaired two-sided t tests were obtained for statistical evaluation.</AbstractText All examination timing parameters of the six anatomical regions analysed were significantly shortened after implementation of Compressed SENSE. On average, scan times were accelerated by 20.2% (p<0.0001) while procedure times were shortened by 16% (p<0.0001). Considering all anatomical regions and all MR protocols, 27% more examinations were performed over the same 4 month period in 2018 compared to 2017.</AbstractText Compressed SENSE allows for a significant acceleration of MR examinations and a considerable increase in the total number of MR examinations is possible.</AbstractText
|
Kinked Again! From Congenital Brachial Plexus Palsy to Adult Neurogenic Thoracic Outlet Syndrome: A Case Report. Neurogenic thoracic outlet syndrome is a chronic, focal lesion of the lower trunk of the brachial plexus or of the T1 and C8 anterior primary rami, often arising due to distortion of neural structures by a fibrous congenital band extending from a C7 transverse process or cervical rib. Accordingly, patients present with chronic weakness or atrophy of the hand, most prominently of the thenar eminence, which receives most innervation from the T1 root. We present clinical, electrophysiologic, and imaging findings in a case of neurogenic thoracic outlet syndrome presenting in an adult with a history most suggestive of congenital brachial plexus palsy, another pathology sharing the mechanism of nerve compression or injury within the supracostoclavicular space. The patient had new right thenar eminence atrophy and a lifelong history of medial forearm sensory deficit and she improved after first rib resection. The convergence of two disorders in the same patient arising in different phases of life illustrates how anatomic or structural variation in this space can predispose to lower brachial plexus injury.</AbstractText
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37116591
|
34275486
|
36950194
|
Respiratory-Correlated 4-Dimensional Magnetic Resonance Fingerprinting for Liver Cancer Radiation Therapy Motion Management.
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Free-breathing non-contrast flow-independent cardiovascular magnetic resonance angiography using cardiac gated, magnetization-prepared 3D Dixon method: assessment of thoracic vasculature in congenital heart disease.
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Reduced coupling between offline neural replay events and default mode network activation in schizophrenia.
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The objective of this study was to develop a respiratory-correlated (RC) 4-dimensional (4D) imaging technique based on magnetic resonance fingerprinting (MRF) (RC-4DMRF) for liver tumor motion management in radiation therapy.</AbstractText Thirteen patients with liver cancer were prospectively enrolled in this study. k-space MRF signals of the liver were acquired during free-breathing using the fast acquisition with steady-state precession sequence on a 3T scanner. The signals were binned into 8 respiratory phases based on respiratory surrogates, and interphase displacement vector fields were estimated using a phase-specific low-rank optimization method. Hereafter, the tissue property maps, including T1 and T2 relaxation times, and proton density, were reconstructed using a pyramid motion-compensated method that alternatively optimized interphase displacement vector fields and subspace images. To evaluate the efficacy of RC-4DMRF, amplitude motion differences and Pearson correlation coefficients were determined to assess measurement agreement in tumor motion between RC-4DMRF and cine magnetic resonance imaging (MRI); mean absolute percentage errors of the RC-4DMRF-derived tissue maps were calculated to reveal tissue quantification accuracy using digital human phantom; and tumor-to-liver contrast-to-noise ratio of RC-4DMRF images was compared with that of planning CT and contrast-enhanced MRI (CE-MRI) images. A paired Student t test was used for statistical significance analysis with a P value threshold of .05.</AbstractText RC-4DMRF achieved excellent agreement in motion measurement with cine MRI, yielding the mean (± standard deviation) Pearson correlation coefficients of 0.95 ± 0.05 and 0.93 ± 0.09 and amplitude motion differences of 1.48 ± 1.06 mm and 0.81 ± 0.64 mm in the superior-inferior and anterior-posterior directions, respectively. Moreover, RC-4DMRF achieved high accuracy in tissue property quantification, with mean absolute percentage errors of 8.8%, 9.6%, and 5.0% for T1, T2, and proton density, respectively. Notably, the tumor contrast-to-noise ratio in RC-4DMRI-derived T1 maps (6.41 ± 3.37) was found to be the highest among all tissue property maps, approximately equal to that of CE-MRI (6.96 ± 1.01, P = .862), and substantially higher than that of planning CT (2.91 ± 1.97, P = .048).</AbstractText RC-4DMRF demonstrated high accuracy in respiratory motion measurement and tissue properties quantification, potentially facilitating tumor motion management in liver radiation therapy.</AbstractText
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To evaluate a non-contrast respiratory- and electrocardiogram-gated 3D cardiovascular magnetic resonance angiography (CMRA) based on magnetization-prepared Dixon method (relaxation-enhanced angiography without contrast and triggering, REACT) for the assessment of the thoracic vasculature in congenital heart disease (CHD) patients.</AbstractText 70 patients with CHD (mean 28 years, range: 10-65 years) were retrospectively identified in this single-center study. REACT-CMRA was applied with respiratory- and cardiac-gating. Image quality (IQ) of REACT-CMRA was compared to standard non-gated multi-phase first-pass-CMRA and respiratory- and electrocardiogram-gated steady-state-CMRA. IQ of different vessels of interest (ascending aorta, left pulmonary artery, left superior pulmonary vein, right coronary ostium, coronary sinus) was independently assessed by two readers on a five-point Likert scale. Measurements of vessel diameters were performed in predefined anatomic landmarks (ascending aorta, left pulmonary artery, left superior pulmonary vein). Both readers assessed artifacts and vascular abnormalities. Friedman test, chi-squared test, and Bland-Altman method were used for statistical analysis.</AbstractText Overall IQ score of REACT-CMRA was higher compared to first-pass-CMRA (3.5 ± 0.4 vs. 2.7 ± 0.4, P < 0.001) and did not differ from steady-state-CMRA (3.5 ± 0.4 vs. 3.5 ± 0.6, P = 0.99). Non-diagnostic IQ of the defined vessels of interest was observed less frequently on REACT-CMRA (1.7 %) compared to steady-state- (4.3 %, P = 0.046) or first-pass-CMRA (20.9 %, P < 0.001). Close agreements in vessel diameter measurements were observed between REACT-CMRA and steady-state-CMRA (e.g. ascending aorta, bias: 0.38 ± 1.0 mm, 95 % limits of agreement (LOA): - 1.62-2.38 mm). REACT-CMRA showed high intra- (bias: 0.04 ± 1.0 mm, 95 % LOA: - 1.9-2.0 mm) and interobserver (bias: 0.20 ± 1.1 mm, 95 % LOA: - 2.0-2.4 mm) agreements regarding vessel diameter measurements. Fat-water separation artifacts were observed in 11/70 (16 %) patients on REACT-CMRA but did not limit diagnostic utility. Six vascular abnormalities were detected on REACT-CMRA that were not seen on standard contrast-enhanced CMRA.</AbstractText Non-contrast-enhanced cardiac-gated REACT-CMRA offers a high diagnostic quality for assessment of the thoracic vasculature in CHD patients.</AbstractText
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Schizophrenia is characterized by an abnormal resting state and default mode network brain activity. However, despite intense study, the mechanisms linking default mode network dynamics to neural computation remain elusive. During rest, sequential hippocampal reactivations, known as 'replay', are played out within default mode network activation windows, highlighting a potential role of replay-default mode network coupling in memory consolidation and model-based mental simulation. Here, we test a hypothesis of reduced replay-default mode network coupling in schizophrenia, using magnetoencephalography and a non-spatial sequence learning task designed to elicit off-task (i.e. resting state) neural replay. Participants with a diagnosis of schizophrenia (<i
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Respiratory-Correlated 4-Dimensional Magnetic Resonance Fingerprinting for Liver Cancer Radiation Therapy Motion Management. The objective of this study was to develop a respiratory-correlated (RC) 4-dimensional (4D) imaging technique based on magnetic resonance fingerprinting (MRF) (RC-4DMRF) for liver tumor motion management in radiation therapy.</AbstractText Thirteen patients with liver cancer were prospectively enrolled in this study. k-space MRF signals of the liver were acquired during free-breathing using the fast acquisition with steady-state precession sequence on a 3T scanner. The signals were binned into 8 respiratory phases based on respiratory surrogates, and interphase displacement vector fields were estimated using a phase-specific low-rank optimization method. Hereafter, the tissue property maps, including T1 and T2 relaxation times, and proton density, were reconstructed using a pyramid motion-compensated method that alternatively optimized interphase displacement vector fields and subspace images. To evaluate the efficacy of RC-4DMRF, amplitude motion differences and Pearson correlation coefficients were determined to assess measurement agreement in tumor motion between RC-4DMRF and cine magnetic resonance imaging (MRI); mean absolute percentage errors of the RC-4DMRF-derived tissue maps were calculated to reveal tissue quantification accuracy using digital human phantom; and tumor-to-liver contrast-to-noise ratio of RC-4DMRF images was compared with that of planning CT and contrast-enhanced MRI (CE-MRI) images. A paired Student t test was used for statistical significance analysis with a P value threshold of .05.</AbstractText RC-4DMRF achieved excellent agreement in motion measurement with cine MRI, yielding the mean (± standard deviation) Pearson correlation coefficients of 0.95 ± 0.05 and 0.93 ± 0.09 and amplitude motion differences of 1.48 ± 1.06 mm and 0.81 ± 0.64 mm in the superior-inferior and anterior-posterior directions, respectively. Moreover, RC-4DMRF achieved high accuracy in tissue property quantification, with mean absolute percentage errors of 8.8%, 9.6%, and 5.0% for T1, T2, and proton density, respectively. Notably, the tumor contrast-to-noise ratio in RC-4DMRI-derived T1 maps (6.41 ± 3.37) was found to be the highest among all tissue property maps, approximately equal to that of CE-MRI (6.96 ± 1.01, P = .862), and substantially higher than that of planning CT (2.91 ± 1.97, P = .048).</AbstractText RC-4DMRF demonstrated high accuracy in respiratory motion measurement and tissue properties quantification, potentially facilitating tumor motion management in liver radiation therapy.</AbstractText
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Free-breathing non-contrast flow-independent cardiovascular magnetic resonance angiography using cardiac gated, magnetization-prepared 3D Dixon method: assessment of thoracic vasculature in congenital heart disease. To evaluate a non-contrast respiratory- and electrocardiogram-gated 3D cardiovascular magnetic resonance angiography (CMRA) based on magnetization-prepared Dixon method (relaxation-enhanced angiography without contrast and triggering, REACT) for the assessment of the thoracic vasculature in congenital heart disease (CHD) patients.</AbstractText 70 patients with CHD (mean 28 years, range: 10-65 years) were retrospectively identified in this single-center study. REACT-CMRA was applied with respiratory- and cardiac-gating. Image quality (IQ) of REACT-CMRA was compared to standard non-gated multi-phase first-pass-CMRA and respiratory- and electrocardiogram-gated steady-state-CMRA. IQ of different vessels of interest (ascending aorta, left pulmonary artery, left superior pulmonary vein, right coronary ostium, coronary sinus) was independently assessed by two readers on a five-point Likert scale. Measurements of vessel diameters were performed in predefined anatomic landmarks (ascending aorta, left pulmonary artery, left superior pulmonary vein). Both readers assessed artifacts and vascular abnormalities. Friedman test, chi-squared test, and Bland-Altman method were used for statistical analysis.</AbstractText Overall IQ score of REACT-CMRA was higher compared to first-pass-CMRA (3.5 ± 0.4 vs. 2.7 ± 0.4, P < 0.001) and did not differ from steady-state-CMRA (3.5 ± 0.4 vs. 3.5 ± 0.6, P = 0.99). Non-diagnostic IQ of the defined vessels of interest was observed less frequently on REACT-CMRA (1.7 %) compared to steady-state- (4.3 %, P = 0.046) or first-pass-CMRA (20.9 %, P < 0.001). Close agreements in vessel diameter measurements were observed between REACT-CMRA and steady-state-CMRA (e.g. ascending aorta, bias: 0.38 ± 1.0 mm, 95 % limits of agreement (LOA): - 1.62-2.38 mm). REACT-CMRA showed high intra- (bias: 0.04 ± 1.0 mm, 95 % LOA: - 1.9-2.0 mm) and interobserver (bias: 0.20 ± 1.1 mm, 95 % LOA: - 2.0-2.4 mm) agreements regarding vessel diameter measurements. Fat-water separation artifacts were observed in 11/70 (16 %) patients on REACT-CMRA but did not limit diagnostic utility. Six vascular abnormalities were detected on REACT-CMRA that were not seen on standard contrast-enhanced CMRA.</AbstractText Non-contrast-enhanced cardiac-gated REACT-CMRA offers a high diagnostic quality for assessment of the thoracic vasculature in CHD patients.</AbstractText
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Reduced coupling between offline neural replay events and default mode network activation in schizophrenia. Schizophrenia is characterized by an abnormal resting state and default mode network brain activity. However, despite intense study, the mechanisms linking default mode network dynamics to neural computation remain elusive. During rest, sequential hippocampal reactivations, known as 'replay', are played out within default mode network activation windows, highlighting a potential role of replay-default mode network coupling in memory consolidation and model-based mental simulation. Here, we test a hypothesis of reduced replay-default mode network coupling in schizophrenia, using magnetoencephalography and a non-spatial sequence learning task designed to elicit off-task (i.e. resting state) neural replay. Participants with a diagnosis of schizophrenia (<i
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35024534
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35649366
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33829065
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Directed functional and structural connectivity in a large-scale model for the mouse cortex.
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Sequential transmission of task-relevant information in cortical neuronal networks.
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Determination of Potential Therapeutic Targets and Prognostic Markers of Ovarian Cancer by Bioinformatics Analysis.
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Inferring the structural connectivity from electrophysiological measurements is a fundamental challenge in systems neuroscience. Directed functional connectivity measures, such as the generalized partial directed coherence (GPDC), provide estimates of the causal influence between areas. However, the relation between causality estimates and structural connectivity is still not clear. We analyzed this problem by evaluating the effectiveness of GPDC to estimate the connectivity of a ground-truth, data-constrained computational model of a large-scale network model of the mouse cortex. The model contains 19 cortical areas composed of spiking neurons, with areas connected by long-range projections with weights obtained from a tract-tracing cortical connectome. We show that GPDC values provide a reasonable estimate of structural connectivity, with an average Pearson correlation over simulations of 0.74. Moreover, even in a typical electrophysiological recording scenario containing five areas, the mean correlation was above 0.6. These results suggest that it may be possible to empirically estimate structural connectivity from functional connectivity even when detailed whole-brain recordings are not achievable.</AbstractText
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Cortical processing of task-relevant information enables recognition of behaviorally meaningful sensory events. It is unclear how task-related information is represented within cortical networks by the activity of individual neurons and their functional interactions. Here, we use two-photon imaging to record neuronal activity from the primary auditory cortex of mice during a pure-tone discrimination task. We find that a subset of neurons transiently encode sensory information used to inform behavioral choice. Using Granger causality analysis, we show that these neurons form functional networks in which information transmits sequentially. Network structures differ for target versus non-target tones, encode behavioral choice, and differ between correct versus incorrect behavioral choices. Correct behavioral choices are associated with shorter communication timescales, larger functional correlations, and greater information redundancy. In summary, specialized neurons in primary auditory cortex integrate task-related information and form functional networks whose structures encode both sensory input and behavioral choice.</AbstractText
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This study is to study the expression of CXCRs in ovarian cancer tissues and their value in prognosis. The expressions of CXCR1-CXCR7 mRNA between ovarian tumor tissues and normal tissues and in different pathological types of ovarian tumor tissues were compared by ONCOMINE online tool. The relationship between the expression of CXCRs and clinical pathological staging was studied by GEPIA. Kaplan-Meier plotter online tool was used to analyze prognosis. Finally, GO and KEGG analyses and protein interaction network analysis were performed for CXCRs by the DAVID software to predict their function, and cBioPortal was used to identify the key functional genes. The expression of CXCR3/4/7 mRNA in ovarian cancer tissues was higher than that in normal ovarian tissues, and the expression of CXCR4 was the highest (fold change = 306.413, <i
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Directed functional and structural connectivity in a large-scale model for the mouse cortex. Inferring the structural connectivity from electrophysiological measurements is a fundamental challenge in systems neuroscience. Directed functional connectivity measures, such as the generalized partial directed coherence (GPDC), provide estimates of the causal influence between areas. However, the relation between causality estimates and structural connectivity is still not clear. We analyzed this problem by evaluating the effectiveness of GPDC to estimate the connectivity of a ground-truth, data-constrained computational model of a large-scale network model of the mouse cortex. The model contains 19 cortical areas composed of spiking neurons, with areas connected by long-range projections with weights obtained from a tract-tracing cortical connectome. We show that GPDC values provide a reasonable estimate of structural connectivity, with an average Pearson correlation over simulations of 0.74. Moreover, even in a typical electrophysiological recording scenario containing five areas, the mean correlation was above 0.6. These results suggest that it may be possible to empirically estimate structural connectivity from functional connectivity even when detailed whole-brain recordings are not achievable.</AbstractText
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Sequential transmission of task-relevant information in cortical neuronal networks. Cortical processing of task-relevant information enables recognition of behaviorally meaningful sensory events. It is unclear how task-related information is represented within cortical networks by the activity of individual neurons and their functional interactions. Here, we use two-photon imaging to record neuronal activity from the primary auditory cortex of mice during a pure-tone discrimination task. We find that a subset of neurons transiently encode sensory information used to inform behavioral choice. Using Granger causality analysis, we show that these neurons form functional networks in which information transmits sequentially. Network structures differ for target versus non-target tones, encode behavioral choice, and differ between correct versus incorrect behavioral choices. Correct behavioral choices are associated with shorter communication timescales, larger functional correlations, and greater information redundancy. In summary, specialized neurons in primary auditory cortex integrate task-related information and form functional networks whose structures encode both sensory input and behavioral choice.</AbstractText
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Determination of Potential Therapeutic Targets and Prognostic Markers of Ovarian Cancer by Bioinformatics Analysis. This study is to study the expression of CXCRs in ovarian cancer tissues and their value in prognosis. The expressions of CXCR1-CXCR7 mRNA between ovarian tumor tissues and normal tissues and in different pathological types of ovarian tumor tissues were compared by ONCOMINE online tool. The relationship between the expression of CXCRs and clinical pathological staging was studied by GEPIA. Kaplan-Meier plotter online tool was used to analyze prognosis. Finally, GO and KEGG analyses and protein interaction network analysis were performed for CXCRs by the DAVID software to predict their function, and cBioPortal was used to identify the key functional genes. The expression of CXCR3/4/7 mRNA in ovarian cancer tissues was higher than that in normal ovarian tissues, and the expression of CXCR4 was the highest (fold change = 306.413, <i
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37308745
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33253827
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36949854
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Right-lateralized sleep spindles are associated with neutral over emotional bias in picture recognition: An overnight study.
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The association between sleep-wake ratio and overnight picture recognition is moderated by BDNF genotype.
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The role of Substance P in the defense line of the respiratory tract and neurological manifestations post COVID-19 infection.
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Sleep is especially important for emotional memories, although the mechanisms for prioritizing emotional content are insufficiently known. As during waking, emotional processing during sleep may be hemispherically asymmetric; right-lateralized rapid-eye movement (REM) sleep theta (~4-7 Hz) is reportedly associated with emotional memory retention. No research exists on lateralized non-REM sleep oscillations. However, sleep spindles, especially when coupled with slow oscillations (SOs), facilitate off-line memory consolidation.Our primary goal was to examine how the lateralization (right-to-left contrast) of REM theta, sleep spindles, and SO-spindle coupling is associated with overnight recognition memory in a task consisting of neutral and emotionally aversive pictures. Thirty-two healthy adults encoded 150 target pictures before overnight sleep. The recognition of target pictures among foils (discriminability, d') was tested immediately, 12 hours, and 24 hours after encoding.Recognition discriminability between targets and foils was similar for neutral and emotional pictures in immediate and 12-h retrievals. After 24 hours, emotional pictures were less accurately discriminated (p < 0.001). Emotional difference at 24-h retrieval was associated with right-to-left contrast in frontal fast spindle density (p < 0.001). The lateralization of SO-spindle coupling was associated with higher neutral versus emotional difference across all retrievals (p = 0.004).Our findings contribute to a largely unstudied area in sleep-related memory research. Hemispheric asymmetry in non-REM sleep oscillations may contribute to how neutral versus emotional information is processed. This is presumably underlain by both mechanistic offline memory consolidation and a trait-like cognitive/affective bias that influences memory encoding and retrieval. Methodological choices and participants' affective traits are likely involved.</AbstractText
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A wealth of studies supports the role of sleep in memory performance. Experimentally controlled studies indicate that prolonged wake after memory encoding is detrimental for memory outcome whereas sleep protects from wake-time interference and promotes memory consolidation. We examined how the natural distribution of wake and sleep between encoding and retrieval associated with overnight picture recognition accuracy among 161 adolescents following their typical sleep schedule with an in-home polysomnography. The memorized pictures varied in their level of arousal (calm to exciting) and valence (negative to positive). Suspecting genotypic influence on the sensitivity for sleep/wake dynamics, we also assessed if these associations were affected by known gene polymorphisms involved in neural plasticity and sleep homeostasis: brain-derived neurotrophic factor (BDNF) Val66Met and Catechol-O-methyltransferase (COMT) Val158Met. In the whole sample, overnight recognition accuracy was associated with the levels of arousal and valence of the pictures, but not with sleep percentage (i.e. the percentage of time spent asleep between memory encoding and retrieval). While the allelic status of BDNF or COMT did not have any main effect on recognition accuracy, a significant moderation by BDNF Val66Met was found (p = .004): the subgroup homozygous for valine allele showed positive association between sleep percentage and recognition accuracy. This was underlain by detrimental influence of wake, rather than by any memory benefit of sleep. Our results complement the mounting evidence that the relation between sleep and memory performance is moderated by BDNF Val66Met. Further studies are needed to clarify the specific mechanisms.</AbstractText
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Substance P (SP) has been a great interest for scientists due to its unique properties and involvement in various physiological and pathological phenomenon. It took almost a century for the current understanding of this peptide so far. Its role in brain and gut were initially discussed and later on it was widely studied and observed in cardiovascular system, asthma, traumatic brain injury, immune response, vasodilation, behavior, inflammation, arthritis, cancer, airway hyper responsiveness and respiratory disorders. Involvement of SP in sudden perinatal death and COVID-19 has also been discussed which shed light on its vital role in respiratory rhythm regulation and initiation of cytokine storming in COVID-19. This article will provide a comprehensive overview of the researches done to understand the basic functions and involvement of SP in different processes of cell and its association with various diseases. This article describes the historical and scientific journey of SP from its discovery until today, including its future perspectives.</AbstractText
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Right-lateralized sleep spindles are associated with neutral over emotional bias in picture recognition: An overnight study. Sleep is especially important for emotional memories, although the mechanisms for prioritizing emotional content are insufficiently known. As during waking, emotional processing during sleep may be hemispherically asymmetric; right-lateralized rapid-eye movement (REM) sleep theta (~4-7 Hz) is reportedly associated with emotional memory retention. No research exists on lateralized non-REM sleep oscillations. However, sleep spindles, especially when coupled with slow oscillations (SOs), facilitate off-line memory consolidation.Our primary goal was to examine how the lateralization (right-to-left contrast) of REM theta, sleep spindles, and SO-spindle coupling is associated with overnight recognition memory in a task consisting of neutral and emotionally aversive pictures. Thirty-two healthy adults encoded 150 target pictures before overnight sleep. The recognition of target pictures among foils (discriminability, d') was tested immediately, 12 hours, and 24 hours after encoding.Recognition discriminability between targets and foils was similar for neutral and emotional pictures in immediate and 12-h retrievals. After 24 hours, emotional pictures were less accurately discriminated (p < 0.001). Emotional difference at 24-h retrieval was associated with right-to-left contrast in frontal fast spindle density (p < 0.001). The lateralization of SO-spindle coupling was associated with higher neutral versus emotional difference across all retrievals (p = 0.004).Our findings contribute to a largely unstudied area in sleep-related memory research. Hemispheric asymmetry in non-REM sleep oscillations may contribute to how neutral versus emotional information is processed. This is presumably underlain by both mechanistic offline memory consolidation and a trait-like cognitive/affective bias that influences memory encoding and retrieval. Methodological choices and participants' affective traits are likely involved.</AbstractText
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The association between sleep-wake ratio and overnight picture recognition is moderated by BDNF genotype. A wealth of studies supports the role of sleep in memory performance. Experimentally controlled studies indicate that prolonged wake after memory encoding is detrimental for memory outcome whereas sleep protects from wake-time interference and promotes memory consolidation. We examined how the natural distribution of wake and sleep between encoding and retrieval associated with overnight picture recognition accuracy among 161 adolescents following their typical sleep schedule with an in-home polysomnography. The memorized pictures varied in their level of arousal (calm to exciting) and valence (negative to positive). Suspecting genotypic influence on the sensitivity for sleep/wake dynamics, we also assessed if these associations were affected by known gene polymorphisms involved in neural plasticity and sleep homeostasis: brain-derived neurotrophic factor (BDNF) Val66Met and Catechol-O-methyltransferase (COMT) Val158Met. In the whole sample, overnight recognition accuracy was associated with the levels of arousal and valence of the pictures, but not with sleep percentage (i.e. the percentage of time spent asleep between memory encoding and retrieval). While the allelic status of BDNF or COMT did not have any main effect on recognition accuracy, a significant moderation by BDNF Val66Met was found (p = .004): the subgroup homozygous for valine allele showed positive association between sleep percentage and recognition accuracy. This was underlain by detrimental influence of wake, rather than by any memory benefit of sleep. Our results complement the mounting evidence that the relation between sleep and memory performance is moderated by BDNF Val66Met. Further studies are needed to clarify the specific mechanisms.</AbstractText
|
The role of Substance P in the defense line of the respiratory tract and neurological manifestations post COVID-19 infection. Substance P (SP) has been a great interest for scientists due to its unique properties and involvement in various physiological and pathological phenomenon. It took almost a century for the current understanding of this peptide so far. Its role in brain and gut were initially discussed and later on it was widely studied and observed in cardiovascular system, asthma, traumatic brain injury, immune response, vasodilation, behavior, inflammation, arthritis, cancer, airway hyper responsiveness and respiratory disorders. Involvement of SP in sudden perinatal death and COVID-19 has also been discussed which shed light on its vital role in respiratory rhythm regulation and initiation of cytokine storming in COVID-19. This article will provide a comprehensive overview of the researches done to understand the basic functions and involvement of SP in different processes of cell and its association with various diseases. This article describes the historical and scientific journey of SP from its discovery until today, including its future perspectives.</AbstractText
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23602726
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12568964
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23914072
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Functional neuroimaging of inner fields-of-view with 2D-selective RF excitations.
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Determination of cortical bone porosity and pore size distribution using a low field pulsed NMR approach.
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A Solid-State NMR Investigation of MQ Silicone Copolymers.
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Echo-planar imaging is widely used in functional neuroimaging but suffers from its pronounced sensitivity to field inhomogeneities that cause geometric distortions and image blurring which both limit the effective in-plane resolution achievable. In this work, it is shown how inner-field-of-view techniques based on 2D-selective RF excitations (2DRF) can be applied to reduce the field-of-view in the phase-encoding direction without aliasing and increase the in-plane resolution accordingly. Free-induction-decay (FID) EPI and echo-train-shifted (T2*-weighted) and standard (T2-weighted) spin-echo (SE) EPI with in-plane resolutions of up to 0.5×1.0mm(2) (slice thickness 5mm) were acquired at 3T. Unwanted signal contributions of 2DRF side excitations were shifted out of the object (FID-EPI) or of the refocusing plane by tilting the excitation plane (SE-EPI). Brain activation in healthy volunteers was investigated with checkerboard and finger-tapping block-design paradigms. Brain activation could be detected with all sequences and contrasts, most reliably with FID-EPI due to its higher signal amplitude and the longer 2DRF excitation that are more sensitive to magnetic field inhomogeneities. In conclusion, inner-FOV EPI based on 2DRF excitations could help to improve the spatial resolution of fMRI of focal target regions, e.g., for applications in the spinal cord.</AbstractText
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The objective of this study was first to prove the concept of a low field pulsed nuclear magnetic resonance (NMR) process for assessing the cortical porosity and pore size distribution of human bone in vitro, and then to apply the technique to detect age-related changes of bone in these parameters. The Carr-Purcell-Meiboom-Gill NMR spin echo train method is used to determine the porosity, and an inversion NMR spin-spin relaxation (T(2)) spectrum is used to assess the pore size distribution in cortical bone. Using these techniques, cortical porosity and pore size distribution of 19 specimens of human cadaveric bone, ranging from 16 to 89 years of age, were assessed. The NMR results were compared with the histomorphometric data of the same bone samples to verify the efficacy of the NMR approach. Moreover, a coefficient (surface relaxivity) relating the pore size to the T(2) relaxation time was determined empirically for the Haversian canals and the osteocytic lacunae. The results of this study demonstrate that the in vitro NMR approach using T(2) relaxation techniques can directly assess the porosity and pore size distribution (Haversian canals and osteocytic lacunae) in human cortical bone. In addition, this study indicates that the age-related changes in cortical porosity relate predominantly to Haversian canals, whereas the porosity of osteocytic lacunae appears to be independent of age.</AbstractText
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The structure of MQ copolymers of the general chemical formula [(CH<sub
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Functional neuroimaging of inner fields-of-view with 2D-selective RF excitations. Echo-planar imaging is widely used in functional neuroimaging but suffers from its pronounced sensitivity to field inhomogeneities that cause geometric distortions and image blurring which both limit the effective in-plane resolution achievable. In this work, it is shown how inner-field-of-view techniques based on 2D-selective RF excitations (2DRF) can be applied to reduce the field-of-view in the phase-encoding direction without aliasing and increase the in-plane resolution accordingly. Free-induction-decay (FID) EPI and echo-train-shifted (T2*-weighted) and standard (T2-weighted) spin-echo (SE) EPI with in-plane resolutions of up to 0.5×1.0mm(2) (slice thickness 5mm) were acquired at 3T. Unwanted signal contributions of 2DRF side excitations were shifted out of the object (FID-EPI) or of the refocusing plane by tilting the excitation plane (SE-EPI). Brain activation in healthy volunteers was investigated with checkerboard and finger-tapping block-design paradigms. Brain activation could be detected with all sequences and contrasts, most reliably with FID-EPI due to its higher signal amplitude and the longer 2DRF excitation that are more sensitive to magnetic field inhomogeneities. In conclusion, inner-FOV EPI based on 2DRF excitations could help to improve the spatial resolution of fMRI of focal target regions, e.g., for applications in the spinal cord.</AbstractText
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Determination of cortical bone porosity and pore size distribution using a low field pulsed NMR approach. The objective of this study was first to prove the concept of a low field pulsed nuclear magnetic resonance (NMR) process for assessing the cortical porosity and pore size distribution of human bone in vitro, and then to apply the technique to detect age-related changes of bone in these parameters. The Carr-Purcell-Meiboom-Gill NMR spin echo train method is used to determine the porosity, and an inversion NMR spin-spin relaxation (T(2)) spectrum is used to assess the pore size distribution in cortical bone. Using these techniques, cortical porosity and pore size distribution of 19 specimens of human cadaveric bone, ranging from 16 to 89 years of age, were assessed. The NMR results were compared with the histomorphometric data of the same bone samples to verify the efficacy of the NMR approach. Moreover, a coefficient (surface relaxivity) relating the pore size to the T(2) relaxation time was determined empirically for the Haversian canals and the osteocytic lacunae. The results of this study demonstrate that the in vitro NMR approach using T(2) relaxation techniques can directly assess the porosity and pore size distribution (Haversian canals and osteocytic lacunae) in human cortical bone. In addition, this study indicates that the age-related changes in cortical porosity relate predominantly to Haversian canals, whereas the porosity of osteocytic lacunae appears to be independent of age.</AbstractText
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A Solid-State NMR Investigation of MQ Silicone Copolymers. The structure of MQ copolymers of the general chemical formula [(CH<sub
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29118724
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27798379
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28053340
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Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration.
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Changes in Structural Connectivity Following a Cognitive Intervention in Children With Traumatic Brain Injury.
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Population screening and treatment of Helicobacter pylori infection.
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It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal-subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD.</AbstractText
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Structural connectivity analysis based on graph theory and diffusion tensor imaging tractography is a novel method that quantifies the topological characteristics in the brain network. This study aimed to examine structural connectivity changes following the Attention Intervention and Management (AIM) program designed to improve attention and executive function (EF) in children with traumatic brain injury (TBI).</AbstractText Seventeen children with complicated mild to severe TBI (13.66 ± 2.68 years; >12 months postinjury) completed magnetic resonance imaging (MRI) and neurobehavioral measures at time 1, 10 of whom completed AIM and assessment at time 2. Eleven matched healthy comparison (HC) children (13.37 ± 2.08 years) completed MRI and neurobehavioral assessment at both time points, but did not complete AIM. Network characteristics were analyzed to quantify the structural connectivity before and after the intervention.</AbstractText Mixed model analyses showed that small-worldness was significantly higher in the TBI group than the HC group at time 1, and both small-worldness and normalized clustering coefficient decreased significantly at time 2 in the TBI group whereas the HC group remained relatively unchanged. Reductions in mean local efficiency were significantly correlated with improvements in verbal inhibition and both parent- and child-reported EF. Increased normalized characteristic path length was significantly correlated with improved sustained attention.</AbstractText The results provide preliminary evidence suggesting that graph theoretical analysis may be a sensitive tool in pediatric TBI for detecting ( a) abnormalities of structural connectivity in brain network and ( b) structural neuroplasticity associated with neurobehavioral improvement following a short-term intervention for attention and EF.</AbstractText
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Helicobacter pylori is an important human pathogen, associated with a substantial burden from both malignant and non-malignant diseases. The bacterium is classed as a human carcinogen, being strongly linked with gastric cancer, the third most common cause of cancer death worldwide and is also associated with common conditions such as dyspepsia and peptic ulcer. Eradication of H. pylori reduces the incidence of gastric cancer and peptic ulcer, as well as the prevalence and costs of managing dyspepsia. Economic analyses suggest that eradication of H. pylori as a means of controlling gastric cancer is cost-effective in high-risk populations. Even in populations at low risk of gastric cancer, there might be other benefits arising from screening and treatment, owing to the effects on non-malignant upper gastrointestinal diseases. However, public health authorities have been slow to consider the benefits of population-based screening and treatment as a means of reducing the morbidity and mortality associated with the infection. There are also concerns about widespread use of eradication therapy, including antimicrobial resistance and a rise in the prevalence of diseases that are negatively associated with H. pylori, such as GERD, Barrett oesophagus, asthma and obesity. This Review summarizes these issues.</AbstractText
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Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration. It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal-subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD.</AbstractText
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Changes in Structural Connectivity Following a Cognitive Intervention in Children With Traumatic Brain Injury. Structural connectivity analysis based on graph theory and diffusion tensor imaging tractography is a novel method that quantifies the topological characteristics in the brain network. This study aimed to examine structural connectivity changes following the Attention Intervention and Management (AIM) program designed to improve attention and executive function (EF) in children with traumatic brain injury (TBI).</AbstractText Seventeen children with complicated mild to severe TBI (13.66 ± 2.68 years; >12 months postinjury) completed magnetic resonance imaging (MRI) and neurobehavioral measures at time 1, 10 of whom completed AIM and assessment at time 2. Eleven matched healthy comparison (HC) children (13.37 ± 2.08 years) completed MRI and neurobehavioral assessment at both time points, but did not complete AIM. Network characteristics were analyzed to quantify the structural connectivity before and after the intervention.</AbstractText Mixed model analyses showed that small-worldness was significantly higher in the TBI group than the HC group at time 1, and both small-worldness and normalized clustering coefficient decreased significantly at time 2 in the TBI group whereas the HC group remained relatively unchanged. Reductions in mean local efficiency were significantly correlated with improvements in verbal inhibition and both parent- and child-reported EF. Increased normalized characteristic path length was significantly correlated with improved sustained attention.</AbstractText The results provide preliminary evidence suggesting that graph theoretical analysis may be a sensitive tool in pediatric TBI for detecting ( a) abnormalities of structural connectivity in brain network and ( b) structural neuroplasticity associated with neurobehavioral improvement following a short-term intervention for attention and EF.</AbstractText
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Population screening and treatment of Helicobacter pylori infection. Helicobacter pylori is an important human pathogen, associated with a substantial burden from both malignant and non-malignant diseases. The bacterium is classed as a human carcinogen, being strongly linked with gastric cancer, the third most common cause of cancer death worldwide and is also associated with common conditions such as dyspepsia and peptic ulcer. Eradication of H. pylori reduces the incidence of gastric cancer and peptic ulcer, as well as the prevalence and costs of managing dyspepsia. Economic analyses suggest that eradication of H. pylori as a means of controlling gastric cancer is cost-effective in high-risk populations. Even in populations at low risk of gastric cancer, there might be other benefits arising from screening and treatment, owing to the effects on non-malignant upper gastrointestinal diseases. However, public health authorities have been slow to consider the benefits of population-based screening and treatment as a means of reducing the morbidity and mortality associated with the infection. There are also concerns about widespread use of eradication therapy, including antimicrobial resistance and a rise in the prevalence of diseases that are negatively associated with H. pylori, such as GERD, Barrett oesophagus, asthma and obesity. This Review summarizes these issues.</AbstractText
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30741161
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27915117
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30182788
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A causal role for the precuneus in network-wide theta and gamma oscillatory activity during complex memory retrieval.
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From intentions to actions: Neural oscillations encode motor processes through phase, amplitude and phase-amplitude coupling.
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Hypercapnia increases brain viscoelasticity.
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Complex memory of personal events is thought to depend on coordinated reinstatement of cortical representations by the medial temporal lobes (MTL). MTL-cortical theta and gamma coupling is believed to mediate such coordination, but which cortical structures are critical for retrieval and how they influence oscillatory coupling is unclear. We used magnetoencephalography (MEG) combined with continuous theta burst stimulation (cTBS) to (i) clarify the roles of theta and gamma oscillations in network-wide communication during naturalistic memory retrieval, and (ii) understand the causal relationship between cortical network nodes and oscillatory communication. Retrieval was associated with MTL-posterior neocortical theta phase coupling and theta-gamma phase-amplitude coupling relative to a rest period. Precuneus cTBS altered MTL-neocortical communication by modulating theta and gamma oscillatory coupling. These findings provide a mechanistic account for MTL-cortical communication and demonstrate that the precuneus is a critical cortical node of oscillatory activity, coordinating cross-regional interactions that drive remembering.</AbstractText
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Goal-directed motor behavior is associated with changes in patterns of rhythmic neuronal activity across widely distributed brain areas. In particular, movement initiation and execution are mediated by patterns of synchronization and desynchronization that occur concurrently across distinct frequency bands and across multiple motor cortical areas. To date, motor-related local oscillatory modulations have been predominantly examined by quantifying increases or suppressions in spectral power. However, beyond signal power, spectral properties such as phase and phase-amplitude coupling (PAC) have also been shown to carry information with regards to the oscillatory dynamics underlying motor processes. Yet, the distinct functional roles of phase, amplitude and PAC across the planning and execution of goal-directed motor behavior remain largely elusive. Here, we address this question with unprecedented resolution thanks to multi-site intracerebral EEG recordings in human subjects while they performed a delayed motor task. To compare the roles of phase, amplitude and PAC, we monitored intracranial brain signals from 748 sites across six medically intractable epilepsy patients at movement execution, and during the delay period where motor intention is present but execution is withheld. In particular, we used a machine-learning framework to identify the key contributions of various neuronal responses. We found a high degree of overlap between brain network patterns observed during planning and those present during execution. Prominent amplitude increases in the delta (2-4Hz) and high gamma (60-200Hz) bands were observed during both planning and execution. In contrast, motor alpha (8-13Hz) and beta (13-30Hz) power were suppressed during execution, but enhanced during the delay period. Interestingly, single-trial classification revealed that low-frequency phase information, rather than spectral power change, was the most discriminant feature in dissociating action from intention. Additionally, despite providing weaker decoding, PAC features led to statistically significant classification of motor states, particularly in anterior cingulate cortex and premotor brain areas. These results advance our understanding of the distinct and partly overlapping involvement of phase, amplitude and the coupling between them, in the neuronal mechanisms underlying motor intentions and executions.</AbstractText
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Brain function, the brain's metabolic activity, cerebral blood flow (CBF), and intracranial pressure are intimately linked within the tightly autoregulated regime of intracranial physiology in which the role of tissue viscoelasticity remains elusive. We applied multifrequency magnetic resonance elastography (MRE) paired with CBF measurements in 14 healthy subjects exposed to 5-min carbon dioxide-enriched breathing air to induce cerebral vasodilatation by hypercapnia. Stiffness and viscosity as quantified by the magnitude and phase angle of the complex shear modulus, |<i
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A causal role for the precuneus in network-wide theta and gamma oscillatory activity during complex memory retrieval. Complex memory of personal events is thought to depend on coordinated reinstatement of cortical representations by the medial temporal lobes (MTL). MTL-cortical theta and gamma coupling is believed to mediate such coordination, but which cortical structures are critical for retrieval and how they influence oscillatory coupling is unclear. We used magnetoencephalography (MEG) combined with continuous theta burst stimulation (cTBS) to (i) clarify the roles of theta and gamma oscillations in network-wide communication during naturalistic memory retrieval, and (ii) understand the causal relationship between cortical network nodes and oscillatory communication. Retrieval was associated with MTL-posterior neocortical theta phase coupling and theta-gamma phase-amplitude coupling relative to a rest period. Precuneus cTBS altered MTL-neocortical communication by modulating theta and gamma oscillatory coupling. These findings provide a mechanistic account for MTL-cortical communication and demonstrate that the precuneus is a critical cortical node of oscillatory activity, coordinating cross-regional interactions that drive remembering.</AbstractText
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From intentions to actions: Neural oscillations encode motor processes through phase, amplitude and phase-amplitude coupling. Goal-directed motor behavior is associated with changes in patterns of rhythmic neuronal activity across widely distributed brain areas. In particular, movement initiation and execution are mediated by patterns of synchronization and desynchronization that occur concurrently across distinct frequency bands and across multiple motor cortical areas. To date, motor-related local oscillatory modulations have been predominantly examined by quantifying increases or suppressions in spectral power. However, beyond signal power, spectral properties such as phase and phase-amplitude coupling (PAC) have also been shown to carry information with regards to the oscillatory dynamics underlying motor processes. Yet, the distinct functional roles of phase, amplitude and PAC across the planning and execution of goal-directed motor behavior remain largely elusive. Here, we address this question with unprecedented resolution thanks to multi-site intracerebral EEG recordings in human subjects while they performed a delayed motor task. To compare the roles of phase, amplitude and PAC, we monitored intracranial brain signals from 748 sites across six medically intractable epilepsy patients at movement execution, and during the delay period where motor intention is present but execution is withheld. In particular, we used a machine-learning framework to identify the key contributions of various neuronal responses. We found a high degree of overlap between brain network patterns observed during planning and those present during execution. Prominent amplitude increases in the delta (2-4Hz) and high gamma (60-200Hz) bands were observed during both planning and execution. In contrast, motor alpha (8-13Hz) and beta (13-30Hz) power were suppressed during execution, but enhanced during the delay period. Interestingly, single-trial classification revealed that low-frequency phase information, rather than spectral power change, was the most discriminant feature in dissociating action from intention. Additionally, despite providing weaker decoding, PAC features led to statistically significant classification of motor states, particularly in anterior cingulate cortex and premotor brain areas. These results advance our understanding of the distinct and partly overlapping involvement of phase, amplitude and the coupling between them, in the neuronal mechanisms underlying motor intentions and executions.</AbstractText
|
Hypercapnia increases brain viscoelasticity. Brain function, the brain's metabolic activity, cerebral blood flow (CBF), and intracranial pressure are intimately linked within the tightly autoregulated regime of intracranial physiology in which the role of tissue viscoelasticity remains elusive. We applied multifrequency magnetic resonance elastography (MRE) paired with CBF measurements in 14 healthy subjects exposed to 5-min carbon dioxide-enriched breathing air to induce cerebral vasodilatation by hypercapnia. Stiffness and viscosity as quantified by the magnitude and phase angle of the complex shear modulus, |<i
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31896755
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34774087
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32015009
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Microfluidic control over topological states in channel-confined nematic flows.
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Targeted high mean arterial pressure aggravates cerebral hemodynamics after extracorporeal resuscitation in swine.
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RGS Proteins as Critical Regulators of Motor Function and Their Implications in Parkinson's Disease.
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Compared to isotropic liquids, orientational order of nematic liquid crystals makes their rheological properties more involved, and thus requires fine control of the flow parameters to govern the orientational patterns. In microfluidic channels with perpendicular surface alignment, nematics discontinuously transition from perpendicular structure at low flow rates to flow-aligned structure at high flow rates. Here we show how precise tuning of the driving pressure can be used to stabilize and manipulate a previously unresearched topologically protected chiral intermediate state which arises before the homeotropic to flow-aligned transition. We characterize the mechanisms underlying the transition and construct a phenomenological model to describe the critical behaviour and the phase diagram of the observed chiral flow state, and evaluate the effect of a forced symmetry breaking by introduction of a chiral dopant. Finally, we induce transitions on demand through channel geometry, application of laser tweezers, and careful control of the flow rate.</AbstractText
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Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65-75 vs 80-90 mmHg) in a porcine model.</AbstractText Pigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65-75 vs 80-90 mmHg, respectively). Animals were followed during 120-min after ROSC.</AbstractText Six animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC.</AbstractText During early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.</AbstractText
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Parkinson disease (PD) is a devastating, largely nonfamilial, age-related disorder caused by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Release of DA from these neurons into the dorsal striatum is crucial for regulating movement and their loss causes PD. Unfortunately, the mechanisms underlying SNc neurodegeneration remain unclear, and currently there is no cure for PD, only symptomatic treatments. Recently, several regulator of G protein signaling (RGS) proteins have emerged as critical modulators of PD pathogenesis and/or motor dysfunction and dyskinesia: RGSs 4, 6, 9, and 10. Striatal RGS4 has been shown to exacerbate motor symptoms of DA loss by suppressing M<sub
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Microfluidic control over topological states in channel-confined nematic flows. Compared to isotropic liquids, orientational order of nematic liquid crystals makes their rheological properties more involved, and thus requires fine control of the flow parameters to govern the orientational patterns. In microfluidic channels with perpendicular surface alignment, nematics discontinuously transition from perpendicular structure at low flow rates to flow-aligned structure at high flow rates. Here we show how precise tuning of the driving pressure can be used to stabilize and manipulate a previously unresearched topologically protected chiral intermediate state which arises before the homeotropic to flow-aligned transition. We characterize the mechanisms underlying the transition and construct a phenomenological model to describe the critical behaviour and the phase diagram of the observed chiral flow state, and evaluate the effect of a forced symmetry breaking by introduction of a chiral dopant. Finally, we induce transitions on demand through channel geometry, application of laser tweezers, and careful control of the flow rate.</AbstractText
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Targeted high mean arterial pressure aggravates cerebral hemodynamics after extracorporeal resuscitation in swine. Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65-75 vs 80-90 mmHg) in a porcine model.</AbstractText Pigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65-75 vs 80-90 mmHg, respectively). Animals were followed during 120-min after ROSC.</AbstractText Six animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC.</AbstractText During early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.</AbstractText
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RGS Proteins as Critical Regulators of Motor Function and Their Implications in Parkinson's Disease. Parkinson disease (PD) is a devastating, largely nonfamilial, age-related disorder caused by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Release of DA from these neurons into the dorsal striatum is crucial for regulating movement and their loss causes PD. Unfortunately, the mechanisms underlying SNc neurodegeneration remain unclear, and currently there is no cure for PD, only symptomatic treatments. Recently, several regulator of G protein signaling (RGS) proteins have emerged as critical modulators of PD pathogenesis and/or motor dysfunction and dyskinesia: RGSs 4, 6, 9, and 10. Striatal RGS4 has been shown to exacerbate motor symptoms of DA loss by suppressing M<sub
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40093526
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28192769
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40715012
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A Meta-Analysis of the Structural Validity of Original and Brief Versions of the Personality Inventory for DSM-5 in Iran.
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Disorganization at the stage of schizophrenia clinical outcome: Clinical-biological study.
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AD16 Modulates Microglial Activation and Polarization to Mitigate Neuroinflammation in Ischemic Stroke Models Through α7nAChR-ERK-STAT3 Signaling.
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<b
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According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors.</AbstractText We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality. Neuropsychological tests included Wisconsin Card Sorting Test (WCST), Stroop Color-Word test. Neurophysiological examination included registration of P300 wave of the evoked cognitive auditory potentials. Environmental factors related to patient's education, family, surrounding and nicotine use, as well as subjectively significant traumatic events in childhood and adolescence were assessed. Using PCR we detected SNP of genes related to the systems of neurotransmission (COMT, SLC6A4 and DRD2), inflammatory response (IL6, TNF), cellular detoxification (GSTM1, GSTT1), DNA methylation (MTHFR, DNMT3b, DNMT1).</AbstractText Disorganization is associated with early schizophrenia onset and history of psychosis in family, low level of insight and compliance, high risk of committing delicts, distraction errors in WCST, lengthened P300 latency of evoked cognitive auditory potentials, low-functional alleles of genes MTHFR (rs1801133) and DNMT3b (rs2424913), high level of urbanicity and psychotraumatic events at early age.</AbstractText Severe disorganization at the stage of schizophrenia clinical outcome is associated with the set of specific biological and social-psychological characteristics that indicate its epigenetic nature and maladaptive social significance.</AbstractText
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Neuroinflammation constitutes a critical pathological event subsequent to ischemic stroke. AD16, a novel anti-neuroinflammatory compound, has demonstrated efficacy in alleviating neuroinflammation in neonatal rats induced by ischemia-hypoxia. This study aims to elucidate the therapeutic utility and underlying mechanisms of AD16 in an adult ischemic stroke rat model.</AbstractText A rat transient middle cerebral artery occlusion (tMCAO) model was employed. Neurological function was evaluated using the Longa and Garcia JH scores, motor function was assessed through rotary rod and CatWalk gait analysis, and brain injury was examined via TTC and Nissl staining. Molecular docking techniques simulate the binding of a target compound to a potential target. Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were used to detect microglia phenotype, pro-inflammatory factors, and activation of signaling molecules.</AbstractText AD16 treatment improved neural function in tMCAO rats, reduced cerebral infarction volume and brain water content, preserved blood-brain barrier integrity, and inhibited pro-inflammatory cytokines. Molecular docking showed AD16 has high affinity for α7nAChR, TLR4, ERK, and STAT3. AD16 increased α7nAChR, CD206, and p-ERK protein levels, while decreasing CD40, CD68, TLR4, and p-STAT3. These effects were reversed by α-BTX (α7nAChR inhibitor) and U0126 (ERK inhibitor).</AbstractText AD16 may inhibit microglia activation and polarization via the α7nAChR-ERK-STAT3 pathway, thus reducing neuroinflammation from cerebral ischemia and protecting the brain. This study suggests AD16 as a potential treatment for ischemic stroke.</AbstractText
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A Meta-Analysis of the Structural Validity of Original and Brief Versions of the Personality Inventory for DSM-5 in Iran. <b
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Disorganization at the stage of schizophrenia clinical outcome: Clinical-biological study. According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors.</AbstractText We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality. Neuropsychological tests included Wisconsin Card Sorting Test (WCST), Stroop Color-Word test. Neurophysiological examination included registration of P300 wave of the evoked cognitive auditory potentials. Environmental factors related to patient's education, family, surrounding and nicotine use, as well as subjectively significant traumatic events in childhood and adolescence were assessed. Using PCR we detected SNP of genes related to the systems of neurotransmission (COMT, SLC6A4 and DRD2), inflammatory response (IL6, TNF), cellular detoxification (GSTM1, GSTT1), DNA methylation (MTHFR, DNMT3b, DNMT1).</AbstractText Disorganization is associated with early schizophrenia onset and history of psychosis in family, low level of insight and compliance, high risk of committing delicts, distraction errors in WCST, lengthened P300 latency of evoked cognitive auditory potentials, low-functional alleles of genes MTHFR (rs1801133) and DNMT3b (rs2424913), high level of urbanicity and psychotraumatic events at early age.</AbstractText Severe disorganization at the stage of schizophrenia clinical outcome is associated with the set of specific biological and social-psychological characteristics that indicate its epigenetic nature and maladaptive social significance.</AbstractText
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AD16 Modulates Microglial Activation and Polarization to Mitigate Neuroinflammation in Ischemic Stroke Models Through α7nAChR-ERK-STAT3 Signaling. Neuroinflammation constitutes a critical pathological event subsequent to ischemic stroke. AD16, a novel anti-neuroinflammatory compound, has demonstrated efficacy in alleviating neuroinflammation in neonatal rats induced by ischemia-hypoxia. This study aims to elucidate the therapeutic utility and underlying mechanisms of AD16 in an adult ischemic stroke rat model.</AbstractText A rat transient middle cerebral artery occlusion (tMCAO) model was employed. Neurological function was evaluated using the Longa and Garcia JH scores, motor function was assessed through rotary rod and CatWalk gait analysis, and brain injury was examined via TTC and Nissl staining. Molecular docking techniques simulate the binding of a target compound to a potential target. Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were used to detect microglia phenotype, pro-inflammatory factors, and activation of signaling molecules.</AbstractText AD16 treatment improved neural function in tMCAO rats, reduced cerebral infarction volume and brain water content, preserved blood-brain barrier integrity, and inhibited pro-inflammatory cytokines. Molecular docking showed AD16 has high affinity for α7nAChR, TLR4, ERK, and STAT3. AD16 increased α7nAChR, CD206, and p-ERK protein levels, while decreasing CD40, CD68, TLR4, and p-STAT3. These effects were reversed by α-BTX (α7nAChR inhibitor) and U0126 (ERK inhibitor).</AbstractText AD16 may inhibit microglia activation and polarization via the α7nAChR-ERK-STAT3 pathway, thus reducing neuroinflammation from cerebral ischemia and protecting the brain. This study suggests AD16 as a potential treatment for ischemic stroke.</AbstractText
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38794001
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28592282
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39582070
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Exploring the Role of Video Playback Visual Cues in Object Retrieval Tasks.
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The role of virtual reality in improving motor performance as revealed by EEG: a randomized clinical trial.
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Flexible four-port MIMO antenna for 5G NR-FR2 tri-band mmWave application with SAR analysis.
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Searching for objects is a common task in daily life and work. For augmented reality (AR) devices without spatial perception systems, the image of the object's last appearance serves as a common search assistance. Compared to using only images as visual cues, videos capturing the process of object placement can provide procedural guidance, potentially enhancing users' search efficiency. However, complete video playback capturing the entire object placement process as visual cues can be excessively lengthy, requiring users to invest significant viewing time. To explore whether segmented or accelerated video playback can still assist users in object retrieval tasks effectively, we conducted a user study. The results indicated that when video playback is covering the first appearance of the object's destination to the object's final appearance (referred to as the destination appearance, DA) and playing at normal speed, search time and cognitive load were significantly reduced. Subsequently, we designed a second user study to evaluate the performance of video playback compared to image cues in object retrieval tasks. The results showed that combining the DA playback starting point with images of the object's last appearance further reduced search time and cognitive load.</AbstractText
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Many studies have demonstrated the usefulness of repetitive task practice by using robotic-assisted gait training (RAGT) devices, including Lokomat, for the treatment of lower limb paresis. Virtual reality (VR) has proved to be a valuable tool to improve neurorehabilitation training. The aim of our pilot randomized clinical trial was to understand the neurophysiological basis of motor function recovery induced by the association between RAGT (by using Lokomat device) and VR (an animated avatar in a 2D VR) by studying electroencephalographic (EEG) oscillations.</AbstractText Twenty-four patients suffering from a first unilateral ischemic stroke in the chronic phase were randomized into two groups. One group performed 40 sessions of Lokomat with VR (RAGT + VR), whereas the other group underwent Lokomat without VR (RAGT-VR). The outcomes (clinical, kinematic, and EEG) were measured before and after the robotic intervention.</AbstractText As compared to the RAGT-VR group, all the patients of the RAGT + VR group improved in the Rivermead Mobility Index and Tinetti Performance Oriented Mobility Assessment. Moreover, they showed stronger event-related spectral perturbations in the high-γ and β bands and larger fronto-central cortical activations in the affected hemisphere.</AbstractText The robotic-based rehabilitation combined with VR in patients with chronic hemiparesis induced an improvement in gait and balance. EEG data suggest that the use of VR may entrain several brain areas (probably encompassing the mirror neuron system) involved in motor planning and learning, thus leading to an enhanced motor performance.</AbstractText Retrospectively registered in Clinical Trials on 21-11-2016, n. NCT02971371 .</AbstractText
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This paper introduces a compact, triband four-port Multiple Input Multiple Output (MIMO) antenna optimized for mmWave 5G and navigation services. The antenna is built on a Rogers RT Duroid 5880 substrate, with dimensions of 31 × 42 mm² and a thickness of 0.4 mm. It utilizes a 50 Ω microstrip line to feed a stub-type radiating patch, creating a dipole-loop type structure on the substrate's top side, with a full ground plane for narrowband. The antenna is initially designed for 38 GHz but was subsequently modified for triband performance by tapering the edges of the stub shape, enabling it to function across multiple frequency ranges. The tapered edges of the radiating patch enhance resonance across the three bands. To improve isolation and bandwidth, a parasitic element is strategically placed between the MIMO elements, results isolation greater than 30 dB at the 32 GHz and 38 GHz bands. The MIMO elements are mirror images placed adjacent to one another, while the other two elements are arranged 180º apart, ensuring compactness. The proposed antenna operates across three frequency bands: 27.76-28.15 GHz (n261), 32.02-32.46 GHz (part of n260 and n261), and 37.39-38.586 GHz (part of n260), offering enhanced resonance and improved isolation. The parasitic element reduces mutual coupling between adjacent elements, improving diversity parameters such as Envelope Correlation Coefficient (ECC) < 0.0010, Diversity Gain (DG) = 10 dB, Channel Capacity Loss (CCL) = 0.15 bits/sec/Hz, Total Active Reflection Coefficient (TARC) < -10 dB, and Mean Effective Gain (MEG) between - 3 and - 12 dB across all ports. Specific Absorption Rate (SAR) analysis for on-body applications confirms safe levels, with values below 1.6 W/kg at the resonating frequencies. Bending tests also show favourable results within the application bandwidth, further validating the antenna's robustness. These technical improvements make the antenna highly suitable for integration into smart devices, defence navigation systems, mobile phones, and future 5G applications.</AbstractText
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Exploring the Role of Video Playback Visual Cues in Object Retrieval Tasks. Searching for objects is a common task in daily life and work. For augmented reality (AR) devices without spatial perception systems, the image of the object's last appearance serves as a common search assistance. Compared to using only images as visual cues, videos capturing the process of object placement can provide procedural guidance, potentially enhancing users' search efficiency. However, complete video playback capturing the entire object placement process as visual cues can be excessively lengthy, requiring users to invest significant viewing time. To explore whether segmented or accelerated video playback can still assist users in object retrieval tasks effectively, we conducted a user study. The results indicated that when video playback is covering the first appearance of the object's destination to the object's final appearance (referred to as the destination appearance, DA) and playing at normal speed, search time and cognitive load were significantly reduced. Subsequently, we designed a second user study to evaluate the performance of video playback compared to image cues in object retrieval tasks. The results showed that combining the DA playback starting point with images of the object's last appearance further reduced search time and cognitive load.</AbstractText
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The role of virtual reality in improving motor performance as revealed by EEG: a randomized clinical trial. Many studies have demonstrated the usefulness of repetitive task practice by using robotic-assisted gait training (RAGT) devices, including Lokomat, for the treatment of lower limb paresis. Virtual reality (VR) has proved to be a valuable tool to improve neurorehabilitation training. The aim of our pilot randomized clinical trial was to understand the neurophysiological basis of motor function recovery induced by the association between RAGT (by using Lokomat device) and VR (an animated avatar in a 2D VR) by studying electroencephalographic (EEG) oscillations.</AbstractText Twenty-four patients suffering from a first unilateral ischemic stroke in the chronic phase were randomized into two groups. One group performed 40 sessions of Lokomat with VR (RAGT + VR), whereas the other group underwent Lokomat without VR (RAGT-VR). The outcomes (clinical, kinematic, and EEG) were measured before and after the robotic intervention.</AbstractText As compared to the RAGT-VR group, all the patients of the RAGT + VR group improved in the Rivermead Mobility Index and Tinetti Performance Oriented Mobility Assessment. Moreover, they showed stronger event-related spectral perturbations in the high-γ and β bands and larger fronto-central cortical activations in the affected hemisphere.</AbstractText The robotic-based rehabilitation combined with VR in patients with chronic hemiparesis induced an improvement in gait and balance. EEG data suggest that the use of VR may entrain several brain areas (probably encompassing the mirror neuron system) involved in motor planning and learning, thus leading to an enhanced motor performance.</AbstractText Retrospectively registered in Clinical Trials on 21-11-2016, n. NCT02971371 .</AbstractText
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Flexible four-port MIMO antenna for 5G NR-FR2 tri-band mmWave application with SAR analysis. This paper introduces a compact, triband four-port Multiple Input Multiple Output (MIMO) antenna optimized for mmWave 5G and navigation services. The antenna is built on a Rogers RT Duroid 5880 substrate, with dimensions of 31 × 42 mm² and a thickness of 0.4 mm. It utilizes a 50 Ω microstrip line to feed a stub-type radiating patch, creating a dipole-loop type structure on the substrate's top side, with a full ground plane for narrowband. The antenna is initially designed for 38 GHz but was subsequently modified for triband performance by tapering the edges of the stub shape, enabling it to function across multiple frequency ranges. The tapered edges of the radiating patch enhance resonance across the three bands. To improve isolation and bandwidth, a parasitic element is strategically placed between the MIMO elements, results isolation greater than 30 dB at the 32 GHz and 38 GHz bands. The MIMO elements are mirror images placed adjacent to one another, while the other two elements are arranged 180º apart, ensuring compactness. The proposed antenna operates across three frequency bands: 27.76-28.15 GHz (n261), 32.02-32.46 GHz (part of n260 and n261), and 37.39-38.586 GHz (part of n260), offering enhanced resonance and improved isolation. The parasitic element reduces mutual coupling between adjacent elements, improving diversity parameters such as Envelope Correlation Coefficient (ECC) < 0.0010, Diversity Gain (DG) = 10 dB, Channel Capacity Loss (CCL) = 0.15 bits/sec/Hz, Total Active Reflection Coefficient (TARC) < -10 dB, and Mean Effective Gain (MEG) between - 3 and - 12 dB across all ports. Specific Absorption Rate (SAR) analysis for on-body applications confirms safe levels, with values below 1.6 W/kg at the resonating frequencies. Bending tests also show favourable results within the application bandwidth, further validating the antenna's robustness. These technical improvements make the antenna highly suitable for integration into smart devices, defence navigation systems, mobile phones, and future 5G applications.</AbstractText
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28518911
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15750038
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22390643
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SU-E-J-130: Study of the Image Quality Degradation in Phase-Based 4DCT Imaging for Radiation Oncology.
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Changes in upper airway size during tidal breathing in children with obstructive sleep apnea syndrome.
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Atherosclerosis as an inflammatory disease.
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Four-dimensional computed tomography (4DCT) integrated into radiation imaging system is a useful tool for accurate targeting. 4DCT has the ability to minimize breathing related artefacts compared to conventional CT but irregular breathing and large tumour motion may cause inappropriate reconstruction. Our aim is to estimate the image quality degradation of 4DCT and to assess the clinical consequences.</AbstractText The performance of the respiratory gating system of the multi-slice CT-simulator Brilliance Big Bore was evaluated employing one-dimensional moving phantom. The binning algorithm was phased-based. 4DCT scans of the test-phantom were acquired applying periodic motion patterns characterized by amplitude and frequency spanning a clinically range and also irregular waveforms simulating realistic breathing cycles. The internal spherical objects of the moving phantom were contoured using semiautomatic segmentation for evaluating uncertainties in volume delineation and motion amplitude calculation. Motion amplitude was determined by a specially written MATLAB program. Afterwards we investigated the influence of the image distortions on the targeting and the consequences of the related uncertainties on the calculated dose distribution of the tumour and the lungs in a group of five lung-cancer patients.</AbstractText The results obtained with the phantom show that 4DCT imaging is still affected by distortions due to residual motion. The inaccuracies are mainly related to the amplitude (R2=0.99, R2=0.97 for 20 mm-dia sphere and 10 mm-dia sphere, respectively) and to the oscillation frequency (R2=0.87 for 20 mm-dia sphere, R2=0.96 for 10 mm-dia sphere) of simulated respiratory cycle and can cause both underestimation and overestimation of the real tumour motion amplitude with an average difference between real and calculated amplitude of about 10%.</AbstractText The resulting inaccuracies on the internal tumour volume delineated do not have significant clinical consequences on lung doses but they could be important on tumour dose distribution if they imply underestimation of the real tumour motion.</AbstractText
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We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS.</AbstractText Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle.</AbstractText We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively).</AbstractText Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor.</AbstractText
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In many ways, atherosclerosis is a chronic inflammatory disorder and this issue is confirmed by recent investigations of that have focused on inflammation, providing new insight into mechanisms of disease. Several recent studies have addressed the role of chemokines in leukocyte accumulation in atherosclerosis, extending our knowledge and understanding of the complex and cell type-specific functions of chemokines in atherosclerosis. Activated T-lymphocytes within the atherosclerotic vessel wall express the CD40 ligand surface molecule, known to play a major role in several immunological pathways. In addition to activated T-lymphocytes, functional CD40 and CD40L are coexpressed by human vascular endothelial cells, smooth muscle cells and human macrophages in vitro as well as in situ in human atherosclerotic lesions. Recent studies indicate that CD40L activates atheroma-associated cells by promoting the expression of molecules thought to be involved in atherosclerosis, such as adhesion molecules, cytokines, matrix metalloproteinases, and tissue factor. Atherosclerosis starts with an innate immune response involving the recruitment and activation of monocytes macrophages that respond to an excessive accumulation of modified lipids within the arterial wall, followed by an adaptive immune response involving antigen-specific T lymphocytes. Effector T cells recognize modified auto-antigens such as oxidized LDL and heat shock proteins (i.e. HSP-60) that are presented by antigen-presenting cells such as macrophages or dendritic cells. The accumulation of inflammatory cells within the arterial wall leads to local production of chemokines, interleukins and proteases that enhance the influx of monocytes and lymphocytes, thereby promoting the progression of atherosclerotic lesions Recent reports have helped explain some of these questions by pointing to a role of contact dependent interaction between CD40 and CD40 ligand (CD40L, renamed CD154) as a stimulus for atheroma-associated cells. Also Macrophages play important roles in the progression of atherosclerosis by exhibiting unique characteristics under the various stimuli, evolving the plaque instability, thrombus formation and remodeling. Macrophage recruitment by abnormal endothelium over developing atherosclerotic plaques, is aided by endothelial expression of adhesion molecules (ICAM-1, VCAM, ELAM). The knowledge of atherosclerosis as an inflammatory disease offers the opportunity to develop novel therapeutic strategies targeting the inflammatory component of the disease.</AbstractText
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SU-E-J-130: Study of the Image Quality Degradation in Phase-Based 4DCT Imaging for Radiation Oncology. Four-dimensional computed tomography (4DCT) integrated into radiation imaging system is a useful tool for accurate targeting. 4DCT has the ability to minimize breathing related artefacts compared to conventional CT but irregular breathing and large tumour motion may cause inappropriate reconstruction. Our aim is to estimate the image quality degradation of 4DCT and to assess the clinical consequences.</AbstractText The performance of the respiratory gating system of the multi-slice CT-simulator Brilliance Big Bore was evaluated employing one-dimensional moving phantom. The binning algorithm was phased-based. 4DCT scans of the test-phantom were acquired applying periodic motion patterns characterized by amplitude and frequency spanning a clinically range and also irregular waveforms simulating realistic breathing cycles. The internal spherical objects of the moving phantom were contoured using semiautomatic segmentation for evaluating uncertainties in volume delineation and motion amplitude calculation. Motion amplitude was determined by a specially written MATLAB program. Afterwards we investigated the influence of the image distortions on the targeting and the consequences of the related uncertainties on the calculated dose distribution of the tumour and the lungs in a group of five lung-cancer patients.</AbstractText The results obtained with the phantom show that 4DCT imaging is still affected by distortions due to residual motion. The inaccuracies are mainly related to the amplitude (R2=0.99, R2=0.97 for 20 mm-dia sphere and 10 mm-dia sphere, respectively) and to the oscillation frequency (R2=0.87 for 20 mm-dia sphere, R2=0.96 for 10 mm-dia sphere) of simulated respiratory cycle and can cause both underestimation and overestimation of the real tumour motion amplitude with an average difference between real and calculated amplitude of about 10%.</AbstractText The resulting inaccuracies on the internal tumour volume delineated do not have significant clinical consequences on lung doses but they could be important on tumour dose distribution if they imply underestimation of the real tumour motion.</AbstractText
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Changes in upper airway size during tidal breathing in children with obstructive sleep apnea syndrome. We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS.</AbstractText Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle.</AbstractText We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively).</AbstractText Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor.</AbstractText
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Atherosclerosis as an inflammatory disease. In many ways, atherosclerosis is a chronic inflammatory disorder and this issue is confirmed by recent investigations of that have focused on inflammation, providing new insight into mechanisms of disease. Several recent studies have addressed the role of chemokines in leukocyte accumulation in atherosclerosis, extending our knowledge and understanding of the complex and cell type-specific functions of chemokines in atherosclerosis. Activated T-lymphocytes within the atherosclerotic vessel wall express the CD40 ligand surface molecule, known to play a major role in several immunological pathways. In addition to activated T-lymphocytes, functional CD40 and CD40L are coexpressed by human vascular endothelial cells, smooth muscle cells and human macrophages in vitro as well as in situ in human atherosclerotic lesions. Recent studies indicate that CD40L activates atheroma-associated cells by promoting the expression of molecules thought to be involved in atherosclerosis, such as adhesion molecules, cytokines, matrix metalloproteinases, and tissue factor. Atherosclerosis starts with an innate immune response involving the recruitment and activation of monocytes macrophages that respond to an excessive accumulation of modified lipids within the arterial wall, followed by an adaptive immune response involving antigen-specific T lymphocytes. Effector T cells recognize modified auto-antigens such as oxidized LDL and heat shock proteins (i.e. HSP-60) that are presented by antigen-presenting cells such as macrophages or dendritic cells. The accumulation of inflammatory cells within the arterial wall leads to local production of chemokines, interleukins and proteases that enhance the influx of monocytes and lymphocytes, thereby promoting the progression of atherosclerotic lesions Recent reports have helped explain some of these questions by pointing to a role of contact dependent interaction between CD40 and CD40 ligand (CD40L, renamed CD154) as a stimulus for atheroma-associated cells. Also Macrophages play important roles in the progression of atherosclerosis by exhibiting unique characteristics under the various stimuli, evolving the plaque instability, thrombus formation and remodeling. Macrophage recruitment by abnormal endothelium over developing atherosclerotic plaques, is aided by endothelial expression of adhesion molecules (ICAM-1, VCAM, ELAM). The knowledge of atherosclerosis as an inflammatory disease offers the opportunity to develop novel therapeutic strategies targeting the inflammatory component of the disease.</AbstractText
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23919374
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22246803
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23487160
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Evaluation of a subject specific dual-transmit approach for improving B1 field homogeneity in cardiovascular magnetic resonance at 3T.
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Flexible transceiver array for ultrahigh field human MR imaging.
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Complexity and specificity of experimentally-induced expectations in motion perception.
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Radiofrequency (RF) shading artifacts degrade image quality while performing cardiovascular magnetic resonance (CMR) at higher field strengths. In this article, we sought to evaluate the effect of local RF (B1 field) shimming by using a dual-source-transmit RF system for cardiac cine imaging and to systematically evaluate the effect of subject body type on the B1 field with and without local RF shimming.</AbstractText We obtained cardiac images from 37 subjects (including 11 patients) by using dual-transmit 3T CMR. B1 maps with and without subject-specific local RF shimming (exploiting the independent control of transmit amplitude and phase of the 2 RF transmitters) were obtained. Metrics quantifying B1 field homogeneity were calculated and compared with subject body habitus.</AbstractText Local RF shimming across the region encompassed by the heart increased the mean flip angle (μ) in that area (88.5 ± 15.2% vs. 81.2 ± 13.3%; P = 0.0014), reduced the B1 field variation by 42.2 ± 13%, and significantly improved the percentage of voxels closer to μ (39% and 82% more voxels were closer to ± 10% and ± 5% of μ, respectively) when compared with no RF shimming. B1 homogeneity was independent of subject body type (body surface area [BSA], body mass index [BMI] or anterior-posterior/right-left patient width ratio [AP/RL]). Subject specific RF (B1) shimming with a dual-transmit system improved local RF homogeneity across all body types.</AbstractText With or without RF shimming, cardiac B1 field homogeneity does not depend on body type, as characterized by BMI, BSA, and AP/RL. For all body types studied, cardiac B1 field homogeneity was significantly improved by performing local RF shimming with 2 independent RF-transmit channels. This finding indicates the need for subject-specific RF shimming.</AbstractText
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A flexible transceiver array, capable of multiple-purpose imaging applications in vivo at ultrahigh magnetic fields was designed, implemented and tested on a 7 T MR scanner. By alternately placing coil elements with primary and secondary harmonics, improved decoupling among coil elements was accomplished without requiring decoupling circuitry between resonant elements, which is commonly required in high-frequency transceiver arrays to achieve sufficient element-isolation during radiofrequency excitation. This flexible array design is capable of maintaining the required decoupling among resonant elements in different array size and geometry and is scalable in coil size and number of resonant elements (i.e., number of channels), yielding improved filling factors for various body parts with different geometry and size. To investigate design feasibility, flexibility, and array performance, a multichannel, 16-element transceiver array was designed and constructed, and in vivo images of the human head, knee, and hand were acquired using a whole-body 7 T MR system. Seven Tesla parallel imaging with generalized autocalibrating partially parallel acquisitions (GRAPPA) performed using this flexible transceiver array was also presented.</AbstractText
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Our perceptions are fundamentally altered by our expectations, i.e., priors about the world. In previous statistical learning experiments (Chalk, Seitz, & Seriès, 2010), we investigated how such priors are formed by presenting subjects with white low contrast moving dots on a blank screen and using a bimodal distribution of motion directions such that two directions were more frequently presented than the others. We found that human observers quickly and automatically developed expectations for the most frequently presented directions of motion. Here, we examine the specificity of these expectations. Can one learn simultaneously to expect different motion directions for dots of different colors? We interleaved moving dot displays of two different colors, either red or green, with different motion direction distributions. When one distribution was bimodal while the other was uniform, we found that subjects learned a single bimodal prior for the two stimuli. On the contrary, when both distributions were similarly structured, we found evidence for the formation of two distinct priors, which significantly influenced the subjects' behavior when no stimulus was presented. Our results can be modeled using a Bayesian framework and discussed in terms of a suboptimality of the statistical learning process under some conditions.</AbstractText
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Evaluation of a subject specific dual-transmit approach for improving B1 field homogeneity in cardiovascular magnetic resonance at 3T. Radiofrequency (RF) shading artifacts degrade image quality while performing cardiovascular magnetic resonance (CMR) at higher field strengths. In this article, we sought to evaluate the effect of local RF (B1 field) shimming by using a dual-source-transmit RF system for cardiac cine imaging and to systematically evaluate the effect of subject body type on the B1 field with and without local RF shimming.</AbstractText We obtained cardiac images from 37 subjects (including 11 patients) by using dual-transmit 3T CMR. B1 maps with and without subject-specific local RF shimming (exploiting the independent control of transmit amplitude and phase of the 2 RF transmitters) were obtained. Metrics quantifying B1 field homogeneity were calculated and compared with subject body habitus.</AbstractText Local RF shimming across the region encompassed by the heart increased the mean flip angle (μ) in that area (88.5 ± 15.2% vs. 81.2 ± 13.3%; P = 0.0014), reduced the B1 field variation by 42.2 ± 13%, and significantly improved the percentage of voxels closer to μ (39% and 82% more voxels were closer to ± 10% and ± 5% of μ, respectively) when compared with no RF shimming. B1 homogeneity was independent of subject body type (body surface area [BSA], body mass index [BMI] or anterior-posterior/right-left patient width ratio [AP/RL]). Subject specific RF (B1) shimming with a dual-transmit system improved local RF homogeneity across all body types.</AbstractText With or without RF shimming, cardiac B1 field homogeneity does not depend on body type, as characterized by BMI, BSA, and AP/RL. For all body types studied, cardiac B1 field homogeneity was significantly improved by performing local RF shimming with 2 independent RF-transmit channels. This finding indicates the need for subject-specific RF shimming.</AbstractText
|
Flexible transceiver array for ultrahigh field human MR imaging. A flexible transceiver array, capable of multiple-purpose imaging applications in vivo at ultrahigh magnetic fields was designed, implemented and tested on a 7 T MR scanner. By alternately placing coil elements with primary and secondary harmonics, improved decoupling among coil elements was accomplished without requiring decoupling circuitry between resonant elements, which is commonly required in high-frequency transceiver arrays to achieve sufficient element-isolation during radiofrequency excitation. This flexible array design is capable of maintaining the required decoupling among resonant elements in different array size and geometry and is scalable in coil size and number of resonant elements (i.e., number of channels), yielding improved filling factors for various body parts with different geometry and size. To investigate design feasibility, flexibility, and array performance, a multichannel, 16-element transceiver array was designed and constructed, and in vivo images of the human head, knee, and hand were acquired using a whole-body 7 T MR system. Seven Tesla parallel imaging with generalized autocalibrating partially parallel acquisitions (GRAPPA) performed using this flexible transceiver array was also presented.</AbstractText
|
Complexity and specificity of experimentally-induced expectations in motion perception. Our perceptions are fundamentally altered by our expectations, i.e., priors about the world. In previous statistical learning experiments (Chalk, Seitz, & Seriès, 2010), we investigated how such priors are formed by presenting subjects with white low contrast moving dots on a blank screen and using a bimodal distribution of motion directions such that two directions were more frequently presented than the others. We found that human observers quickly and automatically developed expectations for the most frequently presented directions of motion. Here, we examine the specificity of these expectations. Can one learn simultaneously to expect different motion directions for dots of different colors? We interleaved moving dot displays of two different colors, either red or green, with different motion direction distributions. When one distribution was bimodal while the other was uniform, we found that subjects learned a single bimodal prior for the two stimuli. On the contrary, when both distributions were similarly structured, we found evidence for the formation of two distinct priors, which significantly influenced the subjects' behavior when no stimulus was presented. Our results can be modeled using a Bayesian framework and discussed in terms of a suboptimality of the statistical learning process under some conditions.</AbstractText
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39914504
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34552241
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40338709
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Subtype-selective effect and molecular regulation of celastrol and triptolide at human nicotinic acetylcholine receptors.
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Kainate receptor modulation by NETO2.
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Anatomy-Aware Deep Unrolling for Task-Oriented Acceleration of Multi-Contrast MRI.
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Celastrol and triptolide, bioactive compounds isolated from Tripterygium wilfordii Hook F, have demonstrated significant pharmacological effects across various biological pathways, making them subjects of extensive research for potential therapeutic applications. Celastrol and triptolide are known to have therapeutic use in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease through neuroprotective action. Nicotinic acetylcholine receptors (nAChRs) are a subtype of cholinergic receptors and are ligand-gated ion channels that play an essential role in regulating synaptic transmission in the central nervous system. The results of this study indicate that celastrol and triptolide inhibit nAChR subtypes in a subtype-specific manner. This inhibitory effect was shown to be reversible, concentration-dependent, and noncompetitive. Mutation experiments were then performed to identify mutations in the binding site of nAChR determined by molecular docking studies and prioritize them based on binding energy, and it was found that triptolide had no inhibitory effect in double mutants of nAChR. These findings confirm that celastrol and triptolide selectively and effectively inhibit α3β2 and α3β4 nAChRs among various nAChR subtypes, and that celastrol and triptolide interact with a specific region of α3β4 nAChRs, which play a key role in the autonomic nervous system, without inhibiting the activity of α7 and α4β2, which act in neurodegenerative diseases.</AbstractText
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Glutamate-gated kainate receptors are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission at the postsynapse and modulate transmitter release at the presynapse<sup
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Multi-contrast magnetic resonance imaging (MC-MRI) plays a crucial role in clinical practice. However, its performance is hindered by long scanning times and the isolation between image acquisition and downstream clinical diagnoses/treatments. Despite the activated research on accelerated MC-MRI, few existing studies prioritize personalized imaging tailored to individual patient characteristics and clinical needs. That is, the current approach often aims to enhance overall image quality, disregarding the specific pathologies or anatomical regions that are of particular interest to clinicians. To tackle this challenge, we propose an anatomy-aware unrolling-based deep network, dubbed as A<sup
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Subtype-selective effect and molecular regulation of celastrol and triptolide at human nicotinic acetylcholine receptors. Celastrol and triptolide, bioactive compounds isolated from Tripterygium wilfordii Hook F, have demonstrated significant pharmacological effects across various biological pathways, making them subjects of extensive research for potential therapeutic applications. Celastrol and triptolide are known to have therapeutic use in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease through neuroprotective action. Nicotinic acetylcholine receptors (nAChRs) are a subtype of cholinergic receptors and are ligand-gated ion channels that play an essential role in regulating synaptic transmission in the central nervous system. The results of this study indicate that celastrol and triptolide inhibit nAChR subtypes in a subtype-specific manner. This inhibitory effect was shown to be reversible, concentration-dependent, and noncompetitive. Mutation experiments were then performed to identify mutations in the binding site of nAChR determined by molecular docking studies and prioritize them based on binding energy, and it was found that triptolide had no inhibitory effect in double mutants of nAChR. These findings confirm that celastrol and triptolide selectively and effectively inhibit α3β2 and α3β4 nAChRs among various nAChR subtypes, and that celastrol and triptolide interact with a specific region of α3β4 nAChRs, which play a key role in the autonomic nervous system, without inhibiting the activity of α7 and α4β2, which act in neurodegenerative diseases.</AbstractText
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Kainate receptor modulation by NETO2. Glutamate-gated kainate receptors are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission at the postsynapse and modulate transmitter release at the presynapse<sup
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Anatomy-Aware Deep Unrolling for Task-Oriented Acceleration of Multi-Contrast MRI. Multi-contrast magnetic resonance imaging (MC-MRI) plays a crucial role in clinical practice. However, its performance is hindered by long scanning times and the isolation between image acquisition and downstream clinical diagnoses/treatments. Despite the activated research on accelerated MC-MRI, few existing studies prioritize personalized imaging tailored to individual patient characteristics and clinical needs. That is, the current approach often aims to enhance overall image quality, disregarding the specific pathologies or anatomical regions that are of particular interest to clinicians. To tackle this challenge, we propose an anatomy-aware unrolling-based deep network, dubbed as A<sup
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40073308
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39495084
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40659608
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Post-Concussion Brain Changes Relative to Pre-Injury White Matter and Cerebral Blood Flow: A Prospective Observational Study.
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Does Equestrian Helmet Type Affect Head Injury? A Study on Equestrian Helmet Use Among Collegiate Athletes.
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Structure-guided engineering of snake toxins for selective modulation of adrenergic and muscarinic receptors.
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Medical clearance for return to play (RTP) after sports-related concussion is based on clinical assessment. It is unknown whether brain physiology has entirely returned to preinjury baseline at the time of clearance. In this longitudinal study, we assessed whether concussed individuals show functional and structural MRI brain changes relative to preinjury levels that persist beyond medical clearance. Secondary objectives were to test whether postconcussion changes exceed uninjured brain variability and to correlate MRI findings with clinical recovery time.</AbstractText For this prospective observational study, healthy athletes without a history of psychiatric, neurologic, or sensory-motor conditions were recruited from a single university sport medicine clinic. Clinical and MRI data were collected at preseason baseline, and those who were later concussed were reassessed at 1-7 days after injury, RTP, 1-3 months after RTP, and 1 year after RTP. A demographically matched control cohort of uninjured athletes was also reassessed at their subsequent preseason baseline. Primary outcomes were postconcussion changes in MRI measures of cerebral blood flow (CBF), white matter mean diffusivity (MD), and fractional anisotropy (FA), evaluated using mixed models. Secondary outcomes were group differences in MRI change scores and correlations of change scores with days to RTP.</AbstractText Of the 187 athletes enrolled in the study, 25 had concussion with follow-up imaging (20.3 ± 1.5 years, 56% male, 44% female) and were compared with 27 controls (19.7 ± 1.8 years, 44% male, 56% female). Concussed athletes showed statistically significant changes from baseline, including decreased frontoinsular CBF (mean and 95% CI -8.97 [-12.80, -5.01] mL/100 g/minute, z = -4.53), along with increased MD (1.94 × 10<sup This study provides direct evidence of persistent postconcussion changes in CBF and white matter at RTP and up to 1 year later. These results support incomplete recovery of brain physiology at medical clearance, with secondary analyses emphasizing the sensitivity of CBF to clinical recovery.</AbstractText
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To characterize helmet use, head injury risk, and to examine rider-related factors that influence these variables.</AbstractText Cross-sectional study.</AbstractText The University of Alabama at Birmingham Equestrian Sports Medicine Collaborative.</AbstractText In total, 357 equestrians competing at the collegiate level participated in this study.</AbstractText χ2 tests were used to evaluate potential associations between a rider's experience level, riding style, and use of helmet designed with MIPS with number of falls, past head injuries, and helmet use frequency.</AbstractText Data regarding helmet use and equestrian-related injuries were collected. χ2 analysis was used to determine potential associations.</AbstractText More than 50% of athletes reported falling off a horse during the course of 1 year. Head injuries occurred with high frequency. Concussion was the most frequently reported type. More than 50% of athletes with self-reported concussion denied receiving medical treatment. The risk of head injury was similar across helmet brands, and between helmets with Multi-Directional Impact Protection System (MIPS) and those without. Riders with the most experience were less likely to report sustaining a head injury than those with less experience. Contrary to current safety guidelines, 78% of equestrians said that they would not replace their helmet after every fall.</AbstractText Collegiate equestrians have a high risk of fall-related traumatic head injury. Despite this risk, they report helmet use practices that are not in line with current recommendations regarding helmet replacement.  This suggests that many of the athletes are using protective equipment that does not adequately protect against head injury. Neither helmet brand nor liner type was associated with lower rate of head injury.</AbstractText
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Adrenergic receptors (ARs) and muscarinic acetylcholine receptors (mAChRs) are essential G protein-coupled receptors (GPCRs) that regulate a wide range of physiological processes. Despite their significance, developing subtype-selective modulators for these receptors has been a formidable challenge due to the high structural and sequence similarities within their subfamilies. In this study, we elucidated the recognition and regulatory mechanisms of ARs and mAChRs by muscarinic toxin 3 (MT3), a cross-reactive ligand derived from snake venom. By leveraging the distinct toxin-receptor interfaces, we engineer a panel of toxin variants capable of selectively modulating α2A and M<sub
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Post-Concussion Brain Changes Relative to Pre-Injury White Matter and Cerebral Blood Flow: A Prospective Observational Study. Medical clearance for return to play (RTP) after sports-related concussion is based on clinical assessment. It is unknown whether brain physiology has entirely returned to preinjury baseline at the time of clearance. In this longitudinal study, we assessed whether concussed individuals show functional and structural MRI brain changes relative to preinjury levels that persist beyond medical clearance. Secondary objectives were to test whether postconcussion changes exceed uninjured brain variability and to correlate MRI findings with clinical recovery time.</AbstractText For this prospective observational study, healthy athletes without a history of psychiatric, neurologic, or sensory-motor conditions were recruited from a single university sport medicine clinic. Clinical and MRI data were collected at preseason baseline, and those who were later concussed were reassessed at 1-7 days after injury, RTP, 1-3 months after RTP, and 1 year after RTP. A demographically matched control cohort of uninjured athletes was also reassessed at their subsequent preseason baseline. Primary outcomes were postconcussion changes in MRI measures of cerebral blood flow (CBF), white matter mean diffusivity (MD), and fractional anisotropy (FA), evaluated using mixed models. Secondary outcomes were group differences in MRI change scores and correlations of change scores with days to RTP.</AbstractText Of the 187 athletes enrolled in the study, 25 had concussion with follow-up imaging (20.3 ± 1.5 years, 56% male, 44% female) and were compared with 27 controls (19.7 ± 1.8 years, 44% male, 56% female). Concussed athletes showed statistically significant changes from baseline, including decreased frontoinsular CBF (mean and 95% CI -8.97 [-12.80, -5.01] mL/100 g/minute, z = -4.53), along with increased MD (1.94 × 10<sup This study provides direct evidence of persistent postconcussion changes in CBF and white matter at RTP and up to 1 year later. These results support incomplete recovery of brain physiology at medical clearance, with secondary analyses emphasizing the sensitivity of CBF to clinical recovery.</AbstractText
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Does Equestrian Helmet Type Affect Head Injury? A Study on Equestrian Helmet Use Among Collegiate Athletes. To characterize helmet use, head injury risk, and to examine rider-related factors that influence these variables.</AbstractText Cross-sectional study.</AbstractText The University of Alabama at Birmingham Equestrian Sports Medicine Collaborative.</AbstractText In total, 357 equestrians competing at the collegiate level participated in this study.</AbstractText χ2 tests were used to evaluate potential associations between a rider's experience level, riding style, and use of helmet designed with MIPS with number of falls, past head injuries, and helmet use frequency.</AbstractText Data regarding helmet use and equestrian-related injuries were collected. χ2 analysis was used to determine potential associations.</AbstractText More than 50% of athletes reported falling off a horse during the course of 1 year. Head injuries occurred with high frequency. Concussion was the most frequently reported type. More than 50% of athletes with self-reported concussion denied receiving medical treatment. The risk of head injury was similar across helmet brands, and between helmets with Multi-Directional Impact Protection System (MIPS) and those without. Riders with the most experience were less likely to report sustaining a head injury than those with less experience. Contrary to current safety guidelines, 78% of equestrians said that they would not replace their helmet after every fall.</AbstractText Collegiate equestrians have a high risk of fall-related traumatic head injury. Despite this risk, they report helmet use practices that are not in line with current recommendations regarding helmet replacement.  This suggests that many of the athletes are using protective equipment that does not adequately protect against head injury. Neither helmet brand nor liner type was associated with lower rate of head injury.</AbstractText
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Structure-guided engineering of snake toxins for selective modulation of adrenergic and muscarinic receptors. Adrenergic receptors (ARs) and muscarinic acetylcholine receptors (mAChRs) are essential G protein-coupled receptors (GPCRs) that regulate a wide range of physiological processes. Despite their significance, developing subtype-selective modulators for these receptors has been a formidable challenge due to the high structural and sequence similarities within their subfamilies. In this study, we elucidated the recognition and regulatory mechanisms of ARs and mAChRs by muscarinic toxin 3 (MT3), a cross-reactive ligand derived from snake venom. By leveraging the distinct toxin-receptor interfaces, we engineer a panel of toxin variants capable of selectively modulating α2A and M<sub
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36344756
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20829391
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36575075
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Epileptiform activity induced metaplasticity impairs bidirectional plasticity in the hippocampal CA1 synapses via GluN2B NMDA receptors.
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The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain.
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[Automatic removal algorithm of electrooculographic artifacts in non-invasive brain-computer interface based on independent component analysis].
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Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. Cognitive impairment and memory consolidation problems are common among TLE patients. To understand the changes in the cellular process of memory in TLE, we studied the long-term depression (LTD) in Schaffer-collateral (Sc) CA1 synapses in an epilepsy model. Long-term potentiation (LTP) was investigated in patient samples and animal models by several groups, but LTD was not studied with the same interest in epilepsy research. Here we induced epileptiform activity in rat hippocampal slices using magnesium-free high-potassium (7.5 mM K +) artificial cerebrospinal fluid (HK-ACSF) and characterized the LTD in Sc-CA1 synapses. We found that epileptiform activity abolished/impaired LTD and depotentiation in the Sc-CA1 synapses. In control slices, application of NMDA (30 μM for 3 min) induced chemical LTD (c-LTD) in Sc-CA1 synapses, whereas epileptiform activity induced slices showed slow onset potentiation. Induction of LTD using 1 Hz, 900 pulses yielded a similar outcome as c-LTD. Both forms of LTD were NMDA receptor dependent. In addition, we found that the polarity changes in the synaptic plasticity in epileptiform-induced slices were blocked by GluN2B antagonists ifenprodil and Ro 25-6981. Our data suggest that epileptiform-induced metaplasticity inhibits LTD in Sc-CA1 synapses. We provide new insight into the cellular mechanism of memory formation during epilepsy.</AbstractText
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Impairment of insulin and IGF-I signaling in the brain is one of the causes of dementia associated with diabetes mellitus and Alzheimer's disease. However, the precise pathological processes are largely unknown. In the present study, we found that SH2-containing inositol 5'-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain. When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons. Interestingly, SHIP2 mRNA and protein expression levels were significantly increased in the brain of type 2 diabetic db/db mice. To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt. Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice. Consistently, terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay demonstrated that the number of apoptosis-positive cells was increased in cerebral cortex of the transgenic mice at an elderly age. Furthermore, SHIP2 transgenic mice exhibited impaired memory performance in the Morris water maze, step-through passive avoidance, and novel-object-recognition tests. Importantly, inhibition of SHIP2 ameliorated the impairment of hippocampal synaptic plasticity and memory formation in db/db mice. These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.</AbstractText
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The non-invasive brain-computer interface (BCI) has gradually become a hot spot of current research, and it has been applied in many fields such as mental disorder detection and physiological monitoring. However, the electroencephalography (EEG) signals required by the non-invasive BCI can be easily contaminated by electrooculographic (EOG) artifacts, which seriously affects the analysis of EEG signals. Therefore, this paper proposed an improved independent component analysis method combined with a frequency filter, which automatically recognizes artifact components based on the correlation coefficient and kurtosis dual threshold. In this method, the frequency difference between EOG and EEG was used to remove the EOG information in the artifact component through frequency filter, so as to retain more EEG information. The experimental results on the public datasets and our laboratory data showed that the method in this paper could effectively improve the effect of EOG artifact removal and improve the loss of EEG information, which is helpful for the promotion of non-invasive BCI.</AbstractText 非侵入式脑-机接口已经逐步成为当前研究的热点，在精神障碍检测、生理监测等多方面都有所应用。但是非侵入式脑-机接口所需的脑电信号容易受到眼电伪迹污染，会严重影响对脑电信号的解码分析。对此，本文提出了一种结合频率滤波器的改进型独立成分分析算法，以相关系数和峰度双重阈值为依据自动识别伪迹组件；利用眼电与脑电频率的差异，通过频率滤波器去除伪迹组件中的眼电信息，从而保留更多脑电信息。在公开数据集和本实验室数据上的实验结果表明，本文算法可以有效提升眼电伪迹去除效果，同时改善脑电信息损失，这有助于非侵入式脑-机接口的推广。.</AbstractText
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Epileptiform activity induced metaplasticity impairs bidirectional plasticity in the hippocampal CA1 synapses via GluN2B NMDA receptors. Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. Cognitive impairment and memory consolidation problems are common among TLE patients. To understand the changes in the cellular process of memory in TLE, we studied the long-term depression (LTD) in Schaffer-collateral (Sc) CA1 synapses in an epilepsy model. Long-term potentiation (LTP) was investigated in patient samples and animal models by several groups, but LTD was not studied with the same interest in epilepsy research. Here we induced epileptiform activity in rat hippocampal slices using magnesium-free high-potassium (7.5 mM K +) artificial cerebrospinal fluid (HK-ACSF) and characterized the LTD in Sc-CA1 synapses. We found that epileptiform activity abolished/impaired LTD and depotentiation in the Sc-CA1 synapses. In control slices, application of NMDA (30 μM for 3 min) induced chemical LTD (c-LTD) in Sc-CA1 synapses, whereas epileptiform activity induced slices showed slow onset potentiation. Induction of LTD using 1 Hz, 900 pulses yielded a similar outcome as c-LTD. Both forms of LTD were NMDA receptor dependent. In addition, we found that the polarity changes in the synaptic plasticity in epileptiform-induced slices were blocked by GluN2B antagonists ifenprodil and Ro 25-6981. Our data suggest that epileptiform-induced metaplasticity inhibits LTD in Sc-CA1 synapses. We provide new insight into the cellular mechanism of memory formation during epilepsy.</AbstractText
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The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain. Impairment of insulin and IGF-I signaling in the brain is one of the causes of dementia associated with diabetes mellitus and Alzheimer's disease. However, the precise pathological processes are largely unknown. In the present study, we found that SH2-containing inositol 5'-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain. When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons. Interestingly, SHIP2 mRNA and protein expression levels were significantly increased in the brain of type 2 diabetic db/db mice. To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt. Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice. Consistently, terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay demonstrated that the number of apoptosis-positive cells was increased in cerebral cortex of the transgenic mice at an elderly age. Furthermore, SHIP2 transgenic mice exhibited impaired memory performance in the Morris water maze, step-through passive avoidance, and novel-object-recognition tests. Importantly, inhibition of SHIP2 ameliorated the impairment of hippocampal synaptic plasticity and memory formation in db/db mice. These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.</AbstractText
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[Automatic removal algorithm of electrooculographic artifacts in non-invasive brain-computer interface based on independent component analysis]. The non-invasive brain-computer interface (BCI) has gradually become a hot spot of current research, and it has been applied in many fields such as mental disorder detection and physiological monitoring. However, the electroencephalography (EEG) signals required by the non-invasive BCI can be easily contaminated by electrooculographic (EOG) artifacts, which seriously affects the analysis of EEG signals. Therefore, this paper proposed an improved independent component analysis method combined with a frequency filter, which automatically recognizes artifact components based on the correlation coefficient and kurtosis dual threshold. In this method, the frequency difference between EOG and EEG was used to remove the EOG information in the artifact component through frequency filter, so as to retain more EEG information. The experimental results on the public datasets and our laboratory data showed that the method in this paper could effectively improve the effect of EOG artifact removal and improve the loss of EEG information, which is helpful for the promotion of non-invasive BCI.</AbstractText 非侵入式脑-机接口已经逐步成为当前研究的热点，在精神障碍检测、生理监测等多方面都有所应用。但是非侵入式脑-机接口所需的脑电信号容易受到眼电伪迹污染，会严重影响对脑电信号的解码分析。对此，本文提出了一种结合频率滤波器的改进型独立成分分析算法，以相关系数和峰度双重阈值为依据自动识别伪迹组件；利用眼电与脑电频率的差异，通过频率滤波器去除伪迹组件中的眼电信息，从而保留更多脑电信息。在公开数据集和本实验室数据上的实验结果表明，本文算法可以有效提升眼电伪迹去除效果，同时改善脑电信息损失，这有助于非侵入式脑-机接口的推广。.</AbstractText
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39521397
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38333818
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40788786
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MultiThal-classifier, a machine learning-based multi-class model for thalassemia diagnosis and classification.
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A soft voting ensemble learning approach for credit card fraud detection.
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An Unsupervised Learning Approach for Reconstructing 3T-Like Images from 0.3T MRI Without Paired Training Data.
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The differential diagnosis between iron deficiency anemia (IDA) and thalassemia trait (TT) remains a significant clinical challenge. This study aimed to develop a machine learning-based multi-class model to differentiate among Microcytic-TT(TT with low mean corpuscular volume), Normocytic-TT (TT with normal mean corpuscular volume), IDA, and healthy individuals.</AbstractText A comprehensive dataset comprising 1,819 individuals was analyzed using six distinct machine learning algorithms. The eXtreme Gradient Boosting (XGBoost) algorithm was ultimately selected to construct the MultiThal-Classifier (M-THAL) model. SMOTENC (Synthetic Minority Over-sampling Technique for Nominal and Continuous features) was employed to address data imbalance. Model performance was evaluated using various metrics, and SHAP values were applied to interpret the model's predictions.Additionally, external validation was conducted to assess the model's robustness and generalizability.</AbstractText After performing 1000 bootstrap resamples of the test set, the average performance metrics of M-THAL and the 95 % confidence interval(CI) were as follows, sensitivity 90.27 % (95 % CI: 84.88-95.26), specificity 97.87 % (95% CI: 97.10-98.55), PPV 93.42 % (95 % CI: 89.34-96.48), NPV 97.82% (95 % CI: 97.00-98.53), F1-score 91.50 % (95% CI: 87.29-95.34), Youden's index 88.15 % (95 % CI: 82.33-93.70), accuracy 97.06 % (95% CI: 96.06-97.99), and AUC 94.07 % (95 % CI: 91.17-96.84).Feature importance analysis identified mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), red cell distribution width - standard deviation(RDW-SD), and hemoglobin (HGB) were identified as the most important features. External validation confirmed the model's robustness and generalizability.</AbstractText The M-THAL effectively distinguishes Normocytic-TT, Microcytic-TT, IDA, and healthy individuals using hematological parameters, offers a rapid and cost-effective screening tool that can be readily implemented in diverse healthcare settings.</AbstractText
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With the advancement of e-commerce and modern technological development, credit cards are widely used for both online and offline purchases, which has increased the number of daily fraudulent transactions. Many organizations and financial institutions worldwide lose billions of dollars annually because of credit card fraud. Due to the global distribution of both legitimate and fraudulent transactions, it is difficult to discern between the two. Furthermore, because only a small proportion of transactions are fraudulent, there is a problem of class imbalance. Hence, an effective fraud-detection methodology is required to sustain the reliability of the payment system. Machine learning has recently emerged as a viable substitute for identifying this type of fraud. However, ML approaches have difficulty identifying fraud with high prediction accuracy, while also decreasing misclassification costs due to the size of the imbalanced data. In this research, a soft voting ensemble learning approach for detecting credit card fraud on imbalanced data is proposed. To do this, the proposed approach is evaluated and compared with numerous sophisticated sampling techniques (i.e., oversampling, undersampling, and hybrid sampling) to overcome the class imbalance problem. We develop several credit card fraud classifiers, including ensemble classifiers, with and without sampling techniques. According to the experimental results, the proposed soft-voting approach outperforms individual classifiers. With a false negative rate (FNR) of 0.0306, it achieves a precision of 0.9870, recall of 0.9694, f1-score of 0.8764, and AUROC of 0.9936.</AbstractText
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Magnetic resonance imaging (MRI) is powerful in medical diagnostics, yet high-field MRI, despite offering superior image quality, incurs significant costs for procurement, installation, maintenance, and operation, restricting its availability and accessibility, especially in low- and middle-income countries. Addressing this, our study proposes an unsupervised learning algorithm based on cycle-consistent generative adversarial networks. This framework transforms 0.3T low-field MRI into higher-quality 3T-like images, bypassing the need for paired low/high-field training data. The proposed architecture integrates two novel modules to enhance reconstruction quality: (1) an attention block that dynamically balances high-field-like features with the original low-field input, and (2) an edge block that refines boundary details, providing more accurate structural reconstruction. The proposed generative model is trained on large-scale, unpaired, public datasets, and further validated on paired low/high-field acquisitions of three major clinical MRI sequences: T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) imaging. It demonstrates notable improvements in tissue contrast and signal-to-noise ratio while preserving anatomical fidelity. This approach utilizes rich information from publicly available MRI resources, providing a data-efficient unsupervised alternative that complements supervised methods to enhance the utility of low-field MRI.</AbstractText
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MultiThal-classifier, a machine learning-based multi-class model for thalassemia diagnosis and classification. The differential diagnosis between iron deficiency anemia (IDA) and thalassemia trait (TT) remains a significant clinical challenge. This study aimed to develop a machine learning-based multi-class model to differentiate among Microcytic-TT(TT with low mean corpuscular volume), Normocytic-TT (TT with normal mean corpuscular volume), IDA, and healthy individuals.</AbstractText A comprehensive dataset comprising 1,819 individuals was analyzed using six distinct machine learning algorithms. The eXtreme Gradient Boosting (XGBoost) algorithm was ultimately selected to construct the MultiThal-Classifier (M-THAL) model. SMOTENC (Synthetic Minority Over-sampling Technique for Nominal and Continuous features) was employed to address data imbalance. Model performance was evaluated using various metrics, and SHAP values were applied to interpret the model's predictions.Additionally, external validation was conducted to assess the model's robustness and generalizability.</AbstractText After performing 1000 bootstrap resamples of the test set, the average performance metrics of M-THAL and the 95 % confidence interval(CI) were as follows, sensitivity 90.27 % (95 % CI: 84.88-95.26), specificity 97.87 % (95% CI: 97.10-98.55), PPV 93.42 % (95 % CI: 89.34-96.48), NPV 97.82% (95 % CI: 97.00-98.53), F1-score 91.50 % (95% CI: 87.29-95.34), Youden's index 88.15 % (95 % CI: 82.33-93.70), accuracy 97.06 % (95% CI: 96.06-97.99), and AUC 94.07 % (95 % CI: 91.17-96.84).Feature importance analysis identified mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), red cell distribution width - standard deviation(RDW-SD), and hemoglobin (HGB) were identified as the most important features. External validation confirmed the model's robustness and generalizability.</AbstractText The M-THAL effectively distinguishes Normocytic-TT, Microcytic-TT, IDA, and healthy individuals using hematological parameters, offers a rapid and cost-effective screening tool that can be readily implemented in diverse healthcare settings.</AbstractText
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A soft voting ensemble learning approach for credit card fraud detection. With the advancement of e-commerce and modern technological development, credit cards are widely used for both online and offline purchases, which has increased the number of daily fraudulent transactions. Many organizations and financial institutions worldwide lose billions of dollars annually because of credit card fraud. Due to the global distribution of both legitimate and fraudulent transactions, it is difficult to discern between the two. Furthermore, because only a small proportion of transactions are fraudulent, there is a problem of class imbalance. Hence, an effective fraud-detection methodology is required to sustain the reliability of the payment system. Machine learning has recently emerged as a viable substitute for identifying this type of fraud. However, ML approaches have difficulty identifying fraud with high prediction accuracy, while also decreasing misclassification costs due to the size of the imbalanced data. In this research, a soft voting ensemble learning approach for detecting credit card fraud on imbalanced data is proposed. To do this, the proposed approach is evaluated and compared with numerous sophisticated sampling techniques (i.e., oversampling, undersampling, and hybrid sampling) to overcome the class imbalance problem. We develop several credit card fraud classifiers, including ensemble classifiers, with and without sampling techniques. According to the experimental results, the proposed soft-voting approach outperforms individual classifiers. With a false negative rate (FNR) of 0.0306, it achieves a precision of 0.9870, recall of 0.9694, f1-score of 0.8764, and AUROC of 0.9936.</AbstractText
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An Unsupervised Learning Approach for Reconstructing 3T-Like Images from 0.3T MRI Without Paired Training Data. Magnetic resonance imaging (MRI) is powerful in medical diagnostics, yet high-field MRI, despite offering superior image quality, incurs significant costs for procurement, installation, maintenance, and operation, restricting its availability and accessibility, especially in low- and middle-income countries. Addressing this, our study proposes an unsupervised learning algorithm based on cycle-consistent generative adversarial networks. This framework transforms 0.3T low-field MRI into higher-quality 3T-like images, bypassing the need for paired low/high-field training data. The proposed architecture integrates two novel modules to enhance reconstruction quality: (1) an attention block that dynamically balances high-field-like features with the original low-field input, and (2) an edge block that refines boundary details, providing more accurate structural reconstruction. The proposed generative model is trained on large-scale, unpaired, public datasets, and further validated on paired low/high-field acquisitions of three major clinical MRI sequences: T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) imaging. It demonstrates notable improvements in tissue contrast and signal-to-noise ratio while preserving anatomical fidelity. This approach utilizes rich information from publicly available MRI resources, providing a data-efficient unsupervised alternative that complements supervised methods to enhance the utility of low-field MRI.</AbstractText
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27389802
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26367817
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26879019
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Amygdala atrophy affects emotion-related activity in face-responsive regions in frontotemporal degeneration.
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Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism.
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The Implication and Significance of Beta 2 Microglobulin: A Conservative Multifunctional Regulator.
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In the healthy brain, modulatory influences from the amygdala commonly explain enhanced activation in face-responsive areas by emotional facial expressions relative to neutral expressions. In the behavioral variant frontotemporal dementia (bvFTD) facial emotion recognition is impaired and has been associated with atrophy of the amygdala. By combining structural and functional MRI in 19 patients with bvFTD and 20 controls we investigated the neural effects of emotion in face-responsive cortex and its relationship with amygdalar gray matter (GM) volume in neurodegeneration. Voxel-based morphometry revealed decreased GM volume in anterior medio-temporal regions including amygdala in patients compared to controls. During fMRI, we presented dynamic facial expressions (fear and chewing) and their spatiotemporally scrambled versions. We found enhanced activation for fearful compared to neutral faces in ventral temporal cortex and superior temporal sulcus in controls, but not in patients. In the bvFTD group left amygdalar GM volume correlated positively with emotion-related activity in left fusiform face area (FFA). This correlation was amygdala-specific and driven by GM in superficial and basolateral (BLA) subnuclei, consistent with reported amygdalar-cortical networks. The data suggests that anterior medio-temporal atrophy in bvFTD affects emotion processing in distant posterior areas.</AbstractText
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Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another's affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another's affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another's physical pain but still have problems with the vicarious representation of more complex emotions that matter in life.</AbstractText
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This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (β2M), a conservative immune molecule in vertebrate.</AbstractText The data used in this review were obtained from PubMed up to October 2015. Terms of β2M, immune response, and infection were used in the search.</AbstractText Articles related to β2M were retrieved and reviewed. Articles focusing on the characteristic and function of β2M were selected. The exclusion criteria of articles were that the studies on β2M-related molecules.</AbstractText β2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases. β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies. It also involves in forming major histocompatibility complex (MHC class I or MHC I) or like heterodimers, covering from antigen presentation to immune homeostasis.</AbstractText Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.</AbstractText
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Amygdala atrophy affects emotion-related activity in face-responsive regions in frontotemporal degeneration. In the healthy brain, modulatory influences from the amygdala commonly explain enhanced activation in face-responsive areas by emotional facial expressions relative to neutral expressions. In the behavioral variant frontotemporal dementia (bvFTD) facial emotion recognition is impaired and has been associated with atrophy of the amygdala. By combining structural and functional MRI in 19 patients with bvFTD and 20 controls we investigated the neural effects of emotion in face-responsive cortex and its relationship with amygdalar gray matter (GM) volume in neurodegeneration. Voxel-based morphometry revealed decreased GM volume in anterior medio-temporal regions including amygdala in patients compared to controls. During fMRI, we presented dynamic facial expressions (fear and chewing) and their spatiotemporally scrambled versions. We found enhanced activation for fearful compared to neutral faces in ventral temporal cortex and superior temporal sulcus in controls, but not in patients. In the bvFTD group left amygdalar GM volume correlated positively with emotion-related activity in left fusiform face area (FFA). This correlation was amygdala-specific and driven by GM in superficial and basolateral (BLA) subnuclei, consistent with reported amygdalar-cortical networks. The data suggests that anterior medio-temporal atrophy in bvFTD affects emotion processing in distant posterior areas.</AbstractText
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Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism. Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another's affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another's affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another's physical pain but still have problems with the vicarious representation of more complex emotions that matter in life.</AbstractText
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The Implication and Significance of Beta 2 Microglobulin: A Conservative Multifunctional Regulator. This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (β2M), a conservative immune molecule in vertebrate.</AbstractText The data used in this review were obtained from PubMed up to October 2015. Terms of β2M, immune response, and infection were used in the search.</AbstractText Articles related to β2M were retrieved and reviewed. Articles focusing on the characteristic and function of β2M were selected. The exclusion criteria of articles were that the studies on β2M-related molecules.</AbstractText β2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases. β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies. It also involves in forming major histocompatibility complex (MHC class I or MHC I) or like heterodimers, covering from antigen presentation to immune homeostasis.</AbstractText Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.</AbstractText
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23259623
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16724373
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22322610
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Update on treatment of psoriatic arthritis.
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Systematic review of treatments for psoriatic arthritis: an evidence based approach and basis for treatment guidelines.
|
CT fluoroscopy-guided cervical interlaminar steroid injections: safety, technique, and radiation dose parameters.
|
Some of this past year's key papers or abstracts on psoriatic arthritis (PsA) assessment and treatment are reviewed in this paper. Treatment begins with identification of the PsA patient. Several screening questionnaires have been developed to be used in dermatology and primary care settings to identify which patients with psoriasis have developed PsA as opposed to other common musculoskeletal problems, such as osteoarthritis and fibromyalgia, thus increasing case-finding and targeting referral. PsA can present in a heterogeneous manner, involving arthritis, enthesitis, dactylitis, spondylitis, and skin and nail disease. Measures of these individual domains have been developed for use in clinical trials and improved PsA-specific composite measures of these domains are being evaluated as well. A quantitative therapy target, Minimal Disease Activity criteria, has been developed by the GRAPPA group. Treatment recommendations have been published by EULAR and GRAPPA. Obesity is a risk factor for the development of PsA and may adversely influence treatment outcomes. Although pharmacologic treatment often begins with methotrexate, a recent study does not provide clear evidence of its effectiveness. Anti-TNF therapies remain the gold standard of effectiveness. New therapeutic options are potentially emerging including ustekinumab, abatacept, several IL-17 inhibitors, apremilast, JAK inhibitors, and possibly IL-6 inhibitors.</AbstractText
|
Psoriatic arthritis (PsA) is a chronic systemic inflammatory disorder characterized by the association of arthritis and psoriasis. In addition to a heterogeneous and variable clinical course, PsA is complex and multifaceted and may include prominent involvement in the peripheral and axial diarthrodial joints, the skin and nails, and in periarticular structures such as entheses. A central mission of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is to develop guidelines, based upon the best scientific evidence, for the optimal treatment of patients with PsA. We outline the specific methods and procedures used in this evidence-based, systematic review of treatments for PsA, which we hope will provide a basis for future treatment guidelines.</AbstractText
|
Cervical epidural steroid injections are approached with trepidation because of concerns over safety, including direct spinal cord injury. CT fluoroscopy is an alternative to conventional fluoroscopy that could potentially help reduce the risk of injury by providing improved localization of the needle tip. We sought to determine rates of technical success and risk of complications in our initial cohort of patients treated with cervical interlaminar ESI performed under CTF guidance.</AbstractText In this retrospective case series, we reviewed procedural details and CTF images of 53 consecutive cervical interlaminar ESIs performed on 50 patients over a period of 8 months. Rates of technical success, incidence of complications, procedure times, and factors that influence radiation exposure were examined.</AbstractText No symptomatic procedural complications were observed. A single case of intrathecal contrast injection was observed, from which the patient was asymptomatic. The remaining injections were all technically successful. Injections were performed at every cervical level, as high as C1-C2. Total procedure times averaged less than 20 minutes. Average CT fluoroscopic time was 24 seconds and median tube current was 70 mA.</AbstractText CTF-guided cervical interlaminar ESI can be performed at all levels in the cervical spine with a low rate of procedural complications. Short total procedure times, CT-fluoroscopy times, and reduced tube current make this procedure a practical alternative to cervical ESI performed under conventional fluoroscopy.</AbstractText
|
Update on treatment of psoriatic arthritis. Some of this past year's key papers or abstracts on psoriatic arthritis (PsA) assessment and treatment are reviewed in this paper. Treatment begins with identification of the PsA patient. Several screening questionnaires have been developed to be used in dermatology and primary care settings to identify which patients with psoriasis have developed PsA as opposed to other common musculoskeletal problems, such as osteoarthritis and fibromyalgia, thus increasing case-finding and targeting referral. PsA can present in a heterogeneous manner, involving arthritis, enthesitis, dactylitis, spondylitis, and skin and nail disease. Measures of these individual domains have been developed for use in clinical trials and improved PsA-specific composite measures of these domains are being evaluated as well. A quantitative therapy target, Minimal Disease Activity criteria, has been developed by the GRAPPA group. Treatment recommendations have been published by EULAR and GRAPPA. Obesity is a risk factor for the development of PsA and may adversely influence treatment outcomes. Although pharmacologic treatment often begins with methotrexate, a recent study does not provide clear evidence of its effectiveness. Anti-TNF therapies remain the gold standard of effectiveness. New therapeutic options are potentially emerging including ustekinumab, abatacept, several IL-17 inhibitors, apremilast, JAK inhibitors, and possibly IL-6 inhibitors.</AbstractText
|
Systematic review of treatments for psoriatic arthritis: an evidence based approach and basis for treatment guidelines. Psoriatic arthritis (PsA) is a chronic systemic inflammatory disorder characterized by the association of arthritis and psoriasis. In addition to a heterogeneous and variable clinical course, PsA is complex and multifaceted and may include prominent involvement in the peripheral and axial diarthrodial joints, the skin and nails, and in periarticular structures such as entheses. A central mission of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is to develop guidelines, based upon the best scientific evidence, for the optimal treatment of patients with PsA. We outline the specific methods and procedures used in this evidence-based, systematic review of treatments for PsA, which we hope will provide a basis for future treatment guidelines.</AbstractText
|
CT fluoroscopy-guided cervical interlaminar steroid injections: safety, technique, and radiation dose parameters. Cervical epidural steroid injections are approached with trepidation because of concerns over safety, including direct spinal cord injury. CT fluoroscopy is an alternative to conventional fluoroscopy that could potentially help reduce the risk of injury by providing improved localization of the needle tip. We sought to determine rates of technical success and risk of complications in our initial cohort of patients treated with cervical interlaminar ESI performed under CTF guidance.</AbstractText In this retrospective case series, we reviewed procedural details and CTF images of 53 consecutive cervical interlaminar ESIs performed on 50 patients over a period of 8 months. Rates of technical success, incidence of complications, procedure times, and factors that influence radiation exposure were examined.</AbstractText No symptomatic procedural complications were observed. A single case of intrathecal contrast injection was observed, from which the patient was asymptomatic. The remaining injections were all technically successful. Injections were performed at every cervical level, as high as C1-C2. Total procedure times averaged less than 20 minutes. Average CT fluoroscopic time was 24 seconds and median tube current was 70 mA.</AbstractText CTF-guided cervical interlaminar ESI can be performed at all levels in the cervical spine with a low rate of procedural complications. Short total procedure times, CT-fluoroscopy times, and reduced tube current make this procedure a practical alternative to cervical ESI performed under conventional fluoroscopy.</AbstractText
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27084431
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18033225
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27209143
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Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts.
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What nephrologists need to know about gadolinium.
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The burden of mental, neurological, and substance use disorders in China and India: a systematic analysis of community representative epidemiological studies.
|
Human brain tumors such as glioblastomas are typically detected using conventional, nonquantitative magnetic resonance imaging (MRI) techniques, such as T2-weighted and contrast enhanced T1-weighted MRI. In this manuscript, we tested whether dynamic quantitative T1 mapping by MRI can localize orthotopic glioma tumors in an objective manner. Quantitative T1 mapping was performed by MRI over multiple time points using the conventional contrast agent Optimark. We compared signal differences to determine the gadolinium concentration in tissues over time. The T1 parametric maps made it easy to identify the regions of contrast enhancement and thus tumor location. Doubling the typical human dose of contrast agent resulted in a clearer demarcation of these tumors. Therefore, T1 mapping of brain tumors is gadolinium dose dependent and improves detection of tumors by MRI. The use of T1 maps provides a quantitative means to evaluate tumor detection by gadolinium-based contrast agents over time. This dynamic quantitative T1 mapping technique will also enable future quantitative evaluation of various targeted MRI contrast agents.</AbstractText
|
Gadolinium chelates are commonly used to improve tissue contrast in MRI. Until recently the use of gadolinium was thought to be risk-free compared with alternative contrast agents. Recent studies, however, have raised serious concerns regarding the safety of gadolinium chelates. Although safe in patients with normal kidney function, administration of these agents in people with renal dysfunction can result in up to three clinical problems that the nephrologist should be familiar with. The first is nephrogenic systemic fibrosis (NSF), which was initially observed in 1997. Although manifesting primarily in skin, NSF can also cause systemic fibrosis, leading to disabling contractures and even death. Gadodiamide is the agent that has been most frequently associated with NSF, but other chelates might also pose a risk. The second clinical problem is that gadolinium chelates cause acute kidney injury, especially at high doses required for angiography. The third problem is that several laboratory artifacts are associated with gadolinium administration, with pseudohypocalcemia being the most important. The risk of a patient experiencing all three of these complications increases as renal function declines. In light of these problems, nephrologists need to re-evaluate the risks and benefits of gadolinium administration in patients with chronic kidney disease stage 3 or greater, as well as in those with acute kidney injury.</AbstractText
|
China and India jointly account for 38% of the world population, so understanding the burden attributed to mental, neurological, and substance use disorders within these two countries is essential. As part of the Lancet/Lancet Psychiatry China-India Mental Health Alliance Series, we aim to provide estimates of the burden of mental, neurological, and substance use disorders for China and India from the Global Burden of Disease Study 2013 (GBD 2013).</AbstractText In this systematic analysis for community representative epidemiological studies, we conducted systematic reviews in line with PRISMA guidelines for community representative epidemiological studies. We extracted estimates of prevalence, incidence, remission and duration, and mortality along with associated uncertainty intervals from GBD 2013. Using these data as primary inputs, DisMod-MR 2.0, a Bayesian meta-regression instrument, used a log rate and incidence-prevalence-mortality mathematical model to develop internally consistent epidemiological models. Disability-adjusted life-year (DALY) changes between 1990 and 2013 were decomposed to quantify change attributable to population growth and ageing. We projected DALYs from 2013 to 2025 for mental, neurological, and substance use disorders using United Nations population data.</AbstractText Around a third of global DALYs attributable to mental, neurological, and substance use disorders were found in China and India (66 million DALYs), a number greater than all developed countries combined (50 million DALYs). Disease burden profiles differed; India showed similarities with other developing countries (around 50% of DALYs attributable to non-communicable disease), whereas China more closely resembled developed countries (around 80% of DALYs attributable to non-communicable disease). The overall population growth in India explains a greater proportion of the increase in mental, neurological, and substance use disorder burden from 1990 to 2013 (44%) than in China (20%). The burden of mental, neurological, and substance use disorders is estimated to increase by 10% in China and 23% in India between 2013 and 2025.</AbstractText The current and projected burden of mental, neurological, and substance use disorders in China and India warrants the urgent prioritisation of programmes focused on targeted prevention, early identification, and effective treatment.</AbstractText China Medical Board, Bill & Melinda Gates Foundation.</AbstractText
|
Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts. Human brain tumors such as glioblastomas are typically detected using conventional, nonquantitative magnetic resonance imaging (MRI) techniques, such as T2-weighted and contrast enhanced T1-weighted MRI. In this manuscript, we tested whether dynamic quantitative T1 mapping by MRI can localize orthotopic glioma tumors in an objective manner. Quantitative T1 mapping was performed by MRI over multiple time points using the conventional contrast agent Optimark. We compared signal differences to determine the gadolinium concentration in tissues over time. The T1 parametric maps made it easy to identify the regions of contrast enhancement and thus tumor location. Doubling the typical human dose of contrast agent resulted in a clearer demarcation of these tumors. Therefore, T1 mapping of brain tumors is gadolinium dose dependent and improves detection of tumors by MRI. The use of T1 maps provides a quantitative means to evaluate tumor detection by gadolinium-based contrast agents over time. This dynamic quantitative T1 mapping technique will also enable future quantitative evaluation of various targeted MRI contrast agents.</AbstractText
|
What nephrologists need to know about gadolinium. Gadolinium chelates are commonly used to improve tissue contrast in MRI. Until recently the use of gadolinium was thought to be risk-free compared with alternative contrast agents. Recent studies, however, have raised serious concerns regarding the safety of gadolinium chelates. Although safe in patients with normal kidney function, administration of these agents in people with renal dysfunction can result in up to three clinical problems that the nephrologist should be familiar with. The first is nephrogenic systemic fibrosis (NSF), which was initially observed in 1997. Although manifesting primarily in skin, NSF can also cause systemic fibrosis, leading to disabling contractures and even death. Gadodiamide is the agent that has been most frequently associated with NSF, but other chelates might also pose a risk. The second clinical problem is that gadolinium chelates cause acute kidney injury, especially at high doses required for angiography. The third problem is that several laboratory artifacts are associated with gadolinium administration, with pseudohypocalcemia being the most important. The risk of a patient experiencing all three of these complications increases as renal function declines. In light of these problems, nephrologists need to re-evaluate the risks and benefits of gadolinium administration in patients with chronic kidney disease stage 3 or greater, as well as in those with acute kidney injury.</AbstractText
|
The burden of mental, neurological, and substance use disorders in China and India: a systematic analysis of community representative epidemiological studies. China and India jointly account for 38% of the world population, so understanding the burden attributed to mental, neurological, and substance use disorders within these two countries is essential. As part of the Lancet/Lancet Psychiatry China-India Mental Health Alliance Series, we aim to provide estimates of the burden of mental, neurological, and substance use disorders for China and India from the Global Burden of Disease Study 2013 (GBD 2013).</AbstractText In this systematic analysis for community representative epidemiological studies, we conducted systematic reviews in line with PRISMA guidelines for community representative epidemiological studies. We extracted estimates of prevalence, incidence, remission and duration, and mortality along with associated uncertainty intervals from GBD 2013. Using these data as primary inputs, DisMod-MR 2.0, a Bayesian meta-regression instrument, used a log rate and incidence-prevalence-mortality mathematical model to develop internally consistent epidemiological models. Disability-adjusted life-year (DALY) changes between 1990 and 2013 were decomposed to quantify change attributable to population growth and ageing. We projected DALYs from 2013 to 2025 for mental, neurological, and substance use disorders using United Nations population data.</AbstractText Around a third of global DALYs attributable to mental, neurological, and substance use disorders were found in China and India (66 million DALYs), a number greater than all developed countries combined (50 million DALYs). Disease burden profiles differed; India showed similarities with other developing countries (around 50% of DALYs attributable to non-communicable disease), whereas China more closely resembled developed countries (around 80% of DALYs attributable to non-communicable disease). The overall population growth in India explains a greater proportion of the increase in mental, neurological, and substance use disorder burden from 1990 to 2013 (44%) than in China (20%). The burden of mental, neurological, and substance use disorders is estimated to increase by 10% in China and 23% in India between 2013 and 2025.</AbstractText The current and projected burden of mental, neurological, and substance use disorders in China and India warrants the urgent prioritisation of programmes focused on targeted prevention, early identification, and effective treatment.</AbstractText China Medical Board, Bill & Melinda Gates Foundation.</AbstractText
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40538922
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33814023
|
40727792
|
Unique and shared influences of anxiety and ADHD on the behavioral profile of autism in early childhood.
|
Insights into attention-deficit/hyperactivity disorder from recent genetic studies.
|
Retraction of "Design, Synthesis, and Biological Evaluation of Notopterol Derivatives as Triple Inhibitors of AChE/BACE1/GSK3β for the Treatment of Alzheimer's Disease".
|
Autism is characterized by a wide range of core and associated behavioral features that can be influenced by co-occurring conditions such as attention-deficit hyperactivity disorder (ADHD) and anxiety disorders. Executive function difficulties are proposed as a common feature of autism and ADHD and are also evident in persons with anxiety disorders. However, little is known about how anxiety disorders or ADHD differentially impact executive functioning or how these difficulties may influence the presentation of core and associated autistic features in young children. In the current study, we explored the unique executive function difficulties associated with co-occurring anxiety and/or ADHD and elucidated how they differentially impact the clinical presentation of autism in young children.</AbstractText We assessed 69 autistic children, aged 3 to 5 years. Anxiety and ADHD were assessed through parent interview using the Preschool Age Psychiatric Assessment (PAPA). Executive functions were assessed using the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). Core autistic features were measured with the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and additional features were measured with the Restricted and Repetitive Behaviors Scale, Revised (RBS-R) and the Sensory Experiences Questionnaire (SEQ). Using an additive main effect general linear model, we examined the unique contributions of an anxiety disorder and/or ADHD on core and associated autistic features as well as executive function. Mediation analyses explored the contribution of the executive function profiles to specific features of autism.</AbstractText Results showed that greater difficulty with attentional shifting was uniquely associated with anxiety, whereas greater difficulty inhibiting behavioral responses was uniquely associated with ADHD. Attentional shifting mediated the relationship between anxiety and ritualistic behaviors, sameness behaviors, sensory hyper-responsivity, and overall autistic features. Conversely, inhibitory control mediated the relationship between ADHD and both irritability and self-injurious behaviors.</AbstractText These findings implicate components of executive functioning as important cognitive processes associated with co-occurring psychiatric conditions in autism. Future research should investigate the impact of early intervention for executive function difficulties on psychiatric and neurodevelopmental outcomes in autistic children.</AbstractText
|
Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder (NDD). In this narrative review, we summarize recent advances in quantitative and molecular genetic research from the past 5-10 years. Combined with large-scale international collaboration, these advances have resulted in fast-paced progress in understanding the etiology of ADHD and how genetic risk factors map on to clinical heterogeneity. Studies are converging on a number of key insights. First, ADHD is a highly polygenic NDD with a complex genetic architecture encompassing risk variants across the spectrum of allelic frequencies, which are implicated in neurobiological processes. Second, genetic studies strongly suggest that ADHD diagnosis shares a large proportion of genetic risks with continuously distributed traits of ADHD in the population, with shared genetic risks also seen across development and sex. Third, ADHD genetic risks are shared with those implicated in many other neurodevelopmental, psychiatric and somatic phenotypes. As sample sizes and the diversity of genetic studies continue to increase through international collaborative efforts, we anticipate further success with gene discovery, characterization of how the ADHD phenotype relates to other human traits and growing potential to use genomic risk factors for understanding clinical trajectories and for precision medicine approaches.</AbstractText
|
[This retracts the article DOI: 10.1021/acsomega.2c03368.].</AbstractText
|
Unique and shared influences of anxiety and ADHD on the behavioral profile of autism in early childhood. Autism is characterized by a wide range of core and associated behavioral features that can be influenced by co-occurring conditions such as attention-deficit hyperactivity disorder (ADHD) and anxiety disorders. Executive function difficulties are proposed as a common feature of autism and ADHD and are also evident in persons with anxiety disorders. However, little is known about how anxiety disorders or ADHD differentially impact executive functioning or how these difficulties may influence the presentation of core and associated autistic features in young children. In the current study, we explored the unique executive function difficulties associated with co-occurring anxiety and/or ADHD and elucidated how they differentially impact the clinical presentation of autism in young children.</AbstractText We assessed 69 autistic children, aged 3 to 5 years. Anxiety and ADHD were assessed through parent interview using the Preschool Age Psychiatric Assessment (PAPA). Executive functions were assessed using the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). Core autistic features were measured with the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and additional features were measured with the Restricted and Repetitive Behaviors Scale, Revised (RBS-R) and the Sensory Experiences Questionnaire (SEQ). Using an additive main effect general linear model, we examined the unique contributions of an anxiety disorder and/or ADHD on core and associated autistic features as well as executive function. Mediation analyses explored the contribution of the executive function profiles to specific features of autism.</AbstractText Results showed that greater difficulty with attentional shifting was uniquely associated with anxiety, whereas greater difficulty inhibiting behavioral responses was uniquely associated with ADHD. Attentional shifting mediated the relationship between anxiety and ritualistic behaviors, sameness behaviors, sensory hyper-responsivity, and overall autistic features. Conversely, inhibitory control mediated the relationship between ADHD and both irritability and self-injurious behaviors.</AbstractText These findings implicate components of executive functioning as important cognitive processes associated with co-occurring psychiatric conditions in autism. Future research should investigate the impact of early intervention for executive function difficulties on psychiatric and neurodevelopmental outcomes in autistic children.</AbstractText
|
Insights into attention-deficit/hyperactivity disorder from recent genetic studies. Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder (NDD). In this narrative review, we summarize recent advances in quantitative and molecular genetic research from the past 5-10 years. Combined with large-scale international collaboration, these advances have resulted in fast-paced progress in understanding the etiology of ADHD and how genetic risk factors map on to clinical heterogeneity. Studies are converging on a number of key insights. First, ADHD is a highly polygenic NDD with a complex genetic architecture encompassing risk variants across the spectrum of allelic frequencies, which are implicated in neurobiological processes. Second, genetic studies strongly suggest that ADHD diagnosis shares a large proportion of genetic risks with continuously distributed traits of ADHD in the population, with shared genetic risks also seen across development and sex. Third, ADHD genetic risks are shared with those implicated in many other neurodevelopmental, psychiatric and somatic phenotypes. As sample sizes and the diversity of genetic studies continue to increase through international collaborative efforts, we anticipate further success with gene discovery, characterization of how the ADHD phenotype relates to other human traits and growing potential to use genomic risk factors for understanding clinical trajectories and for precision medicine approaches.</AbstractText
|
Retraction of "Design, Synthesis, and Biological Evaluation of Notopterol Derivatives as Triple Inhibitors of AChE/BACE1/GSK3β for the Treatment of Alzheimer's Disease". [This retracts the article DOI: 10.1021/acsomega.2c03368.].</AbstractText
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27199652
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12433288
|
27693255
|
Neural Decoding and "Inner" Psychophysics: A Distance-to-Bound Approach for Linking Mind, Brain, and Behavior.
|
Real-time computing without stable states: a new framework for neural computation based on perturbations.
|
Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome.
|
A fundamental challenge for cognitive neuroscience is characterizing how the primitives of psychological theory are neurally implemented. Attempts to meet this challenge are a manifestation of what Fechner called "inner" psychophysics: the theory of the precise mapping between mental quantities and the brain. In his own time, inner psychophysics remained an unrealized ambition for Fechner. We suggest that, today, multivariate pattern analysis (MVPA), or neural "decoding," methods provide a promising starting point for developing an inner psychophysics. A cornerstone of these methods are simple linear classifiers applied to neural activity in high-dimensional activation spaces. We describe an approach to inner psychophysics based on the shared architecture of linear classifiers and observers under decision boundary models such as signal detection theory. Under this approach, distance from a decision boundary through activation space, as estimated by linear classifiers, can be used to predict reaction time in accordance with signal detection theory, and distance-to-bound models of reaction time. Our "neural distance-to-bound" approach is potentially quite general, and simple to implement. Furthermore, our recent work on visual object recognition suggests it is empirically viable. We believe the approach constitutes an important step along the path to an inner psychophysics that links mind, brain, and behavior.</AbstractText
|
A key challenge for neural modeling is to explain how a continuous stream of multimodal input from a rapidly changing environment can be processed by stereotypical recurrent circuits of integrate-and-fire neurons in real time. We propose a new computational model for real-time computing on time-varying input that provides an alternative to paradigms based on Turing machines or attractor neural networks. It does not require a task-dependent construction of neural circuits. Instead, it is based on principles of high-dimensional dynamical systems in combination with statistical learning theory and can be implemented on generic evolved or found recurrent circuitry. It is shown that the inherent transient dynamics of the high-dimensional dynamical system formed by a sufficiently large and heterogeneous neural circuit may serve as universal analog fading memory. Readout neurons can learn to extract in real time from the current state of such recurrent neural circuit information about current and past inputs that may be needed for diverse tasks. Stable internal states are not required for giving a stable output, since transient internal states can be transformed by readout neurons into stable target outputs due to the high dimensionality of the dynamical system. Our approach is based on a rigorous computational model, the liquid state machine, that, unlike Turing machines, does not require sequential transitions between well-defined discrete internal states. It is supported, as the Turing machine is, by rigorous mathematical results that predict universal computational power under idealized conditions, but for the biologically more realistic scenario of real-time processing of time-varying inputs. Our approach provides new perspectives for the interpretation of neural coding, the design of experiments and data analysis in neurophysiology, and the solution of problems in robotics and neurotechnology.</AbstractText
|
Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis syndrome (SMS), which is associated with diverse neurodevelopmental and behavioral symptoms as well as obesity. RAI1 encodes a nuclear protein but little is known about its molecular function or the cell types responsible for SMS symptoms. Using genetically engineered mice, we found that Rai1 preferentially occupies DNA regions near active promoters and promotes the expression of a group of genes involved in circuit assembly and neuronal communication. Behavioral analyses demonstrated that pan-neural loss of Rai1 causes deficits in motor function, learning, and food intake. These SMS-like phenotypes are produced by loss of Rai1 function in distinct neuronal types: Rai1 loss in inhibitory neurons or subcortical glutamatergic neurons causes learning deficits, while Rai1 loss in Sim1<sup
|
Neural Decoding and "Inner" Psychophysics: A Distance-to-Bound Approach for Linking Mind, Brain, and Behavior. A fundamental challenge for cognitive neuroscience is characterizing how the primitives of psychological theory are neurally implemented. Attempts to meet this challenge are a manifestation of what Fechner called "inner" psychophysics: the theory of the precise mapping between mental quantities and the brain. In his own time, inner psychophysics remained an unrealized ambition for Fechner. We suggest that, today, multivariate pattern analysis (MVPA), or neural "decoding," methods provide a promising starting point for developing an inner psychophysics. A cornerstone of these methods are simple linear classifiers applied to neural activity in high-dimensional activation spaces. We describe an approach to inner psychophysics based on the shared architecture of linear classifiers and observers under decision boundary models such as signal detection theory. Under this approach, distance from a decision boundary through activation space, as estimated by linear classifiers, can be used to predict reaction time in accordance with signal detection theory, and distance-to-bound models of reaction time. Our "neural distance-to-bound" approach is potentially quite general, and simple to implement. Furthermore, our recent work on visual object recognition suggests it is empirically viable. We believe the approach constitutes an important step along the path to an inner psychophysics that links mind, brain, and behavior.</AbstractText
|
Real-time computing without stable states: a new framework for neural computation based on perturbations. A key challenge for neural modeling is to explain how a continuous stream of multimodal input from a rapidly changing environment can be processed by stereotypical recurrent circuits of integrate-and-fire neurons in real time. We propose a new computational model for real-time computing on time-varying input that provides an alternative to paradigms based on Turing machines or attractor neural networks. It does not require a task-dependent construction of neural circuits. Instead, it is based on principles of high-dimensional dynamical systems in combination with statistical learning theory and can be implemented on generic evolved or found recurrent circuitry. It is shown that the inherent transient dynamics of the high-dimensional dynamical system formed by a sufficiently large and heterogeneous neural circuit may serve as universal analog fading memory. Readout neurons can learn to extract in real time from the current state of such recurrent neural circuit information about current and past inputs that may be needed for diverse tasks. Stable internal states are not required for giving a stable output, since transient internal states can be transformed by readout neurons into stable target outputs due to the high dimensionality of the dynamical system. Our approach is based on a rigorous computational model, the liquid state machine, that, unlike Turing machines, does not require sequential transitions between well-defined discrete internal states. It is supported, as the Turing machine is, by rigorous mathematical results that predict universal computational power under idealized conditions, but for the biologically more realistic scenario of real-time processing of time-varying inputs. Our approach provides new perspectives for the interpretation of neural coding, the design of experiments and data analysis in neurophysiology, and the solution of problems in robotics and neurotechnology.</AbstractText
|
Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome. Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis syndrome (SMS), which is associated with diverse neurodevelopmental and behavioral symptoms as well as obesity. RAI1 encodes a nuclear protein but little is known about its molecular function or the cell types responsible for SMS symptoms. Using genetically engineered mice, we found that Rai1 preferentially occupies DNA regions near active promoters and promotes the expression of a group of genes involved in circuit assembly and neuronal communication. Behavioral analyses demonstrated that pan-neural loss of Rai1 causes deficits in motor function, learning, and food intake. These SMS-like phenotypes are produced by loss of Rai1 function in distinct neuronal types: Rai1 loss in inhibitory neurons or subcortical glutamatergic neurons causes learning deficits, while Rai1 loss in Sim1<sup
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39253913
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37056668
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39012417
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Therapeutic Potential of Quercetin in Diabetic Neuropathy and Retinopathy: Exploring Molecular Mechanisms.
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Axonal transport deficits in the pathogenesis of diabetic peripheral neuropathy.
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Stubborn Families: Logics of Care of a Family Member with Borderline Personality Disorder.
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Diabetes mellitus poses a significant health challenge globally, often leading to debilitating complications, such as neuropathy and retinopathy. Quercetin, a flavonoid prevalent in fruits and vegetables, has demonstrated potential therapeutic effects in these conditions due to its antioxidant, anti-inflammatory, and neuroprotective properties. This review summarizes and provides a comprehensive understanding of the molecular mechanisms underlying the efficacy of quercetin in ameliorating diabetic neuropathy and retinopathy. A thorough search was carried out across scientific databases, such as SciFinder, PubMed, and Google Scholar, to gather pertinent literature regarding the effect of quercetin on diabetic neuropathy and retinopathy till February 2024. Preclinical studies indicate that quercetin mitigates neuropathic pain, sensory deficits, and nerve damage associated with diabetic neuropathy by improving neuronal function, reducing DNA damage, regulating pro-inflammatory cytokines, enhancing antioxidant enzyme levels and endothelial function, as well as restoring nerve injuries. In diabetic retinopathy, quercetin shows the potential to preserve retinal structure and function, inhibiting neovascularization, preventing retinal cell death, reducing pro-inflammatory cytokines, and increasing neurotrophic factor levels. Moreover, through modulating key signaling pathways, such as AMP-activated Protein Kinase (AMPK) activation, Glucose Transporter 4 (GLUT 4) upregulation, and insulin secretion regulation, quercetin demonstrates efficacy in reducing oxidative stress and inflammation, thereby protecting nerve and retinal tissues. Despite promising preclinical findings, challenges, such as limited bioavailability, necessitate further research to optimize quercetin's clinical application in order to establish its optimal dosage, formulation, and long-term efficacy in clinical settings.</AbstractText
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Diabetic peripheral neuropathy (DPN) is a chronic and prevalent metabolic disease that gravely endangers human health and seriously affects the quality of life of hyperglycemic patients. More seriously, it can lead to amputation and neuropathic pain, imposing a severe financial burden on patients and the healthcare system. Even with strict glycemic control or pancreas transplantation, peripheral nerve damage is difficult to reverse. Most current treatment options for DPN can only treat the symptoms but not the underlying mechanism. Patients with long-term diabetes mellitus (DM) develop axonal transport dysfunction, which could be an important factor in causing or exacerbating DPN. This review explores the underlying mechanisms that may be related to axonal transport impairment and cytoskeletal changes caused by DM, and the relevance of the latter with the occurrence and progression of DPN, including nerve fiber loss, diminished nerve conduction velocity, and impaired nerve regeneration, and also predicts possible therapeutic strategies. Understanding the mechanisms of diabetic neuronal injury is essential to prevent the deterioration of DPN and to develop new therapeutic strategies. Timely and effective improvement of axonal transport impairment is particularly critical for the treatment of peripheral neuropathies.</AbstractText
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This study conducted in-depth, largely unstructured interviews with 31 involved family members in a metropolitan area of the United States (US) Midwest on their experiences of BPD in a close relative. Narrative analysis employing concepts from anthropology (the logic of care and family assemblage) was used to examine the nature and quality of care practices and identify human, environmental, and cultural supports needed for family recovery. Findings indicate that these US family caregivers provided intensive and extensive care over the long term. They acted in situations of risk to their relative, and often disconnected from professional support. Parents labored under unforgiving normalizations: judgments (real or perceived) of not properly raising or "launching" their children and norms of parental self-sacrifice. The dearth of housing options for the young person hindered recovery. While duly recognizing the care practices provided by family members for a relative with BPD, I argue that there is a significant omission. Our conceptualizing of supports for family members of a relative with BPD needs to encompass supports for their own recovery. Respite, mental health care for caregivers, housing, support groups, and collaborative care (with professionals, peers and family members) could productively assist recovery of all family members.</AbstractText
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Therapeutic Potential of Quercetin in Diabetic Neuropathy and Retinopathy: Exploring Molecular Mechanisms. Diabetes mellitus poses a significant health challenge globally, often leading to debilitating complications, such as neuropathy and retinopathy. Quercetin, a flavonoid prevalent in fruits and vegetables, has demonstrated potential therapeutic effects in these conditions due to its antioxidant, anti-inflammatory, and neuroprotective properties. This review summarizes and provides a comprehensive understanding of the molecular mechanisms underlying the efficacy of quercetin in ameliorating diabetic neuropathy and retinopathy. A thorough search was carried out across scientific databases, such as SciFinder, PubMed, and Google Scholar, to gather pertinent literature regarding the effect of quercetin on diabetic neuropathy and retinopathy till February 2024. Preclinical studies indicate that quercetin mitigates neuropathic pain, sensory deficits, and nerve damage associated with diabetic neuropathy by improving neuronal function, reducing DNA damage, regulating pro-inflammatory cytokines, enhancing antioxidant enzyme levels and endothelial function, as well as restoring nerve injuries. In diabetic retinopathy, quercetin shows the potential to preserve retinal structure and function, inhibiting neovascularization, preventing retinal cell death, reducing pro-inflammatory cytokines, and increasing neurotrophic factor levels. Moreover, through modulating key signaling pathways, such as AMP-activated Protein Kinase (AMPK) activation, Glucose Transporter 4 (GLUT 4) upregulation, and insulin secretion regulation, quercetin demonstrates efficacy in reducing oxidative stress and inflammation, thereby protecting nerve and retinal tissues. Despite promising preclinical findings, challenges, such as limited bioavailability, necessitate further research to optimize quercetin's clinical application in order to establish its optimal dosage, formulation, and long-term efficacy in clinical settings.</AbstractText
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Axonal transport deficits in the pathogenesis of diabetic peripheral neuropathy. Diabetic peripheral neuropathy (DPN) is a chronic and prevalent metabolic disease that gravely endangers human health and seriously affects the quality of life of hyperglycemic patients. More seriously, it can lead to amputation and neuropathic pain, imposing a severe financial burden on patients and the healthcare system. Even with strict glycemic control or pancreas transplantation, peripheral nerve damage is difficult to reverse. Most current treatment options for DPN can only treat the symptoms but not the underlying mechanism. Patients with long-term diabetes mellitus (DM) develop axonal transport dysfunction, which could be an important factor in causing or exacerbating DPN. This review explores the underlying mechanisms that may be related to axonal transport impairment and cytoskeletal changes caused by DM, and the relevance of the latter with the occurrence and progression of DPN, including nerve fiber loss, diminished nerve conduction velocity, and impaired nerve regeneration, and also predicts possible therapeutic strategies. Understanding the mechanisms of diabetic neuronal injury is essential to prevent the deterioration of DPN and to develop new therapeutic strategies. Timely and effective improvement of axonal transport impairment is particularly critical for the treatment of peripheral neuropathies.</AbstractText
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Stubborn Families: Logics of Care of a Family Member with Borderline Personality Disorder. This study conducted in-depth, largely unstructured interviews with 31 involved family members in a metropolitan area of the United States (US) Midwest on their experiences of BPD in a close relative. Narrative analysis employing concepts from anthropology (the logic of care and family assemblage) was used to examine the nature and quality of care practices and identify human, environmental, and cultural supports needed for family recovery. Findings indicate that these US family caregivers provided intensive and extensive care over the long term. They acted in situations of risk to their relative, and often disconnected from professional support. Parents labored under unforgiving normalizations: judgments (real or perceived) of not properly raising or "launching" their children and norms of parental self-sacrifice. The dearth of housing options for the young person hindered recovery. While duly recognizing the care practices provided by family members for a relative with BPD, I argue that there is a significant omission. Our conceptualizing of supports for family members of a relative with BPD needs to encompass supports for their own recovery. Respite, mental health care for caregivers, housing, support groups, and collaborative care (with professionals, peers and family members) could productively assist recovery of all family members.</AbstractText
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39933773
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26913374
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40128612
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Hypothyroidism is a risk factor for transient ischemic attack: A meta-analysis.
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Use of Transcranial Doppler in Patients with Severe Traumatic Brain Injuries.
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Reversible reduction in brain myelin content upon marathon running.
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To evaluate whether hypothyroidism is a risk factor for transient ischemic attack (TIA).</AbstractText We systematically searched Embase, PubMed, Cochrane, Vipers database, China Biomedical Literature Database, Wanfang Data, and China National Knowledge Infrastructure for studies assessing the association between hypothyroidism and TIA (publication cut-off in May 2024). Two researchers independently extracted the data based on inclusion and exclusion criteria. Meta-analysis was carried out using Review Manager 5.3 software.</AbstractText A total of 7 studies (combined n=190248) were included. Hypothyroidism showed a significant association with TIA (risk ratio [RR]=1.43 [95% confidence interval [CI]: [1.29-1.57]). The association was significant in clinical hypothyroidism (RR=1.45 [95% CI: [1.31-1.62]) but not evident in subclinical hypothyroidism (RR=1.20 [95% CI: [0.90-1.61]). Sensitivity analysis confirmed the stability and reliability of the results from the 7 studies (Begg's test z=1.2, <i Hypothyroidism, particularly clinical hypothyroidism, may be an independent risk factor for TIA.<b
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Severe traumatic brain injuries (TBI) are associated with a high rate of mortality and disability. Transcranial Doppler (TCD) sonography permits a noninvasive measurement of cerebral blood flow. The purpose of this study is to determine the usefulness of TCD in patients with severe TBI. TCD was performed, from April 2008 to April 2013, on 255 patients with severe TBI, defined as a Glasgow Coma Scale score of ≤8 on admission. TCD was performed on hospital days 1, 2, 3, and 7. Hypoperfusion was defined by having two out of three of the following: 1) mean velocity (Vm) of the middle cerebral artery <35 cm/sec, 2) diastolic velocity (Vd) of the middle cerebral artery <20 cm/sec, or 3) pulsatility index (PI) of >1.4. Vasospasm was defined by the following: Vm of the middle cerebral artery >120 cm/sec and/or a Lindegaard index (LI) >3. One hundred fourteen (45%) had normal measurements. Of these, 92 (80.7%) had a good outcome, 6 (5.3%) had moderate disability, and 16 (14%) died, 4 from brain death. Seventy-two patients (28%) had hypoperfusion and 71 (98.6%) died, 65 from brain death, and 1 patient survived with moderate disability. Sixty-nine patients (27%) had vasospasm, 31 (44.9%) had a good outcome, 16 (23.2%) had severe disability, and 22 (31.9%) died, 13 from brain death. The vasospasm was detected on hospital day 1 in 8 patients, on day 2 in 23 patients, on day 3 in 22 patients, and on day 7 in 16 patients. Patients with normal measurements can be expected to survive. Patients with hypoperfusion have a poor prognosis. Patients with vasospasm have a high incidence of mortality and severe disability. TCD is useful in determining early prognosis.</AbstractText
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Here we use magnetic resonance imaging to study the impact of marathon running on brain structure in humans. We show that the signal for myelin water fraction-a surrogate of myelin content-is substantially reduced upon marathon running in specific brain regions involved in motor coordination and sensory and emotional integration, but recovers within two months. These findings suggest that brain myelin content is temporarily and reversibly diminished by severe exercise, a finding consistent with recent evidence from rodent studies that suggest that myelin lipids may act as glial energy reserves in extreme metabolic conditions.</AbstractText
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Hypothyroidism is a risk factor for transient ischemic attack: A meta-analysis. To evaluate whether hypothyroidism is a risk factor for transient ischemic attack (TIA).</AbstractText We systematically searched Embase, PubMed, Cochrane, Vipers database, China Biomedical Literature Database, Wanfang Data, and China National Knowledge Infrastructure for studies assessing the association between hypothyroidism and TIA (publication cut-off in May 2024). Two researchers independently extracted the data based on inclusion and exclusion criteria. Meta-analysis was carried out using Review Manager 5.3 software.</AbstractText A total of 7 studies (combined n=190248) were included. Hypothyroidism showed a significant association with TIA (risk ratio [RR]=1.43 [95% confidence interval [CI]: [1.29-1.57]). The association was significant in clinical hypothyroidism (RR=1.45 [95% CI: [1.31-1.62]) but not evident in subclinical hypothyroidism (RR=1.20 [95% CI: [0.90-1.61]). Sensitivity analysis confirmed the stability and reliability of the results from the 7 studies (Begg's test z=1.2, <i Hypothyroidism, particularly clinical hypothyroidism, may be an independent risk factor for TIA.<b
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Use of Transcranial Doppler in Patients with Severe Traumatic Brain Injuries. Severe traumatic brain injuries (TBI) are associated with a high rate of mortality and disability. Transcranial Doppler (TCD) sonography permits a noninvasive measurement of cerebral blood flow. The purpose of this study is to determine the usefulness of TCD in patients with severe TBI. TCD was performed, from April 2008 to April 2013, on 255 patients with severe TBI, defined as a Glasgow Coma Scale score of ≤8 on admission. TCD was performed on hospital days 1, 2, 3, and 7. Hypoperfusion was defined by having two out of three of the following: 1) mean velocity (Vm) of the middle cerebral artery <35 cm/sec, 2) diastolic velocity (Vd) of the middle cerebral artery <20 cm/sec, or 3) pulsatility index (PI) of >1.4. Vasospasm was defined by the following: Vm of the middle cerebral artery >120 cm/sec and/or a Lindegaard index (LI) >3. One hundred fourteen (45%) had normal measurements. Of these, 92 (80.7%) had a good outcome, 6 (5.3%) had moderate disability, and 16 (14%) died, 4 from brain death. Seventy-two patients (28%) had hypoperfusion and 71 (98.6%) died, 65 from brain death, and 1 patient survived with moderate disability. Sixty-nine patients (27%) had vasospasm, 31 (44.9%) had a good outcome, 16 (23.2%) had severe disability, and 22 (31.9%) died, 13 from brain death. The vasospasm was detected on hospital day 1 in 8 patients, on day 2 in 23 patients, on day 3 in 22 patients, and on day 7 in 16 patients. Patients with normal measurements can be expected to survive. Patients with hypoperfusion have a poor prognosis. Patients with vasospasm have a high incidence of mortality and severe disability. TCD is useful in determining early prognosis.</AbstractText
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Reversible reduction in brain myelin content upon marathon running. Here we use magnetic resonance imaging to study the impact of marathon running on brain structure in humans. We show that the signal for myelin water fraction-a surrogate of myelin content-is substantially reduced upon marathon running in specific brain regions involved in motor coordination and sensory and emotional integration, but recovers within two months. These findings suggest that brain myelin content is temporarily and reversibly diminished by severe exercise, a finding consistent with recent evidence from rodent studies that suggest that myelin lipids may act as glial energy reserves in extreme metabolic conditions.</AbstractText
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40744900
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15843731
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40249453
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Tumor-driven SRS VMAT planning: Regression models for intermediate and low dose spillage.
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Three-dimensional dose verification of the clinical application of gamma knife stereotactic radiosurgery using polymer gel and MRI.
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The mitochondrial LONP1 protease: molecular targets and role in pathophysiology.
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Stereotactic radiosurgery (SRS) for brain metastases using volumetric modulated arc therapy (VMAT) is increasingly utilized. While high-dose conformity guidelines relative to tumor volume exist, recommendations for intermediate and low-dose regions remain undefined. This study explores tumor-specific characteristics and new dosimetric parameters to develop regression models for standardizing intracranial SRS planning.</AbstractText We introduce two dosimetric quantities: R<sub Strong correlations were found between PTV<sub This study proposes regression-based models for predicting dose spill based on tumor burden, total PTV volume and number of targets. These models provide a framework for model-based SRS planning, offering clinical physicists patient-specific guidance to improve consistency, optimize plan quality, and support future standardization efforts.</AbstractText
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This work seeks to verify multi-shot clinical applications of stereotactic radiosurgery with a Leksell Gamma Knife model C unit employing a polymer gel-MRI based experimental procedure, which has already been shown to be capable of verifying the precision and accuracy of dose delivery in single-shot gamma knife applications. The treatment plan studied in the present work resembles a clinical treatment case of pituitary adenoma using four 8 mm and one 14 mm collimator helmet shots to deliver a prescription dose of 15 Gy to the 50% isodose line (30 Gy maximum dose). For the experimental dose verification of the treatment plan, the same criteria as those used in the clinical treatment planning evaluation were employed. These included comparison of measured and GammaPlan calculated data, in terms of percentage isodose contours on axial, coronal and sagittal planes, as well as 3D plan evaluation criteria such as dose-volume histograms for the target volume, target coverage and conformity indices. Measured percentage isodose contours compared favourably with calculated ones despite individual point fluctuations at low dose contours (e.g., 20%) mainly due to the effect of T2 measurement uncertainty on dose resolution. Dose-volume histogram data were also found in a good agreement while the experimental results for the percentage target coverage and conformity index were 94% and 1.17 relative to corresponding GammaPlan calculations of 96% and 1.12, respectively. Overall, polymer gel results verified the planned dose distribution within experimental uncertainties and uncertainty related to the digitization process of selected GammaPlan output data.</AbstractText
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Lon peptidase 1 (LONP1), a member of the AAA + family, is essential for maintaining mitochondrial function. Recent studies have revealed that LONP1 serves as a multifunctional enzyme, acting not only as a protease but also as a molecular chaperone, interacting with mitochondrial DNA (mtDNA), and playing roles in mitochondrial dynamics, oxidative stress, cellular respiration, and energy metabolism. LONP1 is evolutionarily highly conserved, and mutations or dysfunctions in LONP1 can lead to diseases. There is growing evidence linking LONP1 to various human diseases, such as tumors, neurodegenerative diseases, and heart diseases. This review discusses the discovery, molecular structure, subcellular localization, tissue distribution, and mitochondrial function of LONP1. Furthermore, it summarizes the associations between LONP1 and tumors, neurodegenerative diseases, and heart diseases, exploring its role in different diseases and potential molecular mechanisms. It also analyzes the regulatory effects of related inhibitors and agonists on LONP1. Considering the pleiotropic effects of LONP1, the study of LONP1 is crucial to understanding the relevant pathophysiological processes and developing strategies to modulate and control these related diseases.</AbstractText
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Tumor-driven SRS VMAT planning: Regression models for intermediate and low dose spillage. Stereotactic radiosurgery (SRS) for brain metastases using volumetric modulated arc therapy (VMAT) is increasingly utilized. While high-dose conformity guidelines relative to tumor volume exist, recommendations for intermediate and low-dose regions remain undefined. This study explores tumor-specific characteristics and new dosimetric parameters to develop regression models for standardizing intracranial SRS planning.</AbstractText We introduce two dosimetric quantities: R<sub Strong correlations were found between PTV<sub This study proposes regression-based models for predicting dose spill based on tumor burden, total PTV volume and number of targets. These models provide a framework for model-based SRS planning, offering clinical physicists patient-specific guidance to improve consistency, optimize plan quality, and support future standardization efforts.</AbstractText
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Three-dimensional dose verification of the clinical application of gamma knife stereotactic radiosurgery using polymer gel and MRI. This work seeks to verify multi-shot clinical applications of stereotactic radiosurgery with a Leksell Gamma Knife model C unit employing a polymer gel-MRI based experimental procedure, which has already been shown to be capable of verifying the precision and accuracy of dose delivery in single-shot gamma knife applications. The treatment plan studied in the present work resembles a clinical treatment case of pituitary adenoma using four 8 mm and one 14 mm collimator helmet shots to deliver a prescription dose of 15 Gy to the 50% isodose line (30 Gy maximum dose). For the experimental dose verification of the treatment plan, the same criteria as those used in the clinical treatment planning evaluation were employed. These included comparison of measured and GammaPlan calculated data, in terms of percentage isodose contours on axial, coronal and sagittal planes, as well as 3D plan evaluation criteria such as dose-volume histograms for the target volume, target coverage and conformity indices. Measured percentage isodose contours compared favourably with calculated ones despite individual point fluctuations at low dose contours (e.g., 20%) mainly due to the effect of T2 measurement uncertainty on dose resolution. Dose-volume histogram data were also found in a good agreement while the experimental results for the percentage target coverage and conformity index were 94% and 1.17 relative to corresponding GammaPlan calculations of 96% and 1.12, respectively. Overall, polymer gel results verified the planned dose distribution within experimental uncertainties and uncertainty related to the digitization process of selected GammaPlan output data.</AbstractText
|
The mitochondrial LONP1 protease: molecular targets and role in pathophysiology. Lon peptidase 1 (LONP1), a member of the AAA + family, is essential for maintaining mitochondrial function. Recent studies have revealed that LONP1 serves as a multifunctional enzyme, acting not only as a protease but also as a molecular chaperone, interacting with mitochondrial DNA (mtDNA), and playing roles in mitochondrial dynamics, oxidative stress, cellular respiration, and energy metabolism. LONP1 is evolutionarily highly conserved, and mutations or dysfunctions in LONP1 can lead to diseases. There is growing evidence linking LONP1 to various human diseases, such as tumors, neurodegenerative diseases, and heart diseases. This review discusses the discovery, molecular structure, subcellular localization, tissue distribution, and mitochondrial function of LONP1. Furthermore, it summarizes the associations between LONP1 and tumors, neurodegenerative diseases, and heart diseases, exploring its role in different diseases and potential molecular mechanisms. It also analyzes the regulatory effects of related inhibitors and agonists on LONP1. Considering the pleiotropic effects of LONP1, the study of LONP1 is crucial to understanding the relevant pathophysiological processes and developing strategies to modulate and control these related diseases.</AbstractText
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37223596
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21514250
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36673395
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Large Vessel Vasculitis After the Administration of Oxford-AstraZeneca COVID-19 Vaccine.
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The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.
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Feeding Corn Silage or Grass Hay as Sole Dietary Forage Sources: Overall Mechanism of Forages Regulating Health-Promoting Fatty Acid Status in Milk of Dairy Cows.
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We report a case of a 52-year-old female with Large Vessel Vasculitis (LVV) after vaccination with Oxford-AstraZeneca COVID-19 vaccine. She was presented with fever, started two weeks after the second dose of vaccine. Laboratory values, revealed elevated inflammatory markers and chronic disease anaemia. All the infectious causes were excluded, and immunology tests were negative. Computed Tomography (CT) demonstrated concentric wall thickening of ascending and descending aorta. Positron Emission Tomography (PET) scan showed increased vascular fluorodeoxyglucose (FDG), compatible with LVV. Within one month of treatment with high dose glucocorticoids and iv cyclophosphamide, laboratory findings normalised, and fever resolved.</AbstractText
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The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.</AbstractText
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Different dietary forage sources regulate health-promoting fatty acids (HPFAs), such as conjugated linoleic acids (CLAs) and omega-3 polyunsaturated fatty acids (n-3 PUFAs), in the milk of lactating cows. However, the overall mechanism of forages regulating lipid metabolism from the gastrointestinal tract to the mammary glands (MGs) is not clear. Three isocaloric diets that contained (1) 46% corn silage (CS), (2) a mixture of 23% corn silage and 14% grass hays (MIX), and (3) 28% grass hays (GH) as the forage sources and six cannulated (rumen, proximal duodenum, and terminal ileum) lactating cows were assigned to a double 3 × 3 Latin square design. Our results show that a higher proportion of grass hay in the diets increased the relative contents of short-chain fatty acids (SCFAs), CLAs, and n-3 PUFAs. The lower relative content of SCFA in the milk of CS was predominantly due to the reduction in acetate production in the rumen and arteriovenous differences in the MG, indicating that the de novo synthesis pathways were inhibited. The elevated relative contents of total CLA and n-3 PUFA in the milk of GH were attributed to the increases in apparent intestinal digestion and arteriovenous differences in total CLA and n-3 PUFA, together with the higher Δ<sup
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Large Vessel Vasculitis After the Administration of Oxford-AstraZeneca COVID-19 Vaccine. We report a case of a 52-year-old female with Large Vessel Vasculitis (LVV) after vaccination with Oxford-AstraZeneca COVID-19 vaccine. She was presented with fever, started two weeks after the second dose of vaccine. Laboratory values, revealed elevated inflammatory markers and chronic disease anaemia. All the infectious causes were excluded, and immunology tests were negative. Computed Tomography (CT) demonstrated concentric wall thickening of ascending and descending aorta. Positron Emission Tomography (PET) scan showed increased vascular fluorodeoxyglucose (FDG), compatible with LVV. Within one month of treatment with high dose glucocorticoids and iv cyclophosphamide, laboratory findings normalised, and fever resolved.</AbstractText
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The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.</AbstractText
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Feeding Corn Silage or Grass Hay as Sole Dietary Forage Sources: Overall Mechanism of Forages Regulating Health-Promoting Fatty Acid Status in Milk of Dairy Cows. Different dietary forage sources regulate health-promoting fatty acids (HPFAs), such as conjugated linoleic acids (CLAs) and omega-3 polyunsaturated fatty acids (n-3 PUFAs), in the milk of lactating cows. However, the overall mechanism of forages regulating lipid metabolism from the gastrointestinal tract to the mammary glands (MGs) is not clear. Three isocaloric diets that contained (1) 46% corn silage (CS), (2) a mixture of 23% corn silage and 14% grass hays (MIX), and (3) 28% grass hays (GH) as the forage sources and six cannulated (rumen, proximal duodenum, and terminal ileum) lactating cows were assigned to a double 3 × 3 Latin square design. Our results show that a higher proportion of grass hay in the diets increased the relative contents of short-chain fatty acids (SCFAs), CLAs, and n-3 PUFAs. The lower relative content of SCFA in the milk of CS was predominantly due to the reduction in acetate production in the rumen and arteriovenous differences in the MG, indicating that the de novo synthesis pathways were inhibited. The elevated relative contents of total CLA and n-3 PUFA in the milk of GH were attributed to the increases in apparent intestinal digestion and arteriovenous differences in total CLA and n-3 PUFA, together with the higher Δ<sup
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36877200
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24753177
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37293625
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New Insights into the Spread of MRS-Based Water T2 Values Observed in Highly Fatty Replaced Muscles.
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Using dynamic contrast-enhanced MRI to quantitatively characterize maternal vascular organization in the primate placenta.
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Plp1 in the enteric nervous system is preferentially expressed during early postnatal development in mouse as DM20, whose expression appears reliant on an intronic enhancer.
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The reference standard for assessing water T<sub To investigate the relationship between T<sub Retrospective case-control study.</AbstractText A total of 151 patients with neuromuscular disorders (mean age ± standard deviation = 52.5 ± 22.6 years, 54% male), 44 healthy volunteers (26.5 ± 13.0 years, 57% male).</AbstractText A 3-T; single-voxel stimulated echo acquisition mode (STEAM) MRS, multispin echo (MSE) imaging (for T<sub Mono-exponential and bi-exponential models were fitted to water T<sub Mann-Whitney U tests, Kruskal-Wallis tests. A P-value <0.05 was considered statistically significant.</AbstractText Normal T<sub The findings suggest that the cause for (abnormally) T<sub 3 TECHNICAL EFFICACY: Stage 3.</AbstractText
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The maternal microvasculature of the primate placenta is organized into 10-20 perfusion domains that are functionally optimized to facilitate nutrient exchange to support fetal growth. This study describes a dynamic contrast-enhanced magnetic resonance imaging method for identifying vascular domains and quantifying maternal blood flow in them.</AbstractText A rhesus macaque on the 133rd day of pregnancy (G133, term = 165 days) underwent Doppler ultrasound procedures, dynamic contrast-enhanced magnetic resonance imaging and Cesarean-section delivery. Serial T1 -weighted images acquired throughout intravenous injection of a contrast reagent bolus were analyzed to obtain contrast reagent arrival time maps of the placenta.</AbstractText Watershed segmentation of the arrival time map identified 16 perfusion domains. The number and location of these domains corresponded to anatomical cotyledonary units observed following delivery. Analysis of the contrast reagent wave front through each perfusion domain enabled determination of volumetric flow, which ranged from 9.03 to 44.9 mL/s (25.2 ± 10.3 mL/s). These estimates are supported by Doppler ultrasound results.</AbstractText The dynamic contrast-enhanced magnetic resonance imaging analysis described here provides quantitative estimates of the number of maternal perfusion domains in a primate placenta and estimates flow within each domain. Anticipated extensions of this technique are to the study placental function in non-human primate models of obstetric complications.</AbstractText
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Recently, the myelin proteolipid protein gene (<i
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New Insights into the Spread of MRS-Based Water T2 Values Observed in Highly Fatty Replaced Muscles. The reference standard for assessing water T<sub To investigate the relationship between T<sub Retrospective case-control study.</AbstractText A total of 151 patients with neuromuscular disorders (mean age ± standard deviation = 52.5 ± 22.6 years, 54% male), 44 healthy volunteers (26.5 ± 13.0 years, 57% male).</AbstractText A 3-T; single-voxel stimulated echo acquisition mode (STEAM) MRS, multispin echo (MSE) imaging (for T<sub Mono-exponential and bi-exponential models were fitted to water T<sub Mann-Whitney U tests, Kruskal-Wallis tests. A P-value <0.05 was considered statistically significant.</AbstractText Normal T<sub The findings suggest that the cause for (abnormally) T<sub 3 TECHNICAL EFFICACY: Stage 3.</AbstractText
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Using dynamic contrast-enhanced MRI to quantitatively characterize maternal vascular organization in the primate placenta. The maternal microvasculature of the primate placenta is organized into 10-20 perfusion domains that are functionally optimized to facilitate nutrient exchange to support fetal growth. This study describes a dynamic contrast-enhanced magnetic resonance imaging method for identifying vascular domains and quantifying maternal blood flow in them.</AbstractText A rhesus macaque on the 133rd day of pregnancy (G133, term = 165 days) underwent Doppler ultrasound procedures, dynamic contrast-enhanced magnetic resonance imaging and Cesarean-section delivery. Serial T1 -weighted images acquired throughout intravenous injection of a contrast reagent bolus were analyzed to obtain contrast reagent arrival time maps of the placenta.</AbstractText Watershed segmentation of the arrival time map identified 16 perfusion domains. The number and location of these domains corresponded to anatomical cotyledonary units observed following delivery. Analysis of the contrast reagent wave front through each perfusion domain enabled determination of volumetric flow, which ranged from 9.03 to 44.9 mL/s (25.2 ± 10.3 mL/s). These estimates are supported by Doppler ultrasound results.</AbstractText The dynamic contrast-enhanced magnetic resonance imaging analysis described here provides quantitative estimates of the number of maternal perfusion domains in a primate placenta and estimates flow within each domain. Anticipated extensions of this technique are to the study placental function in non-human primate models of obstetric complications.</AbstractText
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Plp1 in the enteric nervous system is preferentially expressed during early postnatal development in mouse as DM20, whose expression appears reliant on an intronic enhancer. Recently, the myelin proteolipid protein gene (<i
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31956390
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30637843
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32669845
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Advanced multimodality neuroimaging of a giant, thrombosed MCA aneurysm complicated by an acute stroke in a pediatric patient.
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MRI as a diagnostic biomarker for differentiating primary central nervous system lymphoma from glioblastoma: A systematic review and meta-analysis.
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Review of Clinical Outcome Assessments in Pediatric Attention-Deficit/Hyperactivity Disorder.
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A 17-year-old boy presented to our quaternary hospital because of acute mental status changes following prolonged gastrointestinal illness resulting in dehydration. Neuroimaging studies with computed tomography and magnetic resonance imaging (MRI) revealed a giant thrombosed aneurysm of the left middle cerebral artery (MCA) with acute left MCA stroke. An ischemic penumbra was identified based upon the mismatch between diffusion weighted (DWI) and susceptibility weighted (SWI) MRI matching with the perfusion weighted imaging (PWI). On follow-up MRI, the core of ischemia as identified by DWI progressed into the ischemic penumbra identified by SWI. The patient had permanent moderate right hemiparesis and aphasia on last follow-up. In conclusion, thrombosis is a rare complication of a giant aneurysm in children. Advanced neuroimaging using the combination of DWI and noncontrast enhanced SWI is a valuable alternative or possibly adjunct to PWI to identify tissue at risk for progressing stroke.</AbstractText
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Accurate preoperative differentiation of primary central nervous system lymphoma (PCNSL) and glioblastoma is clinically crucial because the treatment strategies differ substantially.</AbstractText To evaluate the diagnostic performance of MRI for differentiating PCNSL from glioblastoma.</AbstractText Systematic review and meta-analysis.</AbstractText Ovid-MEDLINE and EMBASE databases were searched to find relevant original articles up to November 25, 2018. The search term combined synonyms for "lymphoma," "glioblastoma," and "MRI."</AbstractText Patients underwent at least one MRI sequence including diffusion-weighted imaging (DWI), dynamic susceptibility-weighted contrast-enhanced imaging (DSC), dynamic contrast-enhanced imaging (DCE), arterial spin labeling (ASL), susceptibility-weighted imaging (SWI), intravoxel incoherent motion (IVIM), and magnetic resonance spectroscopy (MRS) using 1.5 or 3 T.</AbstractText Quality assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool.</AbstractText Hierarchical logistic regression modeling was used to obtain pooled sensitivity and specificity. Meta-regression was performed.</AbstractText Twenty-two studies with 1182 patients were included. MRI sequences demonstrated high overall diagnostic performance with pooled sensitivity of 91% (95% confidence interval [CI], 87-93%) and specificity of 89% (95% CI, 85-93%). The area under the hierarchical summary receiver operating characteristic curve was 0.92 (95% CI, 0.90-0.94). Studies using DSC or ASL showed high diagnostic performance (sensitivity of 93% [95% CI, 89-97%] and specificity of 91% [95% CI, 86-96%]). Heterogeneity was only detected in specificity (I<sup MRI showed overall high diagnostic performance for differentiating PCNSL from glioblastoma, with studies using DSC or ASL showing high diagnostic performance. Therefore, MRI sequences including DSC or ASL is a potential diagnostic tool for differentiating PCNSL from glioblastoma.</AbstractText 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:560-572.</AbstractText
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Various clinical outcome assessments (COAs) are used in clinical research to assess and monitor treatment efficacy in pediatric attention-deficit/hyperactivity disorder (ADHD) trials. It is unclear whether the concepts assessed are those that are important to patients and their caregivers. The concepts measured by commonly used COAs in this population have not been explicitly compared.</AbstractText We conducted reviews of the qualitative literature to extract information on pediatric ADHD-related concepts reported by pediatric patients, parents, and teachers. Using these concepts, we developed a conceptual framework of pediatric ADHD using both the <i Of the 27 COAs found in the empirical literature, 4 COAs assessed only DSM symptoms. The most comprehensive coverage of our conceptual framework was seen in the Swanson, Nolan, and Pelham Rating Scale-DSM-IV (SNAP-IV). Eighteen COAs were used in at least 1 clinical trial: ADHD-Rating Scale-IV (ADHD<i We identified symptoms and behavioral impacts from qualitative studies in pediatric ADHD that are not included in DSM-based criteria. Most COAs used in pediatric ADHD clinical trials measure only those symptoms listed in the DSM. While these COAs can measure symptom severity, they may not assess the full range of symptoms and impacts important to patients and their caregivers. Future research is needed to measure all concepts important to patients and caregivers within ADHD clinical trials.</AbstractText
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Advanced multimodality neuroimaging of a giant, thrombosed MCA aneurysm complicated by an acute stroke in a pediatric patient. A 17-year-old boy presented to our quaternary hospital because of acute mental status changes following prolonged gastrointestinal illness resulting in dehydration. Neuroimaging studies with computed tomography and magnetic resonance imaging (MRI) revealed a giant thrombosed aneurysm of the left middle cerebral artery (MCA) with acute left MCA stroke. An ischemic penumbra was identified based upon the mismatch between diffusion weighted (DWI) and susceptibility weighted (SWI) MRI matching with the perfusion weighted imaging (PWI). On follow-up MRI, the core of ischemia as identified by DWI progressed into the ischemic penumbra identified by SWI. The patient had permanent moderate right hemiparesis and aphasia on last follow-up. In conclusion, thrombosis is a rare complication of a giant aneurysm in children. Advanced neuroimaging using the combination of DWI and noncontrast enhanced SWI is a valuable alternative or possibly adjunct to PWI to identify tissue at risk for progressing stroke.</AbstractText
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MRI as a diagnostic biomarker for differentiating primary central nervous system lymphoma from glioblastoma: A systematic review and meta-analysis. Accurate preoperative differentiation of primary central nervous system lymphoma (PCNSL) and glioblastoma is clinically crucial because the treatment strategies differ substantially.</AbstractText To evaluate the diagnostic performance of MRI for differentiating PCNSL from glioblastoma.</AbstractText Systematic review and meta-analysis.</AbstractText Ovid-MEDLINE and EMBASE databases were searched to find relevant original articles up to November 25, 2018. The search term combined synonyms for "lymphoma," "glioblastoma," and "MRI."</AbstractText Patients underwent at least one MRI sequence including diffusion-weighted imaging (DWI), dynamic susceptibility-weighted contrast-enhanced imaging (DSC), dynamic contrast-enhanced imaging (DCE), arterial spin labeling (ASL), susceptibility-weighted imaging (SWI), intravoxel incoherent motion (IVIM), and magnetic resonance spectroscopy (MRS) using 1.5 or 3 T.</AbstractText Quality assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool.</AbstractText Hierarchical logistic regression modeling was used to obtain pooled sensitivity and specificity. Meta-regression was performed.</AbstractText Twenty-two studies with 1182 patients were included. MRI sequences demonstrated high overall diagnostic performance with pooled sensitivity of 91% (95% confidence interval [CI], 87-93%) and specificity of 89% (95% CI, 85-93%). The area under the hierarchical summary receiver operating characteristic curve was 0.92 (95% CI, 0.90-0.94). Studies using DSC or ASL showed high diagnostic performance (sensitivity of 93% [95% CI, 89-97%] and specificity of 91% [95% CI, 86-96%]). Heterogeneity was only detected in specificity (I<sup MRI showed overall high diagnostic performance for differentiating PCNSL from glioblastoma, with studies using DSC or ASL showing high diagnostic performance. Therefore, MRI sequences including DSC or ASL is a potential diagnostic tool for differentiating PCNSL from glioblastoma.</AbstractText 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:560-572.</AbstractText
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Review of Clinical Outcome Assessments in Pediatric Attention-Deficit/Hyperactivity Disorder. Various clinical outcome assessments (COAs) are used in clinical research to assess and monitor treatment efficacy in pediatric attention-deficit/hyperactivity disorder (ADHD) trials. It is unclear whether the concepts assessed are those that are important to patients and their caregivers. The concepts measured by commonly used COAs in this population have not been explicitly compared.</AbstractText We conducted reviews of the qualitative literature to extract information on pediatric ADHD-related concepts reported by pediatric patients, parents, and teachers. Using these concepts, we developed a conceptual framework of pediatric ADHD using both the <i Of the 27 COAs found in the empirical literature, 4 COAs assessed only DSM symptoms. The most comprehensive coverage of our conceptual framework was seen in the Swanson, Nolan, and Pelham Rating Scale-DSM-IV (SNAP-IV). Eighteen COAs were used in at least 1 clinical trial: ADHD-Rating Scale-IV (ADHD<i We identified symptoms and behavioral impacts from qualitative studies in pediatric ADHD that are not included in DSM-based criteria. Most COAs used in pediatric ADHD clinical trials measure only those symptoms listed in the DSM. While these COAs can measure symptom severity, they may not assess the full range of symptoms and impacts important to patients and their caregivers. Future research is needed to measure all concepts important to patients and caregivers within ADHD clinical trials.</AbstractText
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39346796
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29356973
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40000425
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Bilateral hearing loss caused by anti-NMDA receptor encephalitis with teratoma: A case report.
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Pitfalls in clinical diagnosis of anti-NMDA receptor encephalitis.
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Neurocyberethics, a new and pertinent approach to neuroethics.
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Autoimmune encephalitis (AE) is an autoimmune disease in the central nervous system. Clinical manifestations include cognitive dysfunction, psychiatric-behavioral abnormalities, epilepsy, motor disorders, speech disorders, and memory impairment. Some patients do not have the characteristic clinical manifestations of the disease when they see a doctor, so they are easily diagnosed incorrectly. Autoimmune antibodies originate from genetic and acquired factors. Clinical data have found a correlation between ovarian teratoma and autoimmune encephalitis. This case reports a 34-year-old woman who was diagnosed with teratoma-associated anti-N-methyl-D- aspartate receptor-mediated autoimmune encephalitis called anti-N-methyl-D-aspartate receptor encephalitis with bilateral hearing loss in 2021. Through this case report, clinicians will pay attention to autoimmune encephalitis and raise awareness of the specific clinical manifestations of autoimmune encephalitis, and focus on early identification. It means that clinicians should be familiar with the representative clinical manifestations of the disease.</AbstractText
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To report pitfalls in the clinical diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.</AbstractText We retrospectively reviewed the clinical information of 221 patients with clinically suspected autoimmune neurological disorders who underwent testing for autoantibodies against neuronal cell-surface antigens between January 1, 2007 and September 10, 2017. Forty-one patients met the diagnostic criteria for probable anti-NMDAR encephalitis (probable criteria), but one was excluded because neither serum nor CSF was examined at the active stage. Thus, in 220 patients, sensitivity and specificity of the probable criteria were assessed.</AbstractText NMDAR-antibodies were detected in 34 of 40 patients (85%) with the probable criteria; however, 2 of the 6 antibody-negative patients had ovarian teratoma. The median age at onset was higher in antibody-negative patients than those with antibodies (49 vs. 27 years, p = 0.015). The age at onset was associated with the probability of antibody detection (p = 0.014); the probability was less than 50% in patients aged 50 years or older. NMDAR-antibodies were also detected in 5 of 180 patients who did not fulfill the probable criteria; these patients presented with isolated epileptic syndrome (n = 2), atypical demyelinating syndrome (n = 2; one with aquaporin 4 antibodies), and autoimmune post-herpes simplex encephalitis (post-HSE) (n = 1). Sensitivity and specificity of the probable criteria was 87.2 and 96.7%, respectively.</AbstractText The probable criteria are valid, but the diversity of clinical phenotype should be taken into account in diagnosing anti-NMDAR encephalitis particularly in patients aged 50 years or older, or with isolated epileptic syndrome, atypical demyelinating syndrome, or post-HSE.</AbstractText
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Ethics in neuroscience presents an evolutionary development that has required a more punctual attention, from the knowledge of functional neuroimaging that defines the structures related to the emotions and cognitive functions. Systematic review in Pub Med according to PRISMA format from the keywords and specific search for the concept of neuroethics, cyberethics and neurocyberethics. The neurocyberethics is not available, despite contemporary advances in neurotechnology and Artificial Intelligence (AI). Even though in the enormous amount of data related to AI in neuroscience, the ethical implications related to the transparency, regulation and rational use of this digital technological development have not been fully considered. In the current era, neurocyberethics needs to be considered, because of its relevance in the landscape of neurotechnology which poses new challenges and dilemmas not contemplated in traditional neuroethics.</AbstractText La ética en la neurociencia presenta un despliegue evolutivo que ha requerido una atención más puntual a partir del conocimiento de la neuroimagen funcional, que define las estructuras relacionadas con las emociones y la cognición. Se llevó a cabo una revisión sistemática en PubMed de acuerdo con el formato PRISMA a partir de las palabras clave neuroética, ciberética y neurociberética. La neurociberética como concepto no figura en los contenidos científicos, pese a los avances contemporáneos de la neurotecnología y la inteligencia artificial. Aun cuando se identifican numerosos aportes relacionados con la inteligencia artificial en la neurociencia, no se han considerado las implicaciones éticas relacionadas con la transparencia, regulación y uso racional de nuevos dispositivos vinculados con este desarrollo neurotecnológico. En la era actual es imprescindible considerar a la neurociberética por su pertinencia conceptual y sus aplicaciones en el panorama de la neurotecnología, lo que propone nuevos retos y dilemas no considerados por la neuroética tradicional.</AbstractText
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Bilateral hearing loss caused by anti-NMDA receptor encephalitis with teratoma: A case report. Autoimmune encephalitis (AE) is an autoimmune disease in the central nervous system. Clinical manifestations include cognitive dysfunction, psychiatric-behavioral abnormalities, epilepsy, motor disorders, speech disorders, and memory impairment. Some patients do not have the characteristic clinical manifestations of the disease when they see a doctor, so they are easily diagnosed incorrectly. Autoimmune antibodies originate from genetic and acquired factors. Clinical data have found a correlation between ovarian teratoma and autoimmune encephalitis. This case reports a 34-year-old woman who was diagnosed with teratoma-associated anti-N-methyl-D- aspartate receptor-mediated autoimmune encephalitis called anti-N-methyl-D-aspartate receptor encephalitis with bilateral hearing loss in 2021. Through this case report, clinicians will pay attention to autoimmune encephalitis and raise awareness of the specific clinical manifestations of autoimmune encephalitis, and focus on early identification. It means that clinicians should be familiar with the representative clinical manifestations of the disease.</AbstractText
|
Pitfalls in clinical diagnosis of anti-NMDA receptor encephalitis. To report pitfalls in the clinical diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.</AbstractText We retrospectively reviewed the clinical information of 221 patients with clinically suspected autoimmune neurological disorders who underwent testing for autoantibodies against neuronal cell-surface antigens between January 1, 2007 and September 10, 2017. Forty-one patients met the diagnostic criteria for probable anti-NMDAR encephalitis (probable criteria), but one was excluded because neither serum nor CSF was examined at the active stage. Thus, in 220 patients, sensitivity and specificity of the probable criteria were assessed.</AbstractText NMDAR-antibodies were detected in 34 of 40 patients (85%) with the probable criteria; however, 2 of the 6 antibody-negative patients had ovarian teratoma. The median age at onset was higher in antibody-negative patients than those with antibodies (49 vs. 27 years, p = 0.015). The age at onset was associated with the probability of antibody detection (p = 0.014); the probability was less than 50% in patients aged 50 years or older. NMDAR-antibodies were also detected in 5 of 180 patients who did not fulfill the probable criteria; these patients presented with isolated epileptic syndrome (n = 2), atypical demyelinating syndrome (n = 2; one with aquaporin 4 antibodies), and autoimmune post-herpes simplex encephalitis (post-HSE) (n = 1). Sensitivity and specificity of the probable criteria was 87.2 and 96.7%, respectively.</AbstractText The probable criteria are valid, but the diversity of clinical phenotype should be taken into account in diagnosing anti-NMDAR encephalitis particularly in patients aged 50 years or older, or with isolated epileptic syndrome, atypical demyelinating syndrome, or post-HSE.</AbstractText
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Neurocyberethics, a new and pertinent approach to neuroethics. Ethics in neuroscience presents an evolutionary development that has required a more punctual attention, from the knowledge of functional neuroimaging that defines the structures related to the emotions and cognitive functions. Systematic review in Pub Med according to PRISMA format from the keywords and specific search for the concept of neuroethics, cyberethics and neurocyberethics. The neurocyberethics is not available, despite contemporary advances in neurotechnology and Artificial Intelligence (AI). Even though in the enormous amount of data related to AI in neuroscience, the ethical implications related to the transparency, regulation and rational use of this digital technological development have not been fully considered. In the current era, neurocyberethics needs to be considered, because of its relevance in the landscape of neurotechnology which poses new challenges and dilemmas not contemplated in traditional neuroethics.</AbstractText La ética en la neurociencia presenta un despliegue evolutivo que ha requerido una atención más puntual a partir del conocimiento de la neuroimagen funcional, que define las estructuras relacionadas con las emociones y la cognición. Se llevó a cabo una revisión sistemática en PubMed de acuerdo con el formato PRISMA a partir de las palabras clave neuroética, ciberética y neurociberética. La neurociberética como concepto no figura en los contenidos científicos, pese a los avances contemporáneos de la neurotecnología y la inteligencia artificial. Aun cuando se identifican numerosos aportes relacionados con la inteligencia artificial en la neurociencia, no se han considerado las implicaciones éticas relacionadas con la transparencia, regulación y uso racional de nuevos dispositivos vinculados con este desarrollo neurotecnológico. En la era actual es imprescindible considerar a la neurociberética por su pertinencia conceptual y sus aplicaciones en el panorama de la neurotecnología, lo que propone nuevos retos y dilemas no considerados por la neuroética tradicional.</AbstractText
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26252988
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16397898
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26347634
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Selective reduction of cerebral cortex GABA neurons in a late gestation model of fetal alcohol spectrum disorder.
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Ethanol promotes neuronal apoptosis by inhibiting phosphatidylserine accumulation.
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Translational treatment of aphasia combining neuromodulation and behavioral intervention for lexical retrieval: implications from a single case study.
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Fetal alcohol spectrum disorders (FASD) are associated with cognitive and behavioral deficits, and decreased volume of the whole brain and cerebral cortex. Rodent models have shown that early postnatal treatments, which mimic ethanol toxicity in the third trimester of human pregnancy, acutely induce widespread apoptotic neuronal degeneration and permanent behavioral deficits. However, the lasting cellular and anatomical effects of early ethanol treatments are still incompletely understood. This study examined changes in neocortex volume, thickness, and cellular organization that persist in adult mice after postnatal day 7 (P7) ethanol treatment. Post mortem brain volumes, measured by both MRI within the skull and by fluid displacement of isolated brains, were reduced 10-13% by ethanol treatment. The cerebral cortex showed a similar reduction (12%) caused mainly by lower surface area (9%). In spite of these large changes, several features of cortical organization showed little evidence of change, including cortical thickness, overall neuron size, and laminar organization. Estimates of total neuron number showed a trend level reduction of about 8%, due mainly to reduced cortical volume but unchanged neuron density. However, counts of calretinin (CR) and parvalbumin (PV) subtypes of GABAergic neurons showed a striking >30% reduction of neuron number. Similar ethanol effects were found in male and female mice, and in C57BL/6By and BALB/cJ mouse strains. Our findings indicate that the cortex has substantial capacity to develop normal cytoarchitectonic organization after early postnatal ethanol toxicity, but there is a selective and persistent reduction of GABA cells that may contribute to the lasting cognitive and behavioral deficits in FASD.</AbstractText
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Prenatal and postnatal ethanol exposure induces abnormal cell death in the nervous system. We have previously reported that docosahexaenoic acid (DHA; 22:6n-3) prevents neuronal apoptosis through promoting phosphatidylserine (PS) accumulation. Previously, we have shown in C6 glioma cells that ethanol inhibits the accumulation of PS caused by DHA supplementation. In this report, we demonstrate that in vitro or in vivo exposure to ethanol inhibits DHA-dependent PS accumulation and neuronal survival. We found that Neuro 2A cells exposed to ethanol accumulated considerably less PS in response to the DHA enrichment and were less effective at phosphorylating Akt and suppressing caspase-3 activity under serum-starved or staurosporine-treated conditions. The in vivo paradigm correlated well with the in vitro findings. We found that the total PS and DHA contents in the fetal hippocampus were slightly but significantly lowered by the prenatal ethanol exposure. Fetal hippocampal cultures obtained at embryonic day 18 from ethanol-treated pregnant rats contained significantly higher apoptotic cells after 7 days in vitro under basal conditions and exhibited particular susceptibility to cell death induced by trophic factor removal in comparison with the pair-fed control group. The reduction of PS and the resulting neuronal cell death inappropriately enhanced during development may contribute to the defects in brain function often observed in fetal alcohol syndrome.</AbstractText
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Transcranial direct current stimulation (tDCS), a non-invasive method of brain stimulation, is an adjunctive research-therapy for aphasia. The concept supporting translational application of tDCS is that brain plasticity, facilitated by language intervention, can be enhanced by non-invasive brain stimulation. This study combined tDCS with an ecologically focused behavioral approach that involved training nouns and verbs in sentences.</AbstractText A 43-year-old, right-handed male with fluent-anomic aphasia who sustained a single-left-hemisphere-temporal-parietal stroke was recruited.</AbstractText Instrumentation included the Soterix Medical 1 × 1 Device. Anodal tDCS was applied over Broca's area. Behavioral materials included: sentence production, naming in the sentence context, and implementation of a social-conversational-discourse treatment.</AbstractText The independent variable of this crossover case-study was tDCS, and the dependent variables were language and quality-of-life measures. In each session the subject received language treatment with the first 20 minutes additionally including tDCS.</AbstractText Performance in naming nouns and verbs in single words and sentences were obtained. Verb production in the sentence context increased after active anodal tDCS and speech-language treatment.</AbstractText Aphasia treatment that involves naming in the sentence context in conjunction with translational application of tDCS may be a promising approach for language-recovery post stroke.</AbstractText
|
Selective reduction of cerebral cortex GABA neurons in a late gestation model of fetal alcohol spectrum disorder. Fetal alcohol spectrum disorders (FASD) are associated with cognitive and behavioral deficits, and decreased volume of the whole brain and cerebral cortex. Rodent models have shown that early postnatal treatments, which mimic ethanol toxicity in the third trimester of human pregnancy, acutely induce widespread apoptotic neuronal degeneration and permanent behavioral deficits. However, the lasting cellular and anatomical effects of early ethanol treatments are still incompletely understood. This study examined changes in neocortex volume, thickness, and cellular organization that persist in adult mice after postnatal day 7 (P7) ethanol treatment. Post mortem brain volumes, measured by both MRI within the skull and by fluid displacement of isolated brains, were reduced 10-13% by ethanol treatment. The cerebral cortex showed a similar reduction (12%) caused mainly by lower surface area (9%). In spite of these large changes, several features of cortical organization showed little evidence of change, including cortical thickness, overall neuron size, and laminar organization. Estimates of total neuron number showed a trend level reduction of about 8%, due mainly to reduced cortical volume but unchanged neuron density. However, counts of calretinin (CR) and parvalbumin (PV) subtypes of GABAergic neurons showed a striking >30% reduction of neuron number. Similar ethanol effects were found in male and female mice, and in C57BL/6By and BALB/cJ mouse strains. Our findings indicate that the cortex has substantial capacity to develop normal cytoarchitectonic organization after early postnatal ethanol toxicity, but there is a selective and persistent reduction of GABA cells that may contribute to the lasting cognitive and behavioral deficits in FASD.</AbstractText
|
Ethanol promotes neuronal apoptosis by inhibiting phosphatidylserine accumulation. Prenatal and postnatal ethanol exposure induces abnormal cell death in the nervous system. We have previously reported that docosahexaenoic acid (DHA; 22:6n-3) prevents neuronal apoptosis through promoting phosphatidylserine (PS) accumulation. Previously, we have shown in C6 glioma cells that ethanol inhibits the accumulation of PS caused by DHA supplementation. In this report, we demonstrate that in vitro or in vivo exposure to ethanol inhibits DHA-dependent PS accumulation and neuronal survival. We found that Neuro 2A cells exposed to ethanol accumulated considerably less PS in response to the DHA enrichment and were less effective at phosphorylating Akt and suppressing caspase-3 activity under serum-starved or staurosporine-treated conditions. The in vivo paradigm correlated well with the in vitro findings. We found that the total PS and DHA contents in the fetal hippocampus were slightly but significantly lowered by the prenatal ethanol exposure. Fetal hippocampal cultures obtained at embryonic day 18 from ethanol-treated pregnant rats contained significantly higher apoptotic cells after 7 days in vitro under basal conditions and exhibited particular susceptibility to cell death induced by trophic factor removal in comparison with the pair-fed control group. The reduction of PS and the resulting neuronal cell death inappropriately enhanced during development may contribute to the defects in brain function often observed in fetal alcohol syndrome.</AbstractText
|
Translational treatment of aphasia combining neuromodulation and behavioral intervention for lexical retrieval: implications from a single case study. Transcranial direct current stimulation (tDCS), a non-invasive method of brain stimulation, is an adjunctive research-therapy for aphasia. The concept supporting translational application of tDCS is that brain plasticity, facilitated by language intervention, can be enhanced by non-invasive brain stimulation. This study combined tDCS with an ecologically focused behavioral approach that involved training nouns and verbs in sentences.</AbstractText A 43-year-old, right-handed male with fluent-anomic aphasia who sustained a single-left-hemisphere-temporal-parietal stroke was recruited.</AbstractText Instrumentation included the Soterix Medical 1 × 1 Device. Anodal tDCS was applied over Broca's area. Behavioral materials included: sentence production, naming in the sentence context, and implementation of a social-conversational-discourse treatment.</AbstractText The independent variable of this crossover case-study was tDCS, and the dependent variables were language and quality-of-life measures. In each session the subject received language treatment with the first 20 minutes additionally including tDCS.</AbstractText Performance in naming nouns and verbs in single words and sentences were obtained. Verb production in the sentence context increased after active anodal tDCS and speech-language treatment.</AbstractText Aphasia treatment that involves naming in the sentence context in conjunction with translational application of tDCS may be a promising approach for language-recovery post stroke.</AbstractText
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35801126
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28631870
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34963039
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Treating phantom limb pain: cryoablation of the posterior tibial nerve.
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Thalamic Deep Brain Stimulation for Neuropathic Pain: Efficacy at Three Years' Follow-Up.
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Why do women consume alcohol during pregnancy or while breastfeeding?
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Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP. In this case report, we will demonstrate successful reduction of PLP in a patient with bilateral phantom toe pain utilizing nerve blockade and subsequent cryoablation of the posterior tibial nerves.</AbstractText
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Chronic neuropathic pain is estimated to affect 3-4.5% of the worldwide population, posing a serious burden to society. Deep Brain Stimulation (DBS) is already established for movement disorders and also used to treat some "off-label" conditions. However, DBS for the treatment of chronic, drug refractory, neuropathic pain, has shown variable outcomes with few studies performed in the last decade. Thus, this procedure has consensus approval in parts of Europe but not the USA. This study prospectively evaluated the efficacy at three years of DBS for neuropathic pain.</AbstractText Sixteen consecutive patients received 36 months post-surgical follow-up in a single-center. Six had phantom limb pain after amputation and ten deafferentation pain after brachial plexus injury, all due to traumas. To evaluate the efficacy of DBS, patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, University of Washington Neuropathic Pain Score (UWNPS), Brief Pain Inventory (BPI), and 36-Item Short-Form Health Survey (SF-36).</AbstractText Contralateral, ventroposterolateral sensory thalamic DBS was performed in sixteen patients with chronic neuropathic pain over 29 months. A postoperative trial of externalized DBS failed in one patient with brachial plexus injury. Fifteen patients proceeded to implantation but one patient with phantom limb pain after amputation was lost for follow-up after 12 months. No surgical complications or stimulation side effects were noted. After 36 months, mean pain relief was sustained, and the median (and interquartile range) of the improvement of VAS score was 52.8% (45.4%) (p = 0.00021), UWNPS was 30.7% (49.2%) (p = 0.0590), BPI was 55.0% (32.0%) (p = 0.00737), and SF-36 was 16.3% (30.3%) (p = 0.4754).</AbstractText DBS demonstrated efficacy at three years for chronic neuropathic pain after traumatic amputation and brachial plexus injury, with benefits sustained across all pain outcomes measures and slightly greater improvement in phantom limb pain.</AbstractText
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Alcohol consumption during pregnancy and breastfeeding cause adverse health outcomes to the mother and child, including Fetal Alcohol Spectrum Disorder (FASD).</AbstractText Systematic literature review and thematic synthesis. Original studies that contained reasons for alcohol consumption in pregnancy and while breastfeeding were included. The Mixed Methods Appraisal Tool (MMAT) and the Confidence in the Evidence of Reviews of Qualitative Research (CerQUAL) approach were utilised. The review protocol is available on PROSPERO (registration number: CRD42018116998).</AbstractText Forty-two eligible studies comprising women from 16 countries were included. Most commonly reported reasons of alcohol use in pregnancy were societal pressure and the belief that only "strong" alcohol and alcohol in large quantities is harmful. Other reasons were: a lack of awareness of adverse effects on the fetus; coping with adverse life experiences; consumption based on intuitive decision-making and influenced by personal/peer experiences; belief in the beneficial properties of alcohol; advice from medical practitioners; unwanted or unplanned pregnancy; alcohol dependence; and consumption as a cultural/traditional custom. Reasons for alcohol use during breastfeeding included the belief that alcohol stimulates breast milk production, unclear advice from medical practitioners, unawareness of the risks of infant exposure and to improve mood and celebrate events.</AbstractText Understanding the context of reasons for alcohol use in pregnancy is crucial for implementing prenatal health education, and preventing FASD and other adverse maternal and child health outcomes.</AbstractText Individual beliefs, knowledge/advice, culture and personal circumstances influence alcohol use in pregnancy. Data are limited for reasons surrounding alcohol use while breastfeeding.</AbstractText
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Treating phantom limb pain: cryoablation of the posterior tibial nerve. Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP. In this case report, we will demonstrate successful reduction of PLP in a patient with bilateral phantom toe pain utilizing nerve blockade and subsequent cryoablation of the posterior tibial nerves.</AbstractText
|
Thalamic Deep Brain Stimulation for Neuropathic Pain: Efficacy at Three Years' Follow-Up. Chronic neuropathic pain is estimated to affect 3-4.5% of the worldwide population, posing a serious burden to society. Deep Brain Stimulation (DBS) is already established for movement disorders and also used to treat some "off-label" conditions. However, DBS for the treatment of chronic, drug refractory, neuropathic pain, has shown variable outcomes with few studies performed in the last decade. Thus, this procedure has consensus approval in parts of Europe but not the USA. This study prospectively evaluated the efficacy at three years of DBS for neuropathic pain.</AbstractText Sixteen consecutive patients received 36 months post-surgical follow-up in a single-center. Six had phantom limb pain after amputation and ten deafferentation pain after brachial plexus injury, all due to traumas. To evaluate the efficacy of DBS, patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, University of Washington Neuropathic Pain Score (UWNPS), Brief Pain Inventory (BPI), and 36-Item Short-Form Health Survey (SF-36).</AbstractText Contralateral, ventroposterolateral sensory thalamic DBS was performed in sixteen patients with chronic neuropathic pain over 29 months. A postoperative trial of externalized DBS failed in one patient with brachial plexus injury. Fifteen patients proceeded to implantation but one patient with phantom limb pain after amputation was lost for follow-up after 12 months. No surgical complications or stimulation side effects were noted. After 36 months, mean pain relief was sustained, and the median (and interquartile range) of the improvement of VAS score was 52.8% (45.4%) (p = 0.00021), UWNPS was 30.7% (49.2%) (p = 0.0590), BPI was 55.0% (32.0%) (p = 0.00737), and SF-36 was 16.3% (30.3%) (p = 0.4754).</AbstractText DBS demonstrated efficacy at three years for chronic neuropathic pain after traumatic amputation and brachial plexus injury, with benefits sustained across all pain outcomes measures and slightly greater improvement in phantom limb pain.</AbstractText
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Why do women consume alcohol during pregnancy or while breastfeeding? Alcohol consumption during pregnancy and breastfeeding cause adverse health outcomes to the mother and child, including Fetal Alcohol Spectrum Disorder (FASD).</AbstractText Systematic literature review and thematic synthesis. Original studies that contained reasons for alcohol consumption in pregnancy and while breastfeeding were included. The Mixed Methods Appraisal Tool (MMAT) and the Confidence in the Evidence of Reviews of Qualitative Research (CerQUAL) approach were utilised. The review protocol is available on PROSPERO (registration number: CRD42018116998).</AbstractText Forty-two eligible studies comprising women from 16 countries were included. Most commonly reported reasons of alcohol use in pregnancy were societal pressure and the belief that only "strong" alcohol and alcohol in large quantities is harmful. Other reasons were: a lack of awareness of adverse effects on the fetus; coping with adverse life experiences; consumption based on intuitive decision-making and influenced by personal/peer experiences; belief in the beneficial properties of alcohol; advice from medical practitioners; unwanted or unplanned pregnancy; alcohol dependence; and consumption as a cultural/traditional custom. Reasons for alcohol use during breastfeeding included the belief that alcohol stimulates breast milk production, unclear advice from medical practitioners, unawareness of the risks of infant exposure and to improve mood and celebrate events.</AbstractText Understanding the context of reasons for alcohol use in pregnancy is crucial for implementing prenatal health education, and preventing FASD and other adverse maternal and child health outcomes.</AbstractText Individual beliefs, knowledge/advice, culture and personal circumstances influence alcohol use in pregnancy. Data are limited for reasons surrounding alcohol use while breastfeeding.</AbstractText
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36430982
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35103827
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36452334
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The Combination of Whole-Brain Features and Local-Lesion Features in DSC-PWI May Improve Ischemic Stroke Outcome Prediction.
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Voxel-level analysis of normalized DSC-PWI time-intensity curves: a potential generalizable approach and its proof of concept in discriminating glioblastoma and metastasis.
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Interoceptive accuracy correlates with precision of time perception in the millisecond range.
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Accurate and reliable outcome predictions can help evaluate the functional recovery of ischemic stroke patients and assist in making treatment plans. Given that recovery factors may be hidden in the whole-brain features, this study aims to validate the role of dynamic radiomics features (DRFs) in the whole brain, DRFs in local ischemic lesions, and their combination in predicting functional outcomes of ischemic stroke patients. First, the DRFs in the whole brain and the DRFs in local lesions of dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) images are calculated. Second, the least absolute shrinkage and selection operator (Lasso) is used to generate four groups of DRFs, including the outstanding DRFs in the whole brain (Lasso (WB)), the outstanding DRFs in local lesions (Lasso (LL)), the combination of them (combined DRFs), and the outstanding DRFs in the combined DRFs (Lasso (combined)). Then, the performance of the four groups of DRFs is evaluated to predict the functional recovery in three months. As a result, Lasso (combined) in the four groups achieves the best AUC score of 0.971, which improves the score by 8.9% compared with Lasso (WB), and by 3.5% compared with Lasso (WB) and combined DRFs. In conclusion, the outstanding combined DRFs generated from the outstanding DRFs in the whole brain and local lesions can predict functional outcomes in ischemic stroke patients better than the single DRFs in the whole brain or local lesions.</AbstractText
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Standard DSC-PWI analyses are based on concrete parameters and values, but an approach that contemplates all points in the time-intensity curves and all voxels in the region-of-interest may provide improved information, and more generalizable models. Therefore, a method of DSC-PWI analysis by means of normalized time-intensity curves point-by-point and voxel-by-voxel is constructed, and its feasibility and performance are tested in presurgical discrimination of glioblastoma and metastasis.</AbstractText In this retrospective study, patients with histologically confirmed glioblastoma or solitary-brain-metastases and presurgical-MR with DSC-PWI (August 2007-March 2020) were retrieved. The enhancing tumor and immediate peritumoral region were segmented on CE-T1wi and coregistered to DSC-PWI. Time-intensity curves of the segmentations were normalized to normal-appearing white matter. For each participant, average and all-voxel-matrix of normalized-curves were obtained. The 10 best discriminatory time-points between each type of tumor were selected. Then, an intensity-histogram analysis on each of these 10 time-points allowed the selection of the best discriminatory voxel-percentile for each. Separate classifier models were trained for enhancing tumor and peritumoral region using binary logistic regressions.</AbstractText A total of 428 patients (321 glioblastomas, 107 metastases) fulfilled the inclusion criteria (256 men; mean age, 60 years; range, 20-86 years). Satisfactory results were obtained to segregate glioblastoma and metastases in training and test sets with AUCs 0.71-0.83, independent accuracies 65-79%, and combined accuracies up to 81-88%.</AbstractText This proof-of-concept study presents a different perspective on brain MR DSC-PWI evaluation by the inclusion of all time-points of the curves and all voxels of segmentations to generate robust diagnostic models of special interest in heterogeneous diseases and populations. The method allows satisfactory presurgical segregation of glioblastoma and metastases.</AbstractText • An original approach to brain MR DSC-PWI analysis, based on a point-by-point and voxel-by-voxel assessment of normalized time-intensity curves, is presented. • The method intends to extract optimized information from MR DSC-PWI sequences by impeding the potential loss of information that may represent the standard evaluation of single concrete perfusion parameters (cerebral blood volume, percentage of signal recovery, or peak height) and values (mean, maximum, or minimum). • The presented approach may be of special interest in technically heterogeneous samples, and intrinsically heterogeneous diseases. Its application enables satisfactory presurgical differentiation of GB and metastases, a usual but difficult diagnostic challenge for neuroradiologist with vital implications in patient management.</AbstractText
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It has been proposed that accuracy in time perception is related to interoceptive accuracy and vagal activity. However, studies investigating time perception in the supra-second range have provided mixed results, and few studies have investigated the sub-second range. Moreover, there is a lack of studies investigating the relationship between precision in time perception and interoceptive accuracy. A recent meta-analytic review of neuroimaging studies proposed a dynamic interaction between two types of timing processing-an endogenous time keeping mechanism and the use of exogenous temporal cues. Interoceptive accuracy may affect both accuracy and precision of primary temporal representations, as they are generated based on the endogenous time keeping mechanism. Temporal accuracy may vary when adapted to the environmental context. In contrast, temporal precision contains some constant noise, which may maintain the relationship with interoceptive accuracy. Based on these assumptions, we hypothesized that interoceptive accuracy would be associated with temporal precision in the sub-second range, while vagal activity would be associated with temporal accuracy. We used the temporal generalization task, which allowed us to calculate the indices of temporal accuracy and temporal precision in line with the existing research, and also compute the index of participants' sensitivity according to the signal detection theory. Specifically, we investigated whether (1) interoceptive accuracy would correlate with temporal accuracy, temporal precision, or sensitivity and (2) resting-state vagal activity would correlate with temporal accuracy, temporal precision, or sensitivity. The results indicated that interoceptive accuracy was positively correlated with temporal precision as well as sensitivity, but not with temporal accuracy, in the sub-second range time perception. Vagal activity was negatively correlated only with sensitivity. Furthermore, we found a moderation effect of sensitivity on the relationship between vagal activity and perceived duration, which affected the association between vagal activity and temporal accuracy. These findings suggest the importance of precision as an aspect of time perception, which future studies should further explore in relation to interoception and vagal activity, and of the moderation effects of factors such as participants' sensitivity in this context.</AbstractText
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The Combination of Whole-Brain Features and Local-Lesion Features in DSC-PWI May Improve Ischemic Stroke Outcome Prediction. Accurate and reliable outcome predictions can help evaluate the functional recovery of ischemic stroke patients and assist in making treatment plans. Given that recovery factors may be hidden in the whole-brain features, this study aims to validate the role of dynamic radiomics features (DRFs) in the whole brain, DRFs in local ischemic lesions, and their combination in predicting functional outcomes of ischemic stroke patients. First, the DRFs in the whole brain and the DRFs in local lesions of dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) images are calculated. Second, the least absolute shrinkage and selection operator (Lasso) is used to generate four groups of DRFs, including the outstanding DRFs in the whole brain (Lasso (WB)), the outstanding DRFs in local lesions (Lasso (LL)), the combination of them (combined DRFs), and the outstanding DRFs in the combined DRFs (Lasso (combined)). Then, the performance of the four groups of DRFs is evaluated to predict the functional recovery in three months. As a result, Lasso (combined) in the four groups achieves the best AUC score of 0.971, which improves the score by 8.9% compared with Lasso (WB), and by 3.5% compared with Lasso (WB) and combined DRFs. In conclusion, the outstanding combined DRFs generated from the outstanding DRFs in the whole brain and local lesions can predict functional outcomes in ischemic stroke patients better than the single DRFs in the whole brain or local lesions.</AbstractText
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Voxel-level analysis of normalized DSC-PWI time-intensity curves: a potential generalizable approach and its proof of concept in discriminating glioblastoma and metastasis. Standard DSC-PWI analyses are based on concrete parameters and values, but an approach that contemplates all points in the time-intensity curves and all voxels in the region-of-interest may provide improved information, and more generalizable models. Therefore, a method of DSC-PWI analysis by means of normalized time-intensity curves point-by-point and voxel-by-voxel is constructed, and its feasibility and performance are tested in presurgical discrimination of glioblastoma and metastasis.</AbstractText In this retrospective study, patients with histologically confirmed glioblastoma or solitary-brain-metastases and presurgical-MR with DSC-PWI (August 2007-March 2020) were retrieved. The enhancing tumor and immediate peritumoral region were segmented on CE-T1wi and coregistered to DSC-PWI. Time-intensity curves of the segmentations were normalized to normal-appearing white matter. For each participant, average and all-voxel-matrix of normalized-curves were obtained. The 10 best discriminatory time-points between each type of tumor were selected. Then, an intensity-histogram analysis on each of these 10 time-points allowed the selection of the best discriminatory voxel-percentile for each. Separate classifier models were trained for enhancing tumor and peritumoral region using binary logistic regressions.</AbstractText A total of 428 patients (321 glioblastomas, 107 metastases) fulfilled the inclusion criteria (256 men; mean age, 60 years; range, 20-86 years). Satisfactory results were obtained to segregate glioblastoma and metastases in training and test sets with AUCs 0.71-0.83, independent accuracies 65-79%, and combined accuracies up to 81-88%.</AbstractText This proof-of-concept study presents a different perspective on brain MR DSC-PWI evaluation by the inclusion of all time-points of the curves and all voxels of segmentations to generate robust diagnostic models of special interest in heterogeneous diseases and populations. The method allows satisfactory presurgical segregation of glioblastoma and metastases.</AbstractText • An original approach to brain MR DSC-PWI analysis, based on a point-by-point and voxel-by-voxel assessment of normalized time-intensity curves, is presented. • The method intends to extract optimized information from MR DSC-PWI sequences by impeding the potential loss of information that may represent the standard evaluation of single concrete perfusion parameters (cerebral blood volume, percentage of signal recovery, or peak height) and values (mean, maximum, or minimum). • The presented approach may be of special interest in technically heterogeneous samples, and intrinsically heterogeneous diseases. Its application enables satisfactory presurgical differentiation of GB and metastases, a usual but difficult diagnostic challenge for neuroradiologist with vital implications in patient management.</AbstractText
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Interoceptive accuracy correlates with precision of time perception in the millisecond range. It has been proposed that accuracy in time perception is related to interoceptive accuracy and vagal activity. However, studies investigating time perception in the supra-second range have provided mixed results, and few studies have investigated the sub-second range. Moreover, there is a lack of studies investigating the relationship between precision in time perception and interoceptive accuracy. A recent meta-analytic review of neuroimaging studies proposed a dynamic interaction between two types of timing processing-an endogenous time keeping mechanism and the use of exogenous temporal cues. Interoceptive accuracy may affect both accuracy and precision of primary temporal representations, as they are generated based on the endogenous time keeping mechanism. Temporal accuracy may vary when adapted to the environmental context. In contrast, temporal precision contains some constant noise, which may maintain the relationship with interoceptive accuracy. Based on these assumptions, we hypothesized that interoceptive accuracy would be associated with temporal precision in the sub-second range, while vagal activity would be associated with temporal accuracy. We used the temporal generalization task, which allowed us to calculate the indices of temporal accuracy and temporal precision in line with the existing research, and also compute the index of participants' sensitivity according to the signal detection theory. Specifically, we investigated whether (1) interoceptive accuracy would correlate with temporal accuracy, temporal precision, or sensitivity and (2) resting-state vagal activity would correlate with temporal accuracy, temporal precision, or sensitivity. The results indicated that interoceptive accuracy was positively correlated with temporal precision as well as sensitivity, but not with temporal accuracy, in the sub-second range time perception. Vagal activity was negatively correlated only with sensitivity. Furthermore, we found a moderation effect of sensitivity on the relationship between vagal activity and perceived duration, which affected the association between vagal activity and temporal accuracy. These findings suggest the importance of precision as an aspect of time perception, which future studies should further explore in relation to interoception and vagal activity, and of the moderation effects of factors such as participants' sensitivity in this context.</AbstractText
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40635012
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40185278
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40767174
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Mutation of the histone demethylase Gasc1 causes ASD-like symptoms in mice.
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Intranasal NAP (Davunetide): Neuroprotection and circadian rhythmicity.
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Health Benefit Package Revision Is an Art as Much as a Science - Lessons Learned on the Organization of the Appraisal Phase.
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Genomic analyses of psychiatric disorders, including autism spectrum disorder (ASD), have revealed many susceptibility genes, suggesting that such disorders may be caused by multiple factors. In this sense, it has long been a question whether there is an abnormal genetic status that comprehensively explains the pathogenesis of neuropsychiatric disorders or a"promising upstream treatment target"that normalizes symptoms.</AbstractText To address this question, we provide important clues with respect to GASC1 (JMJD2 C/KDM4 C), which is a histone demethylase that prominently targets trimethylated histone H3 at lysine 9 (H3 K9 me3). Gasc1 hypomorphic mutant mice were analyzed using molecular biological, biochemical, behavioral battery tests, histological, and electrophysiological techniques.</AbstractText Mice homozygous for a hypomorphic mutation in Gasc1 exhibited abnormal behaviors, including hyperactivity, stereotyped behaviors, and impaired learning and memory, which are reminiscent of those of human psychiatric disorders. Electrophysiological studies of hippocampal slices revealed decreased paired-pulse facilitation and enhanced long-term potentiation, suggesting synaptic dysfunction in the mutants. Increased dendritic spine density in CA1 neurons was also detected in the mutants. Intriguingly, genetic linkage studies of human ASD have mapped a susceptibility locus on chromosome 9p24.1, which contains 78 genes, including the GASC1 gene.</AbstractText Taken together, our data suggest that histone demethylation plays a pivotal role in normal brain development and higher-order brain functions in both mice and humans.</AbstractText
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In this review we examine the neuroprotective potential of NAP (davunetide), a small peptide derived from Activity-Dependent Neuroprotective Protein (ADNP), in the context of neurodevelopmental and neurodegenerative disorders. ADNP, a protein essential for brain development and function, is associated with tauopathy-related diseases, such as Alzheimer's Disease (AD), and circadian rhythm regulation. NAP enhances microtubule stability and prevents tauopathy. In preclinical studies, NAP shows promise in improving cognitive performance and correcting behavioral deficits in different models. Clinical studies on NAP (davunetide) administered via intranasal delivery have demonstrated its safety, favorable bioavailability, and potential efficacy in improving cognitive function, making it a viable therapeutic option. In the pure tauopathy, progressive supranuclear palsy, NAP (davunetide) significantly slowed disease progression in women in a phase II-III clinical trial. Additionally, the complex interactions between ADNP, associated pathways, and circadian regulation and the extensive NAP compensation upon ADNP deficiency attest to further clinical development. Thus, NAP is an example of a reductionist approach in drug delivery, replacing/enhancing the critical large ADNP-related pathways including dysregulated microtubules and tauopathy with a small brain bioavailable investigational drug, davunetide.</AbstractText
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Many low- and middle-income countries are designing or revising their health benefit packages (HBPs), with appraisal-prioritizing services for reimbursement-being a critical phase. This occurs in a complex landscape of multiple criteria, multiple stakeholders, limited evidence, budget constraints, and tight timelines, varying across countries. Existing guidance documents do not fully address these complexities, requiring analysts to balance methodological rigor with practical constraints. This editorial highlights four key themes in organizing appraisal: decision-making structures, trade-offs between criteria, final recommendations, and the use of cost-effectiveness evidence, thresholds, and budgets. These emerged as central challenges in HBP revisions in Iran, Kyrgyzstan, Liberia, Pakistan, and Rwanda. We emphasize cross-country learning to address these challenges pragmatically, recognizing that high-quality, legitimate appraisal is as much an art as a science. More detailed documentation of appraisal processes is needed to refine HBP revision guidelines and strengthen priority-setting in health systems.</AbstractText
|
Mutation of the histone demethylase Gasc1 causes ASD-like symptoms in mice. Genomic analyses of psychiatric disorders, including autism spectrum disorder (ASD), have revealed many susceptibility genes, suggesting that such disorders may be caused by multiple factors. In this sense, it has long been a question whether there is an abnormal genetic status that comprehensively explains the pathogenesis of neuropsychiatric disorders or a"promising upstream treatment target"that normalizes symptoms.</AbstractText To address this question, we provide important clues with respect to GASC1 (JMJD2 C/KDM4 C), which is a histone demethylase that prominently targets trimethylated histone H3 at lysine 9 (H3 K9 me3). Gasc1 hypomorphic mutant mice were analyzed using molecular biological, biochemical, behavioral battery tests, histological, and electrophysiological techniques.</AbstractText Mice homozygous for a hypomorphic mutation in Gasc1 exhibited abnormal behaviors, including hyperactivity, stereotyped behaviors, and impaired learning and memory, which are reminiscent of those of human psychiatric disorders. Electrophysiological studies of hippocampal slices revealed decreased paired-pulse facilitation and enhanced long-term potentiation, suggesting synaptic dysfunction in the mutants. Increased dendritic spine density in CA1 neurons was also detected in the mutants. Intriguingly, genetic linkage studies of human ASD have mapped a susceptibility locus on chromosome 9p24.1, which contains 78 genes, including the GASC1 gene.</AbstractText Taken together, our data suggest that histone demethylation plays a pivotal role in normal brain development and higher-order brain functions in both mice and humans.</AbstractText
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Intranasal NAP (Davunetide): Neuroprotection and circadian rhythmicity. In this review we examine the neuroprotective potential of NAP (davunetide), a small peptide derived from Activity-Dependent Neuroprotective Protein (ADNP), in the context of neurodevelopmental and neurodegenerative disorders. ADNP, a protein essential for brain development and function, is associated with tauopathy-related diseases, such as Alzheimer's Disease (AD), and circadian rhythm regulation. NAP enhances microtubule stability and prevents tauopathy. In preclinical studies, NAP shows promise in improving cognitive performance and correcting behavioral deficits in different models. Clinical studies on NAP (davunetide) administered via intranasal delivery have demonstrated its safety, favorable bioavailability, and potential efficacy in improving cognitive function, making it a viable therapeutic option. In the pure tauopathy, progressive supranuclear palsy, NAP (davunetide) significantly slowed disease progression in women in a phase II-III clinical trial. Additionally, the complex interactions between ADNP, associated pathways, and circadian regulation and the extensive NAP compensation upon ADNP deficiency attest to further clinical development. Thus, NAP is an example of a reductionist approach in drug delivery, replacing/enhancing the critical large ADNP-related pathways including dysregulated microtubules and tauopathy with a small brain bioavailable investigational drug, davunetide.</AbstractText
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Health Benefit Package Revision Is an Art as Much as a Science - Lessons Learned on the Organization of the Appraisal Phase. Many low- and middle-income countries are designing or revising their health benefit packages (HBPs), with appraisal-prioritizing services for reimbursement-being a critical phase. This occurs in a complex landscape of multiple criteria, multiple stakeholders, limited evidence, budget constraints, and tight timelines, varying across countries. Existing guidance documents do not fully address these complexities, requiring analysts to balance methodological rigor with practical constraints. This editorial highlights four key themes in organizing appraisal: decision-making structures, trade-offs between criteria, final recommendations, and the use of cost-effectiveness evidence, thresholds, and budgets. These emerged as central challenges in HBP revisions in Iran, Kyrgyzstan, Liberia, Pakistan, and Rwanda. We emphasize cross-country learning to address these challenges pragmatically, recognizing that high-quality, legitimate appraisal is as much an art as a science. More detailed documentation of appraisal processes is needed to refine HBP revision guidelines and strengthen priority-setting in health systems.</AbstractText
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34657318
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23139193
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34953232
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Deep neural network based CEST and AREX processing: Application in imaging a model of Alzheimer's disease at 3 T.
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Dissociation kinetics of open-chain and macrocyclic gadolinium(III)-aminopolycarboxylate complexes related to magnetic resonance imaging: catalytic effect of endogenous ligands.
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Children's judgments of and reasoning about people with disabilities who produce norm violations.
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To optimize and apply deep neural network based CEST (deepCEST) and apparent exchange dependent-relaxation (deepAREX) for imaging the mouse brain with Alzheimer's disease (AD) at 3T MRI.</AbstractText CEST and T<sub After optimization and training on CEST data of WT mice, deepCEST/deepAREX could rapidly (~1 s) generate precise CEST and AREX results for unseen CEST data of AD mice, indicating the accuracy and generalization of the networks. Significant lower amide weighted (3.5 ppm) signal related to amyloid β-peptide (Aβ) plaque depositions, which was validated by immunohistochemistry results, was detected in both central and anterior brain slices of AD mice compared to WT mice. Decreased magnetization transfer (MT) signal was also found in AD mice especially in the anterior slice.</AbstractText DeepCEST/deepAREX could rapidly generate accurate CEST/AREX contrasts in animal study. The well-optimized deepCEST/deepAREX have potential for AD differentiation at 3T MRI.</AbstractText
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The kinetics of the metal exchange reactions between open-chain Gd(DTPA)(2-) and Gd(DTPA-BMA), macrocyclic Gd(DOTA)(-) and Gd(HP-DO3A) complexes, and Cu(2+)  ions were investigated in the presence of endogenous citrate, phosphate, carbonate and histidinate ligands in the pH range 6-8 in NaCl (0.15 M) at 25 °C. The rates of the exchange reactions of Gd(DTPA)(2-) and Gd(DTPA-BMA) are independent of the Cu(2+) concentration in the presence of citrate and the reactions occur via the dissociation of Gd(3+)  complexes catalyzed by the citrate ions. The HCO(3)(-)/CO(3)(2-) and H(2)PO(4)(-) ions also catalyze the dissociation of complexes. The rates of the dissociation of Gd(DTPA-BMA), catalyzed by the endogenous ligands, are about two orders of magnitude higher than those of the Gd(DTPA)(2-). In fact near to physiological conditions the bicarbonate and carbonate ions show the largest catalytic effect, that significantly increase the dissociation rate of Gd(DTPA-BMA) and make the higher pH values (when the carbonate ion concentration is higher) a risk-factor for the dissociation of complexes in body fluids. The exchange reactions of Gd(DOTA)(-) and Gd(HP-DO3A) with Cu(2+) occur through the proton assisted dissociation of complexes in the pH range 3.5-5 and the endogenous ligands do not affect the dissociation rates of complexes. More insights into the interaction scheme between Gd(DTPA-BMA) and Gd(DTPA)(2-) and endogenous ligands have been obtained by acquiring the (13)C NMR spectra of the corresponding diamagnetic Y(III)-complexes, indicating the increase of the rates of the intramolecular rearrangements in the presence of carbonate and citrate ions. The herein reported results may have implications in the understanding of the etiology of nephrogenic systemic fibrosis, a rare disease that has been associated to the administration of Gd-containing agents to patients with impaired renal function.</AbstractText
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People with disabilities may behave in non-normative ways because they cannot act otherwise. This study explored whether U.S. children aged 3.00 to 8.99 years (N = 105) differ in their evaluations of people who commit norm violations when those persons have perceptual or physical disabilities. Across 12 scenarios, children were asked to explain different characters' non-normative behaviors and to evaluate each character's naughtiness. Characters were typically developing, had a physical disability, or had a hearing disability. Disabilities were described to participants but were not visually depicted. Across moral and conventional norm violations, children aged 4.5 years and older judged characters with disabilities as less naughty than characters without disabilities, whereas younger children (3 and 4 years) judged all characters as equally naughty. Children's explanations for characters' non-normative behaviors (acknowledging characters' physical/auditory limitations and inferring negative attributes) significantly predicted their naughtiness judgments; this was true for participants across the sampled age range. Thus, preschool children demonstrated flexibility in their moral judgments across a variety of everyday behavioral violations, tempering their negative evaluations of persons who committed non-normative behaviors when those persons had unseen disabilities that could reasonably account for their actions. Parents and teachers may be able to build on these early moral intuitions to foster greater acceptance of persons with disabilities.</AbstractText
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Deep neural network based CEST and AREX processing: Application in imaging a model of Alzheimer's disease at 3 T. To optimize and apply deep neural network based CEST (deepCEST) and apparent exchange dependent-relaxation (deepAREX) for imaging the mouse brain with Alzheimer's disease (AD) at 3T MRI.</AbstractText CEST and T<sub After optimization and training on CEST data of WT mice, deepCEST/deepAREX could rapidly (~1 s) generate precise CEST and AREX results for unseen CEST data of AD mice, indicating the accuracy and generalization of the networks. Significant lower amide weighted (3.5 ppm) signal related to amyloid β-peptide (Aβ) plaque depositions, which was validated by immunohistochemistry results, was detected in both central and anterior brain slices of AD mice compared to WT mice. Decreased magnetization transfer (MT) signal was also found in AD mice especially in the anterior slice.</AbstractText DeepCEST/deepAREX could rapidly generate accurate CEST/AREX contrasts in animal study. The well-optimized deepCEST/deepAREX have potential for AD differentiation at 3T MRI.</AbstractText
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Dissociation kinetics of open-chain and macrocyclic gadolinium(III)-aminopolycarboxylate complexes related to magnetic resonance imaging: catalytic effect of endogenous ligands. The kinetics of the metal exchange reactions between open-chain Gd(DTPA)(2-) and Gd(DTPA-BMA), macrocyclic Gd(DOTA)(-) and Gd(HP-DO3A) complexes, and Cu(2+)  ions were investigated in the presence of endogenous citrate, phosphate, carbonate and histidinate ligands in the pH range 6-8 in NaCl (0.15 M) at 25 °C. The rates of the exchange reactions of Gd(DTPA)(2-) and Gd(DTPA-BMA) are independent of the Cu(2+) concentration in the presence of citrate and the reactions occur via the dissociation of Gd(3+)  complexes catalyzed by the citrate ions. The HCO(3)(-)/CO(3)(2-) and H(2)PO(4)(-) ions also catalyze the dissociation of complexes. The rates of the dissociation of Gd(DTPA-BMA), catalyzed by the endogenous ligands, are about two orders of magnitude higher than those of the Gd(DTPA)(2-). In fact near to physiological conditions the bicarbonate and carbonate ions show the largest catalytic effect, that significantly increase the dissociation rate of Gd(DTPA-BMA) and make the higher pH values (when the carbonate ion concentration is higher) a risk-factor for the dissociation of complexes in body fluids. The exchange reactions of Gd(DOTA)(-) and Gd(HP-DO3A) with Cu(2+) occur through the proton assisted dissociation of complexes in the pH range 3.5-5 and the endogenous ligands do not affect the dissociation rates of complexes. More insights into the interaction scheme between Gd(DTPA-BMA) and Gd(DTPA)(2-) and endogenous ligands have been obtained by acquiring the (13)C NMR spectra of the corresponding diamagnetic Y(III)-complexes, indicating the increase of the rates of the intramolecular rearrangements in the presence of carbonate and citrate ions. The herein reported results may have implications in the understanding of the etiology of nephrogenic systemic fibrosis, a rare disease that has been associated to the administration of Gd-containing agents to patients with impaired renal function.</AbstractText
|
Children's judgments of and reasoning about people with disabilities who produce norm violations. People with disabilities may behave in non-normative ways because they cannot act otherwise. This study explored whether U.S. children aged 3.00 to 8.99 years (N = 105) differ in their evaluations of people who commit norm violations when those persons have perceptual or physical disabilities. Across 12 scenarios, children were asked to explain different characters' non-normative behaviors and to evaluate each character's naughtiness. Characters were typically developing, had a physical disability, or had a hearing disability. Disabilities were described to participants but were not visually depicted. Across moral and conventional norm violations, children aged 4.5 years and older judged characters with disabilities as less naughty than characters without disabilities, whereas younger children (3 and 4 years) judged all characters as equally naughty. Children's explanations for characters' non-normative behaviors (acknowledging characters' physical/auditory limitations and inferring negative attributes) significantly predicted their naughtiness judgments; this was true for participants across the sampled age range. Thus, preschool children demonstrated flexibility in their moral judgments across a variety of everyday behavioral violations, tempering their negative evaluations of persons who committed non-normative behaviors when those persons had unseen disabilities that could reasonably account for their actions. Parents and teachers may be able to build on these early moral intuitions to foster greater acceptance of persons with disabilities.</AbstractText
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37626766
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32381505
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36875322
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The 3'UTR VNTR SLC6A3 Genetic Variant and Major Depressive Disorder: A Systematic Review.
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Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus.
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Epidemiology, management, and treatment outcomes of metastatic spinal melanoma.
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Major Depressive Disorder (MDD) is a disabling and particularly persistent mental disorder that is considered to be a priority public health problem. The active human dopamine transporter (DAT), which is encoded by the <i
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Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, trans-synaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry, and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate neuroligin (<i
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Metastatic spinal melanoma is a rare and aggressive disease process with poor prognosis. We review the literature on metastatic spinal melanoma, focusing on its epidemiology, management, and treatment outcomes. Demographics of metastatic spinal melanoma are similar to those for cutaneous melanoma, and cutaneous primary tumors tend to be most common. Decompressive surgical intervention and radiotherapy have traditionally been considered mainstays of treatment, and stereotactic radiosurgery has emerged as a promising approach in the operative management of metastatic spinal melanoma. While survival outcomes for metastatic spinal melanoma remain poor, they have improved in recent years with the advent of immune checkpoint inhibition, used in conjunction with surgery and radiotherapy. New treatment options remain under investigation, especially for patients with disease refractory to immunotherapy. We additionally explore several of these promising future directions. Nevertheless, further investigation of treatment outcomes, ideally incorporating high-quality prospective data from randomized controlled trials, is needed to identify optimal management of metastatic spinal melanoma.</AbstractText
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The 3'UTR VNTR SLC6A3 Genetic Variant and Major Depressive Disorder: A Systematic Review. Major Depressive Disorder (MDD) is a disabling and particularly persistent mental disorder that is considered to be a priority public health problem. The active human dopamine transporter (DAT), which is encoded by the <i
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Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus. Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, trans-synaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry, and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate neuroligin (<i
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Epidemiology, management, and treatment outcomes of metastatic spinal melanoma. Metastatic spinal melanoma is a rare and aggressive disease process with poor prognosis. We review the literature on metastatic spinal melanoma, focusing on its epidemiology, management, and treatment outcomes. Demographics of metastatic spinal melanoma are similar to those for cutaneous melanoma, and cutaneous primary tumors tend to be most common. Decompressive surgical intervention and radiotherapy have traditionally been considered mainstays of treatment, and stereotactic radiosurgery has emerged as a promising approach in the operative management of metastatic spinal melanoma. While survival outcomes for metastatic spinal melanoma remain poor, they have improved in recent years with the advent of immune checkpoint inhibition, used in conjunction with surgery and radiotherapy. New treatment options remain under investigation, especially for patients with disease refractory to immunotherapy. We additionally explore several of these promising future directions. Nevertheless, further investigation of treatment outcomes, ideally incorporating high-quality prospective data from randomized controlled trials, is needed to identify optimal management of metastatic spinal melanoma.</AbstractText
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35759822
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32298793
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35203016
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Multimodal fusion of tomographic sequences of medical images: MRE spatially enhanced by MRI.
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Viscoelasticity of reward and control systems in adolescent risk taking.
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Motor and behavioral phenotype of Dravet syndrome in adulthood.
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In biomedical fields, image analysis is often necessary for an accurate diagnosis. In order to obtain all the information needed to form an in-depth clinical picture, it may be useful to combine the contents of images taken under different diagnostic modes. Multimodal medical image fusion techniques enable complementary information acquired by different imaging devices to be automatically combined into a unique image.</AbstractText In this paper, multimodal medical images fusion method based on multiresolution analysis (MRA) is proposed, with the aim to combine the high geometric content of magnetic resonance imaging (MRI) and the elasticity information of magnetic resonance elastography (MRE), simultaneously acquired on the same organs of a patient. First, the slices of MRE are volumetrically interpolated to exactly overlap, each with a slice of MRI. Then, the spatial details of MRI are extracted by means of MRA and injected into the corresponding slices of MRE. Due to the intrinsic dissimilarity between corresponding slices of MRE and MRI, the spatial details of MRI are modulated by local or global matching functions.</AbstractText The performance of the proposed method is quantitatively assessed considering radiometric and geometric consistency of the fused images with respect to their originals, in a comparison with two popular methods from the literature. For a qualitative evaluation, a visual inspection is carried out.</AbstractText The results show that the proposed method enables an effective MRI-MRE fusion that allows the elasticity information and geometric details of the examined organs to be evaluated in a single image.</AbstractText
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Heightened risk-taking tendencies during adolescence have been hypothesized to be attributable to physiological differences of maturation in key brain regions. The socioemotional system (e.g., nucleus accumbens), which is instrumental in reward response, shows a relatively earlier development trajectory than the cognitive control system (e.g., medial prefrontal cortex), which regulates impulse response. This developmental imbalance between heightened reward seeking and immature cognitive control potentially makes adolescents more susceptible to engaging in risky activities. Here, we assess brain structure in the socioemotional and cognitive control systems through viscoelastic stiffness measured with magnetic resonance elastography (MRE) and volumetry, as well as risk-taking tendencies measured using two experimental tasks in 40 adolescents (mean age ​= ​13.4 years old). MRE measures of regional brain stiffness reflect brain health and development via myelin content and glial matrix makeup, and have been shown to be highly sensitive to cognitive processes as compared to measures of regional brain volume and diffusion weighted imaging metrics. We find here that the viscoelastic and volumetric differences between the nucleus accumbens and the prefrontal cortex are correlated with increased risk-taking behavior in adolescents. These differences in development between the two brain systems can be used as an indicator of those adolescents who are more prone to real world risky activities and a useful measure for characterizing response to intervention.</AbstractText
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In a comparative cross-sectional study, 26 adult individuals with clinically typical, genetically confirmed Dravet syndrome (DS) and an equal number of individuals with early onset, problematic epilepsy, and intellectual disability (ID) of comparable severity were included. The aim of the study was to find out whether patients with DS could be clearly distinguished from the comparison group with regard to neurological and behavioral symptoms. Significant differences were found in that individuals with DS clearly more frequently exhibited a symptom cluster characterized by bradykinesia, hypomimia, hypophonia, (spastic) increased muscle tone, ataxia, sthenic perseveration, and a special interest in colors. To these symptoms must be added, according to the findings of previous examinations, mastication, camptocormia/antecollis on the one hand, and the tendency to visual hallucinations on the other hand, in order to define one neuropsychiatric phenotype of DS in adulthood. To these symptoms must be added, according to the findings of previous investigations, crouch gait with camptocormia/antecollis on the one hand, and the tendency to visual hallucinations on the other hand, in order to define one outlined neuropsychiatric phenotype of DS in adulthood.</AbstractText
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Multimodal fusion of tomographic sequences of medical images: MRE spatially enhanced by MRI. In biomedical fields, image analysis is often necessary for an accurate diagnosis. In order to obtain all the information needed to form an in-depth clinical picture, it may be useful to combine the contents of images taken under different diagnostic modes. Multimodal medical image fusion techniques enable complementary information acquired by different imaging devices to be automatically combined into a unique image.</AbstractText In this paper, multimodal medical images fusion method based on multiresolution analysis (MRA) is proposed, with the aim to combine the high geometric content of magnetic resonance imaging (MRI) and the elasticity information of magnetic resonance elastography (MRE), simultaneously acquired on the same organs of a patient. First, the slices of MRE are volumetrically interpolated to exactly overlap, each with a slice of MRI. Then, the spatial details of MRI are extracted by means of MRA and injected into the corresponding slices of MRE. Due to the intrinsic dissimilarity between corresponding slices of MRE and MRI, the spatial details of MRI are modulated by local or global matching functions.</AbstractText The performance of the proposed method is quantitatively assessed considering radiometric and geometric consistency of the fused images with respect to their originals, in a comparison with two popular methods from the literature. For a qualitative evaluation, a visual inspection is carried out.</AbstractText The results show that the proposed method enables an effective MRI-MRE fusion that allows the elasticity information and geometric details of the examined organs to be evaluated in a single image.</AbstractText
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Viscoelasticity of reward and control systems in adolescent risk taking. Heightened risk-taking tendencies during adolescence have been hypothesized to be attributable to physiological differences of maturation in key brain regions. The socioemotional system (e.g., nucleus accumbens), which is instrumental in reward response, shows a relatively earlier development trajectory than the cognitive control system (e.g., medial prefrontal cortex), which regulates impulse response. This developmental imbalance between heightened reward seeking and immature cognitive control potentially makes adolescents more susceptible to engaging in risky activities. Here, we assess brain structure in the socioemotional and cognitive control systems through viscoelastic stiffness measured with magnetic resonance elastography (MRE) and volumetry, as well as risk-taking tendencies measured using two experimental tasks in 40 adolescents (mean age ​= ​13.4 years old). MRE measures of regional brain stiffness reflect brain health and development via myelin content and glial matrix makeup, and have been shown to be highly sensitive to cognitive processes as compared to measures of regional brain volume and diffusion weighted imaging metrics. We find here that the viscoelastic and volumetric differences between the nucleus accumbens and the prefrontal cortex are correlated with increased risk-taking behavior in adolescents. These differences in development between the two brain systems can be used as an indicator of those adolescents who are more prone to real world risky activities and a useful measure for characterizing response to intervention.</AbstractText
|
Motor and behavioral phenotype of Dravet syndrome in adulthood. In a comparative cross-sectional study, 26 adult individuals with clinically typical, genetically confirmed Dravet syndrome (DS) and an equal number of individuals with early onset, problematic epilepsy, and intellectual disability (ID) of comparable severity were included. The aim of the study was to find out whether patients with DS could be clearly distinguished from the comparison group with regard to neurological and behavioral symptoms. Significant differences were found in that individuals with DS clearly more frequently exhibited a symptom cluster characterized by bradykinesia, hypomimia, hypophonia, (spastic) increased muscle tone, ataxia, sthenic perseveration, and a special interest in colors. To these symptoms must be added, according to the findings of previous examinations, mastication, camptocormia/antecollis on the one hand, and the tendency to visual hallucinations on the other hand, in order to define one neuropsychiatric phenotype of DS in adulthood. To these symptoms must be added, according to the findings of previous investigations, crouch gait with camptocormia/antecollis on the one hand, and the tendency to visual hallucinations on the other hand, in order to define one outlined neuropsychiatric phenotype of DS in adulthood.</AbstractText
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40699745
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29974107
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40778466
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The Role of BCL-2 Expression in Patients with Myelodysplastic Neoplasms.
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An evolutionary transcriptomics approach links CD36 to membrane remodeling in replicative senescence.
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Enhancing Handwriting Performance in Autistic Children: A Randomized Crossover Study on the Effectiveness of a Spatial-Structured Handwriting Intervention Program.
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Myelodysplastic neoplasms (MDS) represent a heterogeneous group of neoplastic bone marrow disorders. A crucial component in regulating bone marrow cell apoptosis is the B-cell CLL/lymphoma 2 (BCL-2) protein. This retrospective study aimed to assess BCL-2 expression by immunohistochemistry in trephine biopsy specimens from 76 patients diagnosed with MDS. The obtained retrospective results were correlated with clinical parameters, including age, sex, MDS subtype, IPSS, IPSS-R, bone marrow blast percentage, Ogata score, response to treatment, blood morphology parameters, and overall survival (OS). The median follow-up duration was 16 months. During the observation period, 58 patients died (median OS of this group: 14.6 months), and 25 patients experienced progression to acute myeloid leukemia. The median BCL-2 expression assessed using the Histoscore (H-score) was 10. Patients with BCL-2 expression below 10 had better survival outcomes than those with expression ≥ 10. Furthermore, patients without detectable BCL-2 expression had significantly better survival compared to those with detectable BCL-2 expression (<i
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Cellular senescence, the irreversible ceasing of cell division, has been associated with organismal aging, prevention of cancerogenesis, and developmental processes. As such, the evolutionary basis and biological features of cellular senescence remain a fascinating area of research. In this study, we conducted comparative RNAseq experiments to detect genes associated with replicative senescence in two different human fibroblast cell lines and at different time points. We identified 841 and 900 genes (core senescence-associated genes) that are significantly up- and downregulated in senescent cells, respectively, in both cell lines. Our functional enrichment analysis showed that downregulated core genes are primarily involved in cell cycle processes while upregulated core gene enrichment indicated various lipid-related processes. We further demonstrated that downregulated genes are significantly more conserved than upregulated genes. Using both transcriptomics and genetic variation data, we identified one of the upregulated, lipid metabolism genes, CD36, as an outlier. We found that overexpression of CD36 induces a senescence-like phenotype and, further, the media of CD36-overexpressing cells alone can induce a senescence-like phenotype in proliferating young cells. Moreover, we used a targeted lipidomics approach and showed that phosphatidylcholines accumulate during replicative senescence in these cells, suggesting that upregulation of CD36 could contribute to membrane remodeling during senescence. Overall, these results contribute to the understanding of evolution and biology of cellular senescence and identify several targets and questions for future studies.</AbstractText
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Handwriting is an essential skill for school-aged children. Research indicates that autistic children often demonstrate poor handwriting fundamentals, which significantly affect their handwriting performance. These children also often exhibit weak central coherence (WCC), a cognitive visual processing characteristic that impairs their ability to integrate details into a cohesive whole in writing tasks. This challenge is particularly pronounced in logographic handwriting, where spatial relationships between radicals are essential for legibility, adding another layer of complexity. The modified geometric-based handwriting intervention program was designed to improve fundamental skills while addressing the spatial demands of logographic characters and the impact of WCC for autistic children. Twenty-two first- and second-grade autistic students were recruited and received a 12-h one-on-one handwriting intervention. Assessments of handwriting performance (legibility and speed), fundamental skills (visual perception, fine motor coordination, and visual-motor integration), and acceptability (motivation and satisfaction) were collected for data analysis. Results showed significant improvements in handwriting legibility, visual perception, and fine motor coordination, with high acceptance ratings from both participants and caregivers. This study provides evidence that the program effectively enhances handwriting legibility and foundational skills while maintaining high motivation levels in autistic children.</AbstractText
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The Role of BCL-2 Expression in Patients with Myelodysplastic Neoplasms. Myelodysplastic neoplasms (MDS) represent a heterogeneous group of neoplastic bone marrow disorders. A crucial component in regulating bone marrow cell apoptosis is the B-cell CLL/lymphoma 2 (BCL-2) protein. This retrospective study aimed to assess BCL-2 expression by immunohistochemistry in trephine biopsy specimens from 76 patients diagnosed with MDS. The obtained retrospective results were correlated with clinical parameters, including age, sex, MDS subtype, IPSS, IPSS-R, bone marrow blast percentage, Ogata score, response to treatment, blood morphology parameters, and overall survival (OS). The median follow-up duration was 16 months. During the observation period, 58 patients died (median OS of this group: 14.6 months), and 25 patients experienced progression to acute myeloid leukemia. The median BCL-2 expression assessed using the Histoscore (H-score) was 10. Patients with BCL-2 expression below 10 had better survival outcomes than those with expression ≥ 10. Furthermore, patients without detectable BCL-2 expression had significantly better survival compared to those with detectable BCL-2 expression (<i
|
An evolutionary transcriptomics approach links CD36 to membrane remodeling in replicative senescence. Cellular senescence, the irreversible ceasing of cell division, has been associated with organismal aging, prevention of cancerogenesis, and developmental processes. As such, the evolutionary basis and biological features of cellular senescence remain a fascinating area of research. In this study, we conducted comparative RNAseq experiments to detect genes associated with replicative senescence in two different human fibroblast cell lines and at different time points. We identified 841 and 900 genes (core senescence-associated genes) that are significantly up- and downregulated in senescent cells, respectively, in both cell lines. Our functional enrichment analysis showed that downregulated core genes are primarily involved in cell cycle processes while upregulated core gene enrichment indicated various lipid-related processes. We further demonstrated that downregulated genes are significantly more conserved than upregulated genes. Using both transcriptomics and genetic variation data, we identified one of the upregulated, lipid metabolism genes, CD36, as an outlier. We found that overexpression of CD36 induces a senescence-like phenotype and, further, the media of CD36-overexpressing cells alone can induce a senescence-like phenotype in proliferating young cells. Moreover, we used a targeted lipidomics approach and showed that phosphatidylcholines accumulate during replicative senescence in these cells, suggesting that upregulation of CD36 could contribute to membrane remodeling during senescence. Overall, these results contribute to the understanding of evolution and biology of cellular senescence and identify several targets and questions for future studies.</AbstractText
|
Enhancing Handwriting Performance in Autistic Children: A Randomized Crossover Study on the Effectiveness of a Spatial-Structured Handwriting Intervention Program. Handwriting is an essential skill for school-aged children. Research indicates that autistic children often demonstrate poor handwriting fundamentals, which significantly affect their handwriting performance. These children also often exhibit weak central coherence (WCC), a cognitive visual processing characteristic that impairs their ability to integrate details into a cohesive whole in writing tasks. This challenge is particularly pronounced in logographic handwriting, where spatial relationships between radicals are essential for legibility, adding another layer of complexity. The modified geometric-based handwriting intervention program was designed to improve fundamental skills while addressing the spatial demands of logographic characters and the impact of WCC for autistic children. Twenty-two first- and second-grade autistic students were recruited and received a 12-h one-on-one handwriting intervention. Assessments of handwriting performance (legibility and speed), fundamental skills (visual perception, fine motor coordination, and visual-motor integration), and acceptability (motivation and satisfaction) were collected for data analysis. Results showed significant improvements in handwriting legibility, visual perception, and fine motor coordination, with high acceptance ratings from both participants and caregivers. This study provides evidence that the program effectively enhances handwriting legibility and foundational skills while maintaining high motivation levels in autistic children.</AbstractText
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35690016
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8038571
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35983980
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Disrupted functional connectivity of the primary auditory cortex in autism.
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'What' and 'where' in the human brain.
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Glucocorticoid treatment in patients with complex regional pain syndrome: A systematic review.
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Autism Spectrum Disorder (ASD) has been found to influence hearing and sensory integration, while brain functional connectivity in ASD has been repeatedly shown to be atypical. However, functional connectivity of the auditory cortex in ASD has not been well studied. In the current study, we used resting-state functional magnetic resonance imaging data, provided by the Autism Brain Imaging Data Exchange (ABIDE), to examine functional connectivity of the primary auditory cortex in ASD. The study subjects included 68 individuals with ASD and 77 individuals without ASD. In the primary dataset, the ASD group showed lesser functional connectivity between the auditory cortex and four regions: the medial occipital cortex, primary motor cortex, insular cortex, and Wernicke's area. In the replication dataset (44 individuals with ASD and 39 individuals without ASD), reduced connectivity to the medial occipital cortex and primary motor cortex was replicated among these four regions, which have previously been shown to be influenced by ASD. Thus, the reduced functional connectivity to these indicated regions may partly explain deficient sensory integration associated with ASD.</AbstractText
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Multiple visual areas in the cortex of nonhuman primates are organized into two hierarchically organized and functionally specialized processing pathways, a 'ventral stream' for object vision and a 'dorsal stream' for spatial vision. Recent findings from positron emission tomography activation studies have localized these pathways within the human brain, yielding insights into cortical hierarchies, specialization of function, and attentional mechanisms.</AbstractText
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The pathophysiology of complex regional pain syndrome (CRPS) is multifactorial, with an exaggerated inflammatory response being the most prominent. Treatment for CRPS is carried out according to the presenting pathophysiological mechanism. Anti-inflammatory treatment with glucocorticoids is therefore an option. The aim of this study was to systematically review the efficacy of glucocorticoids in CRPS.</AbstractText Embase, Medline, Web of Science and Google Scholar were systematically searched for articles focusing on glucocorticoid treatment and CRPS. Screening based on title and abstract was followed by full-text reading (including reference lists) to determine the final set of relevant articles. Bias was assessed using the revised Cochrane risk-of-bias-tool for randomized trials (Rob2).</AbstractText Forty-one studies were included, which reported on 1208 CRPS patients. A wide variety of glucocorticoid administration strategies were applied, with oral being the most frequently chosen. Additionally, researchers found great heterogeneity in outcome parameters, including clinical symptoms, pain relief and range of motion. The use of glucocorticoids caused an improvement of parameters in all but two studies. In particular, improvement in pain relief and range of motion were reported. Using glucocorticoids in CRPS of longer duration (i.e. more than 3 months) appears to be less effective.</AbstractText Based on the present review, there is evidence to support glucocorticoid treatment in CRPS. However, the ideal administration route and dose remain unclear. We therefore recommend future research via an intervention study, as well as studies on the aetiological mechanisms and corresponding optimal treatment because CRPS pathogenesis is only partially understood.</AbstractText Several studies point towards CRPS being an inflammatory response after tissue or nerve damage, with higher levels of pro-inflammatory cytokines in serum, plasma, cerebrospinal fluid and artificial skin blisters. Inflammation provides a possible role for glucocorticoids in treating CRPS. This systematic review provides a structured overview of glucocorticoid treatment in patients with CRPS. Improvement in pain and range of motion is shown. Systematic review registration number: PROSPERO-CRD42020144671.</AbstractText
|
Disrupted functional connectivity of the primary auditory cortex in autism. Autism Spectrum Disorder (ASD) has been found to influence hearing and sensory integration, while brain functional connectivity in ASD has been repeatedly shown to be atypical. However, functional connectivity of the auditory cortex in ASD has not been well studied. In the current study, we used resting-state functional magnetic resonance imaging data, provided by the Autism Brain Imaging Data Exchange (ABIDE), to examine functional connectivity of the primary auditory cortex in ASD. The study subjects included 68 individuals with ASD and 77 individuals without ASD. In the primary dataset, the ASD group showed lesser functional connectivity between the auditory cortex and four regions: the medial occipital cortex, primary motor cortex, insular cortex, and Wernicke's area. In the replication dataset (44 individuals with ASD and 39 individuals without ASD), reduced connectivity to the medial occipital cortex and primary motor cortex was replicated among these four regions, which have previously been shown to be influenced by ASD. Thus, the reduced functional connectivity to these indicated regions may partly explain deficient sensory integration associated with ASD.</AbstractText
|
'What' and 'where' in the human brain. Multiple visual areas in the cortex of nonhuman primates are organized into two hierarchically organized and functionally specialized processing pathways, a 'ventral stream' for object vision and a 'dorsal stream' for spatial vision. Recent findings from positron emission tomography activation studies have localized these pathways within the human brain, yielding insights into cortical hierarchies, specialization of function, and attentional mechanisms.</AbstractText
|
Glucocorticoid treatment in patients with complex regional pain syndrome: A systematic review. The pathophysiology of complex regional pain syndrome (CRPS) is multifactorial, with an exaggerated inflammatory response being the most prominent. Treatment for CRPS is carried out according to the presenting pathophysiological mechanism. Anti-inflammatory treatment with glucocorticoids is therefore an option. The aim of this study was to systematically review the efficacy of glucocorticoids in CRPS.</AbstractText Embase, Medline, Web of Science and Google Scholar were systematically searched for articles focusing on glucocorticoid treatment and CRPS. Screening based on title and abstract was followed by full-text reading (including reference lists) to determine the final set of relevant articles. Bias was assessed using the revised Cochrane risk-of-bias-tool for randomized trials (Rob2).</AbstractText Forty-one studies were included, which reported on 1208 CRPS patients. A wide variety of glucocorticoid administration strategies were applied, with oral being the most frequently chosen. Additionally, researchers found great heterogeneity in outcome parameters, including clinical symptoms, pain relief and range of motion. The use of glucocorticoids caused an improvement of parameters in all but two studies. In particular, improvement in pain relief and range of motion were reported. Using glucocorticoids in CRPS of longer duration (i.e. more than 3 months) appears to be less effective.</AbstractText Based on the present review, there is evidence to support glucocorticoid treatment in CRPS. However, the ideal administration route and dose remain unclear. We therefore recommend future research via an intervention study, as well as studies on the aetiological mechanisms and corresponding optimal treatment because CRPS pathogenesis is only partially understood.</AbstractText Several studies point towards CRPS being an inflammatory response after tissue or nerve damage, with higher levels of pro-inflammatory cytokines in serum, plasma, cerebrospinal fluid and artificial skin blisters. Inflammation provides a possible role for glucocorticoids in treating CRPS. This systematic review provides a structured overview of glucocorticoid treatment in patients with CRPS. Improvement in pain and range of motion is shown. Systematic review registration number: PROSPERO-CRD42020144671.</AbstractText
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34776927
|
33878375
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34797301
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Anosognosia in Amnestic Mild Cognitive Impairment Is Related to Diminished Hippocampal Volume Comparable to Alzheimer's Disease Dementia: Preliminary MRI Findings.
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Early detection of Alzheimer's disease using creatine chemical exchange saturation transfer magnetic resonance imaging.
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Prevalence of refractive errors and color vision deficiency in a population of industry-workers in Abhar, Iran.
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Although the presence of anosognosia in amnestic mild cognitive impairment (aMCI) may be predictive of conversion to Alzheimer's disease (AD), little is known about its neural correlates in AD and aMCI. Four different groups were compared using volumetric and diffusion magnetic resonance imaging metrics in regions of interest (hippocampus and cingulum cortex gray matter, cingulum bundle white matter): aMCI subjects with anosognosia (<i
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Detecting Alzheimer's disease (AD) at an early stage brings a lot of benefits including disease management and actions to slow the progression of the disease. Here, we demonstrate that reduced creatine chemical exchange saturation transfer (CrCEST) contrast has the potential to serve as a new biomarker for early detection of AD. The results on wild type (WT) mice and two age-matched AD models, namely tauopathy (Tau) and Aβ amyloidosis (APP), indicated that CrCEST contrasts of the cortex and corpus callosum in the APP and Tau mice were significantly reduced compared to WT counterpart at an early stage (6-7 months) (p < 0.011). Two main causes of the reduced CrCEST contrast, i.e. cerebral pH and creatine concentration, were investigated. From phantom and hypercapnia experiments, CrCEST showed excellent sensitivity to pH variations. From MRS results, the creatine concentration in WT and AD mouse brain was equivalent, which suggests that the reduced CrCEST contrast was dominated by cerebral pH change involved in the progression of AD. Immunohistochemical analysis revealed that the abnormal cerebral pH in AD mice may relate to neuroinflammation, a known factor that can cause pH reduction.</AbstractText
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Visual impairment due to refractive errors and color vision deficiency (CVD) can affect the visual abilities of workers in workplace. Identifying the prevalence of common visual problems helps us to prevent and treat occupational ocular problems.This study was conducted on 2600 males referring from companies for a routine medical exam to Occupational Medicine Center. In all subjects, visual acuity and refraction were measured. Assessment of color vision was performed by Ishihara color test. In present study, right eyes of subjects were selected to statistical analysis.The mean spherical equivalent was -0.19 ± 1.39 diopter with a range of -11.00 to +10.00 diopter. Whereas 71% of persons were emmetropic, 20% and 9% of them were myopic and hypermetropic, respectively. From a total subjects, 164 of them had CVD with prevalence of color blindness of 6.3%. In comparison with normal subjects, CVD had no significant effect on refractive findings of our subjects (P > .05).Our data present the prevalence of refractive errors and color blindness among Iranian industry-workers. Compared with other studies, our subjects have a lower prevalence of refractive errors, and similar rate of prevalence of color blindness.</AbstractText
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Anosognosia in Amnestic Mild Cognitive Impairment Is Related to Diminished Hippocampal Volume Comparable to Alzheimer's Disease Dementia: Preliminary MRI Findings. Although the presence of anosognosia in amnestic mild cognitive impairment (aMCI) may be predictive of conversion to Alzheimer's disease (AD), little is known about its neural correlates in AD and aMCI. Four different groups were compared using volumetric and diffusion magnetic resonance imaging metrics in regions of interest (hippocampus and cingulum cortex gray matter, cingulum bundle white matter): aMCI subjects with anosognosia (<i
|
Early detection of Alzheimer's disease using creatine chemical exchange saturation transfer magnetic resonance imaging. Detecting Alzheimer's disease (AD) at an early stage brings a lot of benefits including disease management and actions to slow the progression of the disease. Here, we demonstrate that reduced creatine chemical exchange saturation transfer (CrCEST) contrast has the potential to serve as a new biomarker for early detection of AD. The results on wild type (WT) mice and two age-matched AD models, namely tauopathy (Tau) and Aβ amyloidosis (APP), indicated that CrCEST contrasts of the cortex and corpus callosum in the APP and Tau mice were significantly reduced compared to WT counterpart at an early stage (6-7 months) (p < 0.011). Two main causes of the reduced CrCEST contrast, i.e. cerebral pH and creatine concentration, were investigated. From phantom and hypercapnia experiments, CrCEST showed excellent sensitivity to pH variations. From MRS results, the creatine concentration in WT and AD mouse brain was equivalent, which suggests that the reduced CrCEST contrast was dominated by cerebral pH change involved in the progression of AD. Immunohistochemical analysis revealed that the abnormal cerebral pH in AD mice may relate to neuroinflammation, a known factor that can cause pH reduction.</AbstractText
|
Prevalence of refractive errors and color vision deficiency in a population of industry-workers in Abhar, Iran. Visual impairment due to refractive errors and color vision deficiency (CVD) can affect the visual abilities of workers in workplace. Identifying the prevalence of common visual problems helps us to prevent and treat occupational ocular problems.This study was conducted on 2600 males referring from companies for a routine medical exam to Occupational Medicine Center. In all subjects, visual acuity and refraction were measured. Assessment of color vision was performed by Ishihara color test. In present study, right eyes of subjects were selected to statistical analysis.The mean spherical equivalent was -0.19 ± 1.39 diopter with a range of -11.00 to +10.00 diopter. Whereas 71% of persons were emmetropic, 20% and 9% of them were myopic and hypermetropic, respectively. From a total subjects, 164 of them had CVD with prevalence of color blindness of 6.3%. In comparison with normal subjects, CVD had no significant effect on refractive findings of our subjects (P > .05).Our data present the prevalence of refractive errors and color blindness among Iranian industry-workers. Compared with other studies, our subjects have a lower prevalence of refractive errors, and similar rate of prevalence of color blindness.</AbstractText
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40696805
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38688278
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40752707
|
Why psychiatry needs ethnography.
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Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network.
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Alginate/derivatives and their nanoparticles as anti-diabetic therapeutic via cancer, gut, liver and blood health modulation: A review.
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Psychiatrists and anthropologists both rely on observation, discourse analysis and access to participants' internal and external worlds. Ethnographic fieldwork, a key method in medical anthropology, offers a powerful tool to establish a robust evidence base of how to address mental health inequalities in ethnic minority communities.</AbstractText
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The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. Our approach to managing the complexities associated with the differential performance of PRSs serves as a case study that can help future implementers of PRSs to plot an anticipatory course in response to this issue.</AbstractText
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Diabetes mellitus is a metabolic disorder and is associated with hypertension, hyperlipidemia, liver disease, cancer and gut health. Alginate as carbohydrate receives a widespread application in food and medicine development. Through review of literature (2016-2024), this study identifies the relationship between physicochemical properties of alginate, its derivatives and nanoparticles with their biological activities in treating diabetes. Alginate is able to negate hyperglycemia through reducing inflammatory responses, promoting pancreatic insulin secretion, increasing peripheral insulin sensitivity, and inhibiting gastrointestinal digestion and absorption of sugar. It regulates blood pressure, lipid levels, gastrointestinal function and cancer to mitigate the development of diabetes due to these diseases. The anti-diabetic effectiveness of alginate is dependent on complex interplay of molecular weight, mannuronate/guluronate ratio, and type of graft or complex derivatized from it. Low molecular weight, guluronate-rich alginate prevents the pathological onset of diabetes. Low molecular weight, mannuronate-rich alginate functions as a glucose adsorber to prevent systemic glucose absorption. Low molecular weight alginate is apparently active against hypertension, hyperlipidemia and liver diseases, and promotes gastrointestinal health, which benefits diabetes control. Calcium crosslinked, sulfate/propylene glycol ester-grafted and vanadium complexed alginate show improved anti-diabetic actions. Alginate in nanoparticulate form could regulate glucose absorption, gut health and proliferative activity in conjunction with blood glucose homeostasis. Alginate, as a function of chemical compositions and its nanoparticulate characteristics, demonstrates a potential anti-diabetic activity that warrants its application as anti-diabetic therapeutic.</AbstractText
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Why psychiatry needs ethnography. Psychiatrists and anthropologists both rely on observation, discourse analysis and access to participants' internal and external worlds. Ethnographic fieldwork, a key method in medical anthropology, offers a powerful tool to establish a robust evidence base of how to address mental health inequalities in ethnic minority communities.</AbstractText
|
Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network. The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. Our approach to managing the complexities associated with the differential performance of PRSs serves as a case study that can help future implementers of PRSs to plot an anticipatory course in response to this issue.</AbstractText
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Alginate/derivatives and their nanoparticles as anti-diabetic therapeutic via cancer, gut, liver and blood health modulation: A review. Diabetes mellitus is a metabolic disorder and is associated with hypertension, hyperlipidemia, liver disease, cancer and gut health. Alginate as carbohydrate receives a widespread application in food and medicine development. Through review of literature (2016-2024), this study identifies the relationship between physicochemical properties of alginate, its derivatives and nanoparticles with their biological activities in treating diabetes. Alginate is able to negate hyperglycemia through reducing inflammatory responses, promoting pancreatic insulin secretion, increasing peripheral insulin sensitivity, and inhibiting gastrointestinal digestion and absorption of sugar. It regulates blood pressure, lipid levels, gastrointestinal function and cancer to mitigate the development of diabetes due to these diseases. The anti-diabetic effectiveness of alginate is dependent on complex interplay of molecular weight, mannuronate/guluronate ratio, and type of graft or complex derivatized from it. Low molecular weight, guluronate-rich alginate prevents the pathological onset of diabetes. Low molecular weight, mannuronate-rich alginate functions as a glucose adsorber to prevent systemic glucose absorption. Low molecular weight alginate is apparently active against hypertension, hyperlipidemia and liver diseases, and promotes gastrointestinal health, which benefits diabetes control. Calcium crosslinked, sulfate/propylene glycol ester-grafted and vanadium complexed alginate show improved anti-diabetic actions. Alginate in nanoparticulate form could regulate glucose absorption, gut health and proliferative activity in conjunction with blood glucose homeostasis. Alginate, as a function of chemical compositions and its nanoparticulate characteristics, demonstrates a potential anti-diabetic activity that warrants its application as anti-diabetic therapeutic.</AbstractText
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37758961
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35003870
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38042888
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Myocardial perfusion imaging with retrospective gating and integrated correction of attenuation, scatter, respiration, motion, and arrhythmia.
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Compressed sensing for photoacoustic computed tomography based on an untrained neural network with a shape prior.
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Prevalence of undiagnosed dyslexia in African-American primary school children.
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Absolute quantitative myocardial perfusion SPECT requires addressing of aleatory and epistemic uncertainties in conjunction with providing image quality sufficient for lesion detection and characterization. Iterative reconstruction methods enable the mitigation of the root causes of image degradation. This study aimed to determine the feasibility of a new SPECT/CT method with integrated corrections attempting to enable absolute quantitative cardiac imaging (xSPECT Cardiac; xSC).</AbstractText We compared images of prototype xSC and conventional SPECT (Flash3D<sup The quality of all xSC images was acceptable for clinical purposes. A polar map showed more uniform distribution for xSC compared with Flash3D, while lower apical count and higher defect contrast of myocardial infarction (p = 0.0004) were observed on xSC images. Wall motion, 16-gate volume curve, and ejection fraction were at least acceptable, with indication of improvements. The clinical prospectively gated method rejected beats ≥20% in 6 patients, whereas retrospective gating used an average of 98% beats, excluding 2% of beats. We used the list-mode data to create a product equivalent prospectively gated dataset. The dataset showed that the xSC method generated 18% higher count data and images with less noise, with comparable functional variables of volume and LVEF (p = ns).</AbstractText Quantitative myocardial perfusion imaging with the list-mode-based prototype xSPECT Cardiac is feasible, resulting in images of at least acceptable image quality.</AbstractText
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Photoacoustic (PA) computed tomography (PACT) shows great potential in various preclinical and clinical applications. A great number of measurements are the premise that obtains a high-quality image, which implies a low imaging rate or a high system cost. The artifacts or sidelobes could pollute the image if we decrease the number of measured channels or limit the detected view. In this paper, a novel compressed sensing method for PACT using an untrained neural network is proposed, which decreases a half number of the measured channels and recovers enough details. This method uses a neural network to reconstruct without the requirement for any additional learning based on the deep image prior. The model can reconstruct the image only using a few detections with gradient descent. As an unlearned strategy, our method can cooperate with other existing regularization, and further improve the quality. In addition, we introduce a shape prior to easily converge the model to the image. We verify the feasibility of untrained network-based compressed sensing in PA image reconstruction and compare this method with a conventional method using total variation minimization. The experimental results show that our proposed method outperforms 32.72% (SSIM) with the traditional compressed sensing method in the same regularization. It could dramatically reduce the requirement for the number of transducers, by sparsely sampling the raw PA data, and improve the quality of PA image significantly.</AbstractText
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Dyslexia is among the most common neurodevelopmental disorders in children, yet despite its high prevalence all too frequently goes undiagnosed. Consequently dyslexic children all too often fail to receive effective reading interventions. Here we report our findings from a study using a teacher completed evidence-based dyslexia screener to first screen then test predominantly African-American children in grades kindergarten through second grade in two inner city public charter schools in New Orleans. Almost half (49.2%) of the children screened as at risk for dyslexia and of these the majority were found to be dyslexic on more detailed testing. Our results suggest that large numbers of African-American students with dyslexia may be overlooked in schools.</AbstractText
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Myocardial perfusion imaging with retrospective gating and integrated correction of attenuation, scatter, respiration, motion, and arrhythmia. Absolute quantitative myocardial perfusion SPECT requires addressing of aleatory and epistemic uncertainties in conjunction with providing image quality sufficient for lesion detection and characterization. Iterative reconstruction methods enable the mitigation of the root causes of image degradation. This study aimed to determine the feasibility of a new SPECT/CT method with integrated corrections attempting to enable absolute quantitative cardiac imaging (xSPECT Cardiac; xSC).</AbstractText We compared images of prototype xSC and conventional SPECT (Flash3D<sup The quality of all xSC images was acceptable for clinical purposes. A polar map showed more uniform distribution for xSC compared with Flash3D, while lower apical count and higher defect contrast of myocardial infarction (p = 0.0004) were observed on xSC images. Wall motion, 16-gate volume curve, and ejection fraction were at least acceptable, with indication of improvements. The clinical prospectively gated method rejected beats ≥20% in 6 patients, whereas retrospective gating used an average of 98% beats, excluding 2% of beats. We used the list-mode data to create a product equivalent prospectively gated dataset. The dataset showed that the xSC method generated 18% higher count data and images with less noise, with comparable functional variables of volume and LVEF (p = ns).</AbstractText Quantitative myocardial perfusion imaging with the list-mode-based prototype xSPECT Cardiac is feasible, resulting in images of at least acceptable image quality.</AbstractText
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Compressed sensing for photoacoustic computed tomography based on an untrained neural network with a shape prior. Photoacoustic (PA) computed tomography (PACT) shows great potential in various preclinical and clinical applications. A great number of measurements are the premise that obtains a high-quality image, which implies a low imaging rate or a high system cost. The artifacts or sidelobes could pollute the image if we decrease the number of measured channels or limit the detected view. In this paper, a novel compressed sensing method for PACT using an untrained neural network is proposed, which decreases a half number of the measured channels and recovers enough details. This method uses a neural network to reconstruct without the requirement for any additional learning based on the deep image prior. The model can reconstruct the image only using a few detections with gradient descent. As an unlearned strategy, our method can cooperate with other existing regularization, and further improve the quality. In addition, we introduce a shape prior to easily converge the model to the image. We verify the feasibility of untrained network-based compressed sensing in PA image reconstruction and compare this method with a conventional method using total variation minimization. The experimental results show that our proposed method outperforms 32.72% (SSIM) with the traditional compressed sensing method in the same regularization. It could dramatically reduce the requirement for the number of transducers, by sparsely sampling the raw PA data, and improve the quality of PA image significantly.</AbstractText
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Prevalence of undiagnosed dyslexia in African-American primary school children. Dyslexia is among the most common neurodevelopmental disorders in children, yet despite its high prevalence all too frequently goes undiagnosed. Consequently dyslexic children all too often fail to receive effective reading interventions. Here we report our findings from a study using a teacher completed evidence-based dyslexia screener to first screen then test predominantly African-American children in grades kindergarten through second grade in two inner city public charter schools in New Orleans. Almost half (49.2%) of the children screened as at risk for dyslexia and of these the majority were found to be dyslexic on more detailed testing. Our results suggest that large numbers of African-American students with dyslexia may be overlooked in schools.</AbstractText
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38676925
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32816912
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38496144
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Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory in mice.
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Extracellular Vesicle-Derived miR-124 Resolves Radiation-Induced Brain Injury.
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Acute Myopericarditis as the First Manifestation of Familial Mediterranean Fever: A Case Report.
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Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we hypothesize that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to these processes. We show that clusters of the peri-synaptic ECM, recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. Using CS56 co-immunoprecipitation of synaptosomal proteins, we identify several molecules involved in Ca<sup
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Radiation-induced cognitive dysfunction (RICD) is a progressive and debilitating health issue facing patients following cranial radiotherapy to control central nervous system cancers. There has been some success treating RICD in rodents using human neural stem cell (hNSC) transplantation, but the procedure is invasive, requires immunosuppression, and could cause other complications such as teratoma formation. Extracellular vesicles (EV) are nanoscale membrane-bound structures that contain biological contents including mRNA, miRNA, proteins, and lipids that can be readily isolated from conditioned culture media. It has been previously shown that hNSC-derived EV resolves RICD following cranial irradiation using an immunocompromised rodent model. Here, we use immunocompetent wild-type mice to show that hNSC-derived EV treatment administered either intravenously via retro-orbital vein injection or via intracranial transplantation can ameliorate cognitive deficits following 9 Gy head-only irradiation. Cognitive function assessed on the novel place recognition, novel object recognition, and temporal order tasks was not only improved at early (5 weeks) but also at delayed (6 months) postirradiation times with just a single EV treatment. Improved behavioral outcomes were also associated with reduced neuroinflammation as measured by a reduction in activated microglia. To identify the mechanism of action, analysis of EV cargo implicated miRNA (miR-124) as a potential candidate in the mitigation of RICD. Furthermore, viral vector-mediated overexpression of miR-124 in the irradiated brain ameliorated RICD and reduced microglial activation. Our findings demonstrate for the first time that systemic administration of hNSC-derived EV abrogates RICD and neuroinflammation in cranially irradiated wild-type rodents through a mechanism involving miR-124. SIGNIFICANCE: Radiation-induced neurocognitive decrements in immunocompetent mice can be resolved by systemic delivery of hNSC-derived EVs involving a mechanism dependent on expression of miR-124.</AbstractText
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Familial Mediterranean fever (FMF) is an autoinflammatory disorder, characterized by recurrent episodes of fever and polyserositis, and usually presents during the first two decades of life. Acute pericarditis is a rare manifestation of FMF and typically presents with other symptoms of the inflammatory disorder. A 27-year-old Arabian male presented to our hospital with pleuritic chest pain and shortness of breath while lying flat. His electrocardiogram showed changes suggestive of pericarditis, and his inflammatory markers and troponin were raised. His echocardiogram revealed a moderate-sized pericardial effusion with septa and a normal left ventricular function. He had a strong family history of FMF and consanguinity of the parents. He was treated for acute myopericarditis with colchicine and ibuprofen, and his symptoms improved gradually along with his inflammatory markers and troponin. Six weeks after discharge, he had a cardiac MRI, which revealed a thickened pericardium with profound enhancement (features suggestive of pericarditis) and no signs of myocarditis. He was asymptomatic, and his markers and troponin were within the normal range. His colchicine medication was continued indefinitely, and he was referred to a tertiary care hospital with a specialized periodic fever clinic for follow-up and genotype testing.</AbstractText
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Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory in mice. Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we hypothesize that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to these processes. We show that clusters of the peri-synaptic ECM, recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. Using CS56 co-immunoprecipitation of synaptosomal proteins, we identify several molecules involved in Ca<sup
|
Extracellular Vesicle-Derived miR-124 Resolves Radiation-Induced Brain Injury. Radiation-induced cognitive dysfunction (RICD) is a progressive and debilitating health issue facing patients following cranial radiotherapy to control central nervous system cancers. There has been some success treating RICD in rodents using human neural stem cell (hNSC) transplantation, but the procedure is invasive, requires immunosuppression, and could cause other complications such as teratoma formation. Extracellular vesicles (EV) are nanoscale membrane-bound structures that contain biological contents including mRNA, miRNA, proteins, and lipids that can be readily isolated from conditioned culture media. It has been previously shown that hNSC-derived EV resolves RICD following cranial irradiation using an immunocompromised rodent model. Here, we use immunocompetent wild-type mice to show that hNSC-derived EV treatment administered either intravenously via retro-orbital vein injection or via intracranial transplantation can ameliorate cognitive deficits following 9 Gy head-only irradiation. Cognitive function assessed on the novel place recognition, novel object recognition, and temporal order tasks was not only improved at early (5 weeks) but also at delayed (6 months) postirradiation times with just a single EV treatment. Improved behavioral outcomes were also associated with reduced neuroinflammation as measured by a reduction in activated microglia. To identify the mechanism of action, analysis of EV cargo implicated miRNA (miR-124) as a potential candidate in the mitigation of RICD. Furthermore, viral vector-mediated overexpression of miR-124 in the irradiated brain ameliorated RICD and reduced microglial activation. Our findings demonstrate for the first time that systemic administration of hNSC-derived EV abrogates RICD and neuroinflammation in cranially irradiated wild-type rodents through a mechanism involving miR-124. SIGNIFICANCE: Radiation-induced neurocognitive decrements in immunocompetent mice can be resolved by systemic delivery of hNSC-derived EVs involving a mechanism dependent on expression of miR-124.</AbstractText
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Acute Myopericarditis as the First Manifestation of Familial Mediterranean Fever: A Case Report. Familial Mediterranean fever (FMF) is an autoinflammatory disorder, characterized by recurrent episodes of fever and polyserositis, and usually presents during the first two decades of life. Acute pericarditis is a rare manifestation of FMF and typically presents with other symptoms of the inflammatory disorder. A 27-year-old Arabian male presented to our hospital with pleuritic chest pain and shortness of breath while lying flat. His electrocardiogram showed changes suggestive of pericarditis, and his inflammatory markers and troponin were raised. His echocardiogram revealed a moderate-sized pericardial effusion with septa and a normal left ventricular function. He had a strong family history of FMF and consanguinity of the parents. He was treated for acute myopericarditis with colchicine and ibuprofen, and his symptoms improved gradually along with his inflammatory markers and troponin. Six weeks after discharge, he had a cardiac MRI, which revealed a thickened pericardium with profound enhancement (features suggestive of pericarditis) and no signs of myocarditis. He was asymptomatic, and his markers and troponin were within the normal range. His colchicine medication was continued indefinitely, and he was referred to a tertiary care hospital with a specialized periodic fever clinic for follow-up and genotype testing.</AbstractText
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22867024
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23802040
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22180462
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Cellular elements for seeing in the dark: voltage-dependent conductances in cockroach photoreceptors.
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Cracking the bioelectric code: Probing endogenous ionic controls of pattern formation.
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Proton magnetic resonance spectroscopy of the motor cortex in cervical myelopathy.
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The importance of voltage-dependent conductances in sensory information processing is well-established in insect photoreceptors. Here we present the characterization of electrical properties in photoreceptors of the cockroach (Periplaneta americana), a nocturnal insect with a visual system adapted for dim light.</AbstractText Whole-cell patch-clamped photoreceptors had high capacitances and input resistances, indicating large photosensitive rhabdomeres suitable for efficient photon capture and amplification of small photocurrents at low light levels. Two voltage-dependent potassium conductances were found in the photoreceptors: a delayed rectifier type (KDR) and a fast transient inactivating type (KA). Activation of KDR occurred during physiological voltage responses induced by light stimulation, whereas KA was nearly fully inactivated already at the dark resting potential. In addition, hyperpolarization of photoreceptors activated a small-amplitude inward-rectifying (IR) current mediated at least partially by chloride. Computer simulations showed that KDR shapes light responses by opposing the light-induced depolarization and speeding up the membrane time constant, whereas KA and IR have a negligible role in the majority of cells. However, larger KA conductances were found in smaller and rapidly adapting photoreceptors, where KA could have a functional role.</AbstractText The relative expression of KA and KDR in cockroach photoreceptors was opposite to the previously hypothesized framework for dark-active insects, necessitating further comparative work on the conductances. In general, the varying deployment of stereotypical K+ conductances in insect photoreceptors highlights their functional flexibility in neural coding.</AbstractText
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Patterns of resting potential in non-excitable cells of living tissue are now known to be instructive signals for pattern formation during embryogenesis, regeneration and cancer suppression. The development of molecular-level techniques for tracking ion flows and functionally manipulating the activity of ion channels and pumps has begun to reveal the mechanisms by which voltage gradients regulate cell behaviors and the assembly of complex large-scale structures. A recent paper demonstrated that a specific voltage range is necessary for demarcation of eye fields in the frog embryo. Remarkably, artificially setting other somatic cells to the eye-specific voltage range resulted in formation of eyes in aberrant locations, including tissues that are not in the normal anterior ectoderm lineage: eyes could be formed in the gut, on the tail, or in the lateral plate mesoderm. These data challenge the existing models of eye fate restriction and tissue competence maps, and suggest the presence of a bioelectric code-a mapping of physiological properties to anatomical outcomes. This Addendum summarizes the current state of knowledge in developmental bioelectricity, proposes three possible interpretations of the bioelectric code that functionally maps physiological states to anatomical outcomes, and highlights the biggest open questions in this field. We also suggest a speculative hypothesis at the intersection of cognitive science and developmental biology: that bioelectrical signaling among non-excitable cells coupled by gap junctions simulates neural network-like dynamics, and underlies the information processing functions required by complex pattern formation in vivo. Understanding and learning to control the information stored in physiological networks will have transformative implications for developmental biology, regenerative medicine and synthetic bioengineering.</AbstractText
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Alterations in motor function in cervical myelopathy secondary to degenerative disease may be due to local effects of spinal compression or distal effects related to cortical reorganization. This prospective study characterizes differences in metabolite levels in the motor cortex, specifically N-acetylaspartate, creatine, choline, myo-inositol and glutamate plus glutamine, due to alterations in cortical function in patients with reversible spinal cord compression compared with healthy controls. We hypothesized that N-acetylaspartate/creatine levels would be decreased in the motor cortex of patients with cervical myelopathy due to reduced neuronal integrity/function and myo-inositol/creatine levels would be increased due to reactive gliosis. Twenty-four patients with cervical myelopathy and 11 healthy controls underwent proton-magnetic resonance spectroscopy on a 3.0 Tesla Siemens Magnetom Tim Trio MRI. Areas of activation from functional magnetic resonance imaging scans of a finger-tapping paradigm were used to localize a voxel on the side of greater motor deficit in the myelopathy group (n = 10 on right side and n = 14 on left side of the brain) and on each side of the motor cortex in controls. Neurological function was measured with the Neck Disability Index, modified Japanese Orthopaedic Association and American Spinal Injury Association questionnaires. Metabolite levels were measured relative to total creatine within the voxel of interest. No metabolite differences were detected between the right side and left side of the motor cortex in controls. The myelopathy group had significantly decreased neurological function compared with the control group (Neck Disability Index: P < 0.001 and modified Japanese Orthopaedic Association: P < 0.001). There was a significant decrease in the N-acetylaspartate/creatine metabolite ratio in the motor cortex of the myelopathy group (1.21 ± 0.07) compared with the right (1.37 ± 0.03; P = 0.01) and left (1.38 ± 0.03; P = 0.007) motor cortex in controls suggesting neuronal damage or dysfunction distal to the lesion in the spine. No difference was observed in levels of myo-inositol/creatine. Thus, cortical levels of N-acetylaspartate/creatine may be a meaningful biomarker in cervical myelopathy, indicative of neuronal damage or dysfunction.</AbstractText
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Cellular elements for seeing in the dark: voltage-dependent conductances in cockroach photoreceptors. The importance of voltage-dependent conductances in sensory information processing is well-established in insect photoreceptors. Here we present the characterization of electrical properties in photoreceptors of the cockroach (Periplaneta americana), a nocturnal insect with a visual system adapted for dim light.</AbstractText Whole-cell patch-clamped photoreceptors had high capacitances and input resistances, indicating large photosensitive rhabdomeres suitable for efficient photon capture and amplification of small photocurrents at low light levels. Two voltage-dependent potassium conductances were found in the photoreceptors: a delayed rectifier type (KDR) and a fast transient inactivating type (KA). Activation of KDR occurred during physiological voltage responses induced by light stimulation, whereas KA was nearly fully inactivated already at the dark resting potential. In addition, hyperpolarization of photoreceptors activated a small-amplitude inward-rectifying (IR) current mediated at least partially by chloride. Computer simulations showed that KDR shapes light responses by opposing the light-induced depolarization and speeding up the membrane time constant, whereas KA and IR have a negligible role in the majority of cells. However, larger KA conductances were found in smaller and rapidly adapting photoreceptors, where KA could have a functional role.</AbstractText The relative expression of KA and KDR in cockroach photoreceptors was opposite to the previously hypothesized framework for dark-active insects, necessitating further comparative work on the conductances. In general, the varying deployment of stereotypical K+ conductances in insect photoreceptors highlights their functional flexibility in neural coding.</AbstractText
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Cracking the bioelectric code: Probing endogenous ionic controls of pattern formation. Patterns of resting potential in non-excitable cells of living tissue are now known to be instructive signals for pattern formation during embryogenesis, regeneration and cancer suppression. The development of molecular-level techniques for tracking ion flows and functionally manipulating the activity of ion channels and pumps has begun to reveal the mechanisms by which voltage gradients regulate cell behaviors and the assembly of complex large-scale structures. A recent paper demonstrated that a specific voltage range is necessary for demarcation of eye fields in the frog embryo. Remarkably, artificially setting other somatic cells to the eye-specific voltage range resulted in formation of eyes in aberrant locations, including tissues that are not in the normal anterior ectoderm lineage: eyes could be formed in the gut, on the tail, or in the lateral plate mesoderm. These data challenge the existing models of eye fate restriction and tissue competence maps, and suggest the presence of a bioelectric code-a mapping of physiological properties to anatomical outcomes. This Addendum summarizes the current state of knowledge in developmental bioelectricity, proposes three possible interpretations of the bioelectric code that functionally maps physiological states to anatomical outcomes, and highlights the biggest open questions in this field. We also suggest a speculative hypothesis at the intersection of cognitive science and developmental biology: that bioelectrical signaling among non-excitable cells coupled by gap junctions simulates neural network-like dynamics, and underlies the information processing functions required by complex pattern formation in vivo. Understanding and learning to control the information stored in physiological networks will have transformative implications for developmental biology, regenerative medicine and synthetic bioengineering.</AbstractText
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Proton magnetic resonance spectroscopy of the motor cortex in cervical myelopathy. Alterations in motor function in cervical myelopathy secondary to degenerative disease may be due to local effects of spinal compression or distal effects related to cortical reorganization. This prospective study characterizes differences in metabolite levels in the motor cortex, specifically N-acetylaspartate, creatine, choline, myo-inositol and glutamate plus glutamine, due to alterations in cortical function in patients with reversible spinal cord compression compared with healthy controls. We hypothesized that N-acetylaspartate/creatine levels would be decreased in the motor cortex of patients with cervical myelopathy due to reduced neuronal integrity/function and myo-inositol/creatine levels would be increased due to reactive gliosis. Twenty-four patients with cervical myelopathy and 11 healthy controls underwent proton-magnetic resonance spectroscopy on a 3.0 Tesla Siemens Magnetom Tim Trio MRI. Areas of activation from functional magnetic resonance imaging scans of a finger-tapping paradigm were used to localize a voxel on the side of greater motor deficit in the myelopathy group (n = 10 on right side and n = 14 on left side of the brain) and on each side of the motor cortex in controls. Neurological function was measured with the Neck Disability Index, modified Japanese Orthopaedic Association and American Spinal Injury Association questionnaires. Metabolite levels were measured relative to total creatine within the voxel of interest. No metabolite differences were detected between the right side and left side of the motor cortex in controls. The myelopathy group had significantly decreased neurological function compared with the control group (Neck Disability Index: P < 0.001 and modified Japanese Orthopaedic Association: P < 0.001). There was a significant decrease in the N-acetylaspartate/creatine metabolite ratio in the motor cortex of the myelopathy group (1.21 ± 0.07) compared with the right (1.37 ± 0.03; P = 0.01) and left (1.38 ± 0.03; P = 0.007) motor cortex in controls suggesting neuronal damage or dysfunction distal to the lesion in the spine. No difference was observed in levels of myo-inositol/creatine. Thus, cortical levels of N-acetylaspartate/creatine may be a meaningful biomarker in cervical myelopathy, indicative of neuronal damage or dysfunction.</AbstractText
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39245222
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39385241
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38663996
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Hippocampal volume maximally modulates the relationship between subsyndromal symptomatic depression and cognitive impairment in non-demented older adults.
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Prognostic model for predicting Alzheimer's disease conversion using functional connectome manifolds.
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Treatment trends and clinical outcomes of endovascular embolization for unruptured intracranial aneurysms in the pediatric population.
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Subsyndromal symptomatic depression (SSD) is associated with an elevated risk of cognitive impairment in non-demented older adults. Given that hippocampal and middle temporal gyrus atrophy have been shown to cause SSD, our study aimed to investigate the effect of hippocampal volume on the association between SSD and cognitive impairment.</AbstractText 338 non-demented older adults from the ADNI (Alzheimer's Disease Neuroimaging Initiative) cohort who underwent cognitive assessments, questionnaires on depressive symptoms and MRI brain were studied. SSD group is defined as a score of 1-5 based on Geriatric Depression Scale scores. We conducted causal mediation analyses to investigate the effect of hippocampal volume on cognitive performance cross-sectionally.</AbstractText The SSD group displayed lower left and right hippocampal volume (p<0.01) than the non-SSD group. SSD was linked to poorer cognition and smaller hippocampal volume. We found that hippocampal volume partially mediated the effect of SSD on cognitive performance including the global cognition and the cognitive section of Alzheimer's Disease Assessment Scale, with mediation percentages ranging from 6.45 % to 30.46 %. In addition, we found that the thickness of the left middle temporal, right entorhinal and right fusiform gyrus, brain regions linked to AD, mediate the relationship between SSD and cognition with mediation percentages ranging from 8.67 % to 21.44 %.</AbstractText Our article didn't differentiate between mild cognitive impairment and normal population.</AbstractText The associations of SSD and cognitive impairment are linked to alterations in Alzheimer's Disease related brain regions.</AbstractText
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Early detection of Alzheimer's disease (AD) is essential for timely management and consideration of therapeutic options; therefore, detecting the risk of conversion from mild cognitive impairment (MCI) to AD is crucial during neurodegenerative progression. Existing neuroimaging studies have mostly focused on group differences between individuals with MCI (or AD) and cognitively normal (CN), discarding the temporal information of conversion time. Here, we aimed to develop a prognostic model for AD conversion using functional connectivity (FC) and Cox regression suitable for conversion event modeling.</AbstractText We developed a prognostic model using a large-scale Alzheimer's Disease Neuroimaging Initiative dataset, and it was validated using external data obtained from the Open Access Series of Imaging Studies. We considered individuals who were initially CN or had MCI but progressed to AD and those with MCI with no progression to AD during the five-year follow-up period. As the exact conversion time to AD is unknown, we inferred this information using imputation approaches. We generated cortex-wide principal FC gradients using manifold learning techniques and computed subcortical-weighted manifold degrees from baseline functional magnetic resonance imaging data. A penalized Cox regression model with an elastic net penalty was adopted to define a risk score predicting the risk of conversion to AD, using FC gradients and clinical factors as regressors.</AbstractText Our prognostic model predicted the conversion risk and confirmed the role of imaging-derived manifolds in the conversion risk. The brain regions that largely contributed to predicting AD conversion were the heteromodal association and visual cortices, as well as the caudate and hippocampus. Our risk score based on Cox regression was consistent with the expected disease trajectories and correlated with positron emission tomography tracer uptake and symptom severity, reinforcing its clinical usefulness. Our findings were validated using an independent dataset. The cross-sectional application of our model showed a higher risk for AD than that for MCI, which correlated with symptom severity scores in the validation dataset.</AbstractText We proposed a prognostic model predicting the risk of conversion to AD. The associated risk score may provide insights for early intervention in individuals at risk of AD conversion.</AbstractText
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Owing to the relative rarity of unruptured intracranial aneurysms (UIAs) in the pediatric population, evidence regarding treatment modalities and clinical outcomes remains limited.</AbstractText To characterize the use and clinical outcomes of endovascular therapy (EVT) and microsurgical clipping (MSC) for pediatric UIAs over a two-decade interval using a large national registry.</AbstractText Pediatric (<18 years of age) UIA hospitalizations were identified in the National Inpatient Sample from 2002 to 2019. Temporal use and clinical outcomes were compared for treatment with EVT and MSC.</AbstractText Among 734 UIAs identified, 64.9% (n=476) were treated with EVT. Use of EVT significantly increased during the study period from 54.3% (2002-2004) to 78.6% (2017-2019) (P=0.002 by Cochrane-Armitage test). In comparison with those treated with MSC, pediatric patients treated with EVT demonstrated higher rates of favorable outcomes (discharge to home without services) (96.0% vs 91.1%, P=0.006), shorter durations of hospital stay (4.6 vs 10.0 days, P<0.001), and lower rates of ischemic or hemorrhagic procedural-related complications (1% vs 4%, P=0.010). Conservative management also increased significantly over the study period (P<0.001 by Cochrane-Armitage test).</AbstractText A retrospective evaluation of nearly 20 years of population-level data from the United States demonstrates increasing use of EVT for the treatment of pediatric UIAs, with high rates of favorable outcomes and shorter hospital stays in comparison with those treated with microsurgery.</AbstractText
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Hippocampal volume maximally modulates the relationship between subsyndromal symptomatic depression and cognitive impairment in non-demented older adults. Subsyndromal symptomatic depression (SSD) is associated with an elevated risk of cognitive impairment in non-demented older adults. Given that hippocampal and middle temporal gyrus atrophy have been shown to cause SSD, our study aimed to investigate the effect of hippocampal volume on the association between SSD and cognitive impairment.</AbstractText 338 non-demented older adults from the ADNI (Alzheimer's Disease Neuroimaging Initiative) cohort who underwent cognitive assessments, questionnaires on depressive symptoms and MRI brain were studied. SSD group is defined as a score of 1-5 based on Geriatric Depression Scale scores. We conducted causal mediation analyses to investigate the effect of hippocampal volume on cognitive performance cross-sectionally.</AbstractText The SSD group displayed lower left and right hippocampal volume (p<0.01) than the non-SSD group. SSD was linked to poorer cognition and smaller hippocampal volume. We found that hippocampal volume partially mediated the effect of SSD on cognitive performance including the global cognition and the cognitive section of Alzheimer's Disease Assessment Scale, with mediation percentages ranging from 6.45 % to 30.46 %. In addition, we found that the thickness of the left middle temporal, right entorhinal and right fusiform gyrus, brain regions linked to AD, mediate the relationship between SSD and cognition with mediation percentages ranging from 8.67 % to 21.44 %.</AbstractText Our article didn't differentiate between mild cognitive impairment and normal population.</AbstractText The associations of SSD and cognitive impairment are linked to alterations in Alzheimer's Disease related brain regions.</AbstractText
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Prognostic model for predicting Alzheimer's disease conversion using functional connectome manifolds. Early detection of Alzheimer's disease (AD) is essential for timely management and consideration of therapeutic options; therefore, detecting the risk of conversion from mild cognitive impairment (MCI) to AD is crucial during neurodegenerative progression. Existing neuroimaging studies have mostly focused on group differences between individuals with MCI (or AD) and cognitively normal (CN), discarding the temporal information of conversion time. Here, we aimed to develop a prognostic model for AD conversion using functional connectivity (FC) and Cox regression suitable for conversion event modeling.</AbstractText We developed a prognostic model using a large-scale Alzheimer's Disease Neuroimaging Initiative dataset, and it was validated using external data obtained from the Open Access Series of Imaging Studies. We considered individuals who were initially CN or had MCI but progressed to AD and those with MCI with no progression to AD during the five-year follow-up period. As the exact conversion time to AD is unknown, we inferred this information using imputation approaches. We generated cortex-wide principal FC gradients using manifold learning techniques and computed subcortical-weighted manifold degrees from baseline functional magnetic resonance imaging data. A penalized Cox regression model with an elastic net penalty was adopted to define a risk score predicting the risk of conversion to AD, using FC gradients and clinical factors as regressors.</AbstractText Our prognostic model predicted the conversion risk and confirmed the role of imaging-derived manifolds in the conversion risk. The brain regions that largely contributed to predicting AD conversion were the heteromodal association and visual cortices, as well as the caudate and hippocampus. Our risk score based on Cox regression was consistent with the expected disease trajectories and correlated with positron emission tomography tracer uptake and symptom severity, reinforcing its clinical usefulness. Our findings were validated using an independent dataset. The cross-sectional application of our model showed a higher risk for AD than that for MCI, which correlated with symptom severity scores in the validation dataset.</AbstractText We proposed a prognostic model predicting the risk of conversion to AD. The associated risk score may provide insights for early intervention in individuals at risk of AD conversion.</AbstractText
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Treatment trends and clinical outcomes of endovascular embolization for unruptured intracranial aneurysms in the pediatric population. Owing to the relative rarity of unruptured intracranial aneurysms (UIAs) in the pediatric population, evidence regarding treatment modalities and clinical outcomes remains limited.</AbstractText To characterize the use and clinical outcomes of endovascular therapy (EVT) and microsurgical clipping (MSC) for pediatric UIAs over a two-decade interval using a large national registry.</AbstractText Pediatric (<18 years of age) UIA hospitalizations were identified in the National Inpatient Sample from 2002 to 2019. Temporal use and clinical outcomes were compared for treatment with EVT and MSC.</AbstractText Among 734 UIAs identified, 64.9% (n=476) were treated with EVT. Use of EVT significantly increased during the study period from 54.3% (2002-2004) to 78.6% (2017-2019) (P=0.002 by Cochrane-Armitage test). In comparison with those treated with MSC, pediatric patients treated with EVT demonstrated higher rates of favorable outcomes (discharge to home without services) (96.0% vs 91.1%, P=0.006), shorter durations of hospital stay (4.6 vs 10.0 days, P<0.001), and lower rates of ischemic or hemorrhagic procedural-related complications (1% vs 4%, P=0.010). Conservative management also increased significantly over the study period (P<0.001 by Cochrane-Armitage test).</AbstractText A retrospective evaluation of nearly 20 years of population-level data from the United States demonstrates increasing use of EVT for the treatment of pediatric UIAs, with high rates of favorable outcomes and shorter hospital stays in comparison with those treated with microsurgery.</AbstractText
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40271297
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34423308
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40613409
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Pericardial Synovial Sarcoma Masquerading as Hemangioma: A Diagnostic Challenge.
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Gadolinium-Based Contrast Agent Use, Their Safety, and Practice Evolution.
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Recognition of Basic Emotions Through Facial Expressions in Children with Attention-Deficit/Hyperactivity Disorder.
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Pericardial synovial sarcoma (PSS) is a rare primary malignant tumor of the heart with an unclear prognosis. We present the case of a 26-year-old male patient with no significant medical history who presented with New York Heart Association (NYHA) Class II dyspnea and chest pain. Echocardiography and cardiac MRI revealed a large pericardial mass (93 × 70 × 45 mm) with hemorrhagic effusion and imaging features suggestive of hemangioma, including well-defined vascular channels and contrast enhancement. Histopathological analysis following thoracotomy showed spindle cell proliferation without classic features of malignancy (e.g., nuclear atypia and high mitotic activity), supporting the initial diagnosis of spindle cell hemangioma. However, six months later, a recurrent mass excision and immunohistochemistry (IHC) confirmed SS (transducin-like enhancer of split 1/FMS-like tyrosine kinase 1 (TLE1/FLT1) positive). Surgical resection was attempted but was not feasible due to the extensive involvement of critical cardiac structures. The patient was started on chemotherapy with ifosfamide and doxorubicin but succumbed to systemic complications within a year. This case underscores the diagnostic challenge of PSS and highlights the critical role of IHC and molecular diagnostics in distinguishing it from benign mimics, even when initial histopathology is inconclusive.</AbstractText
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Gadolinium-based contrast agents (GBCAs) have provided much needed image enhancement in magnetic resonance imaging (MRI) important in the advancement of disease diagnosis and treatment. The paramagnetic properties of ionized gadolinium have facilitated these advancements, but ionized gadolinium carries toxicity risk. GBCAs were formulated with organic chelates designed to reduce these toxicity risks from unbound gadolinium ions. They were preferred over iodinated contrast used in computed tomography and considered safe for use. As their use expanded, the development of new diseases associated with their use (including nephrogenic systemic fibrosis) has drawn more attention and ultimately caution with their clinical administration in those with impaired renal function. Use of GBCAs in those with preserved renal function was considered to be safe. However, in this new era with emerging clinical and experimental evidence of brain gadolinium deposition in those with repeated exposure, these safety assumptions are once again brought into question. This review article aims to add new perspectives in thinking about the role of GBCA in current clinical use. The new information begs for further discussion and consideration of the risk-benefit ratio of use of GBCAs.</AbstractText
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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects attentional and executive functions, which may interfere with facial emotion recognition. This study explored the recognition of basic and complex emotions in pediatric subjects with ADHD.</AbstractText This was a prospective, cross-sectional, controlled study. A total of 60 participants were included, divided into two groups: the ADHD Group (n = 30) and the Control Group (n = 30) with neurotypical development. Each participant was presented with a series of photographs and video clips of children and adults and was asked to identify the emotion expressed on the face.</AbstractText No significant differences were found in the recognition of basic emotions between the Control Group (M = 44.43; SD = 2.01) and the ADHD Group (M = 43.90; SD = 2.14; t(58) = -0.995; p = 0.324), nor in the recognition of complex emotions [t(58) = 0.514; p = 0.609]. No differences were found by age [Z = 463; p = 0.843] or by sex (p = 0.92). We observed significantly better performance with a large effect size when recognizing child faces (M = 29.56; 95% CI 28.98-30.14) compared with adult faces (M = 14.86; 95% CI 14.46-15.26; p < 0.001; d = 11.03), with performance on adult faces improving with age (rho = 0.39; p = 0.03).</AbstractText The ADHD Group did not show differential performance compared with the neurotypical group in emotion recognition. Performance significantly improved for child faces, suggesting that adult faces should be avoided when assessing this population. Recognition of adult faces improved with age.</AbstractText Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects attentional and executive functions, which may interfere with facial emotion recognition. This study explored the recognition of basic and complex emotions in pediatric subjects with ADHD.</AbstractText This was a prospective, cross-sectional, controlled study. A total of 60 participants were included, divided into two groups: the ADHD Group (n = 30) and the Control Group (n = 30) with neurotypical development. Each participant was presented with a series of photographs and video clips of children and adults and was asked to identify the emotion expressed on the face.</AbstractText No significant differences were found in the recognition of basic emotions between the Control Group (M = 44.43; SD = 2.01) and the ADHD Group (M = 43.90; SD = 2.14; t(58) = –0.995; <i The ADHD Group did not show differential performance compared with the neurotypical group in emotion recognition. Performance significantly improved for child faces, suggesting that adult faces should be avoided when assessing this population. Recognition of adult faces improved with age.</AbstractText
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Pericardial Synovial Sarcoma Masquerading as Hemangioma: A Diagnostic Challenge. Pericardial synovial sarcoma (PSS) is a rare primary malignant tumor of the heart with an unclear prognosis. We present the case of a 26-year-old male patient with no significant medical history who presented with New York Heart Association (NYHA) Class II dyspnea and chest pain. Echocardiography and cardiac MRI revealed a large pericardial mass (93 × 70 × 45 mm) with hemorrhagic effusion and imaging features suggestive of hemangioma, including well-defined vascular channels and contrast enhancement. Histopathological analysis following thoracotomy showed spindle cell proliferation without classic features of malignancy (e.g., nuclear atypia and high mitotic activity), supporting the initial diagnosis of spindle cell hemangioma. However, six months later, a recurrent mass excision and immunohistochemistry (IHC) confirmed SS (transducin-like enhancer of split 1/FMS-like tyrosine kinase 1 (TLE1/FLT1) positive). Surgical resection was attempted but was not feasible due to the extensive involvement of critical cardiac structures. The patient was started on chemotherapy with ifosfamide and doxorubicin but succumbed to systemic complications within a year. This case underscores the diagnostic challenge of PSS and highlights the critical role of IHC and molecular diagnostics in distinguishing it from benign mimics, even when initial histopathology is inconclusive.</AbstractText
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Gadolinium-Based Contrast Agent Use, Their Safety, and Practice Evolution. Gadolinium-based contrast agents (GBCAs) have provided much needed image enhancement in magnetic resonance imaging (MRI) important in the advancement of disease diagnosis and treatment. The paramagnetic properties of ionized gadolinium have facilitated these advancements, but ionized gadolinium carries toxicity risk. GBCAs were formulated with organic chelates designed to reduce these toxicity risks from unbound gadolinium ions. They were preferred over iodinated contrast used in computed tomography and considered safe for use. As their use expanded, the development of new diseases associated with their use (including nephrogenic systemic fibrosis) has drawn more attention and ultimately caution with their clinical administration in those with impaired renal function. Use of GBCAs in those with preserved renal function was considered to be safe. However, in this new era with emerging clinical and experimental evidence of brain gadolinium deposition in those with repeated exposure, these safety assumptions are once again brought into question. This review article aims to add new perspectives in thinking about the role of GBCA in current clinical use. The new information begs for further discussion and consideration of the risk-benefit ratio of use of GBCAs.</AbstractText
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Recognition of Basic Emotions Through Facial Expressions in Children with Attention-Deficit/Hyperactivity Disorder. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects attentional and executive functions, which may interfere with facial emotion recognition. This study explored the recognition of basic and complex emotions in pediatric subjects with ADHD.</AbstractText This was a prospective, cross-sectional, controlled study. A total of 60 participants were included, divided into two groups: the ADHD Group (n = 30) and the Control Group (n = 30) with neurotypical development. Each participant was presented with a series of photographs and video clips of children and adults and was asked to identify the emotion expressed on the face.</AbstractText No significant differences were found in the recognition of basic emotions between the Control Group (M = 44.43; SD = 2.01) and the ADHD Group (M = 43.90; SD = 2.14; t(58) = -0.995; p = 0.324), nor in the recognition of complex emotions [t(58) = 0.514; p = 0.609]. No differences were found by age [Z = 463; p = 0.843] or by sex (p = 0.92). We observed significantly better performance with a large effect size when recognizing child faces (M = 29.56; 95% CI 28.98-30.14) compared with adult faces (M = 14.86; 95% CI 14.46-15.26; p < 0.001; d = 11.03), with performance on adult faces improving with age (rho = 0.39; p = 0.03).</AbstractText The ADHD Group did not show differential performance compared with the neurotypical group in emotion recognition. Performance significantly improved for child faces, suggesting that adult faces should be avoided when assessing this population. Recognition of adult faces improved with age.</AbstractText Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects attentional and executive functions, which may interfere with facial emotion recognition. This study explored the recognition of basic and complex emotions in pediatric subjects with ADHD.</AbstractText This was a prospective, cross-sectional, controlled study. A total of 60 participants were included, divided into two groups: the ADHD Group (n = 30) and the Control Group (n = 30) with neurotypical development. Each participant was presented with a series of photographs and video clips of children and adults and was asked to identify the emotion expressed on the face.</AbstractText No significant differences were found in the recognition of basic emotions between the Control Group (M = 44.43; SD = 2.01) and the ADHD Group (M = 43.90; SD = 2.14; t(58) = –0.995; <i The ADHD Group did not show differential performance compared with the neurotypical group in emotion recognition. Performance significantly improved for child faces, suggesting that adult faces should be avoided when assessing this population. Recognition of adult faces improved with age.</AbstractText
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40460941
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25761794
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40574083
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Sodium-glucose cotransporter-2 inhibitor, dapagliflozin, reverses depressive-like behavior in a mouse model of post-traumatic stress disorder.
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Akt-mediated regulation of antidepressant-sensitive serotonin transporter function, cell-surface expression and phosphorylation.
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Click on Click: Click-Flavone Glycosides Encapsulated in Click-Functionalised Polymersomes for Glioblastoma Therapy.
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Post-traumatic stress disorder (PTSD) is a psychological condition characterized by consistent psychological distress resulting from the experience of intense traumatic events, such as warfare or natural disasters. Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are widely prescribed treatments for PTSD, but their adverse side effects are a significant concern and they have only limited efficacy as a symptomatic treatment for PTSD. Moreover, they have no effect on the core underlying causes of PTSD Studies have reported a potential neuroprotective effect for Sodium-Glucose Cotransporter-2 Inhibitors (SGLTi). This study utilized the single-prolonged stress (SPS) mouse model of PTSD, which involved sequential exposure to different stressors (2 hours of restraint, 20 minutes of forced swimming, 15 minutes of rest, and 1-2 minutes of diethyl ether exposure), to investigate the therapeutic potential of Dapagliflozin (DAPA), a novel SGLTi, in mitigating the SPS-induced depressive-like behavior.</AbstractText Male mice were randomly assigned to four experimental groups: Control group, SPS group, DAPA group (dapagliflozin; 1 mg/kg/day by oral gavage for 7 days), and SPS+DAPA group. Behavioral assessments for depressive-like behaviors were evaluated using the forced swim test and the tail suspension test. Blood and brain tissue samples were collected for analysis stress markers.</AbstractText SPS-treated mice showed significant depressive-like behavior on the seventh day post-treatment, which was reversed by DAPA treatment (1 mg/kg/day). Significant increases in brain tissue mRNA expression of Crh, Bax, Il1b, and Bdnf, as well as serum corticosterone, were observed in the SPS group, while DAPA reversed these effects.</AbstractText This data indicates that DAPA (1 mg/kg) has potential therapeutic effects for the treatment of PTSD-induced depressive-like symptoms.</AbstractText
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The serotonin [5-HT (5-hydroxytryptamine)] transporter (SERT) controls serotonergic neurotransmission in the brain by rapid clearance of 5-HT from the synaptic cleft into presynaptic neurons. SERTs are primary targets for antidepressants for therapeutic intervention of mood disorders. Our previous studies have identified the involvement of several signalling pathways and protein kinases in regulating SERT function, trafficking and phosphorylation. However, whether Akt/PKB (protein kinase) regulates SERT function is not known. In the present study, we made the novel observation that inhibition of Akt resulted in the down-regulation of SERT function through the regulation of SERT trafficking and phosphorylation. Akt inhibitor Akt X {10-(4'-[N-diethylamino)butyl]-2-chlorophenoxazine} reduced the endogenously phosphorylated Akt and significantly decreased 5-HT uptake and 5-HT-uptake capacity. Furthermore, SERT activity is also reduced by siRNA down-regulation of total and phospho-Akt levels. The reduction in SERT activity is paralleled by lower levels of cell-surface SERT protein, reduced SERT exocytosis with no effect on SERT endocytosis and accumulation of SERT in intracellular endocytic compartments with the most prominent localization to late endosomes and lysosomes. Akt2 inhibitor was more effective than Akt1 inhibitor in inhibiting SERT activity. Inhibition of downstream Akt kinase GSK3α/β (glycogen synthase kinase α/β) stimulates SERT function. Akt inhibition leads to a decrease in SERT basal phosphorylation. Our results provide evidence that Akt regulates SERT function and cell-surface expression by regulating the intracellular SERT distribution and plasma membrane availability, which perhaps may be linked to SERT phosphorylation state. Thus any changes in the activation of Akt and/or GSK3α/β could alter SERT-mediated 5-HT clearance and subsequently serotonergic neurotransmission.</AbstractText
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In this study, three new 3,7-dihydroxyflavone (<b
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Sodium-glucose cotransporter-2 inhibitor, dapagliflozin, reverses depressive-like behavior in a mouse model of post-traumatic stress disorder. Post-traumatic stress disorder (PTSD) is a psychological condition characterized by consistent psychological distress resulting from the experience of intense traumatic events, such as warfare or natural disasters. Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are widely prescribed treatments for PTSD, but their adverse side effects are a significant concern and they have only limited efficacy as a symptomatic treatment for PTSD. Moreover, they have no effect on the core underlying causes of PTSD Studies have reported a potential neuroprotective effect for Sodium-Glucose Cotransporter-2 Inhibitors (SGLTi). This study utilized the single-prolonged stress (SPS) mouse model of PTSD, which involved sequential exposure to different stressors (2 hours of restraint, 20 minutes of forced swimming, 15 minutes of rest, and 1-2 minutes of diethyl ether exposure), to investigate the therapeutic potential of Dapagliflozin (DAPA), a novel SGLTi, in mitigating the SPS-induced depressive-like behavior.</AbstractText Male mice were randomly assigned to four experimental groups: Control group, SPS group, DAPA group (dapagliflozin; 1 mg/kg/day by oral gavage for 7 days), and SPS+DAPA group. Behavioral assessments for depressive-like behaviors were evaluated using the forced swim test and the tail suspension test. Blood and brain tissue samples were collected for analysis stress markers.</AbstractText SPS-treated mice showed significant depressive-like behavior on the seventh day post-treatment, which was reversed by DAPA treatment (1 mg/kg/day). Significant increases in brain tissue mRNA expression of Crh, Bax, Il1b, and Bdnf, as well as serum corticosterone, were observed in the SPS group, while DAPA reversed these effects.</AbstractText This data indicates that DAPA (1 mg/kg) has potential therapeutic effects for the treatment of PTSD-induced depressive-like symptoms.</AbstractText
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Akt-mediated regulation of antidepressant-sensitive serotonin transporter function, cell-surface expression and phosphorylation. The serotonin [5-HT (5-hydroxytryptamine)] transporter (SERT) controls serotonergic neurotransmission in the brain by rapid clearance of 5-HT from the synaptic cleft into presynaptic neurons. SERTs are primary targets for antidepressants for therapeutic intervention of mood disorders. Our previous studies have identified the involvement of several signalling pathways and protein kinases in regulating SERT function, trafficking and phosphorylation. However, whether Akt/PKB (protein kinase) regulates SERT function is not known. In the present study, we made the novel observation that inhibition of Akt resulted in the down-regulation of SERT function through the regulation of SERT trafficking and phosphorylation. Akt inhibitor Akt X {10-(4'-[N-diethylamino)butyl]-2-chlorophenoxazine} reduced the endogenously phosphorylated Akt and significantly decreased 5-HT uptake and 5-HT-uptake capacity. Furthermore, SERT activity is also reduced by siRNA down-regulation of total and phospho-Akt levels. The reduction in SERT activity is paralleled by lower levels of cell-surface SERT protein, reduced SERT exocytosis with no effect on SERT endocytosis and accumulation of SERT in intracellular endocytic compartments with the most prominent localization to late endosomes and lysosomes. Akt2 inhibitor was more effective than Akt1 inhibitor in inhibiting SERT activity. Inhibition of downstream Akt kinase GSK3α/β (glycogen synthase kinase α/β) stimulates SERT function. Akt inhibition leads to a decrease in SERT basal phosphorylation. Our results provide evidence that Akt regulates SERT function and cell-surface expression by regulating the intracellular SERT distribution and plasma membrane availability, which perhaps may be linked to SERT phosphorylation state. Thus any changes in the activation of Akt and/or GSK3α/β could alter SERT-mediated 5-HT clearance and subsequently serotonergic neurotransmission.</AbstractText
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Click on Click: Click-Flavone Glycosides Encapsulated in Click-Functionalised Polymersomes for Glioblastoma Therapy. In this study, three new 3,7-dihydroxyflavone (<b
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29390700
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36478992
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30017720
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Improving the magnetic field homogeneity by varying magnetic field structure in a geophone.
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Synthetic computed tomography for low-field magnetic resonance-guided radiotherapy in the abdomen.
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Neurochemistry evaluated by MR spectroscopy in a patient with xeroderma pigmentosum group A.
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The magnetic field structure is a key factor that affects performance of the magneto-electric geophone. In order to enhance the magnetic field homogeneity and magnetic induction intensity of the magnetic field structure, this paper proposes a new magnetic field structure. It consists of two cylindrical permanent magnets: an H-type magnetic boot and an external magnetic yoke. The proposed magnetic field structure can broaden the range of a uniform magnetic field and increase the magnetic field intensity of working air-gap. To confirm the validity of the design, the finite element analysis and real measurement experiments were conducted. The finite element simulations using the ANASYS Electromagnetics Suite 17.2.0 showed that the air-gap magnetic induction intensity is increased and the work space with a uniform magnetic field is broadened. Meanwhile, the output voltage of the coil is increased, and the harmonic distortion rate of output voltage is reduced. According to the real measurement experimental results, compared with the traditional magnetic field structure, the uniform range of the magnetic field is improved 23% in the entire air-gap path, and the magnetic induction intensity enhances 24% over the proposed new magnetic field structure.</AbstractText
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The requirement of computed tomography (CT) for radiotherapy planning may be bypassed by synthetic CT (sCT) generated from magnetic resonance (MR), which has recently led to the clinical introduction of MR-only radiotherapy for specific sites. Further developments are required for abdominal sCT, mostly due to the presence of mobile air pockets affecting the dose calculation. In this study we aimed to overcome this limitation for abdominal sCT at a low field (0.35 T) hybrid MR-Linac.</AbstractText A retrospective analysis was conducted enrolling 168 patients corresponding to 215 MR-CT pairs. After the exclusion criteria, 152 volumetric images were used to train the cycle-consistent generative adversarial network (CycleGAN) and 34 to test the sCT. Image similarity metrics and dose recalculation analysis were performed.</AbstractText The generated sCT faithfully reproduced the original CT and the location of the air pockets agreed with the MR scan. The dose calculation did not require manual bulk density overrides and the mean deviations of the dose-volume histogram dosimetric points were within 1 % of the CT, without any outlier above 2 %. The mean gamma passing rates were above 99 % for the 2 %/ 2 mm analysis and no cases below 95 % were observed.</AbstractText This study presented the implementation of CycleGAN to perform sCT generation in the abdominal region for a low field hybrid MR-Linac. The sCT was shown to correctly allocate the electron density for the mobile air pockets and the dosimetric analysis demonstrated the potential for future implementation of MR-only radiotherapy in the abdomen.</AbstractText
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MRI of a female patient with xeroderma pigmentosum group A (XP-A) showed progressive cerebral atrophy, but no disease-specific lesion. MR spectroscopy with short TE sequences in the bilateral white matter revealed decreased N-acetyl aspartate (neuro-axonal marker) and increased myo-inositol (astroglial marker) with a normal concentration of choline (membrane marker), which are compatible with the neuropathology of XP-A, consisting of a reduced number of neurons, and fibrillary astrogliosis with preservation of myelinated fibers. MR spectroscopy reveals neurochemical derangement in XP-A, which cannot be observed on conventional MRI, and will be useful to monitor the neurochemical derangements of XP-A.</AbstractText
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Improving the magnetic field homogeneity by varying magnetic field structure in a geophone. The magnetic field structure is a key factor that affects performance of the magneto-electric geophone. In order to enhance the magnetic field homogeneity and magnetic induction intensity of the magnetic field structure, this paper proposes a new magnetic field structure. It consists of two cylindrical permanent magnets: an H-type magnetic boot and an external magnetic yoke. The proposed magnetic field structure can broaden the range of a uniform magnetic field and increase the magnetic field intensity of working air-gap. To confirm the validity of the design, the finite element analysis and real measurement experiments were conducted. The finite element simulations using the ANASYS Electromagnetics Suite 17.2.0 showed that the air-gap magnetic induction intensity is increased and the work space with a uniform magnetic field is broadened. Meanwhile, the output voltage of the coil is increased, and the harmonic distortion rate of output voltage is reduced. According to the real measurement experimental results, compared with the traditional magnetic field structure, the uniform range of the magnetic field is improved 23% in the entire air-gap path, and the magnetic induction intensity enhances 24% over the proposed new magnetic field structure.</AbstractText
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Synthetic computed tomography for low-field magnetic resonance-guided radiotherapy in the abdomen. The requirement of computed tomography (CT) for radiotherapy planning may be bypassed by synthetic CT (sCT) generated from magnetic resonance (MR), which has recently led to the clinical introduction of MR-only radiotherapy for specific sites. Further developments are required for abdominal sCT, mostly due to the presence of mobile air pockets affecting the dose calculation. In this study we aimed to overcome this limitation for abdominal sCT at a low field (0.35 T) hybrid MR-Linac.</AbstractText A retrospective analysis was conducted enrolling 168 patients corresponding to 215 MR-CT pairs. After the exclusion criteria, 152 volumetric images were used to train the cycle-consistent generative adversarial network (CycleGAN) and 34 to test the sCT. Image similarity metrics and dose recalculation analysis were performed.</AbstractText The generated sCT faithfully reproduced the original CT and the location of the air pockets agreed with the MR scan. The dose calculation did not require manual bulk density overrides and the mean deviations of the dose-volume histogram dosimetric points were within 1 % of the CT, without any outlier above 2 %. The mean gamma passing rates were above 99 % for the 2 %/ 2 mm analysis and no cases below 95 % were observed.</AbstractText This study presented the implementation of CycleGAN to perform sCT generation in the abdominal region for a low field hybrid MR-Linac. The sCT was shown to correctly allocate the electron density for the mobile air pockets and the dosimetric analysis demonstrated the potential for future implementation of MR-only radiotherapy in the abdomen.</AbstractText
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Neurochemistry evaluated by MR spectroscopy in a patient with xeroderma pigmentosum group A. MRI of a female patient with xeroderma pigmentosum group A (XP-A) showed progressive cerebral atrophy, but no disease-specific lesion. MR spectroscopy with short TE sequences in the bilateral white matter revealed decreased N-acetyl aspartate (neuro-axonal marker) and increased myo-inositol (astroglial marker) with a normal concentration of choline (membrane marker), which are compatible with the neuropathology of XP-A, consisting of a reduced number of neurons, and fibrillary astrogliosis with preservation of myelinated fibers. MR spectroscopy reveals neurochemical derangement in XP-A, which cannot be observed on conventional MRI, and will be useful to monitor the neurochemical derangements of XP-A.</AbstractText
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25251584
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25758543
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25582430
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Assessment of diffuse myocardial fibrosis by using MR imaging in asymptomatic patients with aortic stenosis.
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Gradient nonlinearity correction to improve apparent diffusion coefficient accuracy and standardization in the american college of radiology imaging network 6698 breast cancer trial.
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Audio-visual speech intelligibility benefits with bilateral cochlear implants when talker location varies.
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To assess whether native T1 mapping provides noninvasive estimation of diffuse myocardial fibrosis and whether it correlates with subclinical myocardial dysfunction in asymptomatic patients with aortic stenosis (AS).</AbstractText The local institutional review board approved the study, and all patients gave informed consent. Eighty asymptomatic patients with moderate or severe AS and normal left ventricular (LV) ejection fraction (mean age, 67 years; range, 31-81 years) and 15 sex-matched control subjects (mean age, 33 years; range, 23-41 years) were prospectively enrolled. Patients underwent two-dimensional echocardiography, speckle tracking imaging, and cardiac 3.0-T magnetic resonance (MR) imaging, including mapping of T1 relaxation time by using the modified Look-Locker inversion-recovery sequence. Correlations between native T1 values and the degree of diffuse fibrosis in myocardial specimens obtained during aortic valve replacement surgery were analyzed in a subset of 20 patients. Correlations between parameters of myocardial function and structure and native T1 values were assessed with Pearson correlation coefficients.</AbstractText Native T1 values correlated well with the degree of diffuse myocardial fibrosis in intraoperative myocardial biopsy specimens (r = 0.777, P < .001) and differed significantly between patients with AS and control subjects (1208 msec ± 45 vs 1169 msec ± 21, P < .001). LV volumes and mass differed significantly according to AS groups, categorized by T1 tertiles (all P < .001), as well as degree of AS severity (0.55 cm(2)/m(2) ± 0.14 for lowest native T1 tertile, 0.46 cm(2)/m(2) ± 0.12 for middle native T1 tertile, and 0.45 cm(2)/m(2) ± 0.13 for highest native T1 tertile [P = .008] for indexed aortic valve area at echocardiography). Native T1 correlated significantly with global longitudinal strain measured with two-dimensional speckle tracking imaging (r = 0.598, P < .001), e' velocity (r = -0.437, P < .001), and indexed left atrial volume (r = 0.475, P < .001).</AbstractText Native T1 mapping provides a noninvasive estimation of diffuse myocardial fibrosis and correlates with subclinical myocardial dysfunction in asymptomatic patients with AS.</AbstractText
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To evaluate a gradient nonlinearity correction (GNC) program for quantitative apparent diffusion coefficient (ADC) measurements on phantom and human subject diffusion-weighted (DW) magnetic resonance imaging (MRI) scans in a multicenter breast cancer treatment response study</AbstractText A GNC program using fifth-order spherical harmonics for gradient modeling was applied retrospectively to qualification phantom and human subject scans. Ice-water phantoms of known diffusion coefficient were scanned at five different study centers with different scanners and receiver coils. Human in vivo data consisted of baseline and early-treatment exams on 54 patients from four sites. ADC maps were generated with and without GNC. Regions of interest were defined to quantify absolute errors and changes with GNC over breast imaging positions.</AbstractText Phantom ADC errors varied with region of interest (ROI) position and scanner configuration; the mean error by configuration ranged from 1.4% to 19.9%. GNC significantly reduced the overall mean error for all sites from 9.9% to 0.6% (P = 0.016). Spatial dependence of GNC was highest in the right-left (RL) and anterior-posterior (AP) directions. Human subject mean tumor ADC was reduced 0.2 to 12% by GNC at different sites. By regression, every 1-cm change in tumor ROI position between baseline and follow-up visits resulted in an estimated change of 2.4% in the ADC early-treatment response measurement.</AbstractText GNC is effective for removing large, system-dependent errors in quantitative breast DWI. GNC may be important in ensuring reproducibility in multicenter studies and in reducing errors in longitudinal treatment response measures arising from spatial variations in tumor position between visits.</AbstractText
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One of the key benefits of using cochlear implants (CIs) in both ears rather than just one is improved localization. It is likely that in complex listening scenes, improved localization allows bilateral CI users to orient toward talkers to improve signal-to-noise ratios and gain access to visual cues, but to date, that conjecture has not been tested. To obtain an objective measure of that benefit, seven bilateral CI users were assessed for both auditory-only and audio-visual speech intelligibility in noise using a novel dynamic spatial audio-visual test paradigm. For each trial conducted in spatially distributed noise, first, an auditory-only cueing phrase that was spoken by one of four talkers was selected and presented from one of four locations. Shortly afterward, a target sentence was presented that was either audio-visual or, in another test configuration, audio-only and was spoken by the same talker and from the same location as the cueing phrase. During the target presentation, visual distractors were added at other spatial locations. Results showed that in terms of speech reception thresholds (SRTs), the average improvement for bilateral listening over the better performing ear alone was 9 dB for the audio-visual mode, and 3 dB for audition-alone. Comparison of bilateral performance for audio-visual and audition-alone showed that inclusion of visual cues led to an average SRT improvement of 5 dB. For unilateral device use, no such benefit arose, presumably due to the greatly reduced ability to localize the target talker to acquire visual information. The bilateral CI speech intelligibility advantage over the better ear in the present study is much larger than that previously reported for static talker locations and indicates greater everyday speech benefits and improved cost-benefit than estimated to date.</AbstractText
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Assessment of diffuse myocardial fibrosis by using MR imaging in asymptomatic patients with aortic stenosis. To assess whether native T1 mapping provides noninvasive estimation of diffuse myocardial fibrosis and whether it correlates with subclinical myocardial dysfunction in asymptomatic patients with aortic stenosis (AS).</AbstractText The local institutional review board approved the study, and all patients gave informed consent. Eighty asymptomatic patients with moderate or severe AS and normal left ventricular (LV) ejection fraction (mean age, 67 years; range, 31-81 years) and 15 sex-matched control subjects (mean age, 33 years; range, 23-41 years) were prospectively enrolled. Patients underwent two-dimensional echocardiography, speckle tracking imaging, and cardiac 3.0-T magnetic resonance (MR) imaging, including mapping of T1 relaxation time by using the modified Look-Locker inversion-recovery sequence. Correlations between native T1 values and the degree of diffuse fibrosis in myocardial specimens obtained during aortic valve replacement surgery were analyzed in a subset of 20 patients. Correlations between parameters of myocardial function and structure and native T1 values were assessed with Pearson correlation coefficients.</AbstractText Native T1 values correlated well with the degree of diffuse myocardial fibrosis in intraoperative myocardial biopsy specimens (r = 0.777, P < .001) and differed significantly between patients with AS and control subjects (1208 msec ± 45 vs 1169 msec ± 21, P < .001). LV volumes and mass differed significantly according to AS groups, categorized by T1 tertiles (all P < .001), as well as degree of AS severity (0.55 cm(2)/m(2) ± 0.14 for lowest native T1 tertile, 0.46 cm(2)/m(2) ± 0.12 for middle native T1 tertile, and 0.45 cm(2)/m(2) ± 0.13 for highest native T1 tertile [P = .008] for indexed aortic valve area at echocardiography). Native T1 correlated significantly with global longitudinal strain measured with two-dimensional speckle tracking imaging (r = 0.598, P < .001), e' velocity (r = -0.437, P < .001), and indexed left atrial volume (r = 0.475, P < .001).</AbstractText Native T1 mapping provides a noninvasive estimation of diffuse myocardial fibrosis and correlates with subclinical myocardial dysfunction in asymptomatic patients with AS.</AbstractText
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Gradient nonlinearity correction to improve apparent diffusion coefficient accuracy and standardization in the american college of radiology imaging network 6698 breast cancer trial. To evaluate a gradient nonlinearity correction (GNC) program for quantitative apparent diffusion coefficient (ADC) measurements on phantom and human subject diffusion-weighted (DW) magnetic resonance imaging (MRI) scans in a multicenter breast cancer treatment response study</AbstractText A GNC program using fifth-order spherical harmonics for gradient modeling was applied retrospectively to qualification phantom and human subject scans. Ice-water phantoms of known diffusion coefficient were scanned at five different study centers with different scanners and receiver coils. Human in vivo data consisted of baseline and early-treatment exams on 54 patients from four sites. ADC maps were generated with and without GNC. Regions of interest were defined to quantify absolute errors and changes with GNC over breast imaging positions.</AbstractText Phantom ADC errors varied with region of interest (ROI) position and scanner configuration; the mean error by configuration ranged from 1.4% to 19.9%. GNC significantly reduced the overall mean error for all sites from 9.9% to 0.6% (P = 0.016). Spatial dependence of GNC was highest in the right-left (RL) and anterior-posterior (AP) directions. Human subject mean tumor ADC was reduced 0.2 to 12% by GNC at different sites. By regression, every 1-cm change in tumor ROI position between baseline and follow-up visits resulted in an estimated change of 2.4% in the ADC early-treatment response measurement.</AbstractText GNC is effective for removing large, system-dependent errors in quantitative breast DWI. GNC may be important in ensuring reproducibility in multicenter studies and in reducing errors in longitudinal treatment response measures arising from spatial variations in tumor position between visits.</AbstractText
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Audio-visual speech intelligibility benefits with bilateral cochlear implants when talker location varies. One of the key benefits of using cochlear implants (CIs) in both ears rather than just one is improved localization. It is likely that in complex listening scenes, improved localization allows bilateral CI users to orient toward talkers to improve signal-to-noise ratios and gain access to visual cues, but to date, that conjecture has not been tested. To obtain an objective measure of that benefit, seven bilateral CI users were assessed for both auditory-only and audio-visual speech intelligibility in noise using a novel dynamic spatial audio-visual test paradigm. For each trial conducted in spatially distributed noise, first, an auditory-only cueing phrase that was spoken by one of four talkers was selected and presented from one of four locations. Shortly afterward, a target sentence was presented that was either audio-visual or, in another test configuration, audio-only and was spoken by the same talker and from the same location as the cueing phrase. During the target presentation, visual distractors were added at other spatial locations. Results showed that in terms of speech reception thresholds (SRTs), the average improvement for bilateral listening over the better performing ear alone was 9 dB for the audio-visual mode, and 3 dB for audition-alone. Comparison of bilateral performance for audio-visual and audition-alone showed that inclusion of visual cues led to an average SRT improvement of 5 dB. For unilateral device use, no such benefit arose, presumably due to the greatly reduced ability to localize the target talker to acquire visual information. The bilateral CI speech intelligibility advantage over the better ear in the present study is much larger than that previously reported for static talker locations and indicates greater everyday speech benefits and improved cost-benefit than estimated to date.</AbstractText
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39005039
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36850829
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39365112
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Sensing, feeling and consciousness.
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Energy-Efficient EEG-Based Scheme for Autism Spectrum Disorder Detection Using Wearable Sensors.
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Design and first tests of the trapped electrons experiment T-REX.
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Living organisms achieve homeostasis by using distinct mechanisms tailored to their physiological complexity. Unicellular organisms as well as plants, which are devoid of nervous systems, rely on covert sensing/detecting and equally covert responding mechanisms. Organisms with nervous systems rely on <i
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The deployment of wearable wireless systems that collect physiological indicators to aid in diagnosing neurological disorders represents a potential solution for the new generation of e-health systems. Electroencephalography (EEG), a recording of the brain's electrical activity, is a promising physiological test for the diagnosis of autism spectrum disorders. It can identify the abnormalities of the neural system that are associated with autism spectrum disorders. However, streaming EEG samples remotely for classification can reduce the wireless sensor's lifespan and creates doubt regarding the application's feasibility. Therefore, decreasing data transmission may conserve sensor energy and extend the lifespan of wireless sensor networks. This paper suggests the development of a sensor-based scheme for early age autism detection. The proposed scheme implements an energy-efficient method for signal transformation allowing relevant feature extraction for accurate classification using machine learning algorithms. The experimental results indicate an accuracy of 96%, a sensitivity of 100%, and around 95% of F1 score for all used machine learning models. The results also show that our scheme energy consumption is 97% lower than streaming the raw EEG samples.</AbstractText
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Gyrotrons are essential for electron cyclotron resonance heating in fusion reactors, making efficient operation crucial for advancing fusion energy. Past experiments revealed instability issues due to trapped electrons in the magnetron injection gun (MIG) region, causing undesired currents and operational failures. To address this, tight manufacturing tolerances are required for the MIG geometry [Pagonakis et al., Phys. Plasmas 23, 023105 (2016)]. We present the initial findings of the trapped electrons experiment developed at the Swiss Plasma Center, designed to understand the physics of electron clouds in gyrotron MIGs. T-REX replicates MIG geometries, as well as their typical electric and magnetic fields, and it is supported by 2D particle-in-cell simulations with the FENNECS code [Le Bars et al., Phys. Plasmas 29, 082105 (2022); Le Bars, Ph.D. thesis, EPFL, Lausanne, 2023]. The setup includes two coaxial electrodes in a vacuum chamber atop a superconducting magnet, with a central electrode biased to negative DC voltages and an outer one at the ground, creating a radial electric field (1-2 MV/m) and an axial magnetic field (B < 0.4 T). This setup mimics Penning-Malmberg traps. We present the experimental device and first findings on current distribution and also a qualitative comparison with FENNECS simulations [Le Bars et al., Comput. Phys. Commun. 303, 109268 (2024)]. Planned diagnostics include optical emission spectroscopy, phosphor screen imaging, streak camera imaging, and potentially electric field distribution via the Stark effect. This research aims to enhance gyrotron performance and reliability in fusion energy systems.</AbstractText
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Sensing, feeling and consciousness. Living organisms achieve homeostasis by using distinct mechanisms tailored to their physiological complexity. Unicellular organisms as well as plants, which are devoid of nervous systems, rely on covert sensing/detecting and equally covert responding mechanisms. Organisms with nervous systems rely on <i
|
Energy-Efficient EEG-Based Scheme for Autism Spectrum Disorder Detection Using Wearable Sensors. The deployment of wearable wireless systems that collect physiological indicators to aid in diagnosing neurological disorders represents a potential solution for the new generation of e-health systems. Electroencephalography (EEG), a recording of the brain's electrical activity, is a promising physiological test for the diagnosis of autism spectrum disorders. It can identify the abnormalities of the neural system that are associated with autism spectrum disorders. However, streaming EEG samples remotely for classification can reduce the wireless sensor's lifespan and creates doubt regarding the application's feasibility. Therefore, decreasing data transmission may conserve sensor energy and extend the lifespan of wireless sensor networks. This paper suggests the development of a sensor-based scheme for early age autism detection. The proposed scheme implements an energy-efficient method for signal transformation allowing relevant feature extraction for accurate classification using machine learning algorithms. The experimental results indicate an accuracy of 96%, a sensitivity of 100%, and around 95% of F1 score for all used machine learning models. The results also show that our scheme energy consumption is 97% lower than streaming the raw EEG samples.</AbstractText
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Design and first tests of the trapped electrons experiment T-REX. Gyrotrons are essential for electron cyclotron resonance heating in fusion reactors, making efficient operation crucial for advancing fusion energy. Past experiments revealed instability issues due to trapped electrons in the magnetron injection gun (MIG) region, causing undesired currents and operational failures. To address this, tight manufacturing tolerances are required for the MIG geometry [Pagonakis et al., Phys. Plasmas 23, 023105 (2016)]. We present the initial findings of the trapped electrons experiment developed at the Swiss Plasma Center, designed to understand the physics of electron clouds in gyrotron MIGs. T-REX replicates MIG geometries, as well as their typical electric and magnetic fields, and it is supported by 2D particle-in-cell simulations with the FENNECS code [Le Bars et al., Phys. Plasmas 29, 082105 (2022); Le Bars, Ph.D. thesis, EPFL, Lausanne, 2023]. The setup includes two coaxial electrodes in a vacuum chamber atop a superconducting magnet, with a central electrode biased to negative DC voltages and an outer one at the ground, creating a radial electric field (1-2 MV/m) and an axial magnetic field (B < 0.4 T). This setup mimics Penning-Malmberg traps. We present the experimental device and first findings on current distribution and also a qualitative comparison with FENNECS simulations [Le Bars et al., Comput. Phys. Commun. 303, 109268 (2024)]. Planned diagnostics include optical emission spectroscopy, phosphor screen imaging, streak camera imaging, and potentially electric field distribution via the Stark effect. This research aims to enhance gyrotron performance and reliability in fusion energy systems.</AbstractText
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35603692
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28761930
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35142287
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A novel compound heterozygous mutation in the COA7 gene responsible for a Chinese patient with spinocerebellar ataxia with axonal neuropathy type 3.
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Prevalence of spinocerebellar ataxia 36 in a US population.
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A unifying mechanism governing inter-brain neural relationship during social interactions.
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Spinocerebellar ataxia with axonal neuropathy type 3 (SCAN3) is a very rare autosomal recessive hereditary disease. Mutations in the <i The patient was a 31-year-old woman who presented with early-onset peripheral neuropathy and progressive ataxia. She was asked about her medical history and underwent electrophysiological examination, nerve and muscle biopsy, and gene detection.</AbstractText Whole exome next-generation sequencing identified a novel compound heterozygous mutation of <i We reported the first patient diagnosed with SCAN3 in China. A novel mutation in the gene <i
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To assess the prevalence and clinical features of individuals affected by spinocerebellar ataxia 36 (SCA36) at a large tertiary referral center in the United States.</AbstractText A total of 577 patients with undiagnosed sporadic or familial cerebellar ataxia comprehensively evaluated at a tertiary referral ataxia center were molecularly evaluated for SCA36. Repeat primed PCR and fragment analysis were used to screen for the presence of a repeat expansion in the <i Fragment analysis of triplet repeat primed PCR products identified a GGCCTG hexanucleotide repeat expansion in intron 1 of <i In a US population, SCA36 was observed to be a rare disorder, accounting for 0.7% (4/577 index cases) of disease in a large undiagnosed ataxia cohort.</AbstractText
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A key goal of social neuroscience is to understand the inter-brain neural relationship-the relationship between the neural activity of socially interacting individuals. Decades of research investigating this relationship have focused on the similarity in neural activity across brains. Here, we instead asked how neural activity differs between brains, and how that difference evolves alongside activity patterns shared between brains. Applying this framework to bats engaged in spontaneous social interactions revealed two complementary phenomena characterizing the inter-brain neural relationship: fast fluctuations of activity difference across brains unfolding in parallel with slow activity covariation across brains. A model reproduced these observations and generated multiple predictions that we confirmed using experimental data involving pairs of bats and a larger social group of bats. The model suggests that a simple computational mechanism involving positive and negative feedback could explain diverse experimental observations regarding the inter-brain neural relationship.</AbstractText
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A novel compound heterozygous mutation in the COA7 gene responsible for a Chinese patient with spinocerebellar ataxia with axonal neuropathy type 3. Spinocerebellar ataxia with axonal neuropathy type 3 (SCAN3) is a very rare autosomal recessive hereditary disease. Mutations in the <i The patient was a 31-year-old woman who presented with early-onset peripheral neuropathy and progressive ataxia. She was asked about her medical history and underwent electrophysiological examination, nerve and muscle biopsy, and gene detection.</AbstractText Whole exome next-generation sequencing identified a novel compound heterozygous mutation of <i We reported the first patient diagnosed with SCAN3 in China. A novel mutation in the gene <i
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Prevalence of spinocerebellar ataxia 36 in a US population. To assess the prevalence and clinical features of individuals affected by spinocerebellar ataxia 36 (SCA36) at a large tertiary referral center in the United States.</AbstractText A total of 577 patients with undiagnosed sporadic or familial cerebellar ataxia comprehensively evaluated at a tertiary referral ataxia center were molecularly evaluated for SCA36. Repeat primed PCR and fragment analysis were used to screen for the presence of a repeat expansion in the <i Fragment analysis of triplet repeat primed PCR products identified a GGCCTG hexanucleotide repeat expansion in intron 1 of <i In a US population, SCA36 was observed to be a rare disorder, accounting for 0.7% (4/577 index cases) of disease in a large undiagnosed ataxia cohort.</AbstractText
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A unifying mechanism governing inter-brain neural relationship during social interactions. A key goal of social neuroscience is to understand the inter-brain neural relationship-the relationship between the neural activity of socially interacting individuals. Decades of research investigating this relationship have focused on the similarity in neural activity across brains. Here, we instead asked how neural activity differs between brains, and how that difference evolves alongside activity patterns shared between brains. Applying this framework to bats engaged in spontaneous social interactions revealed two complementary phenomena characterizing the inter-brain neural relationship: fast fluctuations of activity difference across brains unfolding in parallel with slow activity covariation across brains. A model reproduced these observations and generated multiple predictions that we confirmed using experimental data involving pairs of bats and a larger social group of bats. The model suggests that a simple computational mechanism involving positive and negative feedback could explain diverse experimental observations regarding the inter-brain neural relationship.</AbstractText
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39583646
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30525929
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38839713
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Association of plasma neurofilament light chain with microstructural white matter changes in Down syndrome.
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The Effects of Global Signal Regression on Estimates of Resting-State Blood Oxygen-Level-Dependent Functional Magnetic Resonance Imaging and Electroencephalogram Vigilance Correlations.
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Attentional suppression of dynamic versus static salient distractors.
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Both micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.</AbstractText Thirty cognitively stable (CS) adults with DS underwent diffusion-weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts were derived using automatic fiber tracking, and associations with plasma NfL were assessed using Spearman correlation coefficients.</AbstractText Higher Plasma NfL was associated with greater altered diffusion measures of select tracts.</AbstractText Early increases in plasma NfL may reflect early white matter microstructural changes prior to dementia in DS.</AbstractText The onset of such WM changes in DS has not yet been widely studied.WM microstructural properties correlated with plasma neurofilament light chain (NfL).NfL may reflect early, selective WM changes in adults with DS at high risk of developing AD.</AbstractText
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Global signal regression (GSR) is a commonly used although controversial preprocessing approach in the analysis of resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data. Although the effects of GSR on resting-state functional connectivity measures have received much attention, there has been relatively little attention devoted to its effects on studies looking at the relationship between resting-state BOLD measures and independent measures of brain activity. In this study, we used simultaneously acquired electroencephalogram (EEG)-fMRI data in humans to examine the effects of GSR on the correlation between resting-state BOLD fluctuations and EEG vigilance measures. We show that GSR leads to a positive shift in the correlation between the BOLD and vigilance measures. This shift leads to a reduction in the spatial extent of negative correlations in widespread brain areas, including the visual cortex, but leads to the appearance of positive correlations in other areas, such as the cingulate gyrus. The results obtained using GSR are consistent with those of a temporal censoring process in which the correlation is computed using a temporal subset of the data. Since the data from these retained time points are unaffected by the censoring process, this finding suggests that the positive correlations in cingulate gyrus are not simply an artifact of GSR.</AbstractText
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Attention must be carefully controlled to avoid distraction by salient stimuli. The signal suppression hypothesis proposes that salient stimuli can be proactively suppressed to prevent distraction. Although this hypothesis has garnered much support, most previous studies have used one class of salient distractors: color singletons. It therefore remains unclear whether other kinds of salient distractors can also be suppressed. The current study directly compared suppression of a variety of salient stimuli using an attentional capture task that was adapted for eye tracking. The working hypothesis was that static salient stimuli (e.g., color singletons) would be easier to suppress than dynamic salient stimuli (e.g., motion singletons). The results showed that participants could ignore a wide variety of salient distractors. Importantly, suppression was weaker and slower to develop for dynamic salient stimuli than static salient stimuli. A final experiment revealed that adding a static salient feature to a dynamic motion distractor greatly improved suppression. Altogether, the results suggest that an underlying inhibitory process is applied to all kinds of salient distractors, but that suppression is more readily applied to static features than dynamic features.</AbstractText
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Association of plasma neurofilament light chain with microstructural white matter changes in Down syndrome. Both micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.</AbstractText Thirty cognitively stable (CS) adults with DS underwent diffusion-weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts were derived using automatic fiber tracking, and associations with plasma NfL were assessed using Spearman correlation coefficients.</AbstractText Higher Plasma NfL was associated with greater altered diffusion measures of select tracts.</AbstractText Early increases in plasma NfL may reflect early white matter microstructural changes prior to dementia in DS.</AbstractText The onset of such WM changes in DS has not yet been widely studied.WM microstructural properties correlated with plasma neurofilament light chain (NfL).NfL may reflect early, selective WM changes in adults with DS at high risk of developing AD.</AbstractText
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The Effects of Global Signal Regression on Estimates of Resting-State Blood Oxygen-Level-Dependent Functional Magnetic Resonance Imaging and Electroencephalogram Vigilance Correlations. Global signal regression (GSR) is a commonly used although controversial preprocessing approach in the analysis of resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data. Although the effects of GSR on resting-state functional connectivity measures have received much attention, there has been relatively little attention devoted to its effects on studies looking at the relationship between resting-state BOLD measures and independent measures of brain activity. In this study, we used simultaneously acquired electroencephalogram (EEG)-fMRI data in humans to examine the effects of GSR on the correlation between resting-state BOLD fluctuations and EEG vigilance measures. We show that GSR leads to a positive shift in the correlation between the BOLD and vigilance measures. This shift leads to a reduction in the spatial extent of negative correlations in widespread brain areas, including the visual cortex, but leads to the appearance of positive correlations in other areas, such as the cingulate gyrus. The results obtained using GSR are consistent with those of a temporal censoring process in which the correlation is computed using a temporal subset of the data. Since the data from these retained time points are unaffected by the censoring process, this finding suggests that the positive correlations in cingulate gyrus are not simply an artifact of GSR.</AbstractText
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Attentional suppression of dynamic versus static salient distractors. Attention must be carefully controlled to avoid distraction by salient stimuli. The signal suppression hypothesis proposes that salient stimuli can be proactively suppressed to prevent distraction. Although this hypothesis has garnered much support, most previous studies have used one class of salient distractors: color singletons. It therefore remains unclear whether other kinds of salient distractors can also be suppressed. The current study directly compared suppression of a variety of salient stimuli using an attentional capture task that was adapted for eye tracking. The working hypothesis was that static salient stimuli (e.g., color singletons) would be easier to suppress than dynamic salient stimuli (e.g., motion singletons). The results showed that participants could ignore a wide variety of salient distractors. Importantly, suppression was weaker and slower to develop for dynamic salient stimuli than static salient stimuli. A final experiment revealed that adding a static salient feature to a dynamic motion distractor greatly improved suppression. Altogether, the results suggest that an underlying inhibitory process is applied to all kinds of salient distractors, but that suppression is more readily applied to static features than dynamic features.</AbstractText
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27867832
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10940436
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26708675
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A neuroimaging point of view on the diversity of social cognition: evidence for extended influence of experience- and emotion-related factors on face processing.
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The eyes have it: the neuroethology, function and evolution of social gaze.
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Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial.
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Faces are key social stimuli that convey a wealth of information essential for person perception and adaptive interpersonal behaviour. Studies in the domain of cognitive, affective, and social neuroscience have put in light that the processing of faces recruits specific visual regions and activates a distributed set of brain regions related to attentional, emotional, social, and memory processes associated with the perception of faces and the extraction of the numerous information attached to them. Studies using neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have allowed localizing these brain regions and characterizing their functional properties. Magnetoencephalography (MEG) and electroencephalography (EEG) techniques are complementary to fMRI in that they offer a unique insight into the temporal dynamics of mental processes. In this article, I review the contribution of neuroimaging techniques to the knowledge on face processing and person perception with the aim of putting in light the extended influence of experience-related factors, particularly in relation with emotions, on the face processing system. Although the face processing network has evolved under evolutionary selection pressure related to sociality-related needs and is therefore highly conserved throughout the human species, neuroimaging studies put in light both the extension and the flexibility of the brain network involved in face processing. MEG and EEG allow in particular to reveal that the human brain integrates emotion- and experience-related information from the earliest stage of face processing. Altogether, this emphasizes the diversity of social cognitive processes associated with face perception.</AbstractText
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Gaze is an important component of social interaction. The function, evolution and neurobiology of gaze processing are therefore of interest to a number of researchers. This review discusses the evolutionary role of social gaze in vertebrates (focusing on primates), and a hypothesis that this role has changed substantially for primates compared to other animals. This change may have been driven by morphological changes to the face and eyes of primates, limitations in the facial anatomy of other vertebrates, changes in the ecology of the environment in which primates live, and a necessity to communicate information about the environment, emotional and mental states. The eyes represent different levels of signal value depending on the status, disposition and emotional state of the sender and receiver of such signals. There are regions in the monkey and human brain which contain neurons that respond selectively to faces, bodies and eye gaze. The ability to follow another individual's gaze direction is affected in individuals with autism and other psychopathological disorders, and after particular localized brain lesions. The hypothesis that gaze following is "hard-wired" in the brain, and may be localized within a circuit linking the superior temporal sulcus, amygdala and orbitofrontal cortex is discussed.</AbstractText
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Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement.</AbstractText Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36-43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155.</AbstractText The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference -0·01, 95% CI -0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded.</AbstractText Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia.</AbstractText UK Medical Research Council.</AbstractText
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A neuroimaging point of view on the diversity of social cognition: evidence for extended influence of experience- and emotion-related factors on face processing. Faces are key social stimuli that convey a wealth of information essential for person perception and adaptive interpersonal behaviour. Studies in the domain of cognitive, affective, and social neuroscience have put in light that the processing of faces recruits specific visual regions and activates a distributed set of brain regions related to attentional, emotional, social, and memory processes associated with the perception of faces and the extraction of the numerous information attached to them. Studies using neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have allowed localizing these brain regions and characterizing their functional properties. Magnetoencephalography (MEG) and electroencephalography (EEG) techniques are complementary to fMRI in that they offer a unique insight into the temporal dynamics of mental processes. In this article, I review the contribution of neuroimaging techniques to the knowledge on face processing and person perception with the aim of putting in light the extended influence of experience-related factors, particularly in relation with emotions, on the face processing system. Although the face processing network has evolved under evolutionary selection pressure related to sociality-related needs and is therefore highly conserved throughout the human species, neuroimaging studies put in light both the extension and the flexibility of the brain network involved in face processing. MEG and EEG allow in particular to reveal that the human brain integrates emotion- and experience-related information from the earliest stage of face processing. Altogether, this emphasizes the diversity of social cognitive processes associated with face perception.</AbstractText
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The eyes have it: the neuroethology, function and evolution of social gaze. Gaze is an important component of social interaction. The function, evolution and neurobiology of gaze processing are therefore of interest to a number of researchers. This review discusses the evolutionary role of social gaze in vertebrates (focusing on primates), and a hypothesis that this role has changed substantially for primates compared to other animals. This change may have been driven by morphological changes to the face and eyes of primates, limitations in the facial anatomy of other vertebrates, changes in the ecology of the environment in which primates live, and a necessity to communicate information about the environment, emotional and mental states. The eyes represent different levels of signal value depending on the status, disposition and emotional state of the sender and receiver of such signals. There are regions in the monkey and human brain which contain neurons that respond selectively to faces, bodies and eye gaze. The ability to follow another individual's gaze direction is affected in individuals with autism and other psychopathological disorders, and after particular localized brain lesions. The hypothesis that gaze following is "hard-wired" in the brain, and may be localized within a circuit linking the superior temporal sulcus, amygdala and orbitofrontal cortex is discussed.</AbstractText
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Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial. Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement.</AbstractText Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36-43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155.</AbstractText The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference -0·01, 95% CI -0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded.</AbstractText Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia.</AbstractText UK Medical Research Council.</AbstractText
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22105041
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24803034
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21474377
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Brain ischemia and hypometabolism treated by ozone therapy.
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Neurochemical evidence of potential neurotoxicity after prophylactic cranial irradiation.
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Saliva as a tool for monitoring steroid, peptide and immune markers in sport and exercise science.
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Radiation-induced brain injury (RBI) and low-perfusion brain syndromes are mediated by ischemia and hypometabolism and have limited treatment options. Ozone therapy as treatment in vascular diseases has been described, but the effects on brain tissue have not been well documented.</AbstractText We describe a 75-year-old patient with vascular risk factors and meningioma who was treated with stereotactic radiosurgery. 14 months later the patient presented with progressive clinical impairment despite the use of acetylsalicylic acid and corticosteroids. Clinical and imaging evaluations before/after ozone therapy were done by magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT), and positron emission tomography (PET); performance status assessment was done using Barthel Index and World Health Organization/Eastern Cooperative Oncology Group Scale (WHO/ECOG Scale). Ozone therapy was performed by autohemotransfusion.</AbstractText Basal images showed brain areas with ischemia and hypometabolism compatible with ischemic processes and/or RBI. There were no changes in MRI or CT scan images following ozone therapy. However, improvements in brain perfusion and metabolism were demonstrable with SPECT and PET; they correlated with clinical development and performance status scales.</AbstractText This report supports our previous works about the effect of ozone therapy in cerebral blood flow, and it suggests the use of ozone therapy in ischemic and hypometabolic brain syndromes such as stroke or RBI.</AbstractText
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To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid β-related processes could characterize the neurochemical response to cranial radiation.</AbstractText Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation.</AbstractText The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -β were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies.</AbstractText In conclusion, we were able to detect radiation therapy-induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid β metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.</AbstractText
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This paper discusses the use of saliva analysis as a tool for monitoring steroid, peptide, and immune markers of sports training.</AbstractText Salivary gland physiology, regarding the regulation and stimulation of saliva secretion, as well as methodological issues including saliva collection, storage and analysis are addressed in this paper. The effects of exercise on saliva composition are then considered.</AbstractText Exercise elicits changes in salivary levels of steroid hormones, immunoglobulins, antimicrobial proteins and enzymes. Cortisol, testosterone and dehydroepiandrosterone can be assessed in saliva, providing a non-invasive option to assess the catabolic and anabolic effects of exercise. Validation studies using blood and salivary measures of steroid hormones are addressed in this paper. Effects of acute exercise and training on salivary immunoglobulins (SIgA, SIgM, SIgG) and salivary antimicrobial proteins, including α-amylase, lysozyme and lactoferrin, are also discussed.</AbstractText Analysis of cortisol and testosterone in saliva may help detect the onset of non-functional overreaching and subsequently may help to prevent the development of overtraining syndrome. Assessment of salivary immunoglobulins and antimicrobial proteins has been shown to successfully represent the effects of exercise on mucosal immunity. Increases in SIgA and antimicrobial proteins concentration and/or secretion rate are associated with acute exercise whereas conversely, decreases have been reported in athletes over a training season leaving the athlete susceptible for upper respiratory tract infections.</AbstractText The measurement of physiological biomarkers in whole saliva can provide a significant tool for assessing the immunological and endocrinological status associated with exercise and training.</AbstractText
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Brain ischemia and hypometabolism treated by ozone therapy. Radiation-induced brain injury (RBI) and low-perfusion brain syndromes are mediated by ischemia and hypometabolism and have limited treatment options. Ozone therapy as treatment in vascular diseases has been described, but the effects on brain tissue have not been well documented.</AbstractText We describe a 75-year-old patient with vascular risk factors and meningioma who was treated with stereotactic radiosurgery. 14 months later the patient presented with progressive clinical impairment despite the use of acetylsalicylic acid and corticosteroids. Clinical and imaging evaluations before/after ozone therapy were done by magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT), and positron emission tomography (PET); performance status assessment was done using Barthel Index and World Health Organization/Eastern Cooperative Oncology Group Scale (WHO/ECOG Scale). Ozone therapy was performed by autohemotransfusion.</AbstractText Basal images showed brain areas with ischemia and hypometabolism compatible with ischemic processes and/or RBI. There were no changes in MRI or CT scan images following ozone therapy. However, improvements in brain perfusion and metabolism were demonstrable with SPECT and PET; they correlated with clinical development and performance status scales.</AbstractText This report supports our previous works about the effect of ozone therapy in cerebral blood flow, and it suggests the use of ozone therapy in ischemic and hypometabolic brain syndromes such as stroke or RBI.</AbstractText
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Neurochemical evidence of potential neurotoxicity after prophylactic cranial irradiation. To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid β-related processes could characterize the neurochemical response to cranial radiation.</AbstractText Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation.</AbstractText The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -β were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies.</AbstractText In conclusion, we were able to detect radiation therapy-induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid β metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.</AbstractText
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Saliva as a tool for monitoring steroid, peptide and immune markers in sport and exercise science. This paper discusses the use of saliva analysis as a tool for monitoring steroid, peptide, and immune markers of sports training.</AbstractText Salivary gland physiology, regarding the regulation and stimulation of saliva secretion, as well as methodological issues including saliva collection, storage and analysis are addressed in this paper. The effects of exercise on saliva composition are then considered.</AbstractText Exercise elicits changes in salivary levels of steroid hormones, immunoglobulins, antimicrobial proteins and enzymes. Cortisol, testosterone and dehydroepiandrosterone can be assessed in saliva, providing a non-invasive option to assess the catabolic and anabolic effects of exercise. Validation studies using blood and salivary measures of steroid hormones are addressed in this paper. Effects of acute exercise and training on salivary immunoglobulins (SIgA, SIgM, SIgG) and salivary antimicrobial proteins, including α-amylase, lysozyme and lactoferrin, are also discussed.</AbstractText Analysis of cortisol and testosterone in saliva may help detect the onset of non-functional overreaching and subsequently may help to prevent the development of overtraining syndrome. Assessment of salivary immunoglobulins and antimicrobial proteins has been shown to successfully represent the effects of exercise on mucosal immunity. Increases in SIgA and antimicrobial proteins concentration and/or secretion rate are associated with acute exercise whereas conversely, decreases have been reported in athletes over a training season leaving the athlete susceptible for upper respiratory tract infections.</AbstractText The measurement of physiological biomarkers in whole saliva can provide a significant tool for assessing the immunological and endocrinological status associated with exercise and training.</AbstractText
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33902155
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25216287
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33340709
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Free-breathing abdominal T(1) mapping using an optimized MR fingerprinting sequence.
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ECG and navigator-free four-dimensional whole-heart coronary MRA for simultaneous visualization of cardiac anatomy and function.
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Mitochondrial dysfunction as a critical event in the pathophysiology of bipolar disorder.
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In this work, we propose a free-breathing magnetic resonance fingerprinting (MRF) method that can be used to obtain B<sub
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To develop a cardiac and respiratory self-gated four-dimensional (4D) coronary MRA technique for simultaneous cardiac anatomy and function visualization.</AbstractText A contrast-enhanced, ungated spoiled gradient echo sequence with self-gating (SG) and 3DPR trajectory was used for image acquisition. Data were retrospectively binned into different cardiac and respiratory phases based on information extracted from SG projections using principal component analysis. Each cardiac phase was reconstructed using a respiratory motion-corrected self-calibrating SENSE framework, and those belong to the quiescent period were retrospectively combined for coronary visualization. Healthy volunteer studies were conducted to evaluate the efficacy of the SG method, the accuracy of the left ventricle (LV) function parameters and the quality of coronary artery visualization.</AbstractText SG performed reliably for all subjects including one with poor electrocardiogram (ECG). The LV function parameters showed excellent agreement with those from a conventional cine protocol. For coronary imaging, the proposed method yielded comparable apparent signal to noise ratio and coronary sharpness and lower apparent contrast to noise ratio on three subjects compared with an ECG and navigator-gated Cartesian protocol and an ECG-gated, respiratory motion-corrected 3DPR protocol.</AbstractText A fully self-gated 4D whole-heart imaging technique was developed, potentially allowing cardiac anatomy and function assessment from a single measurement.</AbstractText
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The understanding of the pathophysiology of bipolar disorder (BD) remains modest, despite recent advances in neurobiological research. The mitochondrial dysfunction hypothesis of bipolar disorder has been corroborated by several studies involving postmortem brain analysis, neuroimaging, and specific biomarkers in both rodent models and humans. Evidence suggests that BD might be related to abnormal mitochondrial morphology and dynamics, neuroimmune dysfunction, and atypical mitochondrial metabolism and oxidative stress pathways. Mitochondrial dysfunction in mood disorders is also associated with abnormal Ca<sup
|
Free-breathing abdominal T(1) mapping using an optimized MR fingerprinting sequence. In this work, we propose a free-breathing magnetic resonance fingerprinting (MRF) method that can be used to obtain B<sub
|
ECG and navigator-free four-dimensional whole-heart coronary MRA for simultaneous visualization of cardiac anatomy and function. To develop a cardiac and respiratory self-gated four-dimensional (4D) coronary MRA technique for simultaneous cardiac anatomy and function visualization.</AbstractText A contrast-enhanced, ungated spoiled gradient echo sequence with self-gating (SG) and 3DPR trajectory was used for image acquisition. Data were retrospectively binned into different cardiac and respiratory phases based on information extracted from SG projections using principal component analysis. Each cardiac phase was reconstructed using a respiratory motion-corrected self-calibrating SENSE framework, and those belong to the quiescent period were retrospectively combined for coronary visualization. Healthy volunteer studies were conducted to evaluate the efficacy of the SG method, the accuracy of the left ventricle (LV) function parameters and the quality of coronary artery visualization.</AbstractText SG performed reliably for all subjects including one with poor electrocardiogram (ECG). The LV function parameters showed excellent agreement with those from a conventional cine protocol. For coronary imaging, the proposed method yielded comparable apparent signal to noise ratio and coronary sharpness and lower apparent contrast to noise ratio on three subjects compared with an ECG and navigator-gated Cartesian protocol and an ECG-gated, respiratory motion-corrected 3DPR protocol.</AbstractText A fully self-gated 4D whole-heart imaging technique was developed, potentially allowing cardiac anatomy and function assessment from a single measurement.</AbstractText
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Mitochondrial dysfunction as a critical event in the pathophysiology of bipolar disorder. The understanding of the pathophysiology of bipolar disorder (BD) remains modest, despite recent advances in neurobiological research. The mitochondrial dysfunction hypothesis of bipolar disorder has been corroborated by several studies involving postmortem brain analysis, neuroimaging, and specific biomarkers in both rodent models and humans. Evidence suggests that BD might be related to abnormal mitochondrial morphology and dynamics, neuroimmune dysfunction, and atypical mitochondrial metabolism and oxidative stress pathways. Mitochondrial dysfunction in mood disorders is also associated with abnormal Ca<sup
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39976053
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37852264
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40473434
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A finite set of content-free pointers in visual working memory: magnetoencephalography (MEG) evidence.
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Periodic attention deficits after frontoparietal lesions provide causal evidence for rhythmic attentional sampling.
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The Diagnosis and Management of Hepatorenal Syndrome: A Comprehensive Update for the Intensivist.
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Human visual working memory (VWM) is known to be capacity-limited, but the nature of this limit continues to be debated. Recent work has proposed that VWM is supported by a finite (~3) set of content-free pointers, acting as stand-ins for individual objects and binding features together. According to this proposal, the pointers do not represent features within themselves, but rather bind features represented elsewhere together. The current study set out to test if neural hallmarks resembling these content-free pointers can be observed with magnetoencephalography (MEG). Based on two VWM delay-match-to-sample experiments (N = 20 each) examining memory for simple and complex objects, we report a sustained response in MEG over right posterior cortex whose magnitude tracks the core hypothesized properties of this content-free pointer system: load-dependent, capacity-limited, and content-free. These results provide novel evidence for a finite set of content-free pointers underlying VWM.</AbstractText
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Contemporary models conceptualize spatial attention as a blinking spotlight that sequentially samples visual space. Hence, behavior fluctuates over time, even in states of presumed "sustained" attention. Recent evidence has suggested that rhythmic neural activity in the frontoparietal network constitutes the functional basis of rhythmic attentional sampling. However, causal evidence to support this notion remains absent. Using a lateralized spatial attention task, we addressed this issue in patients with focal lesions in the frontoparietal attention network. Our results revealed that frontoparietal lesions introduce periodic attention deficits, i.e., temporally specific behavioral deficits that are aligned with the underlying neural oscillations. Attention-guided perceptual sensitivity was on par with that of healthy controls during optimal phases but was attenuated during the less excitable sub-cycles. Theta-dependent sampling (3-8 Hz) was causally dependent on the prefrontal cortex, while high-alpha/low-beta sampling (8-14 Hz) emerged from parietal areas. Collectively, our findings reveal that lesion-induced high-amplitude, low-frequency brain activity is not epiphenomenal but has immediate behavioral consequences. More generally, these results provide causal evidence for the hypothesis that the functional architecture of attention is inherently rhythmic.</AbstractText
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Intensivists are being increasingly tasked with caring for critically ill patients with cirrhosis (ie, acute-on-chronic liver failure), many of whom develop acute kidney injury (AKI). Among the most morbid and complex causes of AKI in patients with cirrhosis is hepatorenal syndrome (HRS-AKI). Though HRS-AKI accounts for a fraction of AKI cases in the setting of cirrhosis, recent data suggest that effective pharmacologic treatment of HRS-AKI requires rapid diagnosis to allow for prompt intervention. Consequently, a firm understanding of the diagnosis and treatment of HRS-AKI is vital for all intensivists. In this review, we summarize recent developments in the diagnosis and treatment of HRS-AKI. Chief among these is the recent realization that HRS-AKI is not a diagnosis of exclusion, but instead may coexist with other forms of AKI, such as acute tubular injury, or may develop in the context of pre-existing chronic kidney disease. Moreover, with multiple recent trials suggesting that administration of fixed doses of intravenous albumin to unselected patients with cirrhosis and AKI may cause harm via volume overload and pulmonary edema, no longer is a 48-h trial of intravenous albumin recommended for all patients with AKI and cirrhosis. Instead, the newest guidelines recommend thoughtful assessment of volume status in all patients with AKI and cirrhosis and determination of an HRS-AKI diagnosis within 24 h to allow for prompt initiation of effective therapy. Short of liver transplantation, treatment of HRS-AKI is with vasoconstrictive agents. Though commonly used, midodrine/octreotide should largely be abandoned due to lack of efficacy. While recent trials have confirmed the effectiveness of terlipressin, its use is associated with a risk of potentially fatal respiratory failure and therefore requires careful patient selection and monitoring. As such, treatment of HRS-AKI with norepinephrine in the intensive care unit will remain the primary treatment option for many patients.</AbstractText
|
A finite set of content-free pointers in visual working memory: magnetoencephalography (MEG) evidence. Human visual working memory (VWM) is known to be capacity-limited, but the nature of this limit continues to be debated. Recent work has proposed that VWM is supported by a finite (~3) set of content-free pointers, acting as stand-ins for individual objects and binding features together. According to this proposal, the pointers do not represent features within themselves, but rather bind features represented elsewhere together. The current study set out to test if neural hallmarks resembling these content-free pointers can be observed with magnetoencephalography (MEG). Based on two VWM delay-match-to-sample experiments (N = 20 each) examining memory for simple and complex objects, we report a sustained response in MEG over right posterior cortex whose magnitude tracks the core hypothesized properties of this content-free pointer system: load-dependent, capacity-limited, and content-free. These results provide novel evidence for a finite set of content-free pointers underlying VWM.</AbstractText
|
Periodic attention deficits after frontoparietal lesions provide causal evidence for rhythmic attentional sampling. Contemporary models conceptualize spatial attention as a blinking spotlight that sequentially samples visual space. Hence, behavior fluctuates over time, even in states of presumed "sustained" attention. Recent evidence has suggested that rhythmic neural activity in the frontoparietal network constitutes the functional basis of rhythmic attentional sampling. However, causal evidence to support this notion remains absent. Using a lateralized spatial attention task, we addressed this issue in patients with focal lesions in the frontoparietal attention network. Our results revealed that frontoparietal lesions introduce periodic attention deficits, i.e., temporally specific behavioral deficits that are aligned with the underlying neural oscillations. Attention-guided perceptual sensitivity was on par with that of healthy controls during optimal phases but was attenuated during the less excitable sub-cycles. Theta-dependent sampling (3-8 Hz) was causally dependent on the prefrontal cortex, while high-alpha/low-beta sampling (8-14 Hz) emerged from parietal areas. Collectively, our findings reveal that lesion-induced high-amplitude, low-frequency brain activity is not epiphenomenal but has immediate behavioral consequences. More generally, these results provide causal evidence for the hypothesis that the functional architecture of attention is inherently rhythmic.</AbstractText
|
The Diagnosis and Management of Hepatorenal Syndrome: A Comprehensive Update for the Intensivist. Intensivists are being increasingly tasked with caring for critically ill patients with cirrhosis (ie, acute-on-chronic liver failure), many of whom develop acute kidney injury (AKI). Among the most morbid and complex causes of AKI in patients with cirrhosis is hepatorenal syndrome (HRS-AKI). Though HRS-AKI accounts for a fraction of AKI cases in the setting of cirrhosis, recent data suggest that effective pharmacologic treatment of HRS-AKI requires rapid diagnosis to allow for prompt intervention. Consequently, a firm understanding of the diagnosis and treatment of HRS-AKI is vital for all intensivists. In this review, we summarize recent developments in the diagnosis and treatment of HRS-AKI. Chief among these is the recent realization that HRS-AKI is not a diagnosis of exclusion, but instead may coexist with other forms of AKI, such as acute tubular injury, or may develop in the context of pre-existing chronic kidney disease. Moreover, with multiple recent trials suggesting that administration of fixed doses of intravenous albumin to unselected patients with cirrhosis and AKI may cause harm via volume overload and pulmonary edema, no longer is a 48-h trial of intravenous albumin recommended for all patients with AKI and cirrhosis. Instead, the newest guidelines recommend thoughtful assessment of volume status in all patients with AKI and cirrhosis and determination of an HRS-AKI diagnosis within 24 h to allow for prompt initiation of effective therapy. Short of liver transplantation, treatment of HRS-AKI is with vasoconstrictive agents. Though commonly used, midodrine/octreotide should largely be abandoned due to lack of efficacy. While recent trials have confirmed the effectiveness of terlipressin, its use is associated with a risk of potentially fatal respiratory failure and therefore requires careful patient selection and monitoring. As such, treatment of HRS-AKI with norepinephrine in the intensive care unit will remain the primary treatment option for many patients.</AbstractText
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26832709
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18006643
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26715465
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[Clinical significance of dynamic changes in serum inflammatory cell factors after acute paraquat poisoning].
|
Small molecule disruption of G protein beta gamma subunit signaling inhibits neutrophil chemotaxis and inflammation.
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Stories for change: development of a diabetes digital storytelling intervention for refugees and immigrants to minnesota using qualitative methods.
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To investigate the clinical significance of dynamic changes in the serum inflammatory cell factors consisting of β-endorphin (β-EP) , endothelins (ET) , tumor necrosis factor (TNF) , and nitric oxide (NO) after acute paraquat poisoning (APP).</AbstractText The 26 patients with APP (as observation group) were treated and the serum levels of plasma β-EP, ET, TNF, and NO were measured simultaneously. The 20 healthy volunteers from relatives of the patients (as control group) were also included in the study and their serum levels of β-EP, ET, TNF, and NO were measured.</AbstractText In the 26 patients with APP, 10 were cured and 16 died. The serum levels of β-EP, ET, NO, and TNF in the 10 cured patients increased significantly immediately after admission, reached the peak values on day 2, and then decreased gradually and returned to the normal ranges after day 9. The serum levels of β-EP, ET, NO, and TNF in the 16 dead patients increased significantly on admission and kept rising in the course of treatment. The dead patients had significantly increased serum levels of β-EP, ET, NO, and TNF compared with the cured patients (all P<0.01).</AbstractText Compared with those in cured patients with APP, the serum levels of β-EP, ET, NO, and TNF in dead patients with APP are significantly higher, keep rising, and maintain at high levels, indicating a severe condition.</AbstractText
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G protein betagamma subunit-dependent signaling is important for chemoattractant-dependent leukocyte chemotaxis. Selective small molecule targeting of phosphoinositide 3-kinase (PI3-kinase) gamma catalytic activity is a target of interest for anti-inflammatory pharmaceutical development. In this study, we examined whether small-molecule inhibition of Gbetagamma-dependent signaling, including Gbetagamma-dependent activation of PI3-kinase gamma and Rac1, could inhibit chemoattractant-dependent neutrophil migration in vitro and inflammation in vivo. Small-molecule Gbetagamma inhibitors suppressed fMLP-stimulated Rac activation, superoxide production, and PI3-kinase activation in differentiated HL60 cells. These compounds also blocked fMLP-dependent chemotaxis in HL60 cells and primary human neutrophils. Systemic administration inhibited paw edema and neutrophil infiltration in a mouse carrageenan-induced paw edema model. Overall, the data demonstrate that targeting Gbetagamma-regulation may be an effective anti-inflammation strategy.</AbstractText
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Immigrants and refugees are affected by diabetes-related health disparities, with higher rates of incident diabetes and sub-optimal diabetes outcomes. Digital storytelling interventions for chronic diseases, such as diabetes may be especially powerful among immigrants because often limited English proficiency minimizes access to and affects the applicability of the existing health education opportunities. Community-based participatory research (CBPR), whereby community members and academia partner in an equitable relationship through all phases of the research, is an intuitive approach to develop these interventions. The main objective of this study was to develop a diabetes digital storytelling intervention with and for immigrant and refugee populations.</AbstractText We used a CBPR approach to develop a diabetes digital storytelling intervention with and for immigrant and refugee Somali and Latino communities. Building on an established CBPR partnership, we conducted focus groups among community members with type II diabetes for a dual purpose: 1) to inform the intervention as it related to four domains of diabetes self-management (medication management, glucose self-monitoring, physical activity, and nutrition); 2) to identify champion storytellers for the intervention development. Eight participants attended a facilitated workshop for the creation of the digital stories.</AbstractText Each of the eight storytellers, from the Somali and Latino communities with diabetes (four from each group), created a powerful and compelling story about their struggles and accomplishments related to the four domains of diabetes self-management.</AbstractText This report is on a systematic, participatory process for the successful development of a diabetes storytelling intervention for Somali and Latino adults. Processes and products from this work may inform the work of other CBPR partnerships.</AbstractText
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[Clinical significance of dynamic changes in serum inflammatory cell factors after acute paraquat poisoning]. To investigate the clinical significance of dynamic changes in the serum inflammatory cell factors consisting of β-endorphin (β-EP) , endothelins (ET) , tumor necrosis factor (TNF) , and nitric oxide (NO) after acute paraquat poisoning (APP).</AbstractText The 26 patients with APP (as observation group) were treated and the serum levels of plasma β-EP, ET, TNF, and NO were measured simultaneously. The 20 healthy volunteers from relatives of the patients (as control group) were also included in the study and their serum levels of β-EP, ET, TNF, and NO were measured.</AbstractText In the 26 patients with APP, 10 were cured and 16 died. The serum levels of β-EP, ET, NO, and TNF in the 10 cured patients increased significantly immediately after admission, reached the peak values on day 2, and then decreased gradually and returned to the normal ranges after day 9. The serum levels of β-EP, ET, NO, and TNF in the 16 dead patients increased significantly on admission and kept rising in the course of treatment. The dead patients had significantly increased serum levels of β-EP, ET, NO, and TNF compared with the cured patients (all P<0.01).</AbstractText Compared with those in cured patients with APP, the serum levels of β-EP, ET, NO, and TNF in dead patients with APP are significantly higher, keep rising, and maintain at high levels, indicating a severe condition.</AbstractText
|
Small molecule disruption of G protein beta gamma subunit signaling inhibits neutrophil chemotaxis and inflammation. G protein betagamma subunit-dependent signaling is important for chemoattractant-dependent leukocyte chemotaxis. Selective small molecule targeting of phosphoinositide 3-kinase (PI3-kinase) gamma catalytic activity is a target of interest for anti-inflammatory pharmaceutical development. In this study, we examined whether small-molecule inhibition of Gbetagamma-dependent signaling, including Gbetagamma-dependent activation of PI3-kinase gamma and Rac1, could inhibit chemoattractant-dependent neutrophil migration in vitro and inflammation in vivo. Small-molecule Gbetagamma inhibitors suppressed fMLP-stimulated Rac activation, superoxide production, and PI3-kinase activation in differentiated HL60 cells. These compounds also blocked fMLP-dependent chemotaxis in HL60 cells and primary human neutrophils. Systemic administration inhibited paw edema and neutrophil infiltration in a mouse carrageenan-induced paw edema model. Overall, the data demonstrate that targeting Gbetagamma-regulation may be an effective anti-inflammation strategy.</AbstractText
|
Stories for change: development of a diabetes digital storytelling intervention for refugees and immigrants to minnesota using qualitative methods. Immigrants and refugees are affected by diabetes-related health disparities, with higher rates of incident diabetes and sub-optimal diabetes outcomes. Digital storytelling interventions for chronic diseases, such as diabetes may be especially powerful among immigrants because often limited English proficiency minimizes access to and affects the applicability of the existing health education opportunities. Community-based participatory research (CBPR), whereby community members and academia partner in an equitable relationship through all phases of the research, is an intuitive approach to develop these interventions. The main objective of this study was to develop a diabetes digital storytelling intervention with and for immigrant and refugee populations.</AbstractText We used a CBPR approach to develop a diabetes digital storytelling intervention with and for immigrant and refugee Somali and Latino communities. Building on an established CBPR partnership, we conducted focus groups among community members with type II diabetes for a dual purpose: 1) to inform the intervention as it related to four domains of diabetes self-management (medication management, glucose self-monitoring, physical activity, and nutrition); 2) to identify champion storytellers for the intervention development. Eight participants attended a facilitated workshop for the creation of the digital stories.</AbstractText Each of the eight storytellers, from the Somali and Latino communities with diabetes (four from each group), created a powerful and compelling story about their struggles and accomplishments related to the four domains of diabetes self-management.</AbstractText This report is on a systematic, participatory process for the successful development of a diabetes storytelling intervention for Somali and Latino adults. Processes and products from this work may inform the work of other CBPR partnerships.</AbstractText
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39746328
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34393901
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40382846
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Under and Overmentalizing in Personality Disorders: A Principal Component Analysis of Nonadaptive Personality and the Movie Assessment of Social Cognition.
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Subjective Impact of the COVID-19 Pandemic on Schizotypy and General Mental Health in Germany and the United Kingdom, for Independent Samples in May and in October 2020.
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Anticancer potential of pyrazole-triazole derivatives: A multidisciplinary approach combining quantum chemistry, spectroscopy, and molecular docking.
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This secondary analysis of quality control data assessed principal components of personality dysfunction and their relationship to mentalizing in a sample of treatment-seeking women with severe personality disorders.</AbstractText The Schedule for Nonadaptive and Adaptive Personality (SNAP) and the Movie for the Assessment of Social Cognition (MASC) were administered to 37 females in routine quality assessments of a specialized residential treatment program. Principal component analysis (PCA) of SNAP scores was used to determine dimensions of personality most significantly contributing to overall maladaptive personality functioning. Bootstrapped stepwise regression tested the relationship of dimensional personality indices to hypermentalizing and hypomentalizing on the MASC controlling for general psychiatric severity.</AbstractText Four principal components (PCs) explained 71.4% of the variance in personality dysfunction, mapping onto antisocial, obsessive compulsive, borderline, and narcissistic personality constellations. The borderline and antisocial PCs were positively predictive of hypermentalizing. The obsessive-compulsive PC was positively predictive of hypomentalizing, while the antisocial PC was negatively predictive of hypomentalizing.</AbstractText The study reiterates prior findings of a relationship between hypermentalizing and borderline and antisocial personality profiles. It also contributes evidence to the limited research on hypomentalizing as a clinical indicator and potential treatment target for obsessive-compulsive personality, and shows evidence of a negative relationship between antisocial personality disorder and hypomentalizing. These findings provide clinical indications for enhancing and regulating mentalizing via attention to and interpretations of internal and interpersonal events in individuals with personality disorders. Further research is needed to replicate these associations in larger, more representative clinical samples.</AbstractText
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Studies reported a strong impact on mental health during the first wave of the COVID-19 pandemic in March-June, 2020. In this study, we assessed the impact of the pandemic on mental health in general and on schizotypal traits in two independent general population samples of the United Kingdom (May sample N: 239, October sample N: 126; participation at both timepoints: 21) and in two independent general population samples of Germany (May sample N: 543, October sample N: 401; participation at both timepoints: 100) using online surveys. Whereas general psychological symptoms (global symptom index, GSI) and percentage of responders above clinical cut-off for further psychological investigation were higher in the May sample compared to the October sample, schizotypy scores (Schizotypal Personality Questionnaire) were higher in the October sample. We investigated potential associations, using general linear regression models (GLM). For schizotypy scores, we found that loneliness, use of drugs, and financial burden were more strongly corrected with schizotypy in the October compared to the May sample. We identified similar associations for GSI, as for schizotypy scores, in the May and October samples. We furthermore found that living in the United Kingdom was related to higher schizotypal scores or GSI. However, individual estimates of the GLM are highly comparable between the two countries. In conclusion, this study shows that while the general psychological impact is lower in the October than the May sample, potentially showing a normative response to an exceptional situation; schizotypy scores are higher at the second timepoint, which may be due to a stronger impact of estimates of loneliness, drug use, and financial burden. The ongoing, exceptional circumstances within this pandemic might increase the risk for developing psychosis in some individuals. The development of general psychological symptoms and schizotypy scores over time requires further attention and investigation.</AbstractText
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The synthesized pharmacologically active compound 3-ethoxy-5-(3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-4H-1,2,4-triazole (3EMPT) underwent a comprehensive investigation using quantum chemical, spectroscopic, and molecular methods. Pyrazole-triazole hybrids, known for their pharmacological activity, hold promise as potent drugs for a range of diseases. This study aims in examining, optical, electronic, geometrical and biological metrics of novel pyrazole-triazole derivatives. The compound was characterized using FT-IR with experimental results validated against DFT B3LYP/6-311++G(d,p) calculations. Theoretical investigations of UV-Vis absorption spectrum, NMR investigations and Light-Harvesting Efficiency (LHE) were performed using computational methods. The reactivity and chemical stability of 3EMPT were studied using calculated molecular parameters, including Frontier Molecular Orbital energies and Fukui functions. Molecular electrostatic potential (MESP) maps were used to identify electrophilic and nucleophilic regions, while natural bond orbital (NBO) analysis was employed to investigate molecular stability. The possible nonlinear implications were investigated through nonlinear optical (NLO) studies. The bonding nature and regions were elucidated through topological investigations using (ELF) Electron Localization Function, (LOL) Local Orbital Locator, and (RDG) Reduced Density Gradient. Drug-likeness was assessed using Lipinski's Rule of Five. Computational analysis using the GIAO method accurately predicted the 1H and 13C NMR chemical shifts, as evidenced by their close agreement with experimental findings. Molecular docking analysis against 2W17, 6MN0, and 1AH6 proteins revealed the lowest binding energy of -7.09 kcal/mol for 1AH6.</AbstractText
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Under and Overmentalizing in Personality Disorders: A Principal Component Analysis of Nonadaptive Personality and the Movie Assessment of Social Cognition. This secondary analysis of quality control data assessed principal components of personality dysfunction and their relationship to mentalizing in a sample of treatment-seeking women with severe personality disorders.</AbstractText The Schedule for Nonadaptive and Adaptive Personality (SNAP) and the Movie for the Assessment of Social Cognition (MASC) were administered to 37 females in routine quality assessments of a specialized residential treatment program. Principal component analysis (PCA) of SNAP scores was used to determine dimensions of personality most significantly contributing to overall maladaptive personality functioning. Bootstrapped stepwise regression tested the relationship of dimensional personality indices to hypermentalizing and hypomentalizing on the MASC controlling for general psychiatric severity.</AbstractText Four principal components (PCs) explained 71.4% of the variance in personality dysfunction, mapping onto antisocial, obsessive compulsive, borderline, and narcissistic personality constellations. The borderline and antisocial PCs were positively predictive of hypermentalizing. The obsessive-compulsive PC was positively predictive of hypomentalizing, while the antisocial PC was negatively predictive of hypomentalizing.</AbstractText The study reiterates prior findings of a relationship between hypermentalizing and borderline and antisocial personality profiles. It also contributes evidence to the limited research on hypomentalizing as a clinical indicator and potential treatment target for obsessive-compulsive personality, and shows evidence of a negative relationship between antisocial personality disorder and hypomentalizing. These findings provide clinical indications for enhancing and regulating mentalizing via attention to and interpretations of internal and interpersonal events in individuals with personality disorders. Further research is needed to replicate these associations in larger, more representative clinical samples.</AbstractText
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Subjective Impact of the COVID-19 Pandemic on Schizotypy and General Mental Health in Germany and the United Kingdom, for Independent Samples in May and in October 2020. Studies reported a strong impact on mental health during the first wave of the COVID-19 pandemic in March-June, 2020. In this study, we assessed the impact of the pandemic on mental health in general and on schizotypal traits in two independent general population samples of the United Kingdom (May sample N: 239, October sample N: 126; participation at both timepoints: 21) and in two independent general population samples of Germany (May sample N: 543, October sample N: 401; participation at both timepoints: 100) using online surveys. Whereas general psychological symptoms (global symptom index, GSI) and percentage of responders above clinical cut-off for further psychological investigation were higher in the May sample compared to the October sample, schizotypy scores (Schizotypal Personality Questionnaire) were higher in the October sample. We investigated potential associations, using general linear regression models (GLM). For schizotypy scores, we found that loneliness, use of drugs, and financial burden were more strongly corrected with schizotypy in the October compared to the May sample. We identified similar associations for GSI, as for schizotypy scores, in the May and October samples. We furthermore found that living in the United Kingdom was related to higher schizotypal scores or GSI. However, individual estimates of the GLM are highly comparable between the two countries. In conclusion, this study shows that while the general psychological impact is lower in the October than the May sample, potentially showing a normative response to an exceptional situation; schizotypy scores are higher at the second timepoint, which may be due to a stronger impact of estimates of loneliness, drug use, and financial burden. The ongoing, exceptional circumstances within this pandemic might increase the risk for developing psychosis in some individuals. The development of general psychological symptoms and schizotypy scores over time requires further attention and investigation.</AbstractText
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Anticancer potential of pyrazole-triazole derivatives: A multidisciplinary approach combining quantum chemistry, spectroscopy, and molecular docking. The synthesized pharmacologically active compound 3-ethoxy-5-(3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-4H-1,2,4-triazole (3EMPT) underwent a comprehensive investigation using quantum chemical, spectroscopic, and molecular methods. Pyrazole-triazole hybrids, known for their pharmacological activity, hold promise as potent drugs for a range of diseases. This study aims in examining, optical, electronic, geometrical and biological metrics of novel pyrazole-triazole derivatives. The compound was characterized using FT-IR with experimental results validated against DFT B3LYP/6-311++G(d,p) calculations. Theoretical investigations of UV-Vis absorption spectrum, NMR investigations and Light-Harvesting Efficiency (LHE) were performed using computational methods. The reactivity and chemical stability of 3EMPT were studied using calculated molecular parameters, including Frontier Molecular Orbital energies and Fukui functions. Molecular electrostatic potential (MESP) maps were used to identify electrophilic and nucleophilic regions, while natural bond orbital (NBO) analysis was employed to investigate molecular stability. The possible nonlinear implications were investigated through nonlinear optical (NLO) studies. The bonding nature and regions were elucidated through topological investigations using (ELF) Electron Localization Function, (LOL) Local Orbital Locator, and (RDG) Reduced Density Gradient. Drug-likeness was assessed using Lipinski's Rule of Five. Computational analysis using the GIAO method accurately predicted the 1H and 13C NMR chemical shifts, as evidenced by their close agreement with experimental findings. Molecular docking analysis against 2W17, 6MN0, and 1AH6 proteins revealed the lowest binding energy of -7.09 kcal/mol for 1AH6.</AbstractText
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22285719
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21347218
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22665558
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Anatomical and functional correlates of human hippocampal volume asymmetry.
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The neural architecture of the language comprehension network: converging evidence from lesion and connectivity analyses.
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Protracted neuroborreliosis--an unusual cause of encephalomyelitis.
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Hemispheric asymmetry of the human hippocampus is well established, but poorly understood. We studied 110 healthy subjects with 3-Tesla MRI to explore the anatomical and functional correlates of the R>L volume asymmetry. We found that the asymmetry is limited to the anterior hippocampus (hemisphere×region interaction: F(1,109)=42.6, p<.001). Anterior hippocampal volume was correlated strongly with the volumes of all four cortical lobes. In contrast, posterior hippocampal volume was correlated strongly only with occipital lobe volume, moderately with the parietal and temporal lobe volumes and not with the frontal lobe volume. The degree of R>L anterior hippocampal volume asymmetry predicted performance on a measure of basic cognitive abilities. This provides evidence for regional specificity and functional implications of the well-known hemispheric asymmetry of hippocampal volume. We suggest that the developmental profile, genetic mechanisms and functional implications of R>L anterior hippocampal volume asymmetry in the human brain deserve further study.</AbstractText
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While traditional models of language comprehension have focused on the left posterior temporal cortex as the neurological basis for language comprehension, lesion and functional imaging studies indicate the involvement of an extensive network of cortical regions. However, the full extent of this network and the white matter pathways that contribute to it remain to be characterized. In an earlier voxel-based lesion-symptom mapping analysis of data from aphasic patients (Dronkers et al., 2004), several brain regions in the left hemisphere were found to be critical for language comprehension: the left posterior middle temporal gyrus, the anterior part of Brodmann's area 22 in the superior temporal gyrus (anterior STG/BA22), the posterior superior temporal sulcus (STS) extending into Brodmann's area 39 (STS/BA39), the orbital part of the inferior frontal gyrus (BA47), and the middle frontal gyrus (BA46). Here, we investigated the white matter pathways associated with these regions using diffusion tensor imaging from healthy subjects. We also used resting-state functional magnetic resonance imaging data to assess the functional connectivity profiles of these regions. Fiber tractography and functional connectivity analyses indicated that the left MTG, anterior STG/BA22, STS/BA39, and BA47 are part of a richly interconnected network that extends to additional frontal, parietal, and temporal regions in the two hemispheres. The inferior occipito-frontal fasciculus, the arcuate fasciculus, and the middle and inferior longitudinal fasciculi, as well as transcallosal projections via the tapetum were found to be the most prominent white matter pathways bridging the regions important for language comprehension. The left MTG showed a particularly extensive structural and functional connectivity pattern which is consistent with the severity of the impairments associated with MTG lesions and which suggests a central role for this region in language comprehension.</AbstractText
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A 58-year-old lady with waxing and waning of non-specific symptoms including fatigue, dizziness, hearing loss and unsteady gait for 15 months, became acutely confused 12 h prior to presentation. On admission to a district hospital she was feverish and unresponsive. Her travel history consisted of visits to Argentina, Chile and the Outer Hebrides. CT of the brain was normal. Lumbar puncture demonstrated a lymphocytic pleocytosis of 500 cells, protein of 1 g/l, a low glucose ratio with negative cytology and viral PCR (including herpes simplex 1 and 2). MRI revealed multiple abnormal areas of high signal on T2 fluid attenuated inversion recovery sequencing within the cerebellum, temporal lobes and periventricular areas. Western blotting of serum and cerebrospinal fluid for Borrelia burgdoferi were both positive. She was treated with cefuroxime and aciclovir and within 24 h she was alert and responsive. She received 4 weeks of cefuroxime in total and made a good recovery.</AbstractText
|
Anatomical and functional correlates of human hippocampal volume asymmetry. Hemispheric asymmetry of the human hippocampus is well established, but poorly understood. We studied 110 healthy subjects with 3-Tesla MRI to explore the anatomical and functional correlates of the R>L volume asymmetry. We found that the asymmetry is limited to the anterior hippocampus (hemisphere×region interaction: F(1,109)=42.6, p<.001). Anterior hippocampal volume was correlated strongly with the volumes of all four cortical lobes. In contrast, posterior hippocampal volume was correlated strongly only with occipital lobe volume, moderately with the parietal and temporal lobe volumes and not with the frontal lobe volume. The degree of R>L anterior hippocampal volume asymmetry predicted performance on a measure of basic cognitive abilities. This provides evidence for regional specificity and functional implications of the well-known hemispheric asymmetry of hippocampal volume. We suggest that the developmental profile, genetic mechanisms and functional implications of R>L anterior hippocampal volume asymmetry in the human brain deserve further study.</AbstractText
|
The neural architecture of the language comprehension network: converging evidence from lesion and connectivity analyses. While traditional models of language comprehension have focused on the left posterior temporal cortex as the neurological basis for language comprehension, lesion and functional imaging studies indicate the involvement of an extensive network of cortical regions. However, the full extent of this network and the white matter pathways that contribute to it remain to be characterized. In an earlier voxel-based lesion-symptom mapping analysis of data from aphasic patients (Dronkers et al., 2004), several brain regions in the left hemisphere were found to be critical for language comprehension: the left posterior middle temporal gyrus, the anterior part of Brodmann's area 22 in the superior temporal gyrus (anterior STG/BA22), the posterior superior temporal sulcus (STS) extending into Brodmann's area 39 (STS/BA39), the orbital part of the inferior frontal gyrus (BA47), and the middle frontal gyrus (BA46). Here, we investigated the white matter pathways associated with these regions using diffusion tensor imaging from healthy subjects. We also used resting-state functional magnetic resonance imaging data to assess the functional connectivity profiles of these regions. Fiber tractography and functional connectivity analyses indicated that the left MTG, anterior STG/BA22, STS/BA39, and BA47 are part of a richly interconnected network that extends to additional frontal, parietal, and temporal regions in the two hemispheres. The inferior occipito-frontal fasciculus, the arcuate fasciculus, and the middle and inferior longitudinal fasciculi, as well as transcallosal projections via the tapetum were found to be the most prominent white matter pathways bridging the regions important for language comprehension. The left MTG showed a particularly extensive structural and functional connectivity pattern which is consistent with the severity of the impairments associated with MTG lesions and which suggests a central role for this region in language comprehension.</AbstractText
|
Protracted neuroborreliosis--an unusual cause of encephalomyelitis. A 58-year-old lady with waxing and waning of non-specific symptoms including fatigue, dizziness, hearing loss and unsteady gait for 15 months, became acutely confused 12 h prior to presentation. On admission to a district hospital she was feverish and unresponsive. Her travel history consisted of visits to Argentina, Chile and the Outer Hebrides. CT of the brain was normal. Lumbar puncture demonstrated a lymphocytic pleocytosis of 500 cells, protein of 1 g/l, a low glucose ratio with negative cytology and viral PCR (including herpes simplex 1 and 2). MRI revealed multiple abnormal areas of high signal on T2 fluid attenuated inversion recovery sequencing within the cerebellum, temporal lobes and periventricular areas. Western blotting of serum and cerebrospinal fluid for Borrelia burgdoferi were both positive. She was treated with cefuroxime and aciclovir and within 24 h she was alert and responsive. She received 4 weeks of cefuroxime in total and made a good recovery.</AbstractText
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38370678
|
34955448
|
39342454
|
Quantifying the seed sensitivity of cancer subclonal reconstruction algorithms.
|
2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
|
Cortical oscillations and event-related brain potentials during the preparation and execution of deceptive behavior.
|
Intra-tumoural heterogeneity complicates cancer prognosis and impairs treatment success. One of the ways subclonal reconstruction (SRC) quantifies intra-tumoural heterogeneity is by estimating the number of subclones present in bulk DNA sequencing data. SRC algorithms are probabilistic and need to be initialized by a random seed. However, the seeds used in bioinformatics algorithms are rarely reported in the literature. Thus, the impact of the initializing seed on SRC solutions has not been studied. To address this gap, we generated a set of ten random seeds to systematically benchmark the seed sensitivity of three probabilistic SRC algorithms: PyClone-VI, DPClust, and PhyloWGS.</AbstractText We characterized the seed sensitivity of three algorithms across fourteen whole-genome sequences of head and neck squamous cell carcinoma and nine SRC pipelines, each composed of a single nucleotide variant caller, a copy number aberration caller and an SRC algorithm. This led to a total of 1470 subclonal reconstructions, including 1260 single-region and 210 multi-region reconstructions. The number of subclones estimated per patient vary across SRC pipelines, but all three SRC algorithms show substantial seed sensitivity: subclone estimates vary across different seeds for the same set of input using the same SRC algorithm. No seed consistently estimated the mode number of subclones across all patients for any SRC algorithm.</AbstractText These findings highlight the variability in quantifying intra-tumoural heterogeneity introduced by the seed sensitivity of probabilistic SRC algorithms. We recommend that authors, reviewers and editors adopt guidelines to both report and randomize seed choices. It may also be valuable to consider seed-sensitivity in the benchmarking of newly developed SRC algorithms. These findings may be of interest in other areas of bioinformatics where seeded probabilistic algorithms are used and suggest consideration of formal seed reporting standards to enhance reproducibility.</AbstractText
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This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.</AbstractText A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered.</AbstractText Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.</AbstractText
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Deception often occurs in response to a preceding cue (e.g., a precarious question) alerting us about the need to subsequently lie. Here, we simulate this process by adapting a previously established paradigm of intentionally false responding, now instructing participants about the need for deception (vs. truthful responses) by means of a simple cue occurring before each response-relevant target. We analyzed event-related brain potentials (ERPs) as well as cortical oscillations recorded from the scalp. In an experimental study (N = 44), we show that a cue signaling the need for deception involves increased attentional selection (P2, P3a, P3b). Moreover, in the period following the cue and leading up to the target, ERP and oscillatory signatures of anticipation and preparation (Contingent Negative Variation, alpha suppression) were found to be increased during trials requiring a deceptive as compared to a truthful response. Additionally, we replicated earlier findings that target processing involves enhanced motivated attention toward words requiring a deceptive response (LPC). Moreover, a signature of integration effort and semantic inhibition (N400) was observed to be larger for words to which responses have to be intentionally false as compared to those to which responses must be truthful. Our findings support the view of the involvement of a series of basic cognitive processes (especially attention and cognitive control) when responses are deliberately wrong instead of right. Moreover, preceding cues signaling the subsequent need for lying already elicit attentional and preparatory mechanisms facilitating the cognitive operations necessary for later successful lying.</AbstractText
|
Quantifying the seed sensitivity of cancer subclonal reconstruction algorithms. Intra-tumoural heterogeneity complicates cancer prognosis and impairs treatment success. One of the ways subclonal reconstruction (SRC) quantifies intra-tumoural heterogeneity is by estimating the number of subclones present in bulk DNA sequencing data. SRC algorithms are probabilistic and need to be initialized by a random seed. However, the seeds used in bioinformatics algorithms are rarely reported in the literature. Thus, the impact of the initializing seed on SRC solutions has not been studied. To address this gap, we generated a set of ten random seeds to systematically benchmark the seed sensitivity of three probabilistic SRC algorithms: PyClone-VI, DPClust, and PhyloWGS.</AbstractText We characterized the seed sensitivity of three algorithms across fourteen whole-genome sequences of head and neck squamous cell carcinoma and nine SRC pipelines, each composed of a single nucleotide variant caller, a copy number aberration caller and an SRC algorithm. This led to a total of 1470 subclonal reconstructions, including 1260 single-region and 210 multi-region reconstructions. The number of subclones estimated per patient vary across SRC pipelines, but all three SRC algorithms show substantial seed sensitivity: subclone estimates vary across different seeds for the same set of input using the same SRC algorithm. No seed consistently estimated the mode number of subclones across all patients for any SRC algorithm.</AbstractText These findings highlight the variability in quantifying intra-tumoural heterogeneity introduced by the seed sensitivity of probabilistic SRC algorithms. We recommend that authors, reviewers and editors adopt guidelines to both report and randomize seed choices. It may also be valuable to consider seed-sensitivity in the benchmarking of newly developed SRC algorithms. These findings may be of interest in other areas of bioinformatics where seeded probabilistic algorithms are used and suggest consideration of formal seed reporting standards to enhance reproducibility.</AbstractText
|
2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.</AbstractText A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered.</AbstractText Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.</AbstractText
|
Cortical oscillations and event-related brain potentials during the preparation and execution of deceptive behavior. Deception often occurs in response to a preceding cue (e.g., a precarious question) alerting us about the need to subsequently lie. Here, we simulate this process by adapting a previously established paradigm of intentionally false responding, now instructing participants about the need for deception (vs. truthful responses) by means of a simple cue occurring before each response-relevant target. We analyzed event-related brain potentials (ERPs) as well as cortical oscillations recorded from the scalp. In an experimental study (N = 44), we show that a cue signaling the need for deception involves increased attentional selection (P2, P3a, P3b). Moreover, in the period following the cue and leading up to the target, ERP and oscillatory signatures of anticipation and preparation (Contingent Negative Variation, alpha suppression) were found to be increased during trials requiring a deceptive as compared to a truthful response. Additionally, we replicated earlier findings that target processing involves enhanced motivated attention toward words requiring a deceptive response (LPC). Moreover, a signature of integration effort and semantic inhibition (N400) was observed to be larger for words to which responses have to be intentionally false as compared to those to which responses must be truthful. Our findings support the view of the involvement of a series of basic cognitive processes (especially attention and cognitive control) when responses are deliberately wrong instead of right. Moreover, preceding cues signaling the subsequent need for lying already elicit attentional and preparatory mechanisms facilitating the cognitive operations necessary for later successful lying.</AbstractText
|
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