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34932019
A new imaging entity consistent with partial ectopic posterior pituitary gland: report of six cases.
Diffusion-weighted echo-planar imaging of the head and neck using 3-T MRI: Investigation into the usefulness of liquid perfluorocarbon pads and choice of optimal fat suppression method.
The uncertainty of thyroid dose estimate in chest CT.
Abnormal posterior pituitary development including ectopic location has been associated with endocrine manifestations of anterior pituitary dysfunction.</AbstractText We describe an unreported clinical and radiologic entity we call partial ectopic posterior pituitary for which associated endocrine consequences are not known.</AbstractText We selected pediatric head MRI examinations from 2005 to 2017 based on the finding of a double midline sellar and suprasellar bright spot on T1-weighted sequence. Medical history, physical examination, pituitary hormonal profile and bone age evaluation were extracted from the medical record of the selected patients. An experienced pediatric neuroradiologist reviewed head MRIs, which were performed on 3-tesla (T) magnet and included at least sagittal T1-weighted imaging centered on the sella turcica obtained with and without fat suppression.</AbstractText In six cases, two midline bright spots were identified on T1-weighted sequences obtained both with and without fat suppression. While one spot was located at the expected site of the neurohypophysis in the posterior sella, the second one was in the region of the median eminence, suggesting partial ectopic posterior pituitary gland. Growth hormone deficiency, either isolated (n=1) or combined with thyroid stimulating hormone deficiency (n=1) was found. None of the children had clinical signs of posterior pituitary dysfunction.</AbstractText We describe an unreported imaging entity suggesting partial ectopic posterior pituitary gland in six children. Anterior pituitary hormone deficiencies might be detected in those children and long-term follow-up could provide additional information on the development of other pituitary hormone deficiencies.</AbstractText
To investigate whether image quality can be improved using liquid perfluorocarbon pads (Sat Pad) and clarify the optimal fat-suppression method among chemical shift selective (CHESS), water excitation (WEX), and short TI inversion recovery (STIR) methods in diffusion-weighted imaging (DWI) of the head and neck using 3-T magnetic resonance imaging. Correlations between results of visual inspection and quantitative analysis were also examined.</AbstractText This study was approved by our Institutional Review Board and informed consent was waived. DWI was performed on 25 subjects with/without Sat Pad and using three fat-suppression methods (6 patterns). Image quality was evaluated visually (4-point scales and lesion-depiction capability) and by quantitative analysis (signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)). Two-way repeated-measures analysis of variance (ANOVA) was used to detect significant differences in scores of visual evaluation, SNR, and CNR.</AbstractText Mean visual evaluation scores were significantly higher with Sat Pad using STIR than without Sat Pad for all fat-suppression methods (P&lt;0.05). DWI with Sat Pad using STIR tended to be useful for depicting lesions. DWI using STIR showed reduced W-SNR (W: whole area of depicted structure) and CNR (between semispinalis capitis muscle and subcutaneous fat) due to fewer artifacts and uniform fat suppression.</AbstractText Combining Sat Pad with STIR provides good image quality for visual inspections. When numerous artifacts are present and fat suppression is insufficient, higher SNR and CNR do not always provide good diagnostic image quality.</AbstractText
Dose to the thyroid from helical chest CT can vary significantly due to the random tube start point, pitch factor, thyroid position relative to the isocenter, and beam width. We used optically stimulated luminescence dosimeters (OSLDs) and an adult anthropomorphic phantom to investigate the uncertainty of thyroid dose estimate. Maximum gap or overlap in the helical beam was estimated using the above factors. Using the maximum gap/overlap over the thyroid, different possible scenarios were simulated and the degree of missed thyroid tissue by the primary beam was estimated. Results showed a variation of &gt;30% in the average thyroid dose, and &gt;50% if a single dosimeter was used to determine dose to the thyroid. Furthermore, measured doses were compared to those calculated by Monte Carlo simulation software, which automatically matches the anatomy of the localizer radiograph with the stylized computational phantom used for dose calculation. The difference was significant: the dose given by the Monte Carlo software was &#x223c;50% lower than the average dose measured with the phantom in all three chest protocols. In addition, the software does not take the effect of the random tube start angle into account.</AbstractText
A new imaging entity consistent with partial ectopic posterior pituitary gland: report of six cases. Abnormal posterior pituitary development including ectopic location has been associated with endocrine manifestations of anterior pituitary dysfunction.</AbstractText We describe an unreported clinical and radiologic entity we call partial ectopic posterior pituitary for which associated endocrine consequences are not known.</AbstractText We selected pediatric head MRI examinations from 2005 to 2017 based on the finding of a double midline sellar and suprasellar bright spot on T1-weighted sequence. Medical history, physical examination, pituitary hormonal profile and bone age evaluation were extracted from the medical record of the selected patients. An experienced pediatric neuroradiologist reviewed head MRIs, which were performed on 3-tesla (T) magnet and included at least sagittal T1-weighted imaging centered on the sella turcica obtained with and without fat suppression.</AbstractText In six cases, two midline bright spots were identified on T1-weighted sequences obtained both with and without fat suppression. While one spot was located at the expected site of the neurohypophysis in the posterior sella, the second one was in the region of the median eminence, suggesting partial ectopic posterior pituitary gland. Growth hormone deficiency, either isolated (n=1) or combined with thyroid stimulating hormone deficiency (n=1) was found. None of the children had clinical signs of posterior pituitary dysfunction.</AbstractText We describe an unreported imaging entity suggesting partial ectopic posterior pituitary gland in six children. Anterior pituitary hormone deficiencies might be detected in those children and long-term follow-up could provide additional information on the development of other pituitary hormone deficiencies.</AbstractText
Diffusion-weighted echo-planar imaging of the head and neck using 3-T MRI: Investigation into the usefulness of liquid perfluorocarbon pads and choice of optimal fat suppression method. To investigate whether image quality can be improved using liquid perfluorocarbon pads (Sat Pad) and clarify the optimal fat-suppression method among chemical shift selective (CHESS), water excitation (WEX), and short TI inversion recovery (STIR) methods in diffusion-weighted imaging (DWI) of the head and neck using 3-T magnetic resonance imaging. Correlations between results of visual inspection and quantitative analysis were also examined.</AbstractText This study was approved by our Institutional Review Board and informed consent was waived. DWI was performed on 25 subjects with/without Sat Pad and using three fat-suppression methods (6 patterns). Image quality was evaluated visually (4-point scales and lesion-depiction capability) and by quantitative analysis (signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)). Two-way repeated-measures analysis of variance (ANOVA) was used to detect significant differences in scores of visual evaluation, SNR, and CNR.</AbstractText Mean visual evaluation scores were significantly higher with Sat Pad using STIR than without Sat Pad for all fat-suppression methods (P&lt;0.05). DWI with Sat Pad using STIR tended to be useful for depicting lesions. DWI using STIR showed reduced W-SNR (W: whole area of depicted structure) and CNR (between semispinalis capitis muscle and subcutaneous fat) due to fewer artifacts and uniform fat suppression.</AbstractText Combining Sat Pad with STIR provides good image quality for visual inspections. When numerous artifacts are present and fat suppression is insufficient, higher SNR and CNR do not always provide good diagnostic image quality.</AbstractText
The uncertainty of thyroid dose estimate in chest CT. Dose to the thyroid from helical chest CT can vary significantly due to the random tube start point, pitch factor, thyroid position relative to the isocenter, and beam width. We used optically stimulated luminescence dosimeters (OSLDs) and an adult anthropomorphic phantom to investigate the uncertainty of thyroid dose estimate. Maximum gap or overlap in the helical beam was estimated using the above factors. Using the maximum gap/overlap over the thyroid, different possible scenarios were simulated and the degree of missed thyroid tissue by the primary beam was estimated. Results showed a variation of &gt;30% in the average thyroid dose, and &gt;50% if a single dosimeter was used to determine dose to the thyroid. Furthermore, measured doses were compared to those calculated by Monte Carlo simulation software, which automatically matches the anatomy of the localizer radiograph with the stylized computational phantom used for dose calculation. The difference was significant: the dose given by the Monte Carlo software was &#x223c;50% lower than the average dose measured with the phantom in all three chest protocols. In addition, the software does not take the effect of the random tube start angle into account.</AbstractText
40284406
30837838
40388178
Targeting TDP-43 Proteinopathy in hiPSC-Derived Mutated hNPCs with Mitoxantrone Drugs and miRNAs.
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis.
Efficacy and Safety of Eptinezumab in Episodic Cluster Headache: A Randomized Clinical Trial.
<b
TAR DNA binding protein 43 (TDP-43) is a versatile RNA/DNA binding protein involved in RNA-related metabolism. Hyper-phosphorylated and ubiquitinated TDP-43 deposits act as inclusion bodies in the brain and spinal cord of patients with the motor neuron diseases: amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). While the majority of ALS cases (90-95%) are sporadic (sALS), among familial ALS cases 5-10% involve the inheritance of mutations in the <i
Cluster headache, characterized by bouts of excruciating pain attacks, detrimentally affects health and quality of life. Eptinezumab is an anticalcitonin gene-related peptide monoclonal antibody approved for migraine prevention.</AbstractText To evaluate the efficacy and safety of eptinezumab in the preventive treatment of episodic cluster headache.</AbstractText This double-blind, placebo-controlled, randomized (1:1) clinical trial (Eptinezumab in Participants With Episodic Cluster Headache [ALLEVIATE]) was conducted between December 2020 and October 2023. Results are from the initial 4-week randomized phase. The study took place at 64 sites across Europe, the US, and Japan. Included were adults (aged 18-75 years) with a history of episodic cluster headache for 1 or more years (with bouts lasting &#x2265;6 weeks when untreated) and previous acute and preventive medication use.</AbstractText Eptinezumab, 400 mg, or placebo (intravenous infusion).</AbstractText The primary end point was the change from baseline in the number of weekly attacks in weeks 1&#x2009;to&#x2009;2. Safety was assessed using treatment-emergent adverse events.</AbstractText Of 628 total participants screened, 320 entered the second screening period, and 231 met eligibility criteria. Of the 231 participants randomized (eptinezumab, n&#x2009;=&#x2009;118; placebo, n&#x2009;=&#x2009;113), 215 (93%) completed the placebo-controlled period. The participant mean (SD) age was 44 (11) years, and 178 of 229 were male (78%). At baseline, the mean (SD) weekly attacks were 15.2 (8.1) in the eptinezumab group and 15.7 (8.3) in the placebo group. There was no statistically significant difference between eptinezumab and placebo in the change from baseline in the number of weekly attacks over weeks 1&#x2009;to&#x2009;2 (least-squares mean [SE], -4.0 [0.93] vs -4.6 [0.89]; between-group difference, 0.7; 95% CI, -1.3 to 2.6; P&#x2009;=&#x2009;.50). More eptinezumab-treated participants achieved 50% or greater response vs placebo over week 2 (50.9% [54 of 106] vs 37.3% [41 of 110]; odds ratio [OR], 1.77; 95% CI, 1.03-3.07; P =.04), week 3 (62.5% [65 of 104] vs 43.8% [49 of 112]; OR, 2.26; 95% CI, 1.30-3.97; P =.004), and week 4 (66.7% [68 of 102] vs 50.5% [54 of 107]; OR, 2.14; 95% CI, 1.21-3.83; P =.009). Eptinezumab showed numerically larger improvements than placebo for 75% or greater response, average daily pain scores, and across other patient-reported outcomes. Treatment-emergent adverse events occurred in 25.0% of patients (28 of 112) receiving eptinezumab and 26.5% of patients (31 of 117) receiving placebo.</AbstractText Among adults with episodic cluster headache, eptinezumab did not significantly reduce the number of attacks vs placebo, although it was associated with numerically higher responder rates and improvements in average daily pain and patient-reported outcomes. Eptinezumab was generally well tolerated.</AbstractText ClinicalTrials.gov Identifier: NCT04688775.</AbstractText
Targeting TDP-43 Proteinopathy in hiPSC-Derived Mutated hNPCs with Mitoxantrone Drugs and miRNAs. <b
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis. TAR DNA binding protein 43 (TDP-43) is a versatile RNA/DNA binding protein involved in RNA-related metabolism. Hyper-phosphorylated and ubiquitinated TDP-43 deposits act as inclusion bodies in the brain and spinal cord of patients with the motor neuron diseases: amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). While the majority of ALS cases (90-95%) are sporadic (sALS), among familial ALS cases 5-10% involve the inheritance of mutations in the <i
Efficacy and Safety of Eptinezumab in Episodic Cluster Headache: A Randomized Clinical Trial. Cluster headache, characterized by bouts of excruciating pain attacks, detrimentally affects health and quality of life. Eptinezumab is an anticalcitonin gene-related peptide monoclonal antibody approved for migraine prevention.</AbstractText To evaluate the efficacy and safety of eptinezumab in the preventive treatment of episodic cluster headache.</AbstractText This double-blind, placebo-controlled, randomized (1:1) clinical trial (Eptinezumab in Participants With Episodic Cluster Headache [ALLEVIATE]) was conducted between December 2020 and October 2023. Results are from the initial 4-week randomized phase. The study took place at 64 sites across Europe, the US, and Japan. Included were adults (aged 18-75 years) with a history of episodic cluster headache for 1 or more years (with bouts lasting &#x2265;6 weeks when untreated) and previous acute and preventive medication use.</AbstractText Eptinezumab, 400 mg, or placebo (intravenous infusion).</AbstractText The primary end point was the change from baseline in the number of weekly attacks in weeks 1&#x2009;to&#x2009;2. Safety was assessed using treatment-emergent adverse events.</AbstractText Of 628 total participants screened, 320 entered the second screening period, and 231 met eligibility criteria. Of the 231 participants randomized (eptinezumab, n&#x2009;=&#x2009;118; placebo, n&#x2009;=&#x2009;113), 215 (93%) completed the placebo-controlled period. The participant mean (SD) age was 44 (11) years, and 178 of 229 were male (78%). At baseline, the mean (SD) weekly attacks were 15.2 (8.1) in the eptinezumab group and 15.7 (8.3) in the placebo group. There was no statistically significant difference between eptinezumab and placebo in the change from baseline in the number of weekly attacks over weeks 1&#x2009;to&#x2009;2 (least-squares mean [SE], -4.0 [0.93] vs -4.6 [0.89]; between-group difference, 0.7; 95% CI, -1.3 to 2.6; P&#x2009;=&#x2009;.50). More eptinezumab-treated participants achieved 50% or greater response vs placebo over week 2 (50.9% [54 of 106] vs 37.3% [41 of 110]; odds ratio [OR], 1.77; 95% CI, 1.03-3.07; P =.04), week 3 (62.5% [65 of 104] vs 43.8% [49 of 112]; OR, 2.26; 95% CI, 1.30-3.97; P =.004), and week 4 (66.7% [68 of 102] vs 50.5% [54 of 107]; OR, 2.14; 95% CI, 1.21-3.83; P =.009). Eptinezumab showed numerically larger improvements than placebo for 75% or greater response, average daily pain scores, and across other patient-reported outcomes. Treatment-emergent adverse events occurred in 25.0% of patients (28 of 112) receiving eptinezumab and 26.5% of patients (31 of 117) receiving placebo.</AbstractText Among adults with episodic cluster headache, eptinezumab did not significantly reduce the number of attacks vs placebo, although it was associated with numerically higher responder rates and improvements in average daily pain and patient-reported outcomes. Eptinezumab was generally well tolerated.</AbstractText ClinicalTrials.gov Identifier: NCT04688775.</AbstractText
38737279
20026219
39792524
Aberrant concordance among dynamics of spontaneous brain activity in patients with migraine without aura: A multivariate pattern analysis study.
Comparison of characteristics between region-and voxel-based network analyses in resting-state fMRI data.
Treatment of 50 Acute and Chronic Wounds of Multiple Etiologies: A Case Series Looking at Outcomes and Utility of an Extended-Wear Transforming Powder Dressing.
Alterations in the static and dynamic characteristics of spontaneous brain activity have been extensively studied to investigate functional brain changes in migraine without aura (MwoA). However, alterations in concordance among the dynamics of spontaneous brain activity in MwoA remain largely unknown. This study aimed to determine the possibilities of diagnosis based on the concordance indices.</AbstractText Resting-state functional MRI scans were performed on 32 patients with MwoA and 33 matched healthy controls (HCs) in the first cohort, as well as 36 patients with MwoA and 32&#xa0;HCs in the validation cohort. The dynamic indices including fractional amplitude of low-frequency fluctuation, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity were analyzed. We calculated the concordance of grey matter volume-wise (across voxels) and voxel-wise (across time windows) to quantify the degree of integration among different functional levels represented by these dynamic indices. Subsequently, the voxel-wise concordance alterations were analyzed as features for multi-voxel pattern analysis (MVPA) utilizing the support vector machine.</AbstractText Compared with that of HCs, patients with MwoA had lower whole-grey matter volume-wise concordance, and the mean value of volume-wise concordance was negatively correlated with the frequency of migraine attacks. The MVPA results revealed that the most discriminative brain regions were the right thalamus, right cerebellar Crus II, left insula, left precentral gyrus, right cuneus, and left inferior occipital gyrus.</AbstractText Concordance alterations in the dynamics of spontaneous brain activity in brain regions could be an important feature in the identification of patients with MwoA.</AbstractText
Small-world networks are a class of networks that exhibit efficient long-distance communication and tightly interconnected local neighborhoods. In recent years, functional and structural brain networks have been examined using network theory-based methods, and consistently shown to have small-world properties. Moreover, some voxel-based brain networks exhibited properties of scale-free networks, a class of networks with mega-hubs. However, there are considerable inconsistencies across studies in the methods used and the results observed, particularly between region-based and voxel-based brain networks. We constructed functional brain networks at multiple resolutions using the same resting-state fMRI data, and compared various network metrics, degree distribution, and localization of nodes of interest. It was found that the networks with higher resolutions exhibited the properties of small-world networks more prominently. It was also found that voxel-based networks were more robust against network fragmentation compared to region-based networks. Although the degree distributions of all networks followed an exponentially truncated power law rather than true power law, the higher the resolution, the closer the distribution was to a power law. The voxel-based analyses also enhanced visualization of the results in the 3D brain space. It was found that nodes with high connectivity tended have high efficiency, a co-localization of properties that was not as consistently observed in the region-based networks. Our results demonstrate benefits of constructing the brain network at the finest scale the experiment will permit.</AbstractText
Increasing healthcare costs, limited healthcare resources, an aging population, and lifestyle-related diseases make wound management a growing clinical, social, and economic burden. This case series investigated the use of a novel, biocompatible, polymer-based transforming powder dressing (TPD) that transforms in situ to a shape-retentive wound matrix upon hydration for treating wounds of various etiologies.In this institutional review board-approved single-center retrospective case series, the researchers evaluated various acute and chronic wounds treated with TPD over a period of 2 years. Wounds were followed from the first TPD application up to 1 month after the last TPD application or until the wound healed or the patient was lost to follow-up, whichever came first. The researchers evaluated wound etiology, location, number of applications, change in wound surface area, and comorbidities.The researchers identified 50 patients who were treated with TPD and had at least one follow-up visit during the retrospective study period. The majority of wounds treated with TPD were venous leg ulcers (n = 27) followed by traumatic wounds (n = 11) and skin tears (n = 7). Normal rates of wound healing (&gt;10% per week) were observed in the majority of patients (36/50, 72%) over their duration of treatment. Complete healing during the study period was observed in 43% of venous leg ulcers, 55% of traumatic wounds, 71% of skin tears, and 80% of other wound types. No adverse effects of TPD administration were observed. Treatment with TPD resulted in significant reductions in wound area of nearly all wounds, regardless of etiology.</AbstractText
Aberrant concordance among dynamics of spontaneous brain activity in patients with migraine without aura: A multivariate pattern analysis study. Alterations in the static and dynamic characteristics of spontaneous brain activity have been extensively studied to investigate functional brain changes in migraine without aura (MwoA). However, alterations in concordance among the dynamics of spontaneous brain activity in MwoA remain largely unknown. This study aimed to determine the possibilities of diagnosis based on the concordance indices.</AbstractText Resting-state functional MRI scans were performed on 32 patients with MwoA and 33 matched healthy controls (HCs) in the first cohort, as well as 36 patients with MwoA and 32&#xa0;HCs in the validation cohort. The dynamic indices including fractional amplitude of low-frequency fluctuation, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity were analyzed. We calculated the concordance of grey matter volume-wise (across voxels) and voxel-wise (across time windows) to quantify the degree of integration among different functional levels represented by these dynamic indices. Subsequently, the voxel-wise concordance alterations were analyzed as features for multi-voxel pattern analysis (MVPA) utilizing the support vector machine.</AbstractText Compared with that of HCs, patients with MwoA had lower whole-grey matter volume-wise concordance, and the mean value of volume-wise concordance was negatively correlated with the frequency of migraine attacks. The MVPA results revealed that the most discriminative brain regions were the right thalamus, right cerebellar Crus II, left insula, left precentral gyrus, right cuneus, and left inferior occipital gyrus.</AbstractText Concordance alterations in the dynamics of spontaneous brain activity in brain regions could be an important feature in the identification of patients with MwoA.</AbstractText
Comparison of characteristics between region-and voxel-based network analyses in resting-state fMRI data. Small-world networks are a class of networks that exhibit efficient long-distance communication and tightly interconnected local neighborhoods. In recent years, functional and structural brain networks have been examined using network theory-based methods, and consistently shown to have small-world properties. Moreover, some voxel-based brain networks exhibited properties of scale-free networks, a class of networks with mega-hubs. However, there are considerable inconsistencies across studies in the methods used and the results observed, particularly between region-based and voxel-based brain networks. We constructed functional brain networks at multiple resolutions using the same resting-state fMRI data, and compared various network metrics, degree distribution, and localization of nodes of interest. It was found that the networks with higher resolutions exhibited the properties of small-world networks more prominently. It was also found that voxel-based networks were more robust against network fragmentation compared to region-based networks. Although the degree distributions of all networks followed an exponentially truncated power law rather than true power law, the higher the resolution, the closer the distribution was to a power law. The voxel-based analyses also enhanced visualization of the results in the 3D brain space. It was found that nodes with high connectivity tended have high efficiency, a co-localization of properties that was not as consistently observed in the region-based networks. Our results demonstrate benefits of constructing the brain network at the finest scale the experiment will permit.</AbstractText
Treatment of 50 Acute and Chronic Wounds of Multiple Etiologies: A Case Series Looking at Outcomes and Utility of an Extended-Wear Transforming Powder Dressing. Increasing healthcare costs, limited healthcare resources, an aging population, and lifestyle-related diseases make wound management a growing clinical, social, and economic burden. This case series investigated the use of a novel, biocompatible, polymer-based transforming powder dressing (TPD) that transforms in situ to a shape-retentive wound matrix upon hydration for treating wounds of various etiologies.In this institutional review board-approved single-center retrospective case series, the researchers evaluated various acute and chronic wounds treated with TPD over a period of 2 years. Wounds were followed from the first TPD application up to 1 month after the last TPD application or until the wound healed or the patient was lost to follow-up, whichever came first. The researchers evaluated wound etiology, location, number of applications, change in wound surface area, and comorbidities.The researchers identified 50 patients who were treated with TPD and had at least one follow-up visit during the retrospective study period. The majority of wounds treated with TPD were venous leg ulcers (n = 27) followed by traumatic wounds (n = 11) and skin tears (n = 7). Normal rates of wound healing (&gt;10% per week) were observed in the majority of patients (36/50, 72%) over their duration of treatment. Complete healing during the study period was observed in 43% of venous leg ulcers, 55% of traumatic wounds, 71% of skin tears, and 80% of other wound types. No adverse effects of TPD administration were observed. Treatment with TPD resulted in significant reductions in wound area of nearly all wounds, regardless of etiology.</AbstractText
40239796
27114033
40727540
Maresin-1 alleviates lipid peroxidation-induced ferroptosis after radiation-induced brain injury in mice through the RORα/NRF2 pathway.
Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation.
Electroconvulsive therapy in psychoses of epilepsy - A forgotten alternative.
Ferroptosis plays a critical role in radiation-induced brain injury (RIBI). The role of Maresin-1, which has anti-inflammatory and antiferroptotic properties, in RIBI is still unclear. This study aimed to explore the effects and mechanisms of Maresin-1 on ferroptosis after RIBI in mice. A mouse model of RIBI was constructed through whole-brain irradiation. Short-term neurological functions were evaluated by the modified Garcia score and the beam balance score, and long-term neurological functions were evaluated by the Morris water maze and the rotarod test. Changes in the number of NeuN-positive neurons were detected through immunohistochemistry. The lipid peroxidation level was evaluated by detecting the contents of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), glutathione-reduced (GSH) and glutathione-oxidized (GSSG). The expression of the ferroptosis-related markers glutathione peroxidase 4 (GPX4) and cyclooxygenase 2 (COX2) was assessed via Western blotting. Adeno-associated viruses were used to knock down retinoic acid receptor-related orphan receptor alpha (ROR&#x3b1;) or nuclear factor erythroid 2-related factor 2 (NRF2) to explore the mechanism by which Maresin-1 alleviates ferroptosis. The results showed that Maresin-1 could significantly reduce the levels of MDA, 4-HNE, GSSG, and COX2 after RIBI; increase the contents of GSH and GPX4; reduce neuronal loss in the cortex and hippocampus; and improve the short-term and long-term neurological functions of mice. After the knockdown of ROR&#x3b1; or NRF2, the protective effects of Maresin-1 in mediating anti-lipid peroxidation and anti-ferroptosis were abolished. Our study revealed that Maresin-1 partially alleviates lipid peroxidation-induced ferroptosis after RIBI in mice via the ROR&#x3b1; and NRF2 pathways, improving their neurological functions. This study highlights the protective role of Maresin-1 in RIBI and provides a feasible therapeutic strategy for subsequent in-depth research and clinical intervention.</AbstractText
Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, deleting C1qa gene significantly reduces synaptic pruning by Grn(-/-) microglia and mitigates neurodegeneration, behavioral phenotypes, and premature mortality in Grn(-/-) mice. Together, our results uncover a previously unrecognized role of progranulin in suppressing aberrant microglia activation during aging. These results represent an important conceptual advance that complement activation and microglia-mediated synaptic pruning are major drivers, rather than consequences, of neurodegeneration caused by progranulin deficiency.</AbstractText
This case report discusses a 35-year-old woman with refractory temporal lobe epilepsy and no prior psychiatric history who developed persecutory, erotomanic and megalomaniac ideations, auditory hallucinations, and dysphoric mood. Psychiatric symptoms, including psychosis, are well-documented in patients with epilepsy, posing unique management challenges due to potential interactions between antiepileptic and antipsychotic medications. In this case, the patient demonstrated persistent epileptiform activity on electroencephalogram despite treatment with three antiepileptic drugs. Concurrently, standard antipsychotic treatments were ineffective, suggesting drug-resistant psychosis. Notably, complete remission of psychotic symptoms was achieved with electroconvulsive therapy (ECT), a well-established intervention for various psychiatric conditions but rarely reported in the context of epilepsy-associated psychosis. This case underscores the need for novel therapeutic approaches in managing complex comorbidities like drug-resistant psychosis in epilepsy. It also highlights the potential role of ECT as a safe and effective treatment option in these challenging clinical scenarios.</AbstractText
Maresin-1 alleviates lipid peroxidation-induced ferroptosis after radiation-induced brain injury in mice through the RORα/NRF2 pathway. Ferroptosis plays a critical role in radiation-induced brain injury (RIBI). The role of Maresin-1, which has anti-inflammatory and antiferroptotic properties, in RIBI is still unclear. This study aimed to explore the effects and mechanisms of Maresin-1 on ferroptosis after RIBI in mice. A mouse model of RIBI was constructed through whole-brain irradiation. Short-term neurological functions were evaluated by the modified Garcia score and the beam balance score, and long-term neurological functions were evaluated by the Morris water maze and the rotarod test. Changes in the number of NeuN-positive neurons were detected through immunohistochemistry. The lipid peroxidation level was evaluated by detecting the contents of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), glutathione-reduced (GSH) and glutathione-oxidized (GSSG). The expression of the ferroptosis-related markers glutathione peroxidase 4 (GPX4) and cyclooxygenase 2 (COX2) was assessed via Western blotting. Adeno-associated viruses were used to knock down retinoic acid receptor-related orphan receptor alpha (ROR&#x3b1;) or nuclear factor erythroid 2-related factor 2 (NRF2) to explore the mechanism by which Maresin-1 alleviates ferroptosis. The results showed that Maresin-1 could significantly reduce the levels of MDA, 4-HNE, GSSG, and COX2 after RIBI; increase the contents of GSH and GPX4; reduce neuronal loss in the cortex and hippocampus; and improve the short-term and long-term neurological functions of mice. After the knockdown of ROR&#x3b1; or NRF2, the protective effects of Maresin-1 in mediating anti-lipid peroxidation and anti-ferroptosis were abolished. Our study revealed that Maresin-1 partially alleviates lipid peroxidation-induced ferroptosis after RIBI in mice via the ROR&#x3b1; and NRF2 pathways, improving their neurological functions. This study highlights the protective role of Maresin-1 in RIBI and provides a feasible therapeutic strategy for subsequent in-depth research and clinical intervention.</AbstractText
Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation. Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, deleting C1qa gene significantly reduces synaptic pruning by Grn(-/-) microglia and mitigates neurodegeneration, behavioral phenotypes, and premature mortality in Grn(-/-) mice. Together, our results uncover a previously unrecognized role of progranulin in suppressing aberrant microglia activation during aging. These results represent an important conceptual advance that complement activation and microglia-mediated synaptic pruning are major drivers, rather than consequences, of neurodegeneration caused by progranulin deficiency.</AbstractText
Electroconvulsive therapy in psychoses of epilepsy - A forgotten alternative. This case report discusses a 35-year-old woman with refractory temporal lobe epilepsy and no prior psychiatric history who developed persecutory, erotomanic and megalomaniac ideations, auditory hallucinations, and dysphoric mood. Psychiatric symptoms, including psychosis, are well-documented in patients with epilepsy, posing unique management challenges due to potential interactions between antiepileptic and antipsychotic medications. In this case, the patient demonstrated persistent epileptiform activity on electroencephalogram despite treatment with three antiepileptic drugs. Concurrently, standard antipsychotic treatments were ineffective, suggesting drug-resistant psychosis. Notably, complete remission of psychotic symptoms was achieved with electroconvulsive therapy (ECT), a well-established intervention for various psychiatric conditions but rarely reported in the context of epilepsy-associated psychosis. This case underscores the need for novel therapeutic approaches in managing complex comorbidities like drug-resistant psychosis in epilepsy. It also highlights the potential role of ECT as a safe and effective treatment option in these challenging clinical scenarios.</AbstractText
26610283
16424341
27637664
The right temporoparietal junction in attention and social interaction: A transcranial magnetic stimulation study.
Core knowledge of geometry in an Amazonian indigene group.
Anterior Cruciate Ligament Injuries in Children and Adolescents.
The right temporoparietal junction (rTPJ) has been associated with the ability to reorient attention to unexpected stimuli and the capacity to understand others' mental states (theory of mind [ToM]/false belief). Using activation likelihood estimation meta-analysis we previously unraveled that the anterior rTPJ is involved in both, reorienting of attention and ToM, possibly indicating a more general role in attention shifting. Here, we used neuronavigated transcranial magnetic stimulation to directly probe the role of the rTPJ across attentional reorienting and false belief. Task performance in a visual cueing paradigm and false belief cartoon task was investigated after application of continuous theta burst stimulation (cTBS) over anterior rTPJ (versus vertex, for control). We found that attentional reorienting was significantly impaired after rTPJ cTBS compared with control. For the false belief task, error rates in trials demanding a shift in mental state significantly increased. Of note, a significant positive correlation indicated a close relation between the stimulation effect on attentional reorienting and false belief trials. Our findings extend previous neuroimaging evidence by indicating an essential overarching role of the anterior rTPJ for both cognitive functions, reorienting of attention and ToM. Hum Brain Mapp 37:796-807, 2016. &#xa9; 2015 Wiley Periodicals, Inc.</AbstractText
Does geometry constitute a core set of intuitions present in all humans, regardless of their language or schooling? We used two nonverbal tests to probe the conceptual primitives of geometry in the Munduruk&#xfa;, an isolated Amazonian indigene group. Munduruk&#xfa; children and adults spontaneously made use of basic geometric concepts such as points, lines, parallelism, or right angles to detect intruders in simple pictures, and they used distance, angle, and sense relationships in geometrical maps to locate hidden objects. Our results provide evidence for geometrical intuitions in the absence of schooling, experience with graphic symbols or maps, or a rich language of geometrical terms.</AbstractText
Dramatic increases in youth competitive athletic activity, early sport specialization, and year-round training and competition, along with increased awareness of anterior cruciate ligament (ACL) injuries in children, have led to a commensurate increase in the frequency of ACL tears in the skeletally immature. Recent understanding of the risks of nonoperative treatment and surgical delay have supported a trend toward early operative treatment. This article discusses treatment strategies for ACL injuries in children and adolescents, and offers our preferred treatment strategy for skeletally immature youth athletes with ACL tears.</AbstractText
The right temporoparietal junction in attention and social interaction: A transcranial magnetic stimulation study. The right temporoparietal junction (rTPJ) has been associated with the ability to reorient attention to unexpected stimuli and the capacity to understand others' mental states (theory of mind [ToM]/false belief). Using activation likelihood estimation meta-analysis we previously unraveled that the anterior rTPJ is involved in both, reorienting of attention and ToM, possibly indicating a more general role in attention shifting. Here, we used neuronavigated transcranial magnetic stimulation to directly probe the role of the rTPJ across attentional reorienting and false belief. Task performance in a visual cueing paradigm and false belief cartoon task was investigated after application of continuous theta burst stimulation (cTBS) over anterior rTPJ (versus vertex, for control). We found that attentional reorienting was significantly impaired after rTPJ cTBS compared with control. For the false belief task, error rates in trials demanding a shift in mental state significantly increased. Of note, a significant positive correlation indicated a close relation between the stimulation effect on attentional reorienting and false belief trials. Our findings extend previous neuroimaging evidence by indicating an essential overarching role of the anterior rTPJ for both cognitive functions, reorienting of attention and ToM. Hum Brain Mapp 37:796-807, 2016. &#xa9; 2015 Wiley Periodicals, Inc.</AbstractText
Core knowledge of geometry in an Amazonian indigene group. Does geometry constitute a core set of intuitions present in all humans, regardless of their language or schooling? We used two nonverbal tests to probe the conceptual primitives of geometry in the Munduruk&#xfa;, an isolated Amazonian indigene group. Munduruk&#xfa; children and adults spontaneously made use of basic geometric concepts such as points, lines, parallelism, or right angles to detect intruders in simple pictures, and they used distance, angle, and sense relationships in geometrical maps to locate hidden objects. Our results provide evidence for geometrical intuitions in the absence of schooling, experience with graphic symbols or maps, or a rich language of geometrical terms.</AbstractText
Anterior Cruciate Ligament Injuries in Children and Adolescents. Dramatic increases in youth competitive athletic activity, early sport specialization, and year-round training and competition, along with increased awareness of anterior cruciate ligament (ACL) injuries in children, have led to a commensurate increase in the frequency of ACL tears in the skeletally immature. Recent understanding of the risks of nonoperative treatment and surgical delay have supported a trend toward early operative treatment. This article discusses treatment strategies for ACL injuries in children and adolescents, and offers our preferred treatment strategy for skeletally immature youth athletes with ACL tears.</AbstractText
28152057
23445511
24278419
Potent Effects of Flavonoid Nobiletin on Amplitude, Period, and Phase of the Circadian Clock Rhythm in PER2::LUCIFERASE Mouse Embryonic Fibroblasts.
Effect of experimental diabetic retinopathy on the non-image-forming visual system.
A new method for quantitative immunoblotting of endogenous α-synuclein.
Flavonoids are natural polyphenols that are widely found in plants. The effects of flavonoids on obesity and numerous diseases such as cancer, diabetes, and Alzheimer's have been well studied. However, little is known about the relationships between flavonoids and the circadian clock. In this study, we show that continuous or transient application of flavonoids to the culture medium of embryonic fibroblasts from PER2::LUCIFERASE (PER2::LUC) mice induced various modifications in the circadian clock amplitude, period, and phase. Transient application of some of the tested flavonoids to cultured cells induced a phase delay of the PER2::LUC rhythm at the down slope phase. In addition, continuous application of the polymethoxy flavonoids nobiletin and tangeretin increased the amplitude and lengthened the period of the PER2::LUC rhythm. The nobiletin-induced phase delay was blocked by co-treatment with U0126, an ERK inhibitor. In summary, among the tested flavonoids, polymethoxy flavones increased the amplitude, lengthened the period, and delayed the phase of the PER2::LUC circadian rhythm. Therefore, foods that contain polymethoxy flavones may have beneficial effects on circadian rhythm disorders and jet lag.</AbstractText
Diabetic retinopathy is a leading cause of blindness. Intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin, are involved in non-image-forming visual responses such as photoentrainment of circadian rhythms and pupillary light reflex. Since several reports indicate that retinal ganglion cells are affected by diabetes, we investigated the non-image-forming visual system in an advanced stage of experimental diabetes in rats induced by streptozotocin. After 15 wks of diabetes induction, clear alterations in the visual function were observed and all animals developed mature cataracts. At this time point, concomitantly with a significant decrease in the number of Brn3a(+) retinal ganglion cells, no differences in the number of melanopsin-containing cells, melanopsin levels, and retinal projections to the suprachiasmatic nuclei and the olivary pretectal nucleus were observed. At high light intensity, afferent pupil light reflex appears to be conserved in diabetic animals. After 15 wks of diabetes induction, a significant decrease in light-induced c-Fos expression in the suprachiasmatic nuclei was found. In diabetic animals, the locomotor activity pattern was conserved, although a delay in the time needed for re-entrainment after a phase delay was observed. In diabetic animals, lensectomy reversed the alterations in c-Fos expression and in the locomotor activity rhythm. These results suggest that the neuronal substrate of the non-image-forming visual system remained largely unaffected at advanced stages of diabetes, and that lensectomy, a relatively easy and safe surgery, could partially restore circadian alterations induced by diabetes.</AbstractText
&#x3b2;-Sheet-rich aggregates of &#x3b1;-synuclein (&#x3b1;Syn) are the hallmark neuropathology of Parkinson's disease and related synucleinopathies, whereas the principal native structure of &#x3b1;Syn in healthy cells--unfolded monomer or &#x3b1;-helically folded oligomer--is under debate. Our recent crosslinking analysis of &#x3b1;Syn in intact cells showed that a large portion of endogenous &#x3b1;Syn can be trapped as oligomers, most notably as apparent tetramers. One challenge in such studies is accurately quantifying &#x3b1;Syn Western blot signals among samples, as crosslinked &#x3b1;Syn trends toward increased immunoreactivity. Here, we analyzed this phenomenon in detail and found that treatment with the reducible amine-reactive crosslinker DSP strongly increased &#x3b1;Syn immunoreactivity even after cleavage with the reducing agent &#x3b2;-mercaptoethanol. The effect was observed with all &#x3b1;Syn antibodies tested and in all sample types from human brain homogenates to untransfected neuroblastoma cells, permitting easy detection of endogenous &#x3b1;Syn in the latter, which had long been considered impossible. Coomassie staining of blots before and after several hours of washing revealed complete retention of &#x3b1;Syn after DSP/&#x3b2;-mercaptoethanol treatment, in contrast to a marked loss of &#x3b1;Syn without this treatment. The treatment also enhanced immunodetection of the homologs &#x3b2;- and &#x3b3;-synuclein and of histones, another group of small, lysine-rich proteins. We conclude that by neutralizing positive charges and increasing protein hydrophobicity, amine crosslinker treatment promotes adhesion of &#x3b1;Syn to blotting membranes. These data help explain the recent report of fixing &#x3b1;Syn blots with paraformaldehyde after transfer, which we find produces similar but weaker effects. DSP/&#x3b2;-mercaptoethanol treatment of Western blots should be particularly useful to quantify low-abundance &#x3b1;Syn forms such as extracellular and post-translationally modified &#x3b1;Syn and splice variants.</AbstractText
Potent Effects of Flavonoid Nobiletin on Amplitude, Period, and Phase of the Circadian Clock Rhythm in PER2::LUCIFERASE Mouse Embryonic Fibroblasts. Flavonoids are natural polyphenols that are widely found in plants. The effects of flavonoids on obesity and numerous diseases such as cancer, diabetes, and Alzheimer's have been well studied. However, little is known about the relationships between flavonoids and the circadian clock. In this study, we show that continuous or transient application of flavonoids to the culture medium of embryonic fibroblasts from PER2::LUCIFERASE (PER2::LUC) mice induced various modifications in the circadian clock amplitude, period, and phase. Transient application of some of the tested flavonoids to cultured cells induced a phase delay of the PER2::LUC rhythm at the down slope phase. In addition, continuous application of the polymethoxy flavonoids nobiletin and tangeretin increased the amplitude and lengthened the period of the PER2::LUC rhythm. The nobiletin-induced phase delay was blocked by co-treatment with U0126, an ERK inhibitor. In summary, among the tested flavonoids, polymethoxy flavones increased the amplitude, lengthened the period, and delayed the phase of the PER2::LUC circadian rhythm. Therefore, foods that contain polymethoxy flavones may have beneficial effects on circadian rhythm disorders and jet lag.</AbstractText
Effect of experimental diabetic retinopathy on the non-image-forming visual system. Diabetic retinopathy is a leading cause of blindness. Intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin, are involved in non-image-forming visual responses such as photoentrainment of circadian rhythms and pupillary light reflex. Since several reports indicate that retinal ganglion cells are affected by diabetes, we investigated the non-image-forming visual system in an advanced stage of experimental diabetes in rats induced by streptozotocin. After 15 wks of diabetes induction, clear alterations in the visual function were observed and all animals developed mature cataracts. At this time point, concomitantly with a significant decrease in the number of Brn3a(+) retinal ganglion cells, no differences in the number of melanopsin-containing cells, melanopsin levels, and retinal projections to the suprachiasmatic nuclei and the olivary pretectal nucleus were observed. At high light intensity, afferent pupil light reflex appears to be conserved in diabetic animals. After 15 wks of diabetes induction, a significant decrease in light-induced c-Fos expression in the suprachiasmatic nuclei was found. In diabetic animals, the locomotor activity pattern was conserved, although a delay in the time needed for re-entrainment after a phase delay was observed. In diabetic animals, lensectomy reversed the alterations in c-Fos expression and in the locomotor activity rhythm. These results suggest that the neuronal substrate of the non-image-forming visual system remained largely unaffected at advanced stages of diabetes, and that lensectomy, a relatively easy and safe surgery, could partially restore circadian alterations induced by diabetes.</AbstractText
A new method for quantitative immunoblotting of endogenous α-synuclein. &#x3b2;-Sheet-rich aggregates of &#x3b1;-synuclein (&#x3b1;Syn) are the hallmark neuropathology of Parkinson's disease and related synucleinopathies, whereas the principal native structure of &#x3b1;Syn in healthy cells--unfolded monomer or &#x3b1;-helically folded oligomer--is under debate. Our recent crosslinking analysis of &#x3b1;Syn in intact cells showed that a large portion of endogenous &#x3b1;Syn can be trapped as oligomers, most notably as apparent tetramers. One challenge in such studies is accurately quantifying &#x3b1;Syn Western blot signals among samples, as crosslinked &#x3b1;Syn trends toward increased immunoreactivity. Here, we analyzed this phenomenon in detail and found that treatment with the reducible amine-reactive crosslinker DSP strongly increased &#x3b1;Syn immunoreactivity even after cleavage with the reducing agent &#x3b2;-mercaptoethanol. The effect was observed with all &#x3b1;Syn antibodies tested and in all sample types from human brain homogenates to untransfected neuroblastoma cells, permitting easy detection of endogenous &#x3b1;Syn in the latter, which had long been considered impossible. Coomassie staining of blots before and after several hours of washing revealed complete retention of &#x3b1;Syn after DSP/&#x3b2;-mercaptoethanol treatment, in contrast to a marked loss of &#x3b1;Syn without this treatment. The treatment also enhanced immunodetection of the homologs &#x3b2;- and &#x3b3;-synuclein and of histones, another group of small, lysine-rich proteins. We conclude that by neutralizing positive charges and increasing protein hydrophobicity, amine crosslinker treatment promotes adhesion of &#x3b1;Syn to blotting membranes. These data help explain the recent report of fixing &#x3b1;Syn blots with paraformaldehyde after transfer, which we find produces similar but weaker effects. DSP/&#x3b2;-mercaptoethanol treatment of Western blots should be particularly useful to quantify low-abundance &#x3b1;Syn forms such as extracellular and post-translationally modified &#x3b1;Syn and splice variants.</AbstractText
22531374
23202064
22986007
Xenon-induced inhibition of synchronized bursts in a rat cortical neuronal network.
Three-dimensional multiwaveguide probe array for light delivery to distributed brain circuits.
Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxia.
Xenon (Xe) and other inert gases produce anesthesia via an inhibitory mechanism in neuronal networks. To better understand this mechanism, we measured the electrical signals from cultured rat cortical neuronal networks in a multi-electrode array (MEA) under an applied Xe pressure. We used the MEA to measure the firing of the neuronal network with and without Xe gas pressurized to 0.3MPa. The MEA system monitored neuronal spikes on 16 electrodes (each 50&#xd7;50&#x3bc;m(2)) at a sampling rate of 20kHz. The embryo rat cortical cells were first cultured on MEAs without Xe for approximately 3weeks, at which time they produced synchronized bursts that indicate maturity. Then, with an applied Xe pressure, the synchronized bursts quickly ceased, whereas single spikes continued. The Xe-induced inhibition-recovery of neuronal network firing was reversible: after purging Xe from the system, the synchronized bursts gradually resumed. Thus, Xe did not inhibit single neuron firing, yet reversibly inhibited the synaptic transmission. This finding agrees with the channel-blocker and a modified-hydrate hypothesis of anesthesia, but not the lipid-solubility hypothesis.</AbstractText
To deliver light to the brain for neuroscientific and neuroengineering applications like optogenetics, in which light is used to activate or silence neurons expressing specific photosensitive proteins, optical fibers are commonly used. However, an optical fiber is limited to delivering light to a single target within the 3D structure of the brain. Here, we describe the design and fabrication of an array of thin microwaveguides, which terminates at a three-dimensionally distributed set of points, appropriate for delivering light to targets distributed in a 3D pattern throughout the brain.</AbstractText
Congenital nonprogressive spinocerebellar ataxia is characterized by early gross motor delay, hypotonia, gait ataxia, mild dysarthria and dysmetria. The clinical presentation remains fairly stable and may be associated with cerebellar atrophy. To date, only a few families with autosomal dominant congenital nonprogressive spinocerebellar ataxia have been reported. Linkage to 3pter was demonstrated in one large Australian family and this locus was designated spinocerebellar ataxia type 29. The objective of this study is to describe an unreported Canadian family with autosomal dominant congenital nonprogressive spinocerebellar ataxia and to identify the underlying genetic causes in this family and the original Australian family.</AbstractText Exome sequencing was performed for the Australian family, resulting in the identification of a heterozygous mutation in the ITPR1 gene. For the Canadian family, genotyping with microsatellite markers and Sanger sequencing of ITPR1 gene were performed; a heterozygous missense mutation in ITPR1 was identified.</AbstractText ITPR1 encodes inositol 1,4,5-trisphosphate receptor, type 1, a ligand-gated ion channel that mediates calcium release from the endoplasmic reticulum. Deletions of ITPR1 are known to cause spinocerebellar ataxia type 15, a distinct and very slowly progressive form of cerebellar ataxia with onset in adulthood. Our study demonstrates for the first time that, in addition to spinocerebellar ataxia type 15, alteration of ITPR1 function can cause a distinct congenital nonprogressive ataxia; highlighting important clinical heterogeneity associated with the ITPR1 gene and a significant role of the ITPR1-related pathway in the development and maintenance of the normal functions of the cerebellum.</AbstractText
Xenon-induced inhibition of synchronized bursts in a rat cortical neuronal network. Xenon (Xe) and other inert gases produce anesthesia via an inhibitory mechanism in neuronal networks. To better understand this mechanism, we measured the electrical signals from cultured rat cortical neuronal networks in a multi-electrode array (MEA) under an applied Xe pressure. We used the MEA to measure the firing of the neuronal network with and without Xe gas pressurized to 0.3MPa. The MEA system monitored neuronal spikes on 16 electrodes (each 50&#xd7;50&#x3bc;m(2)) at a sampling rate of 20kHz. The embryo rat cortical cells were first cultured on MEAs without Xe for approximately 3weeks, at which time they produced synchronized bursts that indicate maturity. Then, with an applied Xe pressure, the synchronized bursts quickly ceased, whereas single spikes continued. The Xe-induced inhibition-recovery of neuronal network firing was reversible: after purging Xe from the system, the synchronized bursts gradually resumed. Thus, Xe did not inhibit single neuron firing, yet reversibly inhibited the synaptic transmission. This finding agrees with the channel-blocker and a modified-hydrate hypothesis of anesthesia, but not the lipid-solubility hypothesis.</AbstractText
Three-dimensional multiwaveguide probe array for light delivery to distributed brain circuits. To deliver light to the brain for neuroscientific and neuroengineering applications like optogenetics, in which light is used to activate or silence neurons expressing specific photosensitive proteins, optical fibers are commonly used. However, an optical fiber is limited to delivering light to a single target within the 3D structure of the brain. Here, we describe the design and fabrication of an array of thin microwaveguides, which terminates at a three-dimensionally distributed set of points, appropriate for delivering light to targets distributed in a 3D pattern throughout the brain.</AbstractText
Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxia. Congenital nonprogressive spinocerebellar ataxia is characterized by early gross motor delay, hypotonia, gait ataxia, mild dysarthria and dysmetria. The clinical presentation remains fairly stable and may be associated with cerebellar atrophy. To date, only a few families with autosomal dominant congenital nonprogressive spinocerebellar ataxia have been reported. Linkage to 3pter was demonstrated in one large Australian family and this locus was designated spinocerebellar ataxia type 29. The objective of this study is to describe an unreported Canadian family with autosomal dominant congenital nonprogressive spinocerebellar ataxia and to identify the underlying genetic causes in this family and the original Australian family.</AbstractText Exome sequencing was performed for the Australian family, resulting in the identification of a heterozygous mutation in the ITPR1 gene. For the Canadian family, genotyping with microsatellite markers and Sanger sequencing of ITPR1 gene were performed; a heterozygous missense mutation in ITPR1 was identified.</AbstractText ITPR1 encodes inositol 1,4,5-trisphosphate receptor, type 1, a ligand-gated ion channel that mediates calcium release from the endoplasmic reticulum. Deletions of ITPR1 are known to cause spinocerebellar ataxia type 15, a distinct and very slowly progressive form of cerebellar ataxia with onset in adulthood. Our study demonstrates for the first time that, in addition to spinocerebellar ataxia type 15, alteration of ITPR1 function can cause a distinct congenital nonprogressive ataxia; highlighting important clinical heterogeneity associated with the ITPR1 gene and a significant role of the ITPR1-related pathway in the development and maintenance of the normal functions of the cerebellum.</AbstractText
36943516
12614316
36907115
COVID19-associated new-onset movement disorders: a follow-up study.
Long-term follow-up of 44 patients with brachial monomelic amyotrophy.
Difficulty limits of visual mental imagery.
Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited.</AbstractText Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed.</AbstractText Movement disorders began 12.6&#xa0;days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23&#xa0;days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8&#xa0;years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5&#x2009;&#xb1;&#x2009;3&#xa0;weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence.</AbstractText The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.</AbstractText
Monomelic amyotrophy of a single upper limb termed "brachial monomelic amyotrophy" (BMMA) is a benign lower motor neuron disorder in the young, with male preponderance, insidious onset of atrophy and weakness, electromyographic evidence of neurogenic pattern without conduction block, slow progression for 2-4 years followed by a stationary course. The aim of the study was to determine whether (i) atrophy and weakness in the affected limb progresses beyond 5 years; (ii) the illness spreads to the other limbs; and (iii) the disease progresses to amyotrophic lateral sclerosis.</AbstractText Forty-four patients who had a duration of illness of 5 years or more at the last follow-up examination were included in the study. Assessment of symptom profile, neurologic deficit and disability was performed at variable intervals during the follow-up period.</AbstractText Progression of the disease was seen in 37 (84.1%) patients, up to 5 years in 35 (79.5%), 6 years in one and 8 years in another patient. In seven patients (15.9%) the atrophy was accidentally noticed and no further change in the neurologic deficit was observed thereafter. Subsequent to attaining a stationary course, none of the 44 subjects developed fresh symptoms or signs during a mean follow-up period of 9.7 years (range 2.5-23). The mean duration of illness at last follow-up was 12.8 years (range 5-26.5) and in 22 (50%) subjects the disease duration was more than 10 years. Seven patients (15.9%) at presentation had minimal involvement of contralateral upper limb with gross asymmetry and later one more patient developed similar features. Thus, in only a small proportion (18.2%) of patients the neurologic deficit had extended beyond the confines of one upper limb. None of the patients developed involvement of cranial nerves, lower limbs or pyramidal signs.</AbstractText Progression of the neurologic deficit in the affected limb was seen up to 5 years in the majority followed by a stationary phase with no evidence of fresh neurologic deficit during the follow-up period. Spread to the contralateral upper limb with minimal neurologic deficit was seen in less than a fifth of the patients, but involvement of lower limbs was not observed. BMMA did not evolve to amyotrophic lateral sclerosis. These observations underscore the benign and self limiting course of BMMA.</AbstractText
While past work has focused on the representational format of mental imagery, and the similarities of its operation and neural substrate to online perception, surprisingly little has tested the boundaries of the level of detail that mental imagery can generate. To answer this question, we take inspiration from the visual short-term memory literature, a related field which has found that memory capacity is affected by the number of items, whether they are unique, and whether and how they move. We test these factors of set size, color heterogeneity, and transformation in mental imagery through both subjective (Exp 1; Exp 2) and objective (Exp 2) measures - difficulty ratings and a change detection task, respectively - to determine the capacity limits of our mental imagery, and find that limits on mental imagery are similar to those for visual short-term memory. In Experiment 1, participants rated the difficulty of imagining 1-4 colored items as subjectively more difficult when there were more items, when the items had unique colors instead of an identical color, and when they scaled or rotated instead of merely linearly translating. Experiment 2 isolated these subjective difficulty ratings of rotation for uniquely colored items, and added a rotation distance manipulation (10&#xb0; to 110&#xb0;), again finding higher subjective difficulty for more items, and for when those items rotated farther; the objective measure showed a decrease in performance for more items, but not for rotational degree. Congruities between the subjective and objective results suggest similar costs, but some incongruities suggest that subjective reports can be overly optimistic, likely because they are biased by an illusion of detail.</AbstractText
COVID19-associated new-onset movement disorders: a follow-up study. Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited.</AbstractText Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed.</AbstractText Movement disorders began 12.6&#xa0;days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23&#xa0;days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8&#xa0;years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5&#x2009;&#xb1;&#x2009;3&#xa0;weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence.</AbstractText The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.</AbstractText
Long-term follow-up of 44 patients with brachial monomelic amyotrophy. Monomelic amyotrophy of a single upper limb termed "brachial monomelic amyotrophy" (BMMA) is a benign lower motor neuron disorder in the young, with male preponderance, insidious onset of atrophy and weakness, electromyographic evidence of neurogenic pattern without conduction block, slow progression for 2-4 years followed by a stationary course. The aim of the study was to determine whether (i) atrophy and weakness in the affected limb progresses beyond 5 years; (ii) the illness spreads to the other limbs; and (iii) the disease progresses to amyotrophic lateral sclerosis.</AbstractText Forty-four patients who had a duration of illness of 5 years or more at the last follow-up examination were included in the study. Assessment of symptom profile, neurologic deficit and disability was performed at variable intervals during the follow-up period.</AbstractText Progression of the disease was seen in 37 (84.1%) patients, up to 5 years in 35 (79.5%), 6 years in one and 8 years in another patient. In seven patients (15.9%) the atrophy was accidentally noticed and no further change in the neurologic deficit was observed thereafter. Subsequent to attaining a stationary course, none of the 44 subjects developed fresh symptoms or signs during a mean follow-up period of 9.7 years (range 2.5-23). The mean duration of illness at last follow-up was 12.8 years (range 5-26.5) and in 22 (50%) subjects the disease duration was more than 10 years. Seven patients (15.9%) at presentation had minimal involvement of contralateral upper limb with gross asymmetry and later one more patient developed similar features. Thus, in only a small proportion (18.2%) of patients the neurologic deficit had extended beyond the confines of one upper limb. None of the patients developed involvement of cranial nerves, lower limbs or pyramidal signs.</AbstractText Progression of the neurologic deficit in the affected limb was seen up to 5 years in the majority followed by a stationary phase with no evidence of fresh neurologic deficit during the follow-up period. Spread to the contralateral upper limb with minimal neurologic deficit was seen in less than a fifth of the patients, but involvement of lower limbs was not observed. BMMA did not evolve to amyotrophic lateral sclerosis. These observations underscore the benign and self limiting course of BMMA.</AbstractText
Difficulty limits of visual mental imagery. While past work has focused on the representational format of mental imagery, and the similarities of its operation and neural substrate to online perception, surprisingly little has tested the boundaries of the level of detail that mental imagery can generate. To answer this question, we take inspiration from the visual short-term memory literature, a related field which has found that memory capacity is affected by the number of items, whether they are unique, and whether and how they move. We test these factors of set size, color heterogeneity, and transformation in mental imagery through both subjective (Exp 1; Exp 2) and objective (Exp 2) measures - difficulty ratings and a change detection task, respectively - to determine the capacity limits of our mental imagery, and find that limits on mental imagery are similar to those for visual short-term memory. In Experiment 1, participants rated the difficulty of imagining 1-4 colored items as subjectively more difficult when there were more items, when the items had unique colors instead of an identical color, and when they scaled or rotated instead of merely linearly translating. Experiment 2 isolated these subjective difficulty ratings of rotation for uniquely colored items, and added a rotation distance manipulation (10&#xb0; to 110&#xb0;), again finding higher subjective difficulty for more items, and for when those items rotated farther; the objective measure showed a decrease in performance for more items, but not for rotational degree. Congruities between the subjective and objective results suggest similar costs, but some incongruities suggest that subjective reports can be overly optimistic, likely because they are biased by an illusion of detail.</AbstractText
29409999
10478587
30475967
Errors can elicit an error positivity in the absence of an error negativity: Evidence for independent systems of human error monitoring.
On the prognosis of outcome after stroke.
Effect of nut consumption on semen quality and functionality in healthy men consuming a Western-style diet: a randomized controlled trial.
Errors in human behavior elicit a cascade of brain activity related to performance monitoring and error detection. Whereas the early error-related negativity (Ne/ERN) has been assumed to reflect a fast mismatch or prediction error signal in the medial frontal cortex, the later error positivity (Pe) is viewed as a correlate of conscious error processing. A still open question is whether these components represent two independent systems of error monitoring that rely on different types of information to detect an error. Here, we investigated the prediction that the Ne/ERN but not the Pe requires a representation of the correct response to emerge. To this end, we created a condition in which no information about the correct response was available while error detection was still possible. We hypothesized that a Pe, but no Ne/ERN should be obtained in this case. Participants had to classify targets but ignore flankers that were always associated with an incorrect response. Targets but not flankers were masked with varying target-masking intervals. Crucially, on some trials no target at all was presented, thus preventing the representation of a correct response and the emergence of an Ne/ERN. However, because flankers were easily visible and responses to the flankers were always incorrect, detection of these flanker errors was still possible. In line with predictions of a multiple-systems account, we observed a robust Pe in the absence of an Ne/ERN for these errors. Moreover, this Pe relied on the same neural activity as that on trials with a visible target, as revealed by multivariate pattern analysis. These findings demonstrate that the mechanisms reflected by the two components use different types of information to detect errors, providing evidence for independent systems of human error monitoring.</AbstractText
The study was aimed at improving the accuracy of prognosis for recovery of function in patients suffering a first stroke.</AbstractText Two-hundred and forty-eight patients were enrolled. The mean interval since the stroke was 23 days. Patients entered a rehabilitation program lasting 60 days. The predictive value of 12 factors were analysed, namely motor, cognitive and sphincter subitems of Functional Independence Measure at admission (FIM-a), age, sex, education, body mass index (BMI), depression, neglect, aphasia, ideomotor and constructive apraxia. FIM score at discharge was the dependent variable.</AbstractText A multiple regression revealed that only age, cognitive and sphincter subitems of FIM-a, neglect and ideomotor apraxia were significantly associated with outcome. Moreover, these factors accounted for only 72% of the variance in outcome scores. A decision of unfavourable prognosis on the basis of a FIM-a value lower than 40 was incorrect in 2.8% of the patients in this study and in 8.2% of those having a FIM score lower than 40.</AbstractText The use of statistical methods to examine the outcome after stroke is useful for expressing probability on a group basis but is unsuitable for determining the prognosis of individual patients. Such data should not be used for fiscal management. A significant minority of patients presenting with a FIM lower than 40 can regain a useful measure of independence. The errors in prognosis based upon available methods, although small, have unacceptable effects in human terms if they lead to the clinical decisions which deny patients rehabilitation. All of the patients should therefore be admitted for rehabilitation after their first stroke. Severe comorbidity requires special attention.</AbstractText
Human semen quality has declined in industrialized countries. Pollution, smoking, and the consumption of a Western-style diet are all hypothesized as potential causes.</AbstractText We evaluated the effect of chronic consumption of nuts on changes in conventional semen parameters and the potential mechanisms implicated.</AbstractText The FERTINUTS study was a 14-wk randomized, controlled, parallel trial. A total of 119 healthy men, aged 18-35 y, were allocated to 1 of 2 intervention groups: one group was fed the usual Western-style diet enriched with 60 g of a mixture of nuts/d (nut group), and the other was fed the usual Western-style diet avoiding nuts (control group). Semen and blood samples were collected at baseline and at the end of the intervention. Dietary information was recorded throughout the trial. Changes in conventional semen parameters (pH, volume, sperm count and concentration, motility, and morphology) were determined as primary outcomes. The effect of nut consumption on sperm DNA fragmentation (SDF), reactive oxygen species (ROS) production, chromosome anomalies (X, Y, and 18), total DNA methylation, and microRNA expression were measured in sperm samples as potential causes of the changes in the seminogram.</AbstractText Compared with the control group, improvements in total sperm count (P =&#xa0;0.002) and vitality (P =&#xa0;0.003), total motility (P =&#xa0;0.006), progressive motility (P =&#xa0;0.036), and morphology of sperm (P =&#xa0;0.008) were observed in the nut group. Participants in the nut group showed an increase in the consumption of total fat, monounsaturated fatty acids, polyunsaturated fatty acids, magnesium, vitamin E, &#x3b1;-linolenic acid, total omega-3 (n-3) and &#x3c9;-3:&#x3c9;-6 ratio intake during the intervention. Participants in the nut group showed a significant reduction in SDF (P &lt;&#xa0;0.001) and in the expression of hsa-miR-34b-3p (P =&#xa0;0.036). No significant changes in ROS, sperm chromosome anomalies, or DNA methylation were observed between groups.</AbstractText The inclusion of nuts in a Western-style diet significantly improves the total sperm count and the vitality, motility, and morphology of the sperm. These findings could be partly explained by a reduction in the sperm DNA fragmentation. This trial was registered at ISRCTN as ISRCTN12857940.</AbstractText
Errors can elicit an error positivity in the absence of an error negativity: Evidence for independent systems of human error monitoring. Errors in human behavior elicit a cascade of brain activity related to performance monitoring and error detection. Whereas the early error-related negativity (Ne/ERN) has been assumed to reflect a fast mismatch or prediction error signal in the medial frontal cortex, the later error positivity (Pe) is viewed as a correlate of conscious error processing. A still open question is whether these components represent two independent systems of error monitoring that rely on different types of information to detect an error. Here, we investigated the prediction that the Ne/ERN but not the Pe requires a representation of the correct response to emerge. To this end, we created a condition in which no information about the correct response was available while error detection was still possible. We hypothesized that a Pe, but no Ne/ERN should be obtained in this case. Participants had to classify targets but ignore flankers that were always associated with an incorrect response. Targets but not flankers were masked with varying target-masking intervals. Crucially, on some trials no target at all was presented, thus preventing the representation of a correct response and the emergence of an Ne/ERN. However, because flankers were easily visible and responses to the flankers were always incorrect, detection of these flanker errors was still possible. In line with predictions of a multiple-systems account, we observed a robust Pe in the absence of an Ne/ERN for these errors. Moreover, this Pe relied on the same neural activity as that on trials with a visible target, as revealed by multivariate pattern analysis. These findings demonstrate that the mechanisms reflected by the two components use different types of information to detect errors, providing evidence for independent systems of human error monitoring.</AbstractText
On the prognosis of outcome after stroke. The study was aimed at improving the accuracy of prognosis for recovery of function in patients suffering a first stroke.</AbstractText Two-hundred and forty-eight patients were enrolled. The mean interval since the stroke was 23 days. Patients entered a rehabilitation program lasting 60 days. The predictive value of 12 factors were analysed, namely motor, cognitive and sphincter subitems of Functional Independence Measure at admission (FIM-a), age, sex, education, body mass index (BMI), depression, neglect, aphasia, ideomotor and constructive apraxia. FIM score at discharge was the dependent variable.</AbstractText A multiple regression revealed that only age, cognitive and sphincter subitems of FIM-a, neglect and ideomotor apraxia were significantly associated with outcome. Moreover, these factors accounted for only 72% of the variance in outcome scores. A decision of unfavourable prognosis on the basis of a FIM-a value lower than 40 was incorrect in 2.8% of the patients in this study and in 8.2% of those having a FIM score lower than 40.</AbstractText The use of statistical methods to examine the outcome after stroke is useful for expressing probability on a group basis but is unsuitable for determining the prognosis of individual patients. Such data should not be used for fiscal management. A significant minority of patients presenting with a FIM lower than 40 can regain a useful measure of independence. The errors in prognosis based upon available methods, although small, have unacceptable effects in human terms if they lead to the clinical decisions which deny patients rehabilitation. All of the patients should therefore be admitted for rehabilitation after their first stroke. Severe comorbidity requires special attention.</AbstractText
Effect of nut consumption on semen quality and functionality in healthy men consuming a Western-style diet: a randomized controlled trial. Human semen quality has declined in industrialized countries. Pollution, smoking, and the consumption of a Western-style diet are all hypothesized as potential causes.</AbstractText We evaluated the effect of chronic consumption of nuts on changes in conventional semen parameters and the potential mechanisms implicated.</AbstractText The FERTINUTS study was a 14-wk randomized, controlled, parallel trial. A total of 119 healthy men, aged 18-35 y, were allocated to 1 of 2 intervention groups: one group was fed the usual Western-style diet enriched with 60 g of a mixture of nuts/d (nut group), and the other was fed the usual Western-style diet avoiding nuts (control group). Semen and blood samples were collected at baseline and at the end of the intervention. Dietary information was recorded throughout the trial. Changes in conventional semen parameters (pH, volume, sperm count and concentration, motility, and morphology) were determined as primary outcomes. The effect of nut consumption on sperm DNA fragmentation (SDF), reactive oxygen species (ROS) production, chromosome anomalies (X, Y, and 18), total DNA methylation, and microRNA expression were measured in sperm samples as potential causes of the changes in the seminogram.</AbstractText Compared with the control group, improvements in total sperm count (P =&#xa0;0.002) and vitality (P =&#xa0;0.003), total motility (P =&#xa0;0.006), progressive motility (P =&#xa0;0.036), and morphology of sperm (P =&#xa0;0.008) were observed in the nut group. Participants in the nut group showed an increase in the consumption of total fat, monounsaturated fatty acids, polyunsaturated fatty acids, magnesium, vitamin E, &#x3b1;-linolenic acid, total omega-3 (n-3) and &#x3c9;-3:&#x3c9;-6 ratio intake during the intervention. Participants in the nut group showed a significant reduction in SDF (P &lt;&#xa0;0.001) and in the expression of hsa-miR-34b-3p (P =&#xa0;0.036). No significant changes in ROS, sperm chromosome anomalies, or DNA methylation were observed between groups.</AbstractText The inclusion of nuts in a Western-style diet significantly improves the total sperm count and the vitality, motility, and morphology of the sperm. These findings could be partly explained by a reduction in the sperm DNA fragmentation. This trial was registered at ISRCTN as ISRCTN12857940.</AbstractText
40601020
16892186
40602326
Prognostic utility of (18)F-FDG PET/MRI with intravoxel incoherent motion imaging in nasopharyngeal carcinoma.
Amide proton transfer imaging of human brain tumors at 3T.
First reported high-resolution far-infrared spectral study of the CCO-bending mode of ethyl alcohol (CH(3)CH(2)OH), using synchrotron radiation.
Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) enhances tissue diffusion assessment by differentiating true molecular diffusion from microvascular perfusion, surpassing conventional DWI. This prospective study assessed the prognostic utility of <sup We prospectively enrolled 148 patients with primary NPC who underwent pretreatment PET/MRI. Quantitative parameters derived from IVIM-DWI, dynamic contrast-enhanced MRI (DCE-MRI), and <sup IVIM-derived minimal true diffusion coefficient (D<sub Integrated PET/MRI with IVIM imaging enables simultaneous quantification of water molecule diffusion, tumor microvascular perfusion, and glucose metabolism in NPC, yielding complementary imaging biomarkers that demonstrate superior prognostic value compared to conventional TNM staging.</AbstractText ClinicalTrials.gov (NCT03429868), retrospectively registered on February 6, 2018.</AbstractText
Amide proton transfer (APT) imaging is a technique in which the nuclear magnetization of water-exchangeable amide protons of endogenous mobile proteins and peptides in tissue is saturated, resulting in a signal intensity decrease of the free water. In this work, the first human APT data were acquired from 10 patients with brain tumors on a 3T whole-body clinical scanner and compared with T1- (T1w) and T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and diffusion images (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)). The APT-weighted images provided good contrast between tumor and edema. The effect of APT was enhanced by an approximate 4% change in the water signal intensity in tumor regions compared to edema and normal-appearing white matter (NAWM). These preliminary data from patients with brain tumors show that the APT is a unique contrast that can provide complementary information to standard clinical MRI measures.</AbstractText
In this work, the high-resolution (0.0002&#xa0;cm<sup
Prognostic utility of (18)F-FDG PET/MRI with intravoxel incoherent motion imaging in nasopharyngeal carcinoma. Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) enhances tissue diffusion assessment by differentiating true molecular diffusion from microvascular perfusion, surpassing conventional DWI. This prospective study assessed the prognostic utility of <sup We prospectively enrolled 148 patients with primary NPC who underwent pretreatment PET/MRI. Quantitative parameters derived from IVIM-DWI, dynamic contrast-enhanced MRI (DCE-MRI), and <sup IVIM-derived minimal true diffusion coefficient (D<sub Integrated PET/MRI with IVIM imaging enables simultaneous quantification of water molecule diffusion, tumor microvascular perfusion, and glucose metabolism in NPC, yielding complementary imaging biomarkers that demonstrate superior prognostic value compared to conventional TNM staging.</AbstractText ClinicalTrials.gov (NCT03429868), retrospectively registered on February 6, 2018.</AbstractText
Amide proton transfer imaging of human brain tumors at 3T. Amide proton transfer (APT) imaging is a technique in which the nuclear magnetization of water-exchangeable amide protons of endogenous mobile proteins and peptides in tissue is saturated, resulting in a signal intensity decrease of the free water. In this work, the first human APT data were acquired from 10 patients with brain tumors on a 3T whole-body clinical scanner and compared with T1- (T1w) and T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and diffusion images (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)). The APT-weighted images provided good contrast between tumor and edema. The effect of APT was enhanced by an approximate 4% change in the water signal intensity in tumor regions compared to edema and normal-appearing white matter (NAWM). These preliminary data from patients with brain tumors show that the APT is a unique contrast that can provide complementary information to standard clinical MRI measures.</AbstractText
First reported high-resolution far-infrared spectral study of the CCO-bending mode of ethyl alcohol (CH(3)CH(2)OH), using synchrotron radiation. In this work, the high-resolution (0.0002&#xa0;cm<sup
40356622
37541068
40020181
Experience Group Insights of Obese Adults Aged 35-50 with Knee Osteoarthritis.
Predictors of compassion satisfaction among healthcare professionals working in intensive care units: A cross-sectional study.
MYC regulation of the miR-92-Robo1 axis in Slit-mediated commissural axon guidance.
Fifteen patients between 35 and 50 years of age, with a body mass index (BMI) over 35 with knee osteoarthritis participated in small group, facilitator-guided, interactive discussions (experience groups). Using initial inductive coding followed by deductive classification, 2 coders identified themes related to outcomes including difficulty engaging in meaningful work and social isolation in the capability realm, feelings of depression in the comfort realm, and desiring small achievable goals and consistent support in the calm realm. Themes regarding gaps in care included lack of roadmap and inadequate support. The obstacles to health were debilitating pain, despair due to isolation and stigmatization, hopelessness regarding treatment, perceived lack of clinician empathy and distrust, and frustration with the association of knee osteoarthritis with aging. Effective musculoskeletal specialty care can anticipate these patient needs, particularly for circumstances where nonoperative, accommodative health strategies are favored.</AbstractText
To determine the prevalence of compassion satisfaction, related factors, and predictors among healthcare professionals in Thai intensive care units.</AbstractText A cross-sectional study was conducted in 12 intensive care units at a university hospital in Thailand from August to November 2022. All nurses and doctors were invited to complete an anonymous online survey which included: the Professional Quality of Life Scale version 5, Connor-Davidson Resilience Scale, Passion Scale, Flourishing Scale, and Acceptance and Action Questionnaire. Descriptive statistics, Pearson's correlation coefficients, and hierarchical multiple regressions were used for data analysis in SPSS 28.0.</AbstractText A total of 178 nurses and doctors participated (92.13% nurses, 89.89% female, mean 32.10&#xa0;years). Average compassion satisfaction (assessed using the Professional Quality of Life Scale) was moderate, with a mean score of 37.94 (SD&#xa0;=&#xa0;5.58). The final regression model predicting compassion satisfaction was significant and explained 65% of the variance in compassion satisfaction, F (11, 154)&#xa0;=&#xa0;26.00, p&#xa0;&lt;&#xa0;0.001. Four out of 11 predictor variables made unique statistically significant contributions to the final model: resilience (&#x3b2;&#xa0;=&#xa0;0.48, p&#xa0;&lt;&#xa0;0.001), harmonious passion (&#x3b2;&#xa0;=&#xa0;0.24, p&#xa0;&lt;&#xa0;0.001), being a nurse (not a doctor; &#x3b2;&#xa0;=&#xa0;0.17, p&#xa0;&lt;&#xa0;0.05), and holding a postgraduate qualification (&#x3b2;&#xa0;=&#xa0;0.10, p&#xa0;&lt;&#xa0;0.05).</AbstractText Most healthcare professionals in critical care units have a moderate level of compassion satisfaction, which is correlated with resilience, flourishing, and harmonious passion. Resilience and harmonious passion predict compassion satisfaction. These factors are modifiable through intervention.</AbstractText Assessment of staff psychological well-being can identify those at risk for stress and impaired professional quality of life. Resilience and harmonious passion predict compassion satisfaction and can be modified through psychological interventions to promote psychological well-being and professional quality of life in healthcare workers in intensive care units.</AbstractText
In the developing spinal cord, translational repression of Robo1 expression by microRNA-92 (miR-92) in precrossing commissural axons (CAs) inhibits Slit/Robo1-mediated repulsion facilitating commissural axon projection and midline crossing; however, the regulatory mechanisms governing miR-92 expression in the developing commissural neurons are currently lacking. Here, we propose that the transcription factor MYC regulates miR-92 expression in the developing spinal cord (of either sex) to control Robo1 levels in precrossing CAs, modulating Slit/Robo1-mediated repulsion and midline crossing. MYC, miR-92, and Robo1 are differentially expressed in the developing chicken spinal cord. MYC binds to the promoter region upstream of the gga-miR-92 gene <i
Experience Group Insights of Obese Adults Aged 35-50 with Knee Osteoarthritis. Fifteen patients between 35 and 50 years of age, with a body mass index (BMI) over 35 with knee osteoarthritis participated in small group, facilitator-guided, interactive discussions (experience groups). Using initial inductive coding followed by deductive classification, 2 coders identified themes related to outcomes including difficulty engaging in meaningful work and social isolation in the capability realm, feelings of depression in the comfort realm, and desiring small achievable goals and consistent support in the calm realm. Themes regarding gaps in care included lack of roadmap and inadequate support. The obstacles to health were debilitating pain, despair due to isolation and stigmatization, hopelessness regarding treatment, perceived lack of clinician empathy and distrust, and frustration with the association of knee osteoarthritis with aging. Effective musculoskeletal specialty care can anticipate these patient needs, particularly for circumstances where nonoperative, accommodative health strategies are favored.</AbstractText
Predictors of compassion satisfaction among healthcare professionals working in intensive care units: A cross-sectional study. To determine the prevalence of compassion satisfaction, related factors, and predictors among healthcare professionals in Thai intensive care units.</AbstractText A cross-sectional study was conducted in 12 intensive care units at a university hospital in Thailand from August to November 2022. All nurses and doctors were invited to complete an anonymous online survey which included: the Professional Quality of Life Scale version 5, Connor-Davidson Resilience Scale, Passion Scale, Flourishing Scale, and Acceptance and Action Questionnaire. Descriptive statistics, Pearson's correlation coefficients, and hierarchical multiple regressions were used for data analysis in SPSS 28.0.</AbstractText A total of 178 nurses and doctors participated (92.13% nurses, 89.89% female, mean 32.10&#xa0;years). Average compassion satisfaction (assessed using the Professional Quality of Life Scale) was moderate, with a mean score of 37.94 (SD&#xa0;=&#xa0;5.58). The final regression model predicting compassion satisfaction was significant and explained 65% of the variance in compassion satisfaction, F (11, 154)&#xa0;=&#xa0;26.00, p&#xa0;&lt;&#xa0;0.001. Four out of 11 predictor variables made unique statistically significant contributions to the final model: resilience (&#x3b2;&#xa0;=&#xa0;0.48, p&#xa0;&lt;&#xa0;0.001), harmonious passion (&#x3b2;&#xa0;=&#xa0;0.24, p&#xa0;&lt;&#xa0;0.001), being a nurse (not a doctor; &#x3b2;&#xa0;=&#xa0;0.17, p&#xa0;&lt;&#xa0;0.05), and holding a postgraduate qualification (&#x3b2;&#xa0;=&#xa0;0.10, p&#xa0;&lt;&#xa0;0.05).</AbstractText Most healthcare professionals in critical care units have a moderate level of compassion satisfaction, which is correlated with resilience, flourishing, and harmonious passion. Resilience and harmonious passion predict compassion satisfaction. These factors are modifiable through intervention.</AbstractText Assessment of staff psychological well-being can identify those at risk for stress and impaired professional quality of life. Resilience and harmonious passion predict compassion satisfaction and can be modified through psychological interventions to promote psychological well-being and professional quality of life in healthcare workers in intensive care units.</AbstractText
MYC regulation of the miR-92-Robo1 axis in Slit-mediated commissural axon guidance. In the developing spinal cord, translational repression of Robo1 expression by microRNA-92 (miR-92) in precrossing commissural axons (CAs) inhibits Slit/Robo1-mediated repulsion facilitating commissural axon projection and midline crossing; however, the regulatory mechanisms governing miR-92 expression in the developing commissural neurons are currently lacking. Here, we propose that the transcription factor MYC regulates miR-92 expression in the developing spinal cord (of either sex) to control Robo1 levels in precrossing CAs, modulating Slit/Robo1-mediated repulsion and midline crossing. MYC, miR-92, and Robo1 are differentially expressed in the developing chicken spinal cord. MYC binds to the promoter region upstream of the gga-miR-92 gene <i
37822349
33298996
37216541
Multi-feature fusion learning for Alzheimer's disease prediction using EEG signals in resting state.
The variability of functional MRI brain signal increases in Alzheimer's disease at cardiorespiratory frequencies.
Primary cilia TRP channel regulates hippocampal excitability.
Diagnosing Alzheimer's disease (AD) lesions via visual examination of Electroencephalography (EEG) signals poses a considerable challenge. This has prompted the exploration of deep learning techniques, such as Convolutional Neural Networks (CNNs) and Visual Transformers (ViTs), for AD prediction. However, the classification performance of CNN-based methods has often been deemed inadequate. This is primarily attributed to CNNs struggling with extracting meaningful lesion signals from the complex and noisy EEG data.</AbstractText In contrast, ViTs have demonstrated proficiency in capturing global signal patterns. In light of these observations, we propose a novel approach to enhance AD risk assessment. Our proposition involves a hybrid architecture, merging the strengths of CNNs and ViTs to compensate for their respective feature extraction limitations. Our proposed Dual-Branch Feature Fusion Network (DBN) leverages both CNN and ViT components to acquire texture features and global semantic information from EEG signals. These elements are pivotal in capturing dynamic electrical signal changes in the cerebral cortex. Additionally, we introduce Spatial Attention (SA) and Channel Attention (CA) blocks within the network architecture. These attention mechanisms bolster the model's capacity to discern abnormal EEG signal patterns from the amalgamated features. To make well-informed predictions, we employ a two-factor decision-making mechanism. Specifically, we conduct correlation analysis on predicted EEG signals from the same subject to establish consistency.</AbstractText This is then combined with results from the Clinical Neuropsychological Scale (MMSE) assessment to comprehensively evaluate the subject's susceptibility to AD. Our experimental validation on the publicly available OpenNeuro database underscores the efficacy of our approach. Notably, our proposed method attains an impressive 80.23% classification accuracy in distinguishing between AD, Frontotemporal dementia (FTD), and Normal Control (NC) subjects.</AbstractText This outcome outperforms prevailing state-of-the-art methodologies in EEG-based AD prediction. Furthermore, our methodology enables the visualization of salient regions within pathological images, providing invaluable insights for interpreting and analyzing AD predictions.</AbstractText
Biomarkers sensitive to prodromal or early pathophysiological changes in Alzheimer's disease (AD) symptoms could improve disease detection and enable timely interventions. Changes in brain hemodynamics may be associated with the main clinical AD symptoms. To test this possibility, we measured the variability of blood oxygen level-dependent (BOLD) signal in individuals from three independent datasets (totaling 80 AD patients and 90 controls). We detected a replicable increase in brain BOLD signal variability in the AD populations, which constituted a robust biomarker for clearly differentiating AD cases from controls. Fast BOLD scans showed that the elevated BOLD signal variability in AD arises mainly from cardiovascular brain pulsations. Manifesting in abnormal cerebral perfusion and cerebrospinal fluid convection, present observation presents a mechanism explaining earlier observations of impaired glymphatic clearance associated with AD in humans.</AbstractText
Polycystins (PKD2, PKD2L1, and PKD2L2) are members of the transient receptor potential family, which form ciliary ion channels. Most notably, PKD2 dysregulation in the kidney nephron cilia is associated with polycystic kidney disease, but the function of PKD2L1 in neurons is undefined. In this report, we develop animal models to track the expression and subcellular localization of PKD2L1 in the brain. We discover that PKD2L1 localizes and functions as a Ca<sup
Multi-feature fusion learning for Alzheimer's disease prediction using EEG signals in resting state. Diagnosing Alzheimer's disease (AD) lesions via visual examination of Electroencephalography (EEG) signals poses a considerable challenge. This has prompted the exploration of deep learning techniques, such as Convolutional Neural Networks (CNNs) and Visual Transformers (ViTs), for AD prediction. However, the classification performance of CNN-based methods has often been deemed inadequate. This is primarily attributed to CNNs struggling with extracting meaningful lesion signals from the complex and noisy EEG data.</AbstractText In contrast, ViTs have demonstrated proficiency in capturing global signal patterns. In light of these observations, we propose a novel approach to enhance AD risk assessment. Our proposition involves a hybrid architecture, merging the strengths of CNNs and ViTs to compensate for their respective feature extraction limitations. Our proposed Dual-Branch Feature Fusion Network (DBN) leverages both CNN and ViT components to acquire texture features and global semantic information from EEG signals. These elements are pivotal in capturing dynamic electrical signal changes in the cerebral cortex. Additionally, we introduce Spatial Attention (SA) and Channel Attention (CA) blocks within the network architecture. These attention mechanisms bolster the model's capacity to discern abnormal EEG signal patterns from the amalgamated features. To make well-informed predictions, we employ a two-factor decision-making mechanism. Specifically, we conduct correlation analysis on predicted EEG signals from the same subject to establish consistency.</AbstractText This is then combined with results from the Clinical Neuropsychological Scale (MMSE) assessment to comprehensively evaluate the subject's susceptibility to AD. Our experimental validation on the publicly available OpenNeuro database underscores the efficacy of our approach. Notably, our proposed method attains an impressive 80.23% classification accuracy in distinguishing between AD, Frontotemporal dementia (FTD), and Normal Control (NC) subjects.</AbstractText This outcome outperforms prevailing state-of-the-art methodologies in EEG-based AD prediction. Furthermore, our methodology enables the visualization of salient regions within pathological images, providing invaluable insights for interpreting and analyzing AD predictions.</AbstractText
The variability of functional MRI brain signal increases in Alzheimer's disease at cardiorespiratory frequencies. Biomarkers sensitive to prodromal or early pathophysiological changes in Alzheimer's disease (AD) symptoms could improve disease detection and enable timely interventions. Changes in brain hemodynamics may be associated with the main clinical AD symptoms. To test this possibility, we measured the variability of blood oxygen level-dependent (BOLD) signal in individuals from three independent datasets (totaling 80 AD patients and 90 controls). We detected a replicable increase in brain BOLD signal variability in the AD populations, which constituted a robust biomarker for clearly differentiating AD cases from controls. Fast BOLD scans showed that the elevated BOLD signal variability in AD arises mainly from cardiovascular brain pulsations. Manifesting in abnormal cerebral perfusion and cerebrospinal fluid convection, present observation presents a mechanism explaining earlier observations of impaired glymphatic clearance associated with AD in humans.</AbstractText
Primary cilia TRP channel regulates hippocampal excitability. Polycystins (PKD2, PKD2L1, and PKD2L2) are members of the transient receptor potential family, which form ciliary ion channels. Most notably, PKD2 dysregulation in the kidney nephron cilia is associated with polycystic kidney disease, but the function of PKD2L1 in neurons is undefined. In this report, we develop animal models to track the expression and subcellular localization of PKD2L1 in the brain. We discover that PKD2L1 localizes and functions as a Ca<sup
40341870
37781982
40437651
Controlled Antenatal Thyroid Screening Study III: Effects of gestational thyroid status on brain microstructure.
The impact of bullying in childhood and adolescence.
Spontaneous Retroperitoneal Hematoma: Clinical Profile and Predictors of Mortality.
Children born to mothers with gestational thyroid dysfunction may have an increased risk of adverse neurodevelopmental outcomes but the effects of maternal thyroid function on brain microstructure are unknown.</AbstractText To establish whether adolescent white matter microstructure is affected by suboptimal gestational thyroid function (SGTF).</AbstractText The Controlled Antenatal Thyroid Screening (CATS) study randomized mothers with SGTF to levothyroxine or no supplementation from 12 weeks' gestation. For the current study, CATS children underwent microstructural magnetic resonance imaging (MRI), including diffusion MRI to explore white matter microstructure and quantitative magnetization transfer (qMT) imaging to investigate myelin.</AbstractText Seventy-five children aged 11-16 years had usable diffusion and/or qMT data (untreated SGTF (n=19), normal GTF (n=21), or treated SGTF (optimally-treated (n=18), over-treated (n=17)).</AbstractText Primary outcome: to examine the effects of SGTF and its treatment on white matter microstructure. Secondary and exploratory outcomes: to investigate the association of (a) maternal TSH and free T4 levels with white matter microstructure, and (b) white matter microstructure with attention deficit hyperactivity disorder (ADHD) symptom scores.</AbstractText Untreated SGTF was associated with higher mean diffusivity (indicating reduced axonal integrity) compared with normal GTF (p=0.007) within the inferior longitudinal fasciculus, a major white matter tract connecting the occipital and temporal lobes and involved in several cognitive functions. Secondary and exploratory outcomes did not survive corrections for multiple comparisons.</AbstractText Untreated SGTF is associated with altered tract-specific microstructural morphology in adolescence, which may be reversible with levothyroxine administration in pregnancy.</AbstractText
Bullying is a common adversity affecting many children and adolescents. It has been shown to negatively impact the psychological well being not only of targets of bullying, but also that of bullying perpetrators and those witnessing bullying. Bullying is linked to depression and poorer mental health and functioning among children and adolescents. Given the high prevalence of bullying among children and adolescents and the negative mental health sequelae of bullying, this is an area of urgent public health concern. This narrative review brings forth recent research findings in this arena, which could help shape public health policies for addressing and preventing bullying.</AbstractText Recent findings demonstrate an association of bullying among children and adolescents with depression, nonsuicidal self-injury, sleep loss, reduced health-related quality of life, poorer rates of graduation from high school and later mental health problems. A recent systematic review also showed an association of peer-victimization among children and adolescents with activation of amygdala, left parahippocampal gyrus and fusiform gyrus, and alterations in other brain areas.</AbstractText Evidence indicates that bullying in childhood and adolescence is associated with higher odds of developing mental health problems; therefore, early identification and timely intervention is crucial.</AbstractText
Spontaneous retroperitoneal hematoma (SRPHs) is a serious disorder infrequently reported in the literature. Our aim was to analyze the clinical profile and management of a series of cases and to determine mortality predictors.</AbstractText Retrospective cohort study.</AbstractText We studied the consecutive series of patients with a SRPH at a university hospital from 2008 to 2023. Collected variables included clinical, physiological, and analytical characteristics as well as treatments provided. A modified Acute Physiology and Chronic Health Disease Classification System II (m-APACHE II) and Charlson scores were calculated. The association of these factors with mortality during hospital admission and follow-up were evaluated with logistic and Cox regression, respectively.</AbstractText Eighty-five patients with SRPH (mean age 75&#xa0;years, 62.4% males) were identified. Of these, 56 (65.9%) were admitted for reasons other than SRPH, 67 (78.8%) received anticoagulants, and 53 (62.4%) had active bleeding on a CT scan. Seven patients were treated with palliative care. In the remaining 78 patients, management included transfusion (71 cases, 91%), anticoagulation reversal (25 cases, 32.1%), vasoactive drugs (21 cases, 26.9%), and admission to intermediate or critical care units (40 cases, 51.3%). Angiography was indicated in 34 (43.6%) patients, including embolization in 30 of these cases. Surgical drainage was required in two cases. Nineteen patients (24.5%) died during admission. m-APACHE II score (OR&#xa0;=&#xa0;1.21; 1.08-1.36) was a predictive factor. One- and 5-year survival rates among hospital survivors were 68.4% and 29.2%, respectively. Survival was independently associated with the Charlson Comorbidity Index score (HR&#xa0;=&#xa0;1.36; 1.14-1.63) and polypharmacy (HR&#xa0;=&#xa0;1.13; 1.02-1.24).</AbstractText SRPH is a serious disorder that requires complex therapeutic measures (critical care and angiography) in about half of patients. Several well-known scores are good predictors of mortality and could be useful in clinical decision-making.</AbstractText
Controlled Antenatal Thyroid Screening Study III: Effects of gestational thyroid status on brain microstructure. Children born to mothers with gestational thyroid dysfunction may have an increased risk of adverse neurodevelopmental outcomes but the effects of maternal thyroid function on brain microstructure are unknown.</AbstractText To establish whether adolescent white matter microstructure is affected by suboptimal gestational thyroid function (SGTF).</AbstractText The Controlled Antenatal Thyroid Screening (CATS) study randomized mothers with SGTF to levothyroxine or no supplementation from 12 weeks' gestation. For the current study, CATS children underwent microstructural magnetic resonance imaging (MRI), including diffusion MRI to explore white matter microstructure and quantitative magnetization transfer (qMT) imaging to investigate myelin.</AbstractText Seventy-five children aged 11-16 years had usable diffusion and/or qMT data (untreated SGTF (n=19), normal GTF (n=21), or treated SGTF (optimally-treated (n=18), over-treated (n=17)).</AbstractText Primary outcome: to examine the effects of SGTF and its treatment on white matter microstructure. Secondary and exploratory outcomes: to investigate the association of (a) maternal TSH and free T4 levels with white matter microstructure, and (b) white matter microstructure with attention deficit hyperactivity disorder (ADHD) symptom scores.</AbstractText Untreated SGTF was associated with higher mean diffusivity (indicating reduced axonal integrity) compared with normal GTF (p=0.007) within the inferior longitudinal fasciculus, a major white matter tract connecting the occipital and temporal lobes and involved in several cognitive functions. Secondary and exploratory outcomes did not survive corrections for multiple comparisons.</AbstractText Untreated SGTF is associated with altered tract-specific microstructural morphology in adolescence, which may be reversible with levothyroxine administration in pregnancy.</AbstractText
The impact of bullying in childhood and adolescence. Bullying is a common adversity affecting many children and adolescents. It has been shown to negatively impact the psychological well being not only of targets of bullying, but also that of bullying perpetrators and those witnessing bullying. Bullying is linked to depression and poorer mental health and functioning among children and adolescents. Given the high prevalence of bullying among children and adolescents and the negative mental health sequelae of bullying, this is an area of urgent public health concern. This narrative review brings forth recent research findings in this arena, which could help shape public health policies for addressing and preventing bullying.</AbstractText Recent findings demonstrate an association of bullying among children and adolescents with depression, nonsuicidal self-injury, sleep loss, reduced health-related quality of life, poorer rates of graduation from high school and later mental health problems. A recent systematic review also showed an association of peer-victimization among children and adolescents with activation of amygdala, left parahippocampal gyrus and fusiform gyrus, and alterations in other brain areas.</AbstractText Evidence indicates that bullying in childhood and adolescence is associated with higher odds of developing mental health problems; therefore, early identification and timely intervention is crucial.</AbstractText
Spontaneous Retroperitoneal Hematoma: Clinical Profile and Predictors of Mortality. Spontaneous retroperitoneal hematoma (SRPHs) is a serious disorder infrequently reported in the literature. Our aim was to analyze the clinical profile and management of a series of cases and to determine mortality predictors.</AbstractText Retrospective cohort study.</AbstractText We studied the consecutive series of patients with a SRPH at a university hospital from 2008 to 2023. Collected variables included clinical, physiological, and analytical characteristics as well as treatments provided. A modified Acute Physiology and Chronic Health Disease Classification System II (m-APACHE II) and Charlson scores were calculated. The association of these factors with mortality during hospital admission and follow-up were evaluated with logistic and Cox regression, respectively.</AbstractText Eighty-five patients with SRPH (mean age 75&#xa0;years, 62.4% males) were identified. Of these, 56 (65.9%) were admitted for reasons other than SRPH, 67 (78.8%) received anticoagulants, and 53 (62.4%) had active bleeding on a CT scan. Seven patients were treated with palliative care. In the remaining 78 patients, management included transfusion (71 cases, 91%), anticoagulation reversal (25 cases, 32.1%), vasoactive drugs (21 cases, 26.9%), and admission to intermediate or critical care units (40 cases, 51.3%). Angiography was indicated in 34 (43.6%) patients, including embolization in 30 of these cases. Surgical drainage was required in two cases. Nineteen patients (24.5%) died during admission. m-APACHE II score (OR&#xa0;=&#xa0;1.21; 1.08-1.36) was a predictive factor. One- and 5-year survival rates among hospital survivors were 68.4% and 29.2%, respectively. Survival was independently associated with the Charlson Comorbidity Index score (HR&#xa0;=&#xa0;1.36; 1.14-1.63) and polypharmacy (HR&#xa0;=&#xa0;1.13; 1.02-1.24).</AbstractText SRPH is a serious disorder that requires complex therapeutic measures (critical care and angiography) in about half of patients. Several well-known scores are good predictors of mortality and could be useful in clinical decision-making.</AbstractText
39234318
33225223
39532785
Adrenocorticotropic Hormone-Secreting Pituitary Microadenoma Presenting with Acute Psychosis, Delirium and Paroxysmal Sympathetic Hyperactivity.
German guidelines on the diagnosis and treatment of neurosyphilis.
Unraveling the Nexus: The Role of Collapsin Response Mediator Protein 2 Phosphorylation in Neurodegeneration and Neuroregeneration.
Adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are known to be associated with behavioural changes but acute presentation including psychosis and delirium are less common. We report the case of a 42-year-old female patient with a known medical history of hypertension and diabetes mellitus, presenting with acute onset behavioural changes suggestive of psychosis to a tertiary care centre in Muscat, Oman in 2022. Further evaluation revealed an ACTH dependent Cushing's disease with a pituitary microadenoma. The patient was admitted for endoscopic resection of the adenoma. During the peri-operative period, she experienced worsening of psychosis in addition to delirium. She also developed episodes of unresponsiveness, posturing, severe diaphoresis and dyspnoea accompanied by tachycardia and hypertension which were managed with midazolam and levetiracetam. A seizure work-up and computed tomography brain scan were unremarkable. At follow-up, she showed full resolution of symptoms with good blood pressure and glycaemic control.</AbstractText
In view of the importance of neurosyphilis and the difficulties encountered in diagnosing it, the S1 guideline "Neurosyphilis" has been published by the German Society for Neurology (DGN) in accordance with the stipulations of the Association of the Scientific Medical Societies in Germany (AWMF). The present article is an abridged translation of that German guideline.</AbstractText (a) Neurosyphilis can manifest as early neurosyphilis (meningitis, meningovascular neurosyphilis or syphilitic gummas) or late neurosyphilis (tabes dorsalis, general paresis). (b) The following diagnostic criteria help to establish the presence of probable neurosyphilis (always point iv, accompanied by any two of points i to iii): (i) subacute or chronic neuro-psychiatric symptoms; (ii) increased cerebrospinal fluid (CSF) cell count or signs of blood-CSF barrier disruption; (iii) positive effect of anti-neurosyphilis antibiotic therapy on clinical course and CSF findings; (iv) positive TPHA/TPPA or FTA test in serum. (c) The diagnosis of neurosyphilis is confirmed by the subsequent detection of intrathecal production of antibodies against <i The German guideline on the diagnosis and treatment of neurosyphilis is a practical tool to support clinicians in diagnosing and treating patients with neurosyphilis. This article is an abridged translation of this guideline (Klein MW, J.; Angstwurm, K.; Esser, S.; Hahn, K.; Matschke, M.; Scheithauer, S.; Schoefer, H.; Sturzenegger, M.; Wildemann, B. Neurosyphilis, S1-Leitlinie. Deutsche Gesellschaft f&#xfc;r Neurologie, Leitlinien f&#xfc;r Diagnostik und Thearpie in der Neurologie 2020).</AbstractText
Neurodegenerative disease characterized by the progressive damage of the nervous system, and neuropathies caused by the neuronal injury are both led to substantial impairments in neural function and quality of life among geriatric populations. Recovery from nerve damage and neurodegenerative diseases present a significant challenge, as the central nervous system (CNS) has limited capacity for self-repair. Investigating mechanism of neurodegeneration and regeneration is essential for advancing our understanding and development of effective therapies for nerve damage and degenerative conditions, which can significantly enhance patient outcomes. Collapsin response mediator protein 2 (CRMP2) was first identified as a key mediator of axonal growth and guidance is essential for neurogenesis and neuroregeneration. Phosphorylation as a primary modification approach of CRMP2 facilitates its involvement in numerous physiological processes, including axonal guidance, neuroplasticity, and cytoskeleton dynamics. Prior research on CRMP2 phosphorylation has elucidated its involvement in the mechanisms of neurodegenerative diseases and nerve damage. Pharmacological and genetic interventions that alter CRMP2 phosphorylation have shown the potential to influence neurodegenerative diseases and promote nerve regeneration. Even with decades of research delving into the intricacies of CRMP2 phosphorylation, there remains a scarcity of comprehensive literature reviews addressing this topic. This absence of synthesis and integration of findings hampers the field's progress by preventing a holistic understanding of CRMP2's implications in neurobiology, thereby impeding potential advancements in clinical treatments and interventions. This review intends to compile investigations focused on the role of CRMP2 phosphorylation in both neurodegenerative disease models and injury models to summarizing impacts and offer novel insight for clinical therapies.</AbstractText
Adrenocorticotropic Hormone-Secreting Pituitary Microadenoma Presenting with Acute Psychosis, Delirium and Paroxysmal Sympathetic Hyperactivity. Adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are known to be associated with behavioural changes but acute presentation including psychosis and delirium are less common. We report the case of a 42-year-old female patient with a known medical history of hypertension and diabetes mellitus, presenting with acute onset behavioural changes suggestive of psychosis to a tertiary care centre in Muscat, Oman in 2022. Further evaluation revealed an ACTH dependent Cushing's disease with a pituitary microadenoma. The patient was admitted for endoscopic resection of the adenoma. During the peri-operative period, she experienced worsening of psychosis in addition to delirium. She also developed episodes of unresponsiveness, posturing, severe diaphoresis and dyspnoea accompanied by tachycardia and hypertension which were managed with midazolam and levetiracetam. A seizure work-up and computed tomography brain scan were unremarkable. At follow-up, she showed full resolution of symptoms with good blood pressure and glycaemic control.</AbstractText
German guidelines on the diagnosis and treatment of neurosyphilis. In view of the importance of neurosyphilis and the difficulties encountered in diagnosing it, the S1 guideline "Neurosyphilis" has been published by the German Society for Neurology (DGN) in accordance with the stipulations of the Association of the Scientific Medical Societies in Germany (AWMF). The present article is an abridged translation of that German guideline.</AbstractText (a) Neurosyphilis can manifest as early neurosyphilis (meningitis, meningovascular neurosyphilis or syphilitic gummas) or late neurosyphilis (tabes dorsalis, general paresis). (b) The following diagnostic criteria help to establish the presence of probable neurosyphilis (always point iv, accompanied by any two of points i to iii): (i) subacute or chronic neuro-psychiatric symptoms; (ii) increased cerebrospinal fluid (CSF) cell count or signs of blood-CSF barrier disruption; (iii) positive effect of anti-neurosyphilis antibiotic therapy on clinical course and CSF findings; (iv) positive TPHA/TPPA or FTA test in serum. (c) The diagnosis of neurosyphilis is confirmed by the subsequent detection of intrathecal production of antibodies against <i The German guideline on the diagnosis and treatment of neurosyphilis is a practical tool to support clinicians in diagnosing and treating patients with neurosyphilis. This article is an abridged translation of this guideline (Klein MW, J.; Angstwurm, K.; Esser, S.; Hahn, K.; Matschke, M.; Scheithauer, S.; Schoefer, H.; Sturzenegger, M.; Wildemann, B. Neurosyphilis, S1-Leitlinie. Deutsche Gesellschaft f&#xfc;r Neurologie, Leitlinien f&#xfc;r Diagnostik und Thearpie in der Neurologie 2020).</AbstractText
Unraveling the Nexus: The Role of Collapsin Response Mediator Protein 2 Phosphorylation in Neurodegeneration and Neuroregeneration. Neurodegenerative disease characterized by the progressive damage of the nervous system, and neuropathies caused by the neuronal injury are both led to substantial impairments in neural function and quality of life among geriatric populations. Recovery from nerve damage and neurodegenerative diseases present a significant challenge, as the central nervous system (CNS) has limited capacity for self-repair. Investigating mechanism of neurodegeneration and regeneration is essential for advancing our understanding and development of effective therapies for nerve damage and degenerative conditions, which can significantly enhance patient outcomes. Collapsin response mediator protein 2 (CRMP2) was first identified as a key mediator of axonal growth and guidance is essential for neurogenesis and neuroregeneration. Phosphorylation as a primary modification approach of CRMP2 facilitates its involvement in numerous physiological processes, including axonal guidance, neuroplasticity, and cytoskeleton dynamics. Prior research on CRMP2 phosphorylation has elucidated its involvement in the mechanisms of neurodegenerative diseases and nerve damage. Pharmacological and genetic interventions that alter CRMP2 phosphorylation have shown the potential to influence neurodegenerative diseases and promote nerve regeneration. Even with decades of research delving into the intricacies of CRMP2 phosphorylation, there remains a scarcity of comprehensive literature reviews addressing this topic. This absence of synthesis and integration of findings hampers the field's progress by preventing a holistic understanding of CRMP2's implications in neurobiology, thereby impeding potential advancements in clinical treatments and interventions. This review intends to compile investigations focused on the role of CRMP2 phosphorylation in both neurodegenerative disease models and injury models to summarizing impacts and offer novel insight for clinical therapies.</AbstractText
38534539
36586360
39105048
Brain Age Prediction Using Multi-Hop Graph Attention Combined with Convolutional Neural Network.
Advanced brain age correlates with greater rumination and less mindfulness in schizophrenia.
Post-COVID-19 Syndrome Associated With Multiple Autoimmune Diseases (DM I-LADA, Chronic Autoimmune Thyroiditis and Pernicious Anemia): Case Report.
Convolutional neural networks (CNNs) have been used widely to predict biological brain age based on brain magnetic resonance (MR) images. However, CNNs focus mainly on spatially local features and their aggregates and barely on the connective information between distant regions. To overcome this issue, we propose a novel multi-hop graph attention (MGA) module that exploits both the local and global connections of image features when combined with CNNs. After insertion between convolutional layers, MGA first converts the convolution-derived feature map into graph-structured data by using patch embedding and embedding-distance-based scoring. Multi-hop connections between the graph nodes are modeled by using the Markov chain process. After performing multi-hop graph attention, MGA re-converts the graph into an updated feature map and transfers it to the next convolutional layer. We combined the MGA module with sSE (spatial squeeze and excitation)-ResNet18 for our final prediction model (MGA-sSE-ResNet18) and performed various hyperparameter evaluations to identify the optimal parameter combinations. With 2788 three-dimensional T1-weighted MR images of healthy subjects, we verified the effectiveness of MGA-sSE-ResNet18 with comparisons to four established, general-purpose CNNs and two representative brain age prediction models. The proposed model yielded an optimal performance with a mean absolute error of 2.822 years and Pearson's correlation coefficient (PCC) of 0.968, demonstrating the potential of the MGA module to improve the accuracy of brain age prediction.</AbstractText
Individual variation in brain aging trajectories is linked with several physical and mental health outcomes. Greater stress levels, worry, and rumination correspond with advanced brain age, while other individual characteristics, like mindfulness, may be protective of brain health. Multiple lines of evidence point to advanced brain aging in schizophrenia (i.e., neural age estimate&#xa0;&gt;&#xa0;chronological age). Whether psychological dimensions such as mindfulness, rumination, and perceived stress contribute to brain aging in schizophrenia is unknown.</AbstractText We estimated brain age from high-resolution anatomical scans in 54 healthy controls (HC) and 52 individuals with schizophrenia (SZ) and computed the brain predicted age difference (BrainAGE-diff), i.e., the delta between estimated brain age and chronological age. Emotional well-being summary scores were empirically derived to reflect individual differences in trait mindfulness, rumination, and perceived stress. Core analyses evaluated relationships between BrainAGE-diff and emotional well-being, testing for slopes differences across groups.</AbstractText HC showed higher emotional well-being (greater mindfulness and less rumination/stress), relative to SZ. We observed a significant group difference in the relationship between BrainAge-diff and emotional well-being, explained by BrainAGE-diff negatively correlating with emotional well-being scores in SZ, and not in HC. That is, SZ with younger appearing brains (predicted age&#xa0;&lt;&#xa0;chronological age) had emotional summary scores that were more like HC, a relationship that endured after accounting for several demographic and clinical variables.</AbstractText These data reveal clinically relevant aspects of brain age heterogeneity among SZ and point to case-control differences in the relationship between advanced brain aging and emotional well-being.</AbstractText
COVID-19, a global epidemic of infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), not only initially refers to acute manifestations but also chronic symptoms known as Long COVID-19. Long COVID-19 represents a significant burden to healthcare systems worldwide. This syndrome encompasses a wide range of continuing health problems with variable durations and consequences for patients' everyday lives. A notable aspect of Long COVID-19 is the emergence of new-onset autoimmune diseases that could be triggered in predisposed patients with altered immune responses. Common autoimmune conditions that arise in post-COVID patients include autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, etc., but with unclear evidence of associated disease occurrence. We present a case of a female rheumatoid arthritis patient who developed autoimmune thyroid disease, latent autoimmune diabetes of adults (LADA), and pernicious anemia after SARS-CoV-2 infection.</AbstractText
Brain Age Prediction Using Multi-Hop Graph Attention Combined with Convolutional Neural Network. Convolutional neural networks (CNNs) have been used widely to predict biological brain age based on brain magnetic resonance (MR) images. However, CNNs focus mainly on spatially local features and their aggregates and barely on the connective information between distant regions. To overcome this issue, we propose a novel multi-hop graph attention (MGA) module that exploits both the local and global connections of image features when combined with CNNs. After insertion between convolutional layers, MGA first converts the convolution-derived feature map into graph-structured data by using patch embedding and embedding-distance-based scoring. Multi-hop connections between the graph nodes are modeled by using the Markov chain process. After performing multi-hop graph attention, MGA re-converts the graph into an updated feature map and transfers it to the next convolutional layer. We combined the MGA module with sSE (spatial squeeze and excitation)-ResNet18 for our final prediction model (MGA-sSE-ResNet18) and performed various hyperparameter evaluations to identify the optimal parameter combinations. With 2788 three-dimensional T1-weighted MR images of healthy subjects, we verified the effectiveness of MGA-sSE-ResNet18 with comparisons to four established, general-purpose CNNs and two representative brain age prediction models. The proposed model yielded an optimal performance with a mean absolute error of 2.822 years and Pearson's correlation coefficient (PCC) of 0.968, demonstrating the potential of the MGA module to improve the accuracy of brain age prediction.</AbstractText
Advanced brain age correlates with greater rumination and less mindfulness in schizophrenia. Individual variation in brain aging trajectories is linked with several physical and mental health outcomes. Greater stress levels, worry, and rumination correspond with advanced brain age, while other individual characteristics, like mindfulness, may be protective of brain health. Multiple lines of evidence point to advanced brain aging in schizophrenia (i.e., neural age estimate&#xa0;&gt;&#xa0;chronological age). Whether psychological dimensions such as mindfulness, rumination, and perceived stress contribute to brain aging in schizophrenia is unknown.</AbstractText We estimated brain age from high-resolution anatomical scans in 54 healthy controls (HC) and 52 individuals with schizophrenia (SZ) and computed the brain predicted age difference (BrainAGE-diff), i.e., the delta between estimated brain age and chronological age. Emotional well-being summary scores were empirically derived to reflect individual differences in trait mindfulness, rumination, and perceived stress. Core analyses evaluated relationships between BrainAGE-diff and emotional well-being, testing for slopes differences across groups.</AbstractText HC showed higher emotional well-being (greater mindfulness and less rumination/stress), relative to SZ. We observed a significant group difference in the relationship between BrainAge-diff and emotional well-being, explained by BrainAGE-diff negatively correlating with emotional well-being scores in SZ, and not in HC. That is, SZ with younger appearing brains (predicted age&#xa0;&lt;&#xa0;chronological age) had emotional summary scores that were more like HC, a relationship that endured after accounting for several demographic and clinical variables.</AbstractText These data reveal clinically relevant aspects of brain age heterogeneity among SZ and point to case-control differences in the relationship between advanced brain aging and emotional well-being.</AbstractText
Post-COVID-19 Syndrome Associated With Multiple Autoimmune Diseases (DM I-LADA, Chronic Autoimmune Thyroiditis and Pernicious Anemia): Case Report. COVID-19, a global epidemic of infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), not only initially refers to acute manifestations but also chronic symptoms known as Long COVID-19. Long COVID-19 represents a significant burden to healthcare systems worldwide. This syndrome encompasses a wide range of continuing health problems with variable durations and consequences for patients' everyday lives. A notable aspect of Long COVID-19 is the emergence of new-onset autoimmune diseases that could be triggered in predisposed patients with altered immune responses. Common autoimmune conditions that arise in post-COVID patients include autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, etc., but with unclear evidence of associated disease occurrence. We present a case of a female rheumatoid arthritis patient who developed autoimmune thyroid disease, latent autoimmune diabetes of adults (LADA), and pernicious anemia after SARS-CoV-2 infection.</AbstractText
28965423
28839341
29785024
Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review.
Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder.
Targeting skeletal endothelium to ameliorate bone loss.
Up to 30% of patients taking antipsychotics may develop tardive dyskinesia (TD). Recent evidence-based recommendations demonstrate an unmet need for effective TD management. This systematic review was designed to update the evidence for TD treatment, comparing two vesicular monoamine transporter 2 (VMAT2) inhibitors, tetrabenazine and valbenazine. Of 487 PubMed/Embase search results, 11 studies met the review criteria. Valbenazine efficacy was demonstrated in rigorously designed clinical trials that meet the guidelines for AAN Class I evidence. Due to differences in study designs and a lack of standardized and controlled trials with tetrabenazine, a formal meta-analysis comparing the agents was not possible. However, valbenazine appears to have fewer side effects and a more favorable once-daily dosing regimen for the treatment of TD.</AbstractText
The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD.</AbstractText The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-&#xc5;sberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively.</AbstractText The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment (Week 48) indicated that psychiatric stability was maintained in the SCHZ subgroup (PANSS Total, -3.4; PANSS Positive, -1.1; PANSS Negative, -0.1; PANSS General Psychopathology, -2.2; CDSS total, -0.4) and the mood subgroup (MADRS Total, 0.0; YMRS Total, -1.2). These scores remained generally stable during the 4-week drug-free follow-up periods. In the LTE population, mean changes in laboratory parameters, vital signs, ECG, and EPS scales were generally minimal and not clinically significant.</AbstractText Valbenazine appeared to be well tolerated in adults with TD who received up to 48 weeks of treatment. In addition to long-term efficacy results (presented separately), these results suggest that valbenazine may be appropriate for the long-term management of TD regardless of underlying psychiatric diagnosis (SCHZ disorder or mood disorder).</AbstractText
Recent studies have identified a specialized subset of CD31<sup
Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review. Up to 30% of patients taking antipsychotics may develop tardive dyskinesia (TD). Recent evidence-based recommendations demonstrate an unmet need for effective TD management. This systematic review was designed to update the evidence for TD treatment, comparing two vesicular monoamine transporter 2 (VMAT2) inhibitors, tetrabenazine and valbenazine. Of 487 PubMed/Embase search results, 11 studies met the review criteria. Valbenazine efficacy was demonstrated in rigorously designed clinical trials that meet the guidelines for AAN Class I evidence. Due to differences in study designs and a lack of standardized and controlled trials with tetrabenazine, a formal meta-analysis comparing the agents was not possible. However, valbenazine appears to have fewer side effects and a more favorable once-daily dosing regimen for the treatment of TD.</AbstractText
Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD.</AbstractText The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-&#xc5;sberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively.</AbstractText The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment (Week 48) indicated that psychiatric stability was maintained in the SCHZ subgroup (PANSS Total, -3.4; PANSS Positive, -1.1; PANSS Negative, -0.1; PANSS General Psychopathology, -2.2; CDSS total, -0.4) and the mood subgroup (MADRS Total, 0.0; YMRS Total, -1.2). These scores remained generally stable during the 4-week drug-free follow-up periods. In the LTE population, mean changes in laboratory parameters, vital signs, ECG, and EPS scales were generally minimal and not clinically significant.</AbstractText Valbenazine appeared to be well tolerated in adults with TD who received up to 48 weeks of treatment. In addition to long-term efficacy results (presented separately), these results suggest that valbenazine may be appropriate for the long-term management of TD regardless of underlying psychiatric diagnosis (SCHZ disorder or mood disorder).</AbstractText
Targeting skeletal endothelium to ameliorate bone loss. Recent studies have identified a specialized subset of CD31<sup
30004191
23486876
29650376
Involvement of amygdala-prefrontal dysfunction in the influence of negative emotion on the resolution of cognitive conflict in patients with schizophrenia.
Disruption of cerebral networks and cognitive impairment in Alzheimer disease.
Trapezius Muscle Transfer for Restoration of Elbow Extension in a Traumatic Brachial Plexus Injury.
Patients with schizophrenia often have impaired cognition and abnormal conflict control. Conflict control is influenced by the emotional values of stimuli. This study investigated the neural basis of negative emotion interference with conflict control in schizophrenia.</AbstractText Seventeen patients with schizophrenia and 20 healthy controls underwent functional magnetic resonance imaging while performing the emotional Simon task, in which positive or negative emotional pictures were located in congruent or incongruent positions. Analysis was focused on identifying brain regions with the significant interaction among group, emotion, and conflict in whole brain voxel-wise analysis, and abnormality in their functional connectivity in the patient group.</AbstractText The regions showing the targeted interaction was the right amygdala, which exhibited significantly reduced activity in the negative congruent (t&#xa0;=&#xa0;-2.168, p&#xa0;=&#xa0;0.036) and negative incongruent (t&#xa0;=&#xa0;-3.273, p&#xa0;=&#xa0;0.002) conditions in patients versus controls. The right amygdala also showed significantly lower connectivity with the right dorsolateral prefrontal cortex in the cognitive and emotional loading contrast (negative incongruent-positive congruent) in patients versus controls (t&#xa0;=&#xa0;-5.154, p&#xa0;&lt;&#xa0;0.01), but not in the cognitive-only or emotional-only loading contrast.</AbstractText These results suggest that negative emotion interferes with cognitive conflict resolution in patients with schizophrenia due to amygdala-dorsolateral prefrontal cortex disconnection. Based on these findings, interventions targeting conflict control under negative emotional influence may promote cognitive rehabilitation in patients with schizophrenia.</AbstractText
To examine the relation between measures of whole-brain white matter connectivity and cognitive performance in patients with early Alzheimer disease (AD) using a network-based approach and to assess whether network parameters provide information that is complementary to conventional MRI markers of AD.</AbstractText Fifty patients (mean age 78.8 &#xb1; 7.1 years) with early AD were recruited via a memory clinic. In addition, 15 age-, sex-, and education-matched control participants were used as a reference group. All participants underwent a 3-T MRI scan and cognitive assessment. Diffusion tensor imaging-based tractography was used to reconstruct the brain network of each individual, followed by graph theoretical analyses. Overall network efficiency was assessed by measures of local (clustering coefficient, local efficiency) and global (path length, global efficiency) connectivity. Age-, sex-, and education-adjusted cognitive scores were related to network measures and to conventional MRI parameters (i.e., degree of cerebral atrophy and small-vessel disease).</AbstractText The structural brain network of patients showed reduced local efficiency compared to controls. Within the patient group, worse performance in memory and executive functioning was related to decreased local efficiency (r = 0.434; p = 0.002), increased path length (r = -0.538; p &lt; 0.001), and decreased global efficiency (r = 0.431; p = 0.005). Measures of network efficiency explained up to 27% of the variance in cognitive functioning on top of conventional MRI markers (p &lt; 0.01).</AbstractText This study shows that network-based analysis of brain white matter connections provides a novel way to reveal the structural basis of cognitive dysfunction in AD.</AbstractText
Voluntary elbow extension is essential for optimal upper limb positioning required for daily living activities, particularly above-shoulder maneuvers. The authors present a case of traumatic brachial plexus injury in which paralysis of the musculature selectively supplied by the posterior cord was based on magnetic resonance imaging and nerve conduction studies. An attempt at a radial nerve graft at another center was not effective. Ipsilateral hand function improved after multiple local tendon transfers were performed. Restoration of active elbow extension was not possible using the posterior deltoid or the latissimus dorsi because they were denervated by the primary trauma and so the trapezius muscle was used as a donor muscle unit to restore voluntary elbow extension. The patient resumed biking 6 weeks after the transfer procedure. At 2-year follow-up, full active elbow extension was regained, elbow extension power scored 4 of 5, and the patient reported that he could ride his bicycle for 70 miles.</AbstractText
Involvement of amygdala-prefrontal dysfunction in the influence of negative emotion on the resolution of cognitive conflict in patients with schizophrenia. Patients with schizophrenia often have impaired cognition and abnormal conflict control. Conflict control is influenced by the emotional values of stimuli. This study investigated the neural basis of negative emotion interference with conflict control in schizophrenia.</AbstractText Seventeen patients with schizophrenia and 20 healthy controls underwent functional magnetic resonance imaging while performing the emotional Simon task, in which positive or negative emotional pictures were located in congruent or incongruent positions. Analysis was focused on identifying brain regions with the significant interaction among group, emotion, and conflict in whole brain voxel-wise analysis, and abnormality in their functional connectivity in the patient group.</AbstractText The regions showing the targeted interaction was the right amygdala, which exhibited significantly reduced activity in the negative congruent (t&#xa0;=&#xa0;-2.168, p&#xa0;=&#xa0;0.036) and negative incongruent (t&#xa0;=&#xa0;-3.273, p&#xa0;=&#xa0;0.002) conditions in patients versus controls. The right amygdala also showed significantly lower connectivity with the right dorsolateral prefrontal cortex in the cognitive and emotional loading contrast (negative incongruent-positive congruent) in patients versus controls (t&#xa0;=&#xa0;-5.154, p&#xa0;&lt;&#xa0;0.01), but not in the cognitive-only or emotional-only loading contrast.</AbstractText These results suggest that negative emotion interferes with cognitive conflict resolution in patients with schizophrenia due to amygdala-dorsolateral prefrontal cortex disconnection. Based on these findings, interventions targeting conflict control under negative emotional influence may promote cognitive rehabilitation in patients with schizophrenia.</AbstractText
Disruption of cerebral networks and cognitive impairment in Alzheimer disease. To examine the relation between measures of whole-brain white matter connectivity and cognitive performance in patients with early Alzheimer disease (AD) using a network-based approach and to assess whether network parameters provide information that is complementary to conventional MRI markers of AD.</AbstractText Fifty patients (mean age 78.8 &#xb1; 7.1 years) with early AD were recruited via a memory clinic. In addition, 15 age-, sex-, and education-matched control participants were used as a reference group. All participants underwent a 3-T MRI scan and cognitive assessment. Diffusion tensor imaging-based tractography was used to reconstruct the brain network of each individual, followed by graph theoretical analyses. Overall network efficiency was assessed by measures of local (clustering coefficient, local efficiency) and global (path length, global efficiency) connectivity. Age-, sex-, and education-adjusted cognitive scores were related to network measures and to conventional MRI parameters (i.e., degree of cerebral atrophy and small-vessel disease).</AbstractText The structural brain network of patients showed reduced local efficiency compared to controls. Within the patient group, worse performance in memory and executive functioning was related to decreased local efficiency (r = 0.434; p = 0.002), increased path length (r = -0.538; p &lt; 0.001), and decreased global efficiency (r = 0.431; p = 0.005). Measures of network efficiency explained up to 27% of the variance in cognitive functioning on top of conventional MRI markers (p &lt; 0.01).</AbstractText This study shows that network-based analysis of brain white matter connections provides a novel way to reveal the structural basis of cognitive dysfunction in AD.</AbstractText
Trapezius Muscle Transfer for Restoration of Elbow Extension in a Traumatic Brachial Plexus Injury. Voluntary elbow extension is essential for optimal upper limb positioning required for daily living activities, particularly above-shoulder maneuvers. The authors present a case of traumatic brachial plexus injury in which paralysis of the musculature selectively supplied by the posterior cord was based on magnetic resonance imaging and nerve conduction studies. An attempt at a radial nerve graft at another center was not effective. Ipsilateral hand function improved after multiple local tendon transfers were performed. Restoration of active elbow extension was not possible using the posterior deltoid or the latissimus dorsi because they were denervated by the primary trauma and so the trapezius muscle was used as a donor muscle unit to restore voluntary elbow extension. The patient resumed biking 6 weeks after the transfer procedure. At 2-year follow-up, full active elbow extension was regained, elbow extension power scored 4 of 5, and the patient reported that he could ride his bicycle for 70 miles.</AbstractText
33741501
33446327
34388123
Lack of Mucosal Cholinergic Innervation Is Associated With Increased Risk of Enterocolitis in Hirschsprung's Disease.
Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians.
Simulation and optimization of hydraulic performance of small baffled subsurface flow constructed wetland.
Hirschsprung's disease (HSCR) is a congenital intestinal motility disorder defined by the absence of enteric neuronal cells (ganglia) in the distal gut. The development of HSCR-associated enterocolitis remains a life-threatening complication. Absence of enteric ganglia implicates innervation of acetylcholine-secreting (cholinergic) nerve fibers. Cholinergic signals have been reported to control excessive inflammation, but the impact on HSCR-associated enterocolitis is unknown.</AbstractText We enrolled 44 HSCR patients in a prospective multicenter study and grouped them according to their degree of colonic mucosal acetylcholinesterase-positive innervation into low-fiber and high-fiber patient groups. The fiber phenotype was correlated with the tissue cytokine profile as well as immune cell frequencies using Luminex analysis and fluorescence-activated cell sorting analysis of colonic tissue and immune cells. Using confocal immunofluorescence microscopy, macrophages were identified in close proximity to nerve fibers and characterized by RNA-seq analysis. Microbial dysbiosis was analyzed in colonic tissue using 16S-rDNA gene sequencing. Finally, the fiber phenotype was correlated with postoperative enterocolitis manifestation.</AbstractText The presence of mucosal nerve fiber innervation correlated with reduced T-helper 17 cytokines and cell frequencies. In high-fiber tissue, macrophages co-localized with nerve fibers and expressed significantly less interleukin 23 than macrophages from low-fiber tissue. HSCR patients lacking mucosal nerve fibers showed microbial dysbiosis and had a higher incidence of postoperative enterocolitis.</AbstractText The mucosal fiber phenotype might serve as a prognostic marker for enterocolitis development in HSCR patients and may offer an approach to personalized patient care and new therapeutic options.</AbstractText
The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection and raised the question of the neuropathogenicity of coronaviruses. The aim of this review was to summarize the current data about neurological manifestations and diseases linked to human coronaviruses.</AbstractText Articles have been identified by searches of PubMed and Google scholar up to September 25, 2020, using a combination of coronavirus and neurology search terms and adding relevant references in the articles.</AbstractText We found five cohorts providing prevalence data of neurological symptoms among a total of 2533 hospitalized COVID-19 patients, and articles focusing on COVID-19 patients with neurological manifestations including a total of 580 patients. Neurological symptoms involved up to 73% of COVID-19 hospitalized patients, and were mostly headache, myalgias and impaired consciousness. Central nervous system (CNS) manifestations reported in COVID-19 were mostly non-specific encephalopathies that represented between 13% and 40% of all neurological manifestations; post-infectious syndromes including acute demyelinating encephalomyelitis (ADEM, n=13), acute necrotizing encephalopathy (ANE, n=4), Bickerstaff's encephalitis (n=5), generalized myoclonus (n=3) and acute transverse myelitis (n=7); other encephalitis including limbic encephalitis (n=9) and miscellaneous encephalitis with variable radiologic findings (n=26); acute cerebrovascular diseases including ischemic strokes (between 1.3% and 4.7% of COVID-19 patients), hemorrhagic strokes (n=17), cerebral venous thrombosis (n=8) and posterior reversible encephalopathy (n=5). Peripheral nervous system (PNS) manifestations reported in COVID-19 were the following: Guillain-Barr&#xe9; syndrome (n=31) and variants including Miller Fisher syndrome (n=3), polyneuritis cranialis (n=2) and facial diplegia (n=2); isolated oculomotor neuropathy (n=6); critical illness myopathy (n=6). Neuropathological studies in COVID-19 patients demonstrated different patterns of CNS damage, mostly ischemic and hemorrhagic changes with few cases of inflammatory injuries. Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells. We found 10 case reports or case series describing 22 patients with neurological manifestations associated with other human coronaviruses. Among them we found four MERS patients with ADEM or Bickerstaff's encephalitis, two SARS patients with encephalitis who had a positive SARS-CoV PCR in cerebrospinal fluid, five patients with ischemic strokes associated with SARS, eight MERS patients with critical illness neuromyopathy and one MERS patient with Guillain-Barr&#xe9; Syndrome. An autopsy study on SARS-CoV patients demonstrated the presence of the virus in the brain of eight patients.</AbstractText The wide range of neurological manifestations and diseases associated with SARS-CoV-2 is consistent with multiple pathogenic pathways including post-infectious mechanisms, septic-associated encephalopathies, coagulopathy or endothelitis. There was no definite evidence to support direct neuropathogenicity of SARS-CoV-2.</AbstractText
The water body inside the constructed wetland is affected by various factors, and the flow state is relatively complicated. There will always be a certain degree of low velocity area and rapid outflow phenomenon, which makes part of the space in the wetland unable to be effectively used. Based on Computational Fluid Dynamics (CFD) technology, this paper uses Fluent's porous media model and discrete phase model to establish a hydrodynamic model of up and down baffled subsurface flow constructed wetland system. The internal flow field of the wetland is simulated, and the hydraulic performance of different baffle settings and substrate laying methods in the wetland is systematically evaluated. The results show that when the number of baffles is the same, the hydraulic efficiency is higher when the first baffle is located on the lower part of the substrate. Compared with the position of the baffle, the increase in the number of baffles does not significantly improve the hydraulic efficiency of the constructed wetland. The substrate layer thickness ratio has a significant effect on the two parameters of the variance of the hydraulic residence time distribution (&#x3c3;<sup
Lack of Mucosal Cholinergic Innervation Is Associated With Increased Risk of Enterocolitis in Hirschsprung's Disease. Hirschsprung's disease (HSCR) is a congenital intestinal motility disorder defined by the absence of enteric neuronal cells (ganglia) in the distal gut. The development of HSCR-associated enterocolitis remains a life-threatening complication. Absence of enteric ganglia implicates innervation of acetylcholine-secreting (cholinergic) nerve fibers. Cholinergic signals have been reported to control excessive inflammation, but the impact on HSCR-associated enterocolitis is unknown.</AbstractText We enrolled 44 HSCR patients in a prospective multicenter study and grouped them according to their degree of colonic mucosal acetylcholinesterase-positive innervation into low-fiber and high-fiber patient groups. The fiber phenotype was correlated with the tissue cytokine profile as well as immune cell frequencies using Luminex analysis and fluorescence-activated cell sorting analysis of colonic tissue and immune cells. Using confocal immunofluorescence microscopy, macrophages were identified in close proximity to nerve fibers and characterized by RNA-seq analysis. Microbial dysbiosis was analyzed in colonic tissue using 16S-rDNA gene sequencing. Finally, the fiber phenotype was correlated with postoperative enterocolitis manifestation.</AbstractText The presence of mucosal nerve fiber innervation correlated with reduced T-helper 17 cytokines and cell frequencies. In high-fiber tissue, macrophages co-localized with nerve fibers and expressed significantly less interleukin 23 than macrophages from low-fiber tissue. HSCR patients lacking mucosal nerve fibers showed microbial dysbiosis and had a higher incidence of postoperative enterocolitis.</AbstractText The mucosal fiber phenotype might serve as a prognostic marker for enterocolitis development in HSCR patients and may offer an approach to personalized patient care and new therapeutic options.</AbstractText
Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians. The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection and raised the question of the neuropathogenicity of coronaviruses. The aim of this review was to summarize the current data about neurological manifestations and diseases linked to human coronaviruses.</AbstractText Articles have been identified by searches of PubMed and Google scholar up to September 25, 2020, using a combination of coronavirus and neurology search terms and adding relevant references in the articles.</AbstractText We found five cohorts providing prevalence data of neurological symptoms among a total of 2533 hospitalized COVID-19 patients, and articles focusing on COVID-19 patients with neurological manifestations including a total of 580 patients. Neurological symptoms involved up to 73% of COVID-19 hospitalized patients, and were mostly headache, myalgias and impaired consciousness. Central nervous system (CNS) manifestations reported in COVID-19 were mostly non-specific encephalopathies that represented between 13% and 40% of all neurological manifestations; post-infectious syndromes including acute demyelinating encephalomyelitis (ADEM, n=13), acute necrotizing encephalopathy (ANE, n=4), Bickerstaff's encephalitis (n=5), generalized myoclonus (n=3) and acute transverse myelitis (n=7); other encephalitis including limbic encephalitis (n=9) and miscellaneous encephalitis with variable radiologic findings (n=26); acute cerebrovascular diseases including ischemic strokes (between 1.3% and 4.7% of COVID-19 patients), hemorrhagic strokes (n=17), cerebral venous thrombosis (n=8) and posterior reversible encephalopathy (n=5). Peripheral nervous system (PNS) manifestations reported in COVID-19 were the following: Guillain-Barr&#xe9; syndrome (n=31) and variants including Miller Fisher syndrome (n=3), polyneuritis cranialis (n=2) and facial diplegia (n=2); isolated oculomotor neuropathy (n=6); critical illness myopathy (n=6). Neuropathological studies in COVID-19 patients demonstrated different patterns of CNS damage, mostly ischemic and hemorrhagic changes with few cases of inflammatory injuries. Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells. We found 10 case reports or case series describing 22 patients with neurological manifestations associated with other human coronaviruses. Among them we found four MERS patients with ADEM or Bickerstaff's encephalitis, two SARS patients with encephalitis who had a positive SARS-CoV PCR in cerebrospinal fluid, five patients with ischemic strokes associated with SARS, eight MERS patients with critical illness neuromyopathy and one MERS patient with Guillain-Barr&#xe9; Syndrome. An autopsy study on SARS-CoV patients demonstrated the presence of the virus in the brain of eight patients.</AbstractText The wide range of neurological manifestations and diseases associated with SARS-CoV-2 is consistent with multiple pathogenic pathways including post-infectious mechanisms, septic-associated encephalopathies, coagulopathy or endothelitis. There was no definite evidence to support direct neuropathogenicity of SARS-CoV-2.</AbstractText
Simulation and optimization of hydraulic performance of small baffled subsurface flow constructed wetland. The water body inside the constructed wetland is affected by various factors, and the flow state is relatively complicated. There will always be a certain degree of low velocity area and rapid outflow phenomenon, which makes part of the space in the wetland unable to be effectively used. Based on Computational Fluid Dynamics (CFD) technology, this paper uses Fluent's porous media model and discrete phase model to establish a hydrodynamic model of up and down baffled subsurface flow constructed wetland system. The internal flow field of the wetland is simulated, and the hydraulic performance of different baffle settings and substrate laying methods in the wetland is systematically evaluated. The results show that when the number of baffles is the same, the hydraulic efficiency is higher when the first baffle is located on the lower part of the substrate. Compared with the position of the baffle, the increase in the number of baffles does not significantly improve the hydraulic efficiency of the constructed wetland. The substrate layer thickness ratio has a significant effect on the two parameters of the variance of the hydraulic residence time distribution (&#x3c3;<sup
38305999
28174907
38490269
Identification of metabolic pathways and key genes associated with atypical parkinsonism using a systems biology approach.
Cortical Circuits of Callosal GABAergic Neurons.
Increased aortic pressures and pulsatile afterload components promote concentric left ventricular remodeling in adults with transposition of the great arteries and arterial switch operation.
Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.</AbstractText
Anatomical studies have shown that the majority of callosal axons are glutamatergic. However, a small proportion of callosal axons are also immunoreactive for glutamic acid decarboxylase, an enzyme required for gamma-aminobutyric acid (GABA) synthesis and a specific marker for GABAergic neurons. Here, we test the hypothesis that corticocortical parvalbumin-expressing (CC-Parv) neurons connect the two hemispheres of multiple cortical areas, project through the corpus callosum, and are a functional part of the local cortical circuit. Our investigation of this hypothesis takes advantage of viral tracing and optogenetics to determine the anatomical and electrophysiological properties of CC-Parv neurons of the mouse auditory, visual, and motor cortices. We found a direct inhibitory pathway made up of parvalbumin-expressing (Parv) neurons which connects corresponding cortical areas (CC-Parv neurons &#x2192; contralateral cortex). Like other Parv cortical neurons, these neurons provide local inhibition onto nearby pyramidal neurons and receive thalamocortical input. These results demonstrate a previously unknown long-range inhibitory circuit arising from a genetically defined type of GABAergic neuron that is engaged in interhemispheric communication.</AbstractText
Functional abnormalities of the ascending aorta (AA) have been mainly reported in young patients who underwent arterial switch operation (ASO) for transposition of the great arteries (TGA).</AbstractText To compare systolic, diastolic brachial and central blood pressures (bSBP, bDBP, cSBP, cDBP), aortic biomechanical parameters, and left ventricular (LV) afterload criteria in adult ASO patients with healthy controls and to assess their relationships with LV remodeling and aortic size.</AbstractText Forty-one prospectively enrolled patients (16.8 to 35.8&#xa0;years) and 41 age- and sex-matched healthy volunteers underwent cardiac MRI to assess LV remodeling with simultaneous brachial BP estimation. After MRI, carotid-femoral tonometry was performed to measure pulse wave velocity (cfPWV), cSBP and cDBP for further calculation of pulse pressure (cPP), AA distensibility (AA<sub bSBP, bDBP, cSBP,cDBP and cPP were all significantly higher in ASO group than in controls: cSBP (116.5&#xa0;&#xb1;&#xa0;13.8 vs 106.1&#xa0;&#xb1;&#xa0;12.0, p&#xa0;&lt;&#xa0;0.001), cDBP (72.5&#xa0;&#xb1;&#xa0;6.9 vs 67.1&#xa0;&#xb1;&#xa0;9.4, p&#xa0;=&#xa0;0.002), cPP (44.0&#xa0;&#xb1;&#xa0;12.1 vs 39.1&#xa0;&#xb1;&#xa0;8.9, p&#xa0;=&#xa0;0.003) and not related to aortic size. AA<sub Even without reaching arterial hypertension, aortic sBP and PP are increased in the adult TGA population after ASO, altering the pulsatile components of afterload and contributing to LV concentric remodeling.</AbstractText
Identification of metabolic pathways and key genes associated with atypical parkinsonism using a systems biology approach. Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.</AbstractText
Cortical Circuits of Callosal GABAergic Neurons. Anatomical studies have shown that the majority of callosal axons are glutamatergic. However, a small proportion of callosal axons are also immunoreactive for glutamic acid decarboxylase, an enzyme required for gamma-aminobutyric acid (GABA) synthesis and a specific marker for GABAergic neurons. Here, we test the hypothesis that corticocortical parvalbumin-expressing (CC-Parv) neurons connect the two hemispheres of multiple cortical areas, project through the corpus callosum, and are a functional part of the local cortical circuit. Our investigation of this hypothesis takes advantage of viral tracing and optogenetics to determine the anatomical and electrophysiological properties of CC-Parv neurons of the mouse auditory, visual, and motor cortices. We found a direct inhibitory pathway made up of parvalbumin-expressing (Parv) neurons which connects corresponding cortical areas (CC-Parv neurons &#x2192; contralateral cortex). Like other Parv cortical neurons, these neurons provide local inhibition onto nearby pyramidal neurons and receive thalamocortical input. These results demonstrate a previously unknown long-range inhibitory circuit arising from a genetically defined type of GABAergic neuron that is engaged in interhemispheric communication.</AbstractText
Increased aortic pressures and pulsatile afterload components promote concentric left ventricular remodeling in adults with transposition of the great arteries and arterial switch operation. Functional abnormalities of the ascending aorta (AA) have been mainly reported in young patients who underwent arterial switch operation (ASO) for transposition of the great arteries (TGA).</AbstractText To compare systolic, diastolic brachial and central blood pressures (bSBP, bDBP, cSBP, cDBP), aortic biomechanical parameters, and left ventricular (LV) afterload criteria in adult ASO patients with healthy controls and to assess their relationships with LV remodeling and aortic size.</AbstractText Forty-one prospectively enrolled patients (16.8 to 35.8&#xa0;years) and 41 age- and sex-matched healthy volunteers underwent cardiac MRI to assess LV remodeling with simultaneous brachial BP estimation. After MRI, carotid-femoral tonometry was performed to measure pulse wave velocity (cfPWV), cSBP and cDBP for further calculation of pulse pressure (cPP), AA distensibility (AA<sub bSBP, bDBP, cSBP,cDBP and cPP were all significantly higher in ASO group than in controls: cSBP (116.5&#xa0;&#xb1;&#xa0;13.8 vs 106.1&#xa0;&#xb1;&#xa0;12.0, p&#xa0;&lt;&#xa0;0.001), cDBP (72.5&#xa0;&#xb1;&#xa0;6.9 vs 67.1&#xa0;&#xb1;&#xa0;9.4, p&#xa0;=&#xa0;0.002), cPP (44.0&#xa0;&#xb1;&#xa0;12.1 vs 39.1&#xa0;&#xb1;&#xa0;8.9, p&#xa0;=&#xa0;0.003) and not related to aortic size. AA<sub Even without reaching arterial hypertension, aortic sBP and PP are increased in the adult TGA population after ASO, altering the pulsatile components of afterload and contributing to LV concentric remodeling.</AbstractText
35243039
28686805
34542805
Safety of gadolinium based contrast agents in magnetic resonance imaging-guided radiotherapy - An investigation of chelate stability using relaxometry.
A generalized ratiometric chemical exchange saturation transfer (CEST) MRI approach for mapping renal pH using iopamidol.
Direct Comparison of [(18)F]F-DPA with [(18)F]DPA-714 and [(11)C]PBR28 for Neuroinflammation Imaging in the same Alzheimer's Disease Model Mice and Healthy Controls.
With the introduction of hybrid magnetic resonance linacs (MR-linac), improved imaging has enabled daily treatment adaptation. However, the use of gadolinium based contrast agents (GBCAs) is desired to further improve MR image contrast. GBCAs are in the form of a non-toxic metalorganic gadolinium complex, but toxic un-chelated aqueous gadolinium(III), Gd<sup GBCAs, gadoteric acid, gadobutrol and gadoxectic acid were investigated in a concentration range of 10-100&#xa0;mM. Measurements were performed on a 500&#xa0;MHz nuclear MR (NMR) spectrometer with a high-resolution inversion recovery sequence to determine T<sub The overall measurement uncertainty was estimated to &#xb1;0.0053&#xa0;ms<sup This study did not find any measurable degradation of GBCAs due to irradiation with high-energy X-rays, however, in-vivo investigations are needed to provide the clinical basis for safe use of contrast agents in a radiotherapy workflow.</AbstractText
To extend the pH detection range of iopamidol-based ratiometric chemical exchange saturation transfer (CEST) MRI at sub-high magnetic field and establish quantitative renal pH MRI.</AbstractText Chemical exchange saturation transfer imaging was performed on iopamidol phantoms with pH of 5.5 to 8.0 and in vivo on rat kidneys (n&#x2009;=&#x2009;5) during iopamidol administration at a 4.7&#x2009;T. Iopamidol CEST effects were described using a multipool Lorentzian model. A generalized ratiometric analysis was conducted by ratioing resolved iopamidol CEST effects at 4.3 and 5.5&#x2009;ppm obtained under 1.0 and 2.0&#x2009;&#xb5;T, respectively. The pH detection range was established for both the standard ratiometric analysis and the proposed resolved approach. Renal pH was mapped in vivo with regional pH assessed by one-way analysis of variance.</AbstractText Good-fitting performance was observed in multipool Lorentzian resolving of CEST effects (R<sup The proposed ratiometric approach extended the iopamidol pH detection range, enabling the renal pH mapping in vivo, which is promising for pH imaging studies at sub-high or low fields with potential clinical applicability. Magn Reson Med 79:1553-1558, 2018. &#xa9; 2017 International Society for Magnetic Resonance in Medicine.</AbstractText
In this study we compared the recently developed TSPO tracer [<sup To compare the radiotracer uptake, percentage of injected dose/mL (%ID/mL), standardized uptake value ratios to cerebellum (SUVR<sub The peak uptake of [<sup [<sup
Safety of gadolinium based contrast agents in magnetic resonance imaging-guided radiotherapy - An investigation of chelate stability using relaxometry. With the introduction of hybrid magnetic resonance linacs (MR-linac), improved imaging has enabled daily treatment adaptation. However, the use of gadolinium based contrast agents (GBCAs) is desired to further improve MR image contrast. GBCAs are in the form of a non-toxic metalorganic gadolinium complex, but toxic un-chelated aqueous gadolinium(III), Gd<sup GBCAs, gadoteric acid, gadobutrol and gadoxectic acid were investigated in a concentration range of 10-100&#xa0;mM. Measurements were performed on a 500&#xa0;MHz nuclear MR (NMR) spectrometer with a high-resolution inversion recovery sequence to determine T<sub The overall measurement uncertainty was estimated to &#xb1;0.0053&#xa0;ms<sup This study did not find any measurable degradation of GBCAs due to irradiation with high-energy X-rays, however, in-vivo investigations are needed to provide the clinical basis for safe use of contrast agents in a radiotherapy workflow.</AbstractText
A generalized ratiometric chemical exchange saturation transfer (CEST) MRI approach for mapping renal pH using iopamidol. To extend the pH detection range of iopamidol-based ratiometric chemical exchange saturation transfer (CEST) MRI at sub-high magnetic field and establish quantitative renal pH MRI.</AbstractText Chemical exchange saturation transfer imaging was performed on iopamidol phantoms with pH of 5.5 to 8.0 and in vivo on rat kidneys (n&#x2009;=&#x2009;5) during iopamidol administration at a 4.7&#x2009;T. Iopamidol CEST effects were described using a multipool Lorentzian model. A generalized ratiometric analysis was conducted by ratioing resolved iopamidol CEST effects at 4.3 and 5.5&#x2009;ppm obtained under 1.0 and 2.0&#x2009;&#xb5;T, respectively. The pH detection range was established for both the standard ratiometric analysis and the proposed resolved approach. Renal pH was mapped in vivo with regional pH assessed by one-way analysis of variance.</AbstractText Good-fitting performance was observed in multipool Lorentzian resolving of CEST effects (R<sup The proposed ratiometric approach extended the iopamidol pH detection range, enabling the renal pH mapping in vivo, which is promising for pH imaging studies at sub-high or low fields with potential clinical applicability. Magn Reson Med 79:1553-1558, 2018. &#xa9; 2017 International Society for Magnetic Resonance in Medicine.</AbstractText
Direct Comparison of [(18)F]F-DPA with [(18)F]DPA-714 and [(11)C]PBR28 for Neuroinflammation Imaging in the same Alzheimer's Disease Model Mice and Healthy Controls. In this study we compared the recently developed TSPO tracer [<sup To compare the radiotracer uptake, percentage of injected dose/mL (%ID/mL), standardized uptake value ratios to cerebellum (SUVR<sub The peak uptake of [<sup [<sup
39659930
38976057
38800295
Machine learning models using multiparametric MRI for preoperative risk stratification in endometrial cancer.
Diagnostic accuracy and reliability of CT-based Node-RADS for colon cancer.
A Giant, Neglected Leiomyosarcoma on the Left Shoulder.
This study evaluated the efficacy of machine learning and radiomics of preoperative multiparameter MRIs in predicting low- vs high-risk histopathologic features and early vs advanced FIGO stage (IA vs IB or higher) in endometrial cancer. This retrospective study of patients with endometrial cancer histologically confirmed from 2008 through 2023 excluded those with: (a) previous treatment for endometrial carcinoma, (b) incomplete MRI examinations or low-quality MR images, (c) incomplete pathology reports, (d) non-visualized tumors on MRI, or (e) distant metastases. In total, 110 radiomic features were extracted using commercial PACS built-in software following segmentation after sagittal T2-weighted imaging (T2WI), contrast enhanced T1-weighted imaging (CE-T1WI), and diffusion weighted imaging (DWI). The radiomic features from each imaging sequence were utilized for initial modeling. A combined model, which included features retained from all 3 sequences, was then established. The area under the receiver operating characteristic curve (AUC) determined the efficacy of each model. For 5 specific histopathologic features, the combined model achieved AUCs of 0.87 (95% CI, 0.85-0.90), 0.90 (95% CI, 0.88-0.92), 0.88 (95% CI, 0.87-0.90), 0.88 (95% CI, 0.86-0.92), and 0.87 (95% CI, 0.86-0.90). This model incorporated 38 radiomic features: 12 from T2WI, 17 from CE-T1WI, and 9 from DWI. In conclusion, an MRI radiomics-based model can differentiate between early- and advanced-stage endometrial cancer and between low- and high-risk histologic markers, giving it the potential to predict high risk and stratify preoperative risk in those with endometrial cancer. The findings may aid personalized preoperative assessments to guide clinical decision-making in endometrial cancer.</AbstractText
The Node-RADS classification was recently published as a classification system to better characterize lymph nodes in oncological imaging. The present analysis investigated the diagnostic benefit of the Node-RADS classification of staging computed tomography (CT) images to categorize and stage lymph nodes in patients with colon cancer.</AbstractText All patients were surgically resected and the lymph nodes were histopathological analyzed. All investigated lymph nodes were scored in accordance to the Node-RADS classification by two experienced radiologists. Interreader variability was assessed with Cohen's kappa analysis, discrimination analysis was performed with Mann-Whitney-U test and diagnostic accuracy was assessed with receiver-operating characteristics (ROC) curve analysis.</AbstractText Overall, 108 patients (n&#x2009;=&#x2009;49 females, 45.3%) with a mean age of 70.08&#x2009;&#xb1;&#x2009;14.34 years were included. In discrimination analysis, the total Node-RADS score showed statistically significant differences between N- and N&#x2009;+&#x2009;stage (for reader 1: mean 1.89&#x2009;&#xb1;&#x2009;1.09 score for N- versus 2.93&#x2009;&#xb1;&#x2009;1.62 score for N+, for reader 2: 1.33&#x2009;&#xb1;&#x2009;0.48 score for N- versus 3.65&#x2009;&#xb1;&#x2009;0.94 score for N+, p&#x2009;=&#x2009;0.001, respectively). ROC curve analysis for lymph node discrimination showed an area under the curve of 0.68. A threshold value of 2 resulted in a sensitivity of 0.62 and a specificity of 0.71.</AbstractText Node-RADS score derived from staging CT shows only limited diagnostic accuracy to correctly predict nodal positivity in colon cancer. The interreader variability seems to be high and should question the clinical translation for this tumour entity.</AbstractText
This paper examines the impact of delayed diagnosis and treatment on the prognosis of patients with leiomyosarcomas (LMS). We present a case study highlighting the consequences of neglected LMS, focusing on vascular involvement and metastatic potential. Our findings underscore the importance of early detection and intervention in improving patient outcomes. Additionally, we discuss the challenges associated with diagnosing rare skin LMS and the implications of limited access to medical screening. Through a comprehensive analysis of the literature, we elucidate the critical role of routine surveillance in detecting these malignancies at an earlier stage, thus facilitating timely intervention and potentially curative treatment. This study underscores the urgency of raising awareness among both healthcare providers and the general population about the significance of early detection and prompt management in mitigating the adverse outcomes associated with neglected LMS.</AbstractText
Machine learning models using multiparametric MRI for preoperative risk stratification in endometrial cancer. This study evaluated the efficacy of machine learning and radiomics of preoperative multiparameter MRIs in predicting low- vs high-risk histopathologic features and early vs advanced FIGO stage (IA vs IB or higher) in endometrial cancer. This retrospective study of patients with endometrial cancer histologically confirmed from 2008 through 2023 excluded those with: (a) previous treatment for endometrial carcinoma, (b) incomplete MRI examinations or low-quality MR images, (c) incomplete pathology reports, (d) non-visualized tumors on MRI, or (e) distant metastases. In total, 110 radiomic features were extracted using commercial PACS built-in software following segmentation after sagittal T2-weighted imaging (T2WI), contrast enhanced T1-weighted imaging (CE-T1WI), and diffusion weighted imaging (DWI). The radiomic features from each imaging sequence were utilized for initial modeling. A combined model, which included features retained from all 3 sequences, was then established. The area under the receiver operating characteristic curve (AUC) determined the efficacy of each model. For 5 specific histopathologic features, the combined model achieved AUCs of 0.87 (95% CI, 0.85-0.90), 0.90 (95% CI, 0.88-0.92), 0.88 (95% CI, 0.87-0.90), 0.88 (95% CI, 0.86-0.92), and 0.87 (95% CI, 0.86-0.90). This model incorporated 38 radiomic features: 12 from T2WI, 17 from CE-T1WI, and 9 from DWI. In conclusion, an MRI radiomics-based model can differentiate between early- and advanced-stage endometrial cancer and between low- and high-risk histologic markers, giving it the potential to predict high risk and stratify preoperative risk in those with endometrial cancer. The findings may aid personalized preoperative assessments to guide clinical decision-making in endometrial cancer.</AbstractText
Diagnostic accuracy and reliability of CT-based Node-RADS for colon cancer. The Node-RADS classification was recently published as a classification system to better characterize lymph nodes in oncological imaging. The present analysis investigated the diagnostic benefit of the Node-RADS classification of staging computed tomography (CT) images to categorize and stage lymph nodes in patients with colon cancer.</AbstractText All patients were surgically resected and the lymph nodes were histopathological analyzed. All investigated lymph nodes were scored in accordance to the Node-RADS classification by two experienced radiologists. Interreader variability was assessed with Cohen's kappa analysis, discrimination analysis was performed with Mann-Whitney-U test and diagnostic accuracy was assessed with receiver-operating characteristics (ROC) curve analysis.</AbstractText Overall, 108 patients (n&#x2009;=&#x2009;49 females, 45.3%) with a mean age of 70.08&#x2009;&#xb1;&#x2009;14.34 years were included. In discrimination analysis, the total Node-RADS score showed statistically significant differences between N- and N&#x2009;+&#x2009;stage (for reader 1: mean 1.89&#x2009;&#xb1;&#x2009;1.09 score for N- versus 2.93&#x2009;&#xb1;&#x2009;1.62 score for N+, for reader 2: 1.33&#x2009;&#xb1;&#x2009;0.48 score for N- versus 3.65&#x2009;&#xb1;&#x2009;0.94 score for N+, p&#x2009;=&#x2009;0.001, respectively). ROC curve analysis for lymph node discrimination showed an area under the curve of 0.68. A threshold value of 2 resulted in a sensitivity of 0.62 and a specificity of 0.71.</AbstractText Node-RADS score derived from staging CT shows only limited diagnostic accuracy to correctly predict nodal positivity in colon cancer. The interreader variability seems to be high and should question the clinical translation for this tumour entity.</AbstractText
A Giant, Neglected Leiomyosarcoma on the Left Shoulder. This paper examines the impact of delayed diagnosis and treatment on the prognosis of patients with leiomyosarcomas (LMS). We present a case study highlighting the consequences of neglected LMS, focusing on vascular involvement and metastatic potential. Our findings underscore the importance of early detection and intervention in improving patient outcomes. Additionally, we discuss the challenges associated with diagnosing rare skin LMS and the implications of limited access to medical screening. Through a comprehensive analysis of the literature, we elucidate the critical role of routine surveillance in detecting these malignancies at an earlier stage, thus facilitating timely intervention and potentially curative treatment. This study underscores the urgency of raising awareness among both healthcare providers and the general population about the significance of early detection and prompt management in mitigating the adverse outcomes associated with neglected LMS.</AbstractText
16242909
7768280
31247290
Metabotropic glutamate receptors mediate lipopolysaccharide-induced fever and sickness behavior.
The dopamine receptor agonist 7-OH-DPAT modulates the acquisition and expression of morphine-induced place preference.
Experimental alcoholism primes structural and functional impairment of the glymphatic pathway.
Several mechanisms have been proposed for neuroimmune communication supporting the sickness syndrome (fever, anorexia, inactivity, and cachexia) following infection. We examined the role of glutamate as a neurochemical intermediary of sickness behavior induced by intraperitoneal lipopolysaccharide (LPS). Mice implanted with biotelemetry devices capable of detecting body temperature (Tb) were administered LPS (50 or 500 microg/kg i.p., serotype 0111:B4) with or without i.p. pretreatment with vehicle or broad-spectrum antagonists selective for N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic (AMPA)/kainite, or metabotropic glutamate (mGlu) receptors. While NMDA and AMPA/kainate receptor antagonism failed to attenuate LPS-induced sickness behavior, antagonism of metabotropic receptors with l(+)-AP3 reduced the febrile (0-11h: control: 37.32+/-0.16 degrees C, l(+)-AP3: 36.66+/-0.27), anorexic (control: -87+/-5%, l(+)-AP3: 48+/-12% scotophase food intake), and cachexic (control: -8.9+/-0.4%, l(+)-AP3: -6.1+/-1.3% body weight) effects of 500 microg/kg LPS, and produced a biphasic Tb effect in response to 50 microg/kg LPS (1h: -0.90+/-0.26; 6h: 1.78+/-0.35 degrees C relative to baseline). At this dose the Tb of l(+)-AP3-treated mice was 1.18 degrees C lower than controls 2h post-injection, and 0.68 degrees C greater that controls 8h post-injection. These results suggest a role for mGlu receptors in mediating fever, anorexia, and cachexia possibly via activation of extra-vagal pathways, since the attenuating effect of l(+)-AP3 increased with increasing dosages of LPS. Given the critical role ascribed to mGlu receptors in neurotransmitter release and astrocytic processes, it is possible that these observations reflect an l(+)-AP3-induced attenuation of these systems.</AbstractText
The present study investigated the effects of systemic administration of the putative dopamine D3 receptor agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) on the acquisition and expression of morphine-induced place preference in male Wistar rats. Using a a 3-day schedule of conditioning it was found that 7-OH-DPAT in a broad dose range (0.01, 0.25 and 5.0 mg/kg) did not produce significant place preference. However, the administration of either 0.25 or 5.0 mg/kg of 7-OH-DPAT 15 min prior to the exposure to morphine (1 mg/kg) prevented the acquisition of a morphine place preference, whereas the 0.01 mg/kg dose of the dopamine receptor agonist was uneffective. In addition, when 7-OH-DPAT was acutely administered 15 min prior to the testing session of an already established morphine place preference, the 0.01 mg/kg dose prevented the expression of this conditioned response. This effect was not observed with either 0.25 and 5.0 mg/kg doses of this dopamine D3 receptor agonist. It was suggested that the different dose related effects of 7-OH-DPAT on the acquisition and expression of morphine place preference might be related to the intrinsic ability of this agonist for interacting with pre- and postsynaptic dopamine D3 receptors located in limbic projecting areas of the mesencephalic dopamine system, although involvement of dopamine D2 receptors cannot be excluded. The pattern of effects seen with 7-OH-DPAT suggests that it may be useful for treating opiate dependence and craving.</AbstractText
Alcoholism is a risk factor for the development of cognitive decline and dementia. Here we demonstrated that the glymphatic function in the brain was impaired by alcohol administration. Acute moderate alcohol administration substantially retarded and reduced the entry of subarachnoid cerebrospinal fluid (CSF) via the paravascular space into the cerebral parenchyma, thus impaired CSF-interstitial fluid (ISF) exchange and parenchymal amyloid &#x3b2; (A&#x3b2;) peptide clearance. The elevated release of &#x3b2;-endorphin and reduced cerebrovascular pulsatility after acute alcohol administration may account for the impairment of the glymphatic function. Chronic moderate alcohol consumption led to pronounced activation of astrocytes and a widespread loss of perivascular AQP4 polarization in the brain, which results in an irreversible impairment of the glymphatic function. The results of the study suggest that impaired glymphatic functions and reduced parenchymal A&#x3b2; clearance found in both acute and chronic alcohol treatment may contribute to the development of cognitive decline and dementia in alcoholism.</AbstractText
Metabotropic glutamate receptors mediate lipopolysaccharide-induced fever and sickness behavior. Several mechanisms have been proposed for neuroimmune communication supporting the sickness syndrome (fever, anorexia, inactivity, and cachexia) following infection. We examined the role of glutamate as a neurochemical intermediary of sickness behavior induced by intraperitoneal lipopolysaccharide (LPS). Mice implanted with biotelemetry devices capable of detecting body temperature (Tb) were administered LPS (50 or 500 microg/kg i.p., serotype 0111:B4) with or without i.p. pretreatment with vehicle or broad-spectrum antagonists selective for N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic (AMPA)/kainite, or metabotropic glutamate (mGlu) receptors. While NMDA and AMPA/kainate receptor antagonism failed to attenuate LPS-induced sickness behavior, antagonism of metabotropic receptors with l(+)-AP3 reduced the febrile (0-11h: control: 37.32+/-0.16 degrees C, l(+)-AP3: 36.66+/-0.27), anorexic (control: -87+/-5%, l(+)-AP3: 48+/-12% scotophase food intake), and cachexic (control: -8.9+/-0.4%, l(+)-AP3: -6.1+/-1.3% body weight) effects of 500 microg/kg LPS, and produced a biphasic Tb effect in response to 50 microg/kg LPS (1h: -0.90+/-0.26; 6h: 1.78+/-0.35 degrees C relative to baseline). At this dose the Tb of l(+)-AP3-treated mice was 1.18 degrees C lower than controls 2h post-injection, and 0.68 degrees C greater that controls 8h post-injection. These results suggest a role for mGlu receptors in mediating fever, anorexia, and cachexia possibly via activation of extra-vagal pathways, since the attenuating effect of l(+)-AP3 increased with increasing dosages of LPS. Given the critical role ascribed to mGlu receptors in neurotransmitter release and astrocytic processes, it is possible that these observations reflect an l(+)-AP3-induced attenuation of these systems.</AbstractText
The dopamine receptor agonist 7-OH-DPAT modulates the acquisition and expression of morphine-induced place preference. The present study investigated the effects of systemic administration of the putative dopamine D3 receptor agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) on the acquisition and expression of morphine-induced place preference in male Wistar rats. Using a a 3-day schedule of conditioning it was found that 7-OH-DPAT in a broad dose range (0.01, 0.25 and 5.0 mg/kg) did not produce significant place preference. However, the administration of either 0.25 or 5.0 mg/kg of 7-OH-DPAT 15 min prior to the exposure to morphine (1 mg/kg) prevented the acquisition of a morphine place preference, whereas the 0.01 mg/kg dose of the dopamine receptor agonist was uneffective. In addition, when 7-OH-DPAT was acutely administered 15 min prior to the testing session of an already established morphine place preference, the 0.01 mg/kg dose prevented the expression of this conditioned response. This effect was not observed with either 0.25 and 5.0 mg/kg doses of this dopamine D3 receptor agonist. It was suggested that the different dose related effects of 7-OH-DPAT on the acquisition and expression of morphine place preference might be related to the intrinsic ability of this agonist for interacting with pre- and postsynaptic dopamine D3 receptors located in limbic projecting areas of the mesencephalic dopamine system, although involvement of dopamine D2 receptors cannot be excluded. The pattern of effects seen with 7-OH-DPAT suggests that it may be useful for treating opiate dependence and craving.</AbstractText
Experimental alcoholism primes structural and functional impairment of the glymphatic pathway. Alcoholism is a risk factor for the development of cognitive decline and dementia. Here we demonstrated that the glymphatic function in the brain was impaired by alcohol administration. Acute moderate alcohol administration substantially retarded and reduced the entry of subarachnoid cerebrospinal fluid (CSF) via the paravascular space into the cerebral parenchyma, thus impaired CSF-interstitial fluid (ISF) exchange and parenchymal amyloid &#x3b2; (A&#x3b2;) peptide clearance. The elevated release of &#x3b2;-endorphin and reduced cerebrovascular pulsatility after acute alcohol administration may account for the impairment of the glymphatic function. Chronic moderate alcohol consumption led to pronounced activation of astrocytes and a widespread loss of perivascular AQP4 polarization in the brain, which results in an irreversible impairment of the glymphatic function. The results of the study suggest that impaired glymphatic functions and reduced parenchymal A&#x3b2; clearance found in both acute and chronic alcohol treatment may contribute to the development of cognitive decline and dementia in alcoholism.</AbstractText
38857886
37946527
38519637
Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.
Brain Abscess Caused by Oral Cavity Bacteria: A Nationwide, Population-based Cohort Study.
Correlation between magnetic resonance imaging proton density fat fraction (MRI-PDFF) and liver biopsy to assess hepatic steatosis in obesity.
Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at the National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM), and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n&#xa0;=&#xa0;8) and A. levis (n&#xa0;=&#xa0;1), from brain abscess (n&#xa0;=&#xa0;4), respiratory tract (n&#xa0;=&#xa0;3), and corneal scraping (n&#xa0;=&#xa0;2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the internal transcribed spacer ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed the lowest minimum inhibitory concentrations (MICs) for triazoles and the highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin, and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.</AbstractText We describe clinical, phenotypic, and genotypic characteristics of Acrophialophora species. This species causes mild infection to fatal infection in immunosuppressed individuals. Triazoles are effective in treating such infections.</AbstractText
Oral cavity bacteria are the most frequent etiology of brain abscess. Yet, data on the clinical presentation and outcome are scarce.</AbstractText We performed a nationwide, population-based study comprising all adults (aged &#x2265;18 years) with brain abscess due to oral cavity bacteria in Denmark from 2007 through 2020. Prognostic factors for unfavorable outcome (Glasgow outcome scale, 1-4) were examined using modified Poisson regression to compute adjusted relative risks (RRs) with 95% confidence intervals (CIs).</AbstractText Among 287 identified patients, the median age was 58 years (interquartile range, 47-66), and 96 of 287 (33%) were female. Preexisting functional impairment was absent or mild in 253 of 280 (90%), and risk factors for brain abscess included immunocompromise in 95 of 287 (33%), dental infection in 68 of 287 (24%), and ear-nose-throat infection in 33 of 287 (12%). Overall, a neurological deficit was present in 246 of 276 (86%) and in combination with headache and fever in 64 of 287 (22%). Identified microorganisms were primarily the Streptococcus anginosus group, Fusobacterium, Actinomyces, and Aggregatibacter spp., and 117 of 287 (41%) were polymicrobial. Unfavorable outcome occurred in 92 of 246 (37%) at 6 months after discharge and was associated with antibiotics before neurosurgery (RR, 3.28; 95% CI, 1.53-7.04), rupture (RR, 1.89; 95% CI, 1.34-2.65), and immunocompromise (RR, 1.80; 95% CI, 1.29-2.51), but not with specific targeted antibiotic regimens. Identified dental infection was associated with favorable prognosis (RR, 0.58; 95% CI, .36-.93).</AbstractText Brain abscess due to oral cavity bacteria often occurred in previously healthy individuals without predisposing dental infections. Important risk factors for unfavorable outcome were rupture and immunocompromise. However, outcome was not associated with specific antibiotic regimens supporting carbapenem-sparing strategies.</AbstractText
Obesity is highly associated with Non-alcoholic fatty liver disease (NAFLD) and increased risk of liver cirrhosis and liver cancer-related death. We determined the diagnostic performance of the complex-based chemical shift technique MRI-PDFF for quantifying liver fat and its correlation with histopathologic findings in an obese population within 24&#xa0;h before bariatric surgery. This was a prospective, cross-sectional, Institutional Review Board-approved study of PDFF-MRI of the liver and MRI-DIXON image volume before bariatric surgery. Liver tissues were obtained during bariatric surgery. The prevalence of NAFLD in the investigated cohort was as high as 94%. Histologic hepatic steatosis grades 0, 1, 2, and 3 were observed in 3 (6%), 25 (50%), 14 (28%), and 8 (16%) of 50 obese patients, respectively. The mean percentages of MRI-PDFF from the anterior and posterior right hepatic lobe and left lobe vs. isolate left hepatic lobe were 15.6% (standard deviation [SD], 9.28%) vs. 16.29% (SD, 9.25%). There was a strong correlation between the percentage of steatotic hepatocytes and MRI-PDFF in the left hepatic lobe (r&#x2009;=&#x2009;0.82, p&#x2009;&lt;&#x2009;0.001) and the mean value (r&#x2009;=&#x2009;0.78, p&#x2009;&lt;&#x2009;0.001). There was a strong correlation between MRI-derived subcutaneous adipose tissue volume and total body fat mass by dual-energy X-ray absorptiometry, especially at the L2-3 and L4 level (r&#x2009;=&#x2009;0.85, p&#x2009;&lt;&#x2009;0.001). MRI-PDFF showed good performance in assessing hepatic steatosis and was an excellent noninvasive technique for monitoring hepatic steatosis in an obese population.</AbstractText
Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India. Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at the National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM), and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n&#xa0;=&#xa0;8) and A. levis (n&#xa0;=&#xa0;1), from brain abscess (n&#xa0;=&#xa0;4), respiratory tract (n&#xa0;=&#xa0;3), and corneal scraping (n&#xa0;=&#xa0;2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the internal transcribed spacer ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed the lowest minimum inhibitory concentrations (MICs) for triazoles and the highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin, and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.</AbstractText We describe clinical, phenotypic, and genotypic characteristics of Acrophialophora species. This species causes mild infection to fatal infection in immunosuppressed individuals. Triazoles are effective in treating such infections.</AbstractText
Brain Abscess Caused by Oral Cavity Bacteria: A Nationwide, Population-based Cohort Study. Oral cavity bacteria are the most frequent etiology of brain abscess. Yet, data on the clinical presentation and outcome are scarce.</AbstractText We performed a nationwide, population-based study comprising all adults (aged &#x2265;18 years) with brain abscess due to oral cavity bacteria in Denmark from 2007 through 2020. Prognostic factors for unfavorable outcome (Glasgow outcome scale, 1-4) were examined using modified Poisson regression to compute adjusted relative risks (RRs) with 95% confidence intervals (CIs).</AbstractText Among 287 identified patients, the median age was 58 years (interquartile range, 47-66), and 96 of 287 (33%) were female. Preexisting functional impairment was absent or mild in 253 of 280 (90%), and risk factors for brain abscess included immunocompromise in 95 of 287 (33%), dental infection in 68 of 287 (24%), and ear-nose-throat infection in 33 of 287 (12%). Overall, a neurological deficit was present in 246 of 276 (86%) and in combination with headache and fever in 64 of 287 (22%). Identified microorganisms were primarily the Streptococcus anginosus group, Fusobacterium, Actinomyces, and Aggregatibacter spp., and 117 of 287 (41%) were polymicrobial. Unfavorable outcome occurred in 92 of 246 (37%) at 6 months after discharge and was associated with antibiotics before neurosurgery (RR, 3.28; 95% CI, 1.53-7.04), rupture (RR, 1.89; 95% CI, 1.34-2.65), and immunocompromise (RR, 1.80; 95% CI, 1.29-2.51), but not with specific targeted antibiotic regimens. Identified dental infection was associated with favorable prognosis (RR, 0.58; 95% CI, .36-.93).</AbstractText Brain abscess due to oral cavity bacteria often occurred in previously healthy individuals without predisposing dental infections. Important risk factors for unfavorable outcome were rupture and immunocompromise. However, outcome was not associated with specific antibiotic regimens supporting carbapenem-sparing strategies.</AbstractText
Correlation between magnetic resonance imaging proton density fat fraction (MRI-PDFF) and liver biopsy to assess hepatic steatosis in obesity. Obesity is highly associated with Non-alcoholic fatty liver disease (NAFLD) and increased risk of liver cirrhosis and liver cancer-related death. We determined the diagnostic performance of the complex-based chemical shift technique MRI-PDFF for quantifying liver fat and its correlation with histopathologic findings in an obese population within 24&#xa0;h before bariatric surgery. This was a prospective, cross-sectional, Institutional Review Board-approved study of PDFF-MRI of the liver and MRI-DIXON image volume before bariatric surgery. Liver tissues were obtained during bariatric surgery. The prevalence of NAFLD in the investigated cohort was as high as 94%. Histologic hepatic steatosis grades 0, 1, 2, and 3 were observed in 3 (6%), 25 (50%), 14 (28%), and 8 (16%) of 50 obese patients, respectively. The mean percentages of MRI-PDFF from the anterior and posterior right hepatic lobe and left lobe vs. isolate left hepatic lobe were 15.6% (standard deviation [SD], 9.28%) vs. 16.29% (SD, 9.25%). There was a strong correlation between the percentage of steatotic hepatocytes and MRI-PDFF in the left hepatic lobe (r&#x2009;=&#x2009;0.82, p&#x2009;&lt;&#x2009;0.001) and the mean value (r&#x2009;=&#x2009;0.78, p&#x2009;&lt;&#x2009;0.001). There was a strong correlation between MRI-derived subcutaneous adipose tissue volume and total body fat mass by dual-energy X-ray absorptiometry, especially at the L2-3 and L4 level (r&#x2009;=&#x2009;0.85, p&#x2009;&lt;&#x2009;0.001). MRI-PDFF showed good performance in assessing hepatic steatosis and was an excellent noninvasive technique for monitoring hepatic steatosis in an obese population.</AbstractText
38915631
26993424
39635901
Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration.
Midcingulate cortex: Structure, connections, homologies, functions and diseases.
Chemotherapy and radiotherapy for advanced pancreatic cancer.
During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here we analyzed the role of microglia in the synapse disassembly of degenerating postsynaptic neurons in the inner retina. After inducing transient intraocular pressure elevation to injure retinal ganglion cells, microglia increase in number, shift to ameboid morphology, and exhibit greater process movement. Furthermore, due to the greater number of microglia, there is increased colocalization of microglia with synaptic components throughout the inner plexiform layer and with excitatory synaptic sites along individual ganglion cell dendrites. Microglia depletion partially restores ganglion cell function, suggesting that microglia activation may be neurotoxic in early neurodegeneration. Our results demonstrate the important role of microglia in synapse disassembly in degenerating circuits, highlighting their recruitment to synaptic sites early after neuronal injury.</AbstractText
Midcingulate cortex (MCC) has risen in prominence as human imaging identifies unique structural and functional activity therein and this is the first review of its structure, connections, functions and disease vulnerabilities. The MCC has two divisions (anterior, aMCC and posterior, pMCC) that represent functional units and the cytoarchitecture, connections and neurocytology of each is shown with immunohistochemistry and receptor binding. The MCC is not a division of anterior cingulate cortex (ACC) and the "dorsal ACC" designation is a misnomer as it incorrectly implies that MCC is a division of ACC. Interpretation of findings among species and developing models of human diseases requires detailed comparative studies which is shown here for five species with flat maps and immunohistochemistry (human, monkey, rabbit, rat, mouse). The largest neurons in human cingulate cortex are in layer Vb of area 24 d in pMCC which project to the spinal cord. This area is part of the caudal cingulate premotor area which is involved in multisensory orientation of the head and body in space and neuron responses are tuned for the force and direction of movement. In contrast, the rostral cingulate premotor area in aMCC is involved in action-reinforcement associations and selection based on the amount of reward or aversive properties of a potential movement. The aMCC is activated by nociceptive information from the midline, mediodorsal and intralaminar thalamic nuclei which evoke fear and mediates nocifensive behaviors. This subregion also has high dopaminergic afferents and high dopamine-1 receptor binding and is engaged in reward processes. Opposing pain/avoidance and reward/approach functions are selected by assessment of potential outcomes and error detection according to feedback-mediated, decision making. Parietal afferents differentially terminate in MCC and provide for multisensory control in an eye- and head-centric manner. Finally, MCC vulnerability in human disease confirms the unique organization of MCC and supports the predictive validity of the MCC dichotomy. Vulnerability of aMCC is shown in chronic pain, obsessive-compulsive disorder with checking symptoms and attention-deficit/hyperactivity disorder and methylphenidate and pain medications selectively impact aMCC. In contrast, pMCC vulnerabilities are for progressive supranuclear palsy, unipolar depression and posttraumatic stress disorder. Thus, there is an emerging picture of the organization, functions and diseases of MCC. Future work will take this type of modular analysis to individual areas of which there are at least 10 in MCC.</AbstractText
Pancreatic cancer (PC) is a lethal disease with few effective treatment options. Many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review synthesises all the randomised data available to help better inform patient and clinician decision-making. It updates the previous version of the review, published in 2018.</AbstractText To assess the effects of chemotherapy, radiotherapy, or both on overall survival, severe or life-threatening adverse events, and quality of life in people undergoing first-line treatment of advanced pancreatic cancer.</AbstractText We searched for published and unpublished studies in CENTRAL, MEDLINE, Embase, and CANCERLIT, and handsearched various sources for additional studies. The latest search dates were in March and July 2023.</AbstractText We included randomised controlled trials comparing chemotherapy, radiotherapy, or both with another intervention or best supportive care. Participants were required to have locally advanced, unresectable pancreatic cancer or metastatic pancreatic cancer not amenable to curative intent treatment. Histological confirmation was required. Trials were required to report overall survival.</AbstractText We used standard methodological procedures expected by Cochrane.</AbstractText We included 75 studies in the review and 51 in the meta-analysis (11,333 participants). We divided the studies into seven categories: any anti-cancer treatment versus best supportive care; various chemotherapy types versus gemcitabine; gemcitabine-based combinations versus gemcitabine alone; various chemotherapy combinations versus gemcitabine plus nab-paclitaxel; fluoropyrimidine-based studies; miscellaneous studies; and radiotherapy studies. In general, the included studies were at low risk for random sequence generation, detection bias, attrition bias, and reporting bias, at unclear risk for allocation concealment, and high risk for performance bias. Compared to best supportive care, chemotherapy likely results in little to no difference in overall survival (OS) (hazard ratio (HR) 1.08, 95% confidence interval (CI) 0.88 to 1.33; absolute risk of death at 12 months of 971 per 1000 versus 962 per 1000; 4 studies, 298 participants; moderate-certainty evidence). The adverse effects of chemotherapy and impacts on quality of life (QoL) were uncertain. Many of the chemotherapy regimens were outdated. Eight studies compared non-gemcitabine-based chemotherapy regimens to gemcitabine. These showed that 5-fluorouracil (5FU) likely reduces OS (HR 1.69, 95% CI 1.26 to 2.27; risk of death at 12 months of 914 per 1000 versus 767 per 1000; 1 study, 126 participants; moderate certainty), and grade 3/4 adverse events (QoL not reported). Fixed dose rate gemcitabine likely improves OS (HR 0.79, 95% CI 0.66 to 0.94; risk of death at 12 months of 683 per 1000 versus 767 per 1000; 2 studies, 644 participants; moderate certainty), and likely increase grade 3/4 adverse events (QoL not reported). FOLFIRINOX improves OS (HR 0.51, 95% CI 0.43 to 0.60; risk of death at 12 months of 524 per 1000 versus 767 per 1000; P &lt; 0.001; 2 studies, 652 participants; high certainty), and delays deterioration in QoL, but increases grade 3/4 adverse events. Twenty-eight studies compared gemcitabine-based combinations to gemcitabine. Gemcitabine plus platinum may result in little to no difference in OS (HR 0.94, 95% CI 0.81 to 1.08; risk of death at 12 months of 745 per 1000 versus 767 per 1000; 6 studies, 1140 participants; low certainty), may increase grade 3/4 adverse events, and likely worsens QoL. Gemcitabine plus fluoropyrimidine improves OS (HR 0.88, 95% CI 0.81 to 0.95; risk of death at 12 months of 722 per 1000 versus 767 per 1000; 10 studies, 2718 participants; high certainty), likely increases grade 3/4 adverse events, and likely improves QoL. Gemcitabine plus topoisomerase inhibitors result in little to no difference in OS (HR 1.01, 95% CI 0.87 to 1.16; risk of death at 12 months of 770 per 1000 versus 767 per 1000; 3 studies, 839 participants; high certainty), likely increases grade 3/4 adverse events, and likely does not alter QoL. Gemcitabine plus taxane result in a large improvement in OS (HR 0.71, 95% CI 0.62 to 0.81; risk of death at 12 months of 644 per 1000 versus 767 per 1000; 2 studies, 986 participants; high certainty), and likely increases grade 3/4 adverse events and improves QoL. Nine studies compared chemotherapy combinations to gemcitabine plus nab-paclitaxel. Fluoropyrimidine-based combination regimens improve OS (HR 0.79, 95% CI 0.70 to 0.89; risk of death at 12 months of 542 per 1000 versus 628 per 1000; 6 studies, 1285 participants; high certainty). The treatment arms had distinct toxicity profiles, and there was little to no difference in QoL. Alternative schedules of gemcitabine plus nab-paclitaxel likely result in little to no difference in OS (HR 1.10, 95% CI 0.82 to 1.47; risk of death at 12 months of 663 per 1000 versus 628 per 1000; 2 studies, 367 participants; moderate certainty) or QoL, but may increase grade 3/4 adverse events. Four studies compared fluoropyrimidine-based combinations to fluoropyrimidines alone, with poor quality evidence. Fluoropyrimidine-based combinations are likely to result in little to no impact on OS (HR 0.84, 95% CI 0.61 to 1.15; risk of death at 12 months of 765 per 1000 versus 704 per 1000; P = 0.27; 4 studies, 491 participants; moderate certainty) versus fluoropyrimidines alone. The evidence suggests that there was little to no difference in grade 3/4 adverse events or QoL between the two groups. We included only one radiotherapy (iodine-125 brachytherapy) study with 165 participants. The evidence is very uncertain about the effect of radiotherapy on outcomes.</AbstractText Combination chemotherapy remains standard of care for metastatic pancreatic cancer. Both FOLFIRINOX and gemcitabine plus a taxane improve OS compared to gemcitabine alone. Furthermore, the evidence suggests that fluoropyrimidine-based combination chemotherapy regimens improve OS compared to gemcitabine plus nab-paclitaxel. The effects of radiotherapy were uncertain as only one low-quality trial was included. Selection of the most appropriate chemotherapy for individuals still remains unpersonalised, with clinicopathological stratification remaining elusive. Biomarker development is essential to assist in rationalising treatment selection for patients.</AbstractText
Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration. During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here we analyzed the role of microglia in the synapse disassembly of degenerating postsynaptic neurons in the inner retina. After inducing transient intraocular pressure elevation to injure retinal ganglion cells, microglia increase in number, shift to ameboid morphology, and exhibit greater process movement. Furthermore, due to the greater number of microglia, there is increased colocalization of microglia with synaptic components throughout the inner plexiform layer and with excitatory synaptic sites along individual ganglion cell dendrites. Microglia depletion partially restores ganglion cell function, suggesting that microglia activation may be neurotoxic in early neurodegeneration. Our results demonstrate the important role of microglia in synapse disassembly in degenerating circuits, highlighting their recruitment to synaptic sites early after neuronal injury.</AbstractText
Midcingulate cortex: Structure, connections, homologies, functions and diseases. Midcingulate cortex (MCC) has risen in prominence as human imaging identifies unique structural and functional activity therein and this is the first review of its structure, connections, functions and disease vulnerabilities. The MCC has two divisions (anterior, aMCC and posterior, pMCC) that represent functional units and the cytoarchitecture, connections and neurocytology of each is shown with immunohistochemistry and receptor binding. The MCC is not a division of anterior cingulate cortex (ACC) and the "dorsal ACC" designation is a misnomer as it incorrectly implies that MCC is a division of ACC. Interpretation of findings among species and developing models of human diseases requires detailed comparative studies which is shown here for five species with flat maps and immunohistochemistry (human, monkey, rabbit, rat, mouse). The largest neurons in human cingulate cortex are in layer Vb of area 24 d in pMCC which project to the spinal cord. This area is part of the caudal cingulate premotor area which is involved in multisensory orientation of the head and body in space and neuron responses are tuned for the force and direction of movement. In contrast, the rostral cingulate premotor area in aMCC is involved in action-reinforcement associations and selection based on the amount of reward or aversive properties of a potential movement. The aMCC is activated by nociceptive information from the midline, mediodorsal and intralaminar thalamic nuclei which evoke fear and mediates nocifensive behaviors. This subregion also has high dopaminergic afferents and high dopamine-1 receptor binding and is engaged in reward processes. Opposing pain/avoidance and reward/approach functions are selected by assessment of potential outcomes and error detection according to feedback-mediated, decision making. Parietal afferents differentially terminate in MCC and provide for multisensory control in an eye- and head-centric manner. Finally, MCC vulnerability in human disease confirms the unique organization of MCC and supports the predictive validity of the MCC dichotomy. Vulnerability of aMCC is shown in chronic pain, obsessive-compulsive disorder with checking symptoms and attention-deficit/hyperactivity disorder and methylphenidate and pain medications selectively impact aMCC. In contrast, pMCC vulnerabilities are for progressive supranuclear palsy, unipolar depression and posttraumatic stress disorder. Thus, there is an emerging picture of the organization, functions and diseases of MCC. Future work will take this type of modular analysis to individual areas of which there are at least 10 in MCC.</AbstractText
Chemotherapy and radiotherapy for advanced pancreatic cancer. Pancreatic cancer (PC) is a lethal disease with few effective treatment options. Many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review synthesises all the randomised data available to help better inform patient and clinician decision-making. It updates the previous version of the review, published in 2018.</AbstractText To assess the effects of chemotherapy, radiotherapy, or both on overall survival, severe or life-threatening adverse events, and quality of life in people undergoing first-line treatment of advanced pancreatic cancer.</AbstractText We searched for published and unpublished studies in CENTRAL, MEDLINE, Embase, and CANCERLIT, and handsearched various sources for additional studies. The latest search dates were in March and July 2023.</AbstractText We included randomised controlled trials comparing chemotherapy, radiotherapy, or both with another intervention or best supportive care. Participants were required to have locally advanced, unresectable pancreatic cancer or metastatic pancreatic cancer not amenable to curative intent treatment. Histological confirmation was required. Trials were required to report overall survival.</AbstractText We used standard methodological procedures expected by Cochrane.</AbstractText We included 75 studies in the review and 51 in the meta-analysis (11,333 participants). We divided the studies into seven categories: any anti-cancer treatment versus best supportive care; various chemotherapy types versus gemcitabine; gemcitabine-based combinations versus gemcitabine alone; various chemotherapy combinations versus gemcitabine plus nab-paclitaxel; fluoropyrimidine-based studies; miscellaneous studies; and radiotherapy studies. In general, the included studies were at low risk for random sequence generation, detection bias, attrition bias, and reporting bias, at unclear risk for allocation concealment, and high risk for performance bias. Compared to best supportive care, chemotherapy likely results in little to no difference in overall survival (OS) (hazard ratio (HR) 1.08, 95% confidence interval (CI) 0.88 to 1.33; absolute risk of death at 12 months of 971 per 1000 versus 962 per 1000; 4 studies, 298 participants; moderate-certainty evidence). The adverse effects of chemotherapy and impacts on quality of life (QoL) were uncertain. Many of the chemotherapy regimens were outdated. Eight studies compared non-gemcitabine-based chemotherapy regimens to gemcitabine. These showed that 5-fluorouracil (5FU) likely reduces OS (HR 1.69, 95% CI 1.26 to 2.27; risk of death at 12 months of 914 per 1000 versus 767 per 1000; 1 study, 126 participants; moderate certainty), and grade 3/4 adverse events (QoL not reported). Fixed dose rate gemcitabine likely improves OS (HR 0.79, 95% CI 0.66 to 0.94; risk of death at 12 months of 683 per 1000 versus 767 per 1000; 2 studies, 644 participants; moderate certainty), and likely increase grade 3/4 adverse events (QoL not reported). FOLFIRINOX improves OS (HR 0.51, 95% CI 0.43 to 0.60; risk of death at 12 months of 524 per 1000 versus 767 per 1000; P &lt; 0.001; 2 studies, 652 participants; high certainty), and delays deterioration in QoL, but increases grade 3/4 adverse events. Twenty-eight studies compared gemcitabine-based combinations to gemcitabine. Gemcitabine plus platinum may result in little to no difference in OS (HR 0.94, 95% CI 0.81 to 1.08; risk of death at 12 months of 745 per 1000 versus 767 per 1000; 6 studies, 1140 participants; low certainty), may increase grade 3/4 adverse events, and likely worsens QoL. Gemcitabine plus fluoropyrimidine improves OS (HR 0.88, 95% CI 0.81 to 0.95; risk of death at 12 months of 722 per 1000 versus 767 per 1000; 10 studies, 2718 participants; high certainty), likely increases grade 3/4 adverse events, and likely improves QoL. Gemcitabine plus topoisomerase inhibitors result in little to no difference in OS (HR 1.01, 95% CI 0.87 to 1.16; risk of death at 12 months of 770 per 1000 versus 767 per 1000; 3 studies, 839 participants; high certainty), likely increases grade 3/4 adverse events, and likely does not alter QoL. Gemcitabine plus taxane result in a large improvement in OS (HR 0.71, 95% CI 0.62 to 0.81; risk of death at 12 months of 644 per 1000 versus 767 per 1000; 2 studies, 986 participants; high certainty), and likely increases grade 3/4 adverse events and improves QoL. Nine studies compared chemotherapy combinations to gemcitabine plus nab-paclitaxel. Fluoropyrimidine-based combination regimens improve OS (HR 0.79, 95% CI 0.70 to 0.89; risk of death at 12 months of 542 per 1000 versus 628 per 1000; 6 studies, 1285 participants; high certainty). The treatment arms had distinct toxicity profiles, and there was little to no difference in QoL. Alternative schedules of gemcitabine plus nab-paclitaxel likely result in little to no difference in OS (HR 1.10, 95% CI 0.82 to 1.47; risk of death at 12 months of 663 per 1000 versus 628 per 1000; 2 studies, 367 participants; moderate certainty) or QoL, but may increase grade 3/4 adverse events. Four studies compared fluoropyrimidine-based combinations to fluoropyrimidines alone, with poor quality evidence. Fluoropyrimidine-based combinations are likely to result in little to no impact on OS (HR 0.84, 95% CI 0.61 to 1.15; risk of death at 12 months of 765 per 1000 versus 704 per 1000; P = 0.27; 4 studies, 491 participants; moderate certainty) versus fluoropyrimidines alone. The evidence suggests that there was little to no difference in grade 3/4 adverse events or QoL between the two groups. We included only one radiotherapy (iodine-125 brachytherapy) study with 165 participants. The evidence is very uncertain about the effect of radiotherapy on outcomes.</AbstractText Combination chemotherapy remains standard of care for metastatic pancreatic cancer. Both FOLFIRINOX and gemcitabine plus a taxane improve OS compared to gemcitabine alone. Furthermore, the evidence suggests that fluoropyrimidine-based combination chemotherapy regimens improve OS compared to gemcitabine plus nab-paclitaxel. The effects of radiotherapy were uncertain as only one low-quality trial was included. Selection of the most appropriate chemotherapy for individuals still remains unpersonalised, with clinicopathological stratification remaining elusive. Biomarker development is essential to assist in rationalising treatment selection for patients.</AbstractText
37227982
26741961
37303946
Perfusion CT imaging as a diagnostic and prognostic tool for dementia: prospective case-control study.
Differentiating Radiation-Induced Necrosis from Recurrent Brain Tumor Using MR Perfusion and Spectroscopy: A Meta-Analysis.
Management Outcomes of Large Renal Angiomyolipoma Presenting with Wunderlich Syndrome-Experience from a Tertiary Center.
As functional changes precede structural changes in dementia, we aimed to elucidate changes on cerebral perfusion CT (PCT) for early diagnosis of dementia; and to differentiate Alzheimer's disease (AD) from vascular dementia (VaD). We also aimed to study correlation between Montreal Cognitive Assessment (MOCA) score and PCT parameters.</AbstractText We conducted a prospective case-control study enrolling 25 dementia patients (15 cases of VaD, 10 cases of AD) and 25 age-matched controls. PCT was performed on a 256-slice CT scanner. Using perfusion software, colour maps were generated for cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time and time-to-peak. These colour maps were first visually inspected for any abnormalities. Subsequently, quantitative assessment of perfusion parameters was done using symmetrical freehand region of interests drawn in bilateral frontal, temporal, parietal regions, basal ganglia and hippocampi.</AbstractText Strategic infarcts were present in 93.3% cases and white matter ischaemic changes in 100% cases of VaD. A global reduction in CBF and CBV was also observed in cases of VaD; whereas these parameters were significantly lower mainly in temporoparietal regions and hippocampi of patients with AD. There was significant positive correlation between MOCA score and various perfusion parameters in both forms of dementia.</AbstractText PCT is a reliable imaging modality for early diagnosis of dementia and in differentiating VaD from AD. As perfusion parameters show positive correlation with MOCA score, they could be used as a surrogate marker of cognitive status in the follow-up of patients with dementia.</AbstractText
This meta-analysis examined roles of several metabolites in differentiating recurrent tumor from necrosis in patients with brain tumors using MR perfusion and spectroscopy.</AbstractText Medline, Cochrane, EMBASE, and Google Scholar were searched for studies using perfusion MRI and/or MR spectroscopy published up to March 4, 2015 which differentiated between recurrent tumor vs. necrosis in patients with primary brain tumors or brain metastasis. Only two-armed, prospective or retrospective studies were included. A meta-analysis was performed on the difference in relative cerebral blood volume (rCBV), ratios of choline/creatine (Cho/Cr) and/or choline/N-acetyl aspartate (Cho/NAA) between participants undergoing MRI evaluation. A &#x3c7;2-based test of homogeneity was performed using Cochran's Q statistic and I2.</AbstractText Of 397 patients in 13 studies who were analyzed, the majority had tumor recurrence. As there was evidence of heterogeneity among 10 of the studies which used rCBV for evaluation (Q statistic = 31.634, I2 = 97.11%, P &lt; 0.0001) a random-effects analysis was applied. The pooled difference in means (2.18, 95%CI = 0.85 to 3.50) indicated that the average rCBV in a contrast-enhancing lesion was significantly higher in tumor recurrence compared with radiation injury (P = 0.001). Based on a fixed-effect model of analysis encompassing the six studies which used Cho/Cr ratios for evaluation (Q statistic = 8.388, I2 = 40.39%, P = 0.137), the pooled difference in means (0.77, 95%CI = 0.57 to 0.98) of the average Cho/Cr ratio was significantly higher in tumor recurrence than in tumor necrosis (P = 0.001). There was significant difference in ratios of Cho to NAA between recurrent tumor and necrosis (1.02, 95%CI = 0.03 to 2.00, P = 0.044).</AbstractText MR spectroscopy and MR perfusion using Cho/NAA and Cho/Cr ratios and rCBV may increase the accuracy of differentiating necrosis from recurrent tumor in patients with primary brain tumors or metastases.</AbstractText
Renal angiomyolipoma is an uncommon, benign-mixed mesenchymal tumor consisting of thick-walled blood vessels, smooth muscles, and mature adipose tissues. Twenty percent of these tumors are associated with tuberous sclerosis. Wunderlich syndrome (WS), an acute nontraumatic spontaneous perirenal hemorrhage, can be a presentation of large angiomyolipoma. This study evaluated the presentation, management, and complications of renal angiomyolipoma with WS in eight patients who presented to the emergency department between January 2019 and December 2021. The presenting symptoms included flank pain, palpable mass, hematuria, and bleeding in the perinephric space on computerized tomography. Demographic data, symptoms at presentation, comorbidities, hemodynamic parameters, the association with tuberous sclerosis, transfusion requirements, need for angioembolization, surgical management, Clavien-Dindo complication, duration of hospital stay, and 30-day readmission rates were evaluated. The mean age of presentation was 38 years. Of the eight patients, five (62.5%) were females and 3(37.5%) were males. Two (25%) patients had tuberous sclerosis with angiomyolipoma, and three (37.5%) patients presented with hypotension. The mean packed cell transfusion was three units, and the mean tumor size was 7.85 cm (3.5-25 cm). Three of them (37.5%) required emergency angioembolization to prevent exsanguination. Embolization was unsuccessful in one patient (33%) who underwent emergency open partial nephrectomy, and one (33%) patient developed post-embolization syndrome. A total of six patients underwent elective surgery-four underwent partial nephrectomy (laparoscopic - 1, robotic - 1, open - 2) and two underwent open nephrectomy. Three patients encountered Clavien-Dindo complications (Grade 1, n = 2 and IIIA, n = 2). WS is a rare, life-threatening complication in patients with large angiomyolipoma. Judicious optimization, angioembolization, and prompt surgical intervention will help deliver better outcomes.</AbstractText
Perfusion CT imaging as a diagnostic and prognostic tool for dementia: prospective case-control study. As functional changes precede structural changes in dementia, we aimed to elucidate changes on cerebral perfusion CT (PCT) for early diagnosis of dementia; and to differentiate Alzheimer's disease (AD) from vascular dementia (VaD). We also aimed to study correlation between Montreal Cognitive Assessment (MOCA) score and PCT parameters.</AbstractText We conducted a prospective case-control study enrolling 25 dementia patients (15 cases of VaD, 10 cases of AD) and 25 age-matched controls. PCT was performed on a 256-slice CT scanner. Using perfusion software, colour maps were generated for cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time and time-to-peak. These colour maps were first visually inspected for any abnormalities. Subsequently, quantitative assessment of perfusion parameters was done using symmetrical freehand region of interests drawn in bilateral frontal, temporal, parietal regions, basal ganglia and hippocampi.</AbstractText Strategic infarcts were present in 93.3% cases and white matter ischaemic changes in 100% cases of VaD. A global reduction in CBF and CBV was also observed in cases of VaD; whereas these parameters were significantly lower mainly in temporoparietal regions and hippocampi of patients with AD. There was significant positive correlation between MOCA score and various perfusion parameters in both forms of dementia.</AbstractText PCT is a reliable imaging modality for early diagnosis of dementia and in differentiating VaD from AD. As perfusion parameters show positive correlation with MOCA score, they could be used as a surrogate marker of cognitive status in the follow-up of patients with dementia.</AbstractText
Differentiating Radiation-Induced Necrosis from Recurrent Brain Tumor Using MR Perfusion and Spectroscopy: A Meta-Analysis. This meta-analysis examined roles of several metabolites in differentiating recurrent tumor from necrosis in patients with brain tumors using MR perfusion and spectroscopy.</AbstractText Medline, Cochrane, EMBASE, and Google Scholar were searched for studies using perfusion MRI and/or MR spectroscopy published up to March 4, 2015 which differentiated between recurrent tumor vs. necrosis in patients with primary brain tumors or brain metastasis. Only two-armed, prospective or retrospective studies were included. A meta-analysis was performed on the difference in relative cerebral blood volume (rCBV), ratios of choline/creatine (Cho/Cr) and/or choline/N-acetyl aspartate (Cho/NAA) between participants undergoing MRI evaluation. A &#x3c7;2-based test of homogeneity was performed using Cochran's Q statistic and I2.</AbstractText Of 397 patients in 13 studies who were analyzed, the majority had tumor recurrence. As there was evidence of heterogeneity among 10 of the studies which used rCBV for evaluation (Q statistic = 31.634, I2 = 97.11%, P &lt; 0.0001) a random-effects analysis was applied. The pooled difference in means (2.18, 95%CI = 0.85 to 3.50) indicated that the average rCBV in a contrast-enhancing lesion was significantly higher in tumor recurrence compared with radiation injury (P = 0.001). Based on a fixed-effect model of analysis encompassing the six studies which used Cho/Cr ratios for evaluation (Q statistic = 8.388, I2 = 40.39%, P = 0.137), the pooled difference in means (0.77, 95%CI = 0.57 to 0.98) of the average Cho/Cr ratio was significantly higher in tumor recurrence than in tumor necrosis (P = 0.001). There was significant difference in ratios of Cho to NAA between recurrent tumor and necrosis (1.02, 95%CI = 0.03 to 2.00, P = 0.044).</AbstractText MR spectroscopy and MR perfusion using Cho/NAA and Cho/Cr ratios and rCBV may increase the accuracy of differentiating necrosis from recurrent tumor in patients with primary brain tumors or metastases.</AbstractText
Management Outcomes of Large Renal Angiomyolipoma Presenting with Wunderlich Syndrome-Experience from a Tertiary Center. Renal angiomyolipoma is an uncommon, benign-mixed mesenchymal tumor consisting of thick-walled blood vessels, smooth muscles, and mature adipose tissues. Twenty percent of these tumors are associated with tuberous sclerosis. Wunderlich syndrome (WS), an acute nontraumatic spontaneous perirenal hemorrhage, can be a presentation of large angiomyolipoma. This study evaluated the presentation, management, and complications of renal angiomyolipoma with WS in eight patients who presented to the emergency department between January 2019 and December 2021. The presenting symptoms included flank pain, palpable mass, hematuria, and bleeding in the perinephric space on computerized tomography. Demographic data, symptoms at presentation, comorbidities, hemodynamic parameters, the association with tuberous sclerosis, transfusion requirements, need for angioembolization, surgical management, Clavien-Dindo complication, duration of hospital stay, and 30-day readmission rates were evaluated. The mean age of presentation was 38 years. Of the eight patients, five (62.5%) were females and 3(37.5%) were males. Two (25%) patients had tuberous sclerosis with angiomyolipoma, and three (37.5%) patients presented with hypotension. The mean packed cell transfusion was three units, and the mean tumor size was 7.85 cm (3.5-25 cm). Three of them (37.5%) required emergency angioembolization to prevent exsanguination. Embolization was unsuccessful in one patient (33%) who underwent emergency open partial nephrectomy, and one (33%) patient developed post-embolization syndrome. A total of six patients underwent elective surgery-four underwent partial nephrectomy (laparoscopic - 1, robotic - 1, open - 2) and two underwent open nephrectomy. Three patients encountered Clavien-Dindo complications (Grade 1, n = 2 and IIIA, n = 2). WS is a rare, life-threatening complication in patients with large angiomyolipoma. Judicious optimization, angioembolization, and prompt surgical intervention will help deliver better outcomes.</AbstractText
36169203
40106582
34291309
Spike-wave discharges in Sprague-Dawley rats reflect precise intra- and interhemispheric synchronization of somatosensory cortex.
Interneuron-specific dual-AAV SCN1A gene replacement corrects epileptic phenotypes in mouse models of Dravet syndrome.
The categorical use of a continuous time representation.
Spike-wave discharges (SWDs) are among the most prominent electrical signals recordable from the rat cerebrum. Increased by inbreeding, SWDs have served as an animal model of human genetic absence seizures. Yet, SWDs are ubiquitous in inbred and outbred rats, suggesting they reflect normal brain function. We hypothesized that SWDs represent oscillatory neural ensemble activity underlying sensory encoding. To test this hypothesis, we simultaneously mapped SWDs from wide areas (8 &#xd7; 8 mm) of both hemispheres in anesthetized rats, using 256-electrode epicortical arrays that covered primary and secondary somatosensory, auditory and visual cortex bilaterally. We also recorded the laminar pattern of SWDs with linear microelectrode arrays. We compared the spatial and temporal organization of SWDs to somatosensory-evoked potentials (SEPs), as well as auditory- and visual-evoked potentials (AEPs and VEPs) to examine similarities and/or differences between sensory-evoked and spontaneous oscillations in the same animals. We discovered that SWDs are confined to the facial representation of primary and secondary somatosensory cortex (SI and SII, respectively), areas that are preferentially engaged during environmental exploration in the rat. Furthermore, these oscillations exhibit highly synchronized bilateral traveling waves in SI and SII, simultaneously forming closely matched spread patterns in both hemispheres. We propose that SWDs could reflect a previously unappreciated capacity for rat somatosensory cortex to perform precise spatial and temporal analysis of rapidly changing sensory input at the level of large neural ensembles synchronized both within and between the cerebral hemispheres.<b
Dravet syndrome (DS) is a severe developmental epileptic encephalopathy marked by treatment-resistant seizures, developmental delay, intellectual disability, motor deficits, and a 10 to 20% rate of premature death. Most patients with DS harbor loss-of-function mutations in one copy of <i
The abstract concept of time is mentally represented as a spatially oriented line, with the past associated with the left space and the future associated with the right. Although the line is supposed to be continuous, most available evidence is also consistent with a categorical representation that only discriminates between past and future. The aim of the present study was to test the continuous or categorical nature of the mental timeline. Italian participants judged the temporal reference of 20 temporal expressions by pressing keys on either the left or the right. In Experiment 1 (N&#x2009;=&#x2009;32), all words were presented at the center of the screen. In Experiment 2 (N&#x2009;=&#x2009;32), each word was presented on the screen in a central, left, or right position. In Experiment 3 (N&#x2009;=&#x2009;32), all text was mirror-reversed. In all experiments, participants were asked to place the 20 temporal expressions on a 10-cm line. The results showed a clear Spatial-TEmporal Association of Response Codes (STEARC) effect which did not vary in strength depending on the location of the temporal expressions on the line. However, there was also a clear Distance effect: latencies were slower for words that were closer to the present than further away. We conclude that the mental timeline is a continuous representation that can be used in a categorical way when an explicit past vs. future discrimination is required by the task.</AbstractText
Spike-wave discharges in Sprague-Dawley rats reflect precise intra- and interhemispheric synchronization of somatosensory cortex. Spike-wave discharges (SWDs) are among the most prominent electrical signals recordable from the rat cerebrum. Increased by inbreeding, SWDs have served as an animal model of human genetic absence seizures. Yet, SWDs are ubiquitous in inbred and outbred rats, suggesting they reflect normal brain function. We hypothesized that SWDs represent oscillatory neural ensemble activity underlying sensory encoding. To test this hypothesis, we simultaneously mapped SWDs from wide areas (8 &#xd7; 8 mm) of both hemispheres in anesthetized rats, using 256-electrode epicortical arrays that covered primary and secondary somatosensory, auditory and visual cortex bilaterally. We also recorded the laminar pattern of SWDs with linear microelectrode arrays. We compared the spatial and temporal organization of SWDs to somatosensory-evoked potentials (SEPs), as well as auditory- and visual-evoked potentials (AEPs and VEPs) to examine similarities and/or differences between sensory-evoked and spontaneous oscillations in the same animals. We discovered that SWDs are confined to the facial representation of primary and secondary somatosensory cortex (SI and SII, respectively), areas that are preferentially engaged during environmental exploration in the rat. Furthermore, these oscillations exhibit highly synchronized bilateral traveling waves in SI and SII, simultaneously forming closely matched spread patterns in both hemispheres. We propose that SWDs could reflect a previously unappreciated capacity for rat somatosensory cortex to perform precise spatial and temporal analysis of rapidly changing sensory input at the level of large neural ensembles synchronized both within and between the cerebral hemispheres.<b
Interneuron-specific dual-AAV SCN1A gene replacement corrects epileptic phenotypes in mouse models of Dravet syndrome. Dravet syndrome (DS) is a severe developmental epileptic encephalopathy marked by treatment-resistant seizures, developmental delay, intellectual disability, motor deficits, and a 10 to 20% rate of premature death. Most patients with DS harbor loss-of-function mutations in one copy of <i
The categorical use of a continuous time representation. The abstract concept of time is mentally represented as a spatially oriented line, with the past associated with the left space and the future associated with the right. Although the line is supposed to be continuous, most available evidence is also consistent with a categorical representation that only discriminates between past and future. The aim of the present study was to test the continuous or categorical nature of the mental timeline. Italian participants judged the temporal reference of 20 temporal expressions by pressing keys on either the left or the right. In Experiment 1 (N&#x2009;=&#x2009;32), all words were presented at the center of the screen. In Experiment 2 (N&#x2009;=&#x2009;32), each word was presented on the screen in a central, left, or right position. In Experiment 3 (N&#x2009;=&#x2009;32), all text was mirror-reversed. In all experiments, participants were asked to place the 20 temporal expressions on a 10-cm line. The results showed a clear Spatial-TEmporal Association of Response Codes (STEARC) effect which did not vary in strength depending on the location of the temporal expressions on the line. However, there was also a clear Distance effect: latencies were slower for words that were closer to the present than further away. We conclude that the mental timeline is a continuous representation that can be used in a categorical way when an explicit past vs. future discrimination is required by the task.</AbstractText
33643162
30760743
33664130
The Relationship Between Referral of Touch and the Feeling of Ownership in the Rubber Hand Illusion.
Belief of agency changes dynamics in sensorimotor networks.
Both Default and Multiple-Demand Regions Represent Semantic Goal Information.
The rubber hand illusion (RHI) is one of the most commonly used paradigms to examine the sense of body ownership. Touches are synchronously applied to the real hand, hidden from view, and a false hand in an anatomically congruent position. During the illusion one may perceive that the feeling of touch arises from the false hand (referral of touch), and that the false hand is one's own. The relationship between referral of touch and body ownership in the illusion is unclear, and some articles average responses to statements addressing these experiences, which may be inappropriate depending on the research question of interest. To address these concerns, we re-analyzed three freely available datasets to better understand the relationship between referral of touch and feeling of ownership in the RHI. We found that most participants who report a feeling of ownership also report referral of touch, and that referral of touch and ownership show a moderately strong positive relationship that was highly replicable. In addition, referral of touch tends to be reported more strongly and more frequently than the feeling of ownership over the hand. The former observations confirm that referral of touch and ownership are related experiences in the RHI. The latter, however, indicate that when pooling the statements one may obtain a higher number of illusion 'responders' compared to considering the ownership statements in isolation. These results have implications for the RHI as an experimental paradigm.</AbstractText
Controlling an event through one's own action usually induces a sense of agency, a feeling that arises when an expected outcome matches the intention. The neural correlates of this feeling remain controversial however, as experimental manipulation of the action-outcome chain often introduces mismatch or prediction errors that strongly correlate with the sense of agency. Here, we took a different approach and manipulated the causal belief (self-attribution vs. computer-attribution) by external cues during matched visuo-motor tapping conditions. With magneto-encephalography, we studied the sense of agency from a network perspective, investigating in source space the modulation of local population activity and changes in functional connectivity with motor cortex. Our results show that during the belief of agency primary motor cortex&#xa0;(M1) shows stronger functional connectivity (mediated by the beta band) to inferior parietal lobe and right middle temporal gyrus (MTG). Furthermore, the local feed-forward activity (gamma band power) in extrastriate body area and MTG disappears with that belief. After changes in action context, left M1 shows stronger connectivity in the alpha band with right premotor cortex and left insular-temporal cortex a network that might support active inference in social action context. Finally, a better tapping performance in this rhythmic task was related to alpha power modulations in the bilateral cerebellum and bilateral fusiform body-area, with power suppression during a more precise performance. These findings highlight the role of multiple networks supporting the sense of agency by changing their relative contribution for different causal beliefs.</AbstractText
We used a semantic feature-matching task combined with multivoxel pattern decoding to test contrasting accounts of the role of the default mode network (DMN) in cognitive flexibility. By one view, DMN and multiple-demand cortex have opposing roles in cognition, with DMN and multiple-demand regions within the dorsal attention network (DAN) supporting internal and external cognition, respectively. Consequently, while multiple-demand regions can decode current goal information, semantically relevant DMN regions might decode conceptual similarity regardless of task demands. Alternatively, DMN regions, like multiple-demand cortex, might show sensitivity to changing task demands, since both networks dynamically alter their patterns of connectivity depending on the context. Our task required human participants (any sex) to integrate conceptual knowledge with changing task goals, such that successive decisions were based on different features of the items (color, shape, and size). This allowed us to simultaneously decode semantic category and current goal information using whole-brain searchlight decoding. As expected, multiple-demand cortex, including DAN and frontoparietal control network, represented information about currently relevant conceptual features. Similar decoding results were found in DMN, including in angular gyrus and posterior cingulate cortex, indicating that DMN and multiple-demand regions can support the same function rather than being strictly competitive. Semantic category could be decoded in lateral occipital cortex independently of task demands, but not in most regions of DMN. Conceptual information related to the current goal dominates the multivariate response within DMN, which supports flexible retrieval by modulating its response to suit the task demands, alongside regions of multiple-demand cortex.<b
The Relationship Between Referral of Touch and the Feeling of Ownership in the Rubber Hand Illusion. The rubber hand illusion (RHI) is one of the most commonly used paradigms to examine the sense of body ownership. Touches are synchronously applied to the real hand, hidden from view, and a false hand in an anatomically congruent position. During the illusion one may perceive that the feeling of touch arises from the false hand (referral of touch), and that the false hand is one's own. The relationship between referral of touch and body ownership in the illusion is unclear, and some articles average responses to statements addressing these experiences, which may be inappropriate depending on the research question of interest. To address these concerns, we re-analyzed three freely available datasets to better understand the relationship between referral of touch and feeling of ownership in the RHI. We found that most participants who report a feeling of ownership also report referral of touch, and that referral of touch and ownership show a moderately strong positive relationship that was highly replicable. In addition, referral of touch tends to be reported more strongly and more frequently than the feeling of ownership over the hand. The former observations confirm that referral of touch and ownership are related experiences in the RHI. The latter, however, indicate that when pooling the statements one may obtain a higher number of illusion 'responders' compared to considering the ownership statements in isolation. These results have implications for the RHI as an experimental paradigm.</AbstractText
Belief of agency changes dynamics in sensorimotor networks. Controlling an event through one's own action usually induces a sense of agency, a feeling that arises when an expected outcome matches the intention. The neural correlates of this feeling remain controversial however, as experimental manipulation of the action-outcome chain often introduces mismatch or prediction errors that strongly correlate with the sense of agency. Here, we took a different approach and manipulated the causal belief (self-attribution vs. computer-attribution) by external cues during matched visuo-motor tapping conditions. With magneto-encephalography, we studied the sense of agency from a network perspective, investigating in source space the modulation of local population activity and changes in functional connectivity with motor cortex. Our results show that during the belief of agency primary motor cortex&#xa0;(M1) shows stronger functional connectivity (mediated by the beta band) to inferior parietal lobe and right middle temporal gyrus (MTG). Furthermore, the local feed-forward activity (gamma band power) in extrastriate body area and MTG disappears with that belief. After changes in action context, left M1 shows stronger connectivity in the alpha band with right premotor cortex and left insular-temporal cortex a network that might support active inference in social action context. Finally, a better tapping performance in this rhythmic task was related to alpha power modulations in the bilateral cerebellum and bilateral fusiform body-area, with power suppression during a more precise performance. These findings highlight the role of multiple networks supporting the sense of agency by changing their relative contribution for different causal beliefs.</AbstractText
Both Default and Multiple-Demand Regions Represent Semantic Goal Information. We used a semantic feature-matching task combined with multivoxel pattern decoding to test contrasting accounts of the role of the default mode network (DMN) in cognitive flexibility. By one view, DMN and multiple-demand cortex have opposing roles in cognition, with DMN and multiple-demand regions within the dorsal attention network (DAN) supporting internal and external cognition, respectively. Consequently, while multiple-demand regions can decode current goal information, semantically relevant DMN regions might decode conceptual similarity regardless of task demands. Alternatively, DMN regions, like multiple-demand cortex, might show sensitivity to changing task demands, since both networks dynamically alter their patterns of connectivity depending on the context. Our task required human participants (any sex) to integrate conceptual knowledge with changing task goals, such that successive decisions were based on different features of the items (color, shape, and size). This allowed us to simultaneously decode semantic category and current goal information using whole-brain searchlight decoding. As expected, multiple-demand cortex, including DAN and frontoparietal control network, represented information about currently relevant conceptual features. Similar decoding results were found in DMN, including in angular gyrus and posterior cingulate cortex, indicating that DMN and multiple-demand regions can support the same function rather than being strictly competitive. Semantic category could be decoded in lateral occipital cortex independently of task demands, but not in most regions of DMN. Conceptual information related to the current goal dominates the multivariate response within DMN, which supports flexible retrieval by modulating its response to suit the task demands, alongside regions of multiple-demand cortex.<b
27881953
29184208
27172277
Connectomic Analysis of Brain Networks: Novel Techniques and Future Directions.
Temporally precise single-cell-resolution optogenetics.
Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial.
Brain networks, localized or brain-wide, exist only at the cellular level, i.e., between specific pre- and post-synaptic neurons, which are connected through functionally diverse synapses located at specific points of their cell membranes. "Connectomics" is the emerging subfield of neuroanatomy explicitly aimed at elucidating the wiring of brain networks with cellular resolution and a quantified accuracy. Such data are indispensable for realistic modeling of brain circuitry and function. A connectomic analysis, therefore, needs to identify and measure the soma, dendrites, axonal path, and branching patterns together with the synapses and gap junctions of the neurons involved in any given brain circuit or network. However, because of the submicron caliber, 3D complexity, and high packing density of most such structures, as well as the fact that axons frequently extend over long distances to make synapses in remote brain regions, creating connectomic maps is technically challenging and requires multi-scale approaches, Such approaches involve the combination of the most sensitive cell labeling and analysis methods available, as well as the development of new ones able to resolve individual cells and synapses with increasing high-throughput. In this review, we provide an overview of recently introduced high-resolution methods, which researchers wanting to enter the field of connectomics may consider. It includes several molecular labeling tools, some of which specifically label synapses, and covers a number of novel imaging tools such as brain clearing protocols and microscopy approaches. Apart from describing the tools, we also provide an assessment of their qualities. The criteria we use assess the qualities that tools need in order to contribute to deciphering the key levels of circuit organization. We conclude with a brief future outlook for neuroanatomic research, computational methods, and network modeling, where we also point out several outstanding issues like structure-function relations and the complexity of neural models.</AbstractText
Optogenetic control of individual neurons with high temporal precision within intact mammalian brain circuitry would enable powerful explorations of how neural circuits operate. Two-photon computer-generated holography enables precise sculpting of light and could in principle enable simultaneous illumination of many neurons in a network, with the requisite temporal precision to simulate accurate neural codes. We designed a high-efficacy soma-targeted opsin, finding that fusing the N-terminal 150 residues of kainate receptor subunit 2 (KA2) to the recently discovered high-photocurrent channelrhodopsin CoChR restricted expression of this opsin primarily to the cell body of mammalian cortical neurons. In combination with two-photon holographic stimulation, we found that this somatic CoChR (soCoChR) enabled photostimulation of individual cells in mouse cortical brain slices with single-cell resolution and &lt;1-ms temporal precision. We used soCoChR to perform connectivity mapping on intact cortical circuits.</AbstractText
Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention.</AbstractText To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment.</AbstractText A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater.</AbstractText A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat.</AbstractText Between-group differences in postintervention Hamilton Depression Rating Scale scores.</AbstractText The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: -6.53, 95% CI, -9.90 to -3.16, P&#x2009;&lt;&#x2009;.001; week 2: -6.35, 95% CI, -9.95 to -2.74, P&#x2009;=&#x2009;.001; week 4: -4.50, 95% CI, -8.17 to -0.84, P&#x2009;=&#x2009;.02; and week 6: -4.27, 95% CI, -7.94 to -0.61, P&#x2009;=&#x2009;.02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild.</AbstractText Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit.</AbstractText clinicaltrials.gov Identifier: NCT01625546.</AbstractText
Connectomic Analysis of Brain Networks: Novel Techniques and Future Directions. Brain networks, localized or brain-wide, exist only at the cellular level, i.e., between specific pre- and post-synaptic neurons, which are connected through functionally diverse synapses located at specific points of their cell membranes. "Connectomics" is the emerging subfield of neuroanatomy explicitly aimed at elucidating the wiring of brain networks with cellular resolution and a quantified accuracy. Such data are indispensable for realistic modeling of brain circuitry and function. A connectomic analysis, therefore, needs to identify and measure the soma, dendrites, axonal path, and branching patterns together with the synapses and gap junctions of the neurons involved in any given brain circuit or network. However, because of the submicron caliber, 3D complexity, and high packing density of most such structures, as well as the fact that axons frequently extend over long distances to make synapses in remote brain regions, creating connectomic maps is technically challenging and requires multi-scale approaches, Such approaches involve the combination of the most sensitive cell labeling and analysis methods available, as well as the development of new ones able to resolve individual cells and synapses with increasing high-throughput. In this review, we provide an overview of recently introduced high-resolution methods, which researchers wanting to enter the field of connectomics may consider. It includes several molecular labeling tools, some of which specifically label synapses, and covers a number of novel imaging tools such as brain clearing protocols and microscopy approaches. Apart from describing the tools, we also provide an assessment of their qualities. The criteria we use assess the qualities that tools need in order to contribute to deciphering the key levels of circuit organization. We conclude with a brief future outlook for neuroanatomic research, computational methods, and network modeling, where we also point out several outstanding issues like structure-function relations and the complexity of neural models.</AbstractText
Temporally precise single-cell-resolution optogenetics. Optogenetic control of individual neurons with high temporal precision within intact mammalian brain circuitry would enable powerful explorations of how neural circuits operate. Two-photon computer-generated holography enables precise sculpting of light and could in principle enable simultaneous illumination of many neurons in a network, with the requisite temporal precision to simulate accurate neural codes. We designed a high-efficacy soma-targeted opsin, finding that fusing the N-terminal 150 residues of kainate receptor subunit 2 (KA2) to the recently discovered high-photocurrent channelrhodopsin CoChR restricted expression of this opsin primarily to the cell body of mammalian cortical neurons. In combination with two-photon holographic stimulation, we found that this somatic CoChR (soCoChR) enabled photostimulation of individual cells in mouse cortical brain slices with single-cell resolution and &lt;1-ms temporal precision. We used soCoChR to perform connectivity mapping on intact cortical circuits.</AbstractText
Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial. Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention.</AbstractText To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment.</AbstractText A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater.</AbstractText A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat.</AbstractText Between-group differences in postintervention Hamilton Depression Rating Scale scores.</AbstractText The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: -6.53, 95% CI, -9.90 to -3.16, P&#x2009;&lt;&#x2009;.001; week 2: -6.35, 95% CI, -9.95 to -2.74, P&#x2009;=&#x2009;.001; week 4: -4.50, 95% CI, -8.17 to -0.84, P&#x2009;=&#x2009;.02; and week 6: -4.27, 95% CI, -7.94 to -0.61, P&#x2009;=&#x2009;.02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild.</AbstractText Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit.</AbstractText clinicaltrials.gov Identifier: NCT01625546.</AbstractText
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The Mindful Brain: A Systematic Review of the Neural Correlates of Trait Mindfulness.
Risk proneness modulates the impact of impulsivity on brain functional connectivity.
Molecular networking and computational NMR analyses uncover six polyketide-terpene hybrids from termite-associated Xylaria isolates.
Trait self-report mindfulness scales measure one's disposition to pay nonjudgmental attention to the present moment. Concerns have been raised about the validity of trait mindfulness scales. Despite this, there is extensive literature correlating mindfulness scales with objective brain measures, with the goal of providing insight into mechanisms of mindfulness, and insight into associated positive mental health outcomes. Here, we systematically examined the neural correlates of trait mindfulness. We assessed 68 correlational studies across structural magnetic resonance imaging, task-based fMRI, resting-state fMRI, and EEG. Several consistent findings were identified, associating greater trait mindfulness with decreased amygdala reactivity to emotional stimuli, increased cortical thickness in frontal regions and insular cortex regions, and decreased connectivity within the default-mode network. These findings converged with results from intervention studies and those that included mindfulness experts. On the other hand, the connections between trait mindfulness and EEG metrics remain inconclusive, as do the associations between trait mindfulness and between-network resting-state fMRI metrics. ERP measures from EEG used to measure attentional or emotional processing may not show reliable individual variation. Research on body awareness and self-relevant processing is scarce. For a more robust correlational neuroscience of trait mindfulness, we recommend larger sample sizes, data-driven, multivariate approaches to self-report and brain measures, and careful consideration of test-retest reliability. In addition, we should leave behind simplistic explanations of mindfulness, as there are many ways to be mindful, and leave behind simplistic explanations of the brain, as distributed networks of brain areas support mindfulness.</AbstractText
Impulsivity and sensation seeking are considered to be among the most important personality traits involved in risk-taking behavior. This study is focused on whether the association of these personality traits and brain functional connectivity depends on individuals' risk proneness. Risk proneness was assessed with the DOSPERT-30 scale and corroborated with performance in a motorcycle simulator. The associations of impulsivity- and sensation seeking-related traits with the between and within coupling of seven major brain functional networks, estimated from electroencefalograma (EEG) recordings, differ according to whether an individual is risk prone or not. In risk-prone individuals, (lack of) premeditation enhanced the coupling of the ventral attention and limbic networks. At the same time, emotion seeking increased the coupling of the frontoparietal network and the default mode networks (DMNs). Finally, (lack of) perseverance had a positive impact on the coupling of anterior temporal nodes of the limbic network whilst having a negative impact on some frontal nodes of the frontoparietal network and the DMNs. In general, the results suggest that the predisposition to behave riskily modulates the way in which impulsivity traits are linked to brain functionality, seemingly making the brain networks prepare for an immediate, automatic, and maladaptive response.</AbstractText
Fungi constitute the Earth's second most diverse kingdom, however only a small percentage of these have been thoroughly examined and categorized for their secondary metabolites, which still limits our understanding of the ecological chemical and pharmacological potential of fungi. In this study, we explored members of the co-evolved termite-associated fungal genus Xylaria and identified a family of highly oxygenated polyketide-terpene hybrid natural products using an MS/MS molecular networking-based dereplication approach. Overall, we isolated six no yet reported xylasporin derivatives, of which xylasporin A (1) features a rare cyclic-carbonate moiety. Extensive comparative spectrometric (HRMS<sup
The Mindful Brain: A Systematic Review of the Neural Correlates of Trait Mindfulness. Trait self-report mindfulness scales measure one's disposition to pay nonjudgmental attention to the present moment. Concerns have been raised about the validity of trait mindfulness scales. Despite this, there is extensive literature correlating mindfulness scales with objective brain measures, with the goal of providing insight into mechanisms of mindfulness, and insight into associated positive mental health outcomes. Here, we systematically examined the neural correlates of trait mindfulness. We assessed 68 correlational studies across structural magnetic resonance imaging, task-based fMRI, resting-state fMRI, and EEG. Several consistent findings were identified, associating greater trait mindfulness with decreased amygdala reactivity to emotional stimuli, increased cortical thickness in frontal regions and insular cortex regions, and decreased connectivity within the default-mode network. These findings converged with results from intervention studies and those that included mindfulness experts. On the other hand, the connections between trait mindfulness and EEG metrics remain inconclusive, as do the associations between trait mindfulness and between-network resting-state fMRI metrics. ERP measures from EEG used to measure attentional or emotional processing may not show reliable individual variation. Research on body awareness and self-relevant processing is scarce. For a more robust correlational neuroscience of trait mindfulness, we recommend larger sample sizes, data-driven, multivariate approaches to self-report and brain measures, and careful consideration of test-retest reliability. In addition, we should leave behind simplistic explanations of mindfulness, as there are many ways to be mindful, and leave behind simplistic explanations of the brain, as distributed networks of brain areas support mindfulness.</AbstractText
Risk proneness modulates the impact of impulsivity on brain functional connectivity. Impulsivity and sensation seeking are considered to be among the most important personality traits involved in risk-taking behavior. This study is focused on whether the association of these personality traits and brain functional connectivity depends on individuals' risk proneness. Risk proneness was assessed with the DOSPERT-30 scale and corroborated with performance in a motorcycle simulator. The associations of impulsivity- and sensation seeking-related traits with the between and within coupling of seven major brain functional networks, estimated from electroencefalograma (EEG) recordings, differ according to whether an individual is risk prone or not. In risk-prone individuals, (lack of) premeditation enhanced the coupling of the ventral attention and limbic networks. At the same time, emotion seeking increased the coupling of the frontoparietal network and the default mode networks (DMNs). Finally, (lack of) perseverance had a positive impact on the coupling of anterior temporal nodes of the limbic network whilst having a negative impact on some frontal nodes of the frontoparietal network and the DMNs. In general, the results suggest that the predisposition to behave riskily modulates the way in which impulsivity traits are linked to brain functionality, seemingly making the brain networks prepare for an immediate, automatic, and maladaptive response.</AbstractText
Molecular networking and computational NMR analyses uncover six polyketide-terpene hybrids from termite-associated Xylaria isolates. Fungi constitute the Earth's second most diverse kingdom, however only a small percentage of these have been thoroughly examined and categorized for their secondary metabolites, which still limits our understanding of the ecological chemical and pharmacological potential of fungi. In this study, we explored members of the co-evolved termite-associated fungal genus Xylaria and identified a family of highly oxygenated polyketide-terpene hybrid natural products using an MS/MS molecular networking-based dereplication approach. Overall, we isolated six no yet reported xylasporin derivatives, of which xylasporin A (1) features a rare cyclic-carbonate moiety. Extensive comparative spectrometric (HRMS<sup
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24677253
32194570
Clinical experience regarding safety and diagnostic value of cardiovascular magnetic resonance in patients with a subcutaneous implanted cardioverter/defibrillator (S-ICD) at 1.5 T.
Inlet and outlet valve flow and regurgitant volume may be directly and reliably quantified with accelerated, volumetric phase-contrast MRI.
Role of Viral and Host microRNAs in Immune Regulation of Epstein-Barr Virus-Associated Diseases.
Cardiovascular magnetic resonance (CMR) studies in patients with implanted cardioverter/defibrillators (ICD) are increasingly required in daily clinical practice. However, the clinical experience regarding the feasibility as well as clinical value of CMR studies in patients with subcutaneous ICD (S-ICD) is still limited. Besides safety issues, image quality and analysis can be impaired primarily due the presence of image artefacts associated with the generator.</AbstractText Twenty-three patients with an implanted S-ICD (EMBLEM, Boston Scientific, Marlborough, Massachusetts, USA; MR-conditional) with suspected cardiomyopathy and/or myocarditis underwent multi-parametric CMR imaging. Studies were performed on a 1.5 T CMR scanner after device interrogation and comprised standard a) balanced steady state free precession cine, b) T2 weighted-edema, c) velocity-encoded cine flow, d) myocardial perfusion, e) late-gadolinium-enhancement (LGE)-imaging and f) 3D-CMR angiography of the aorta. In case of substantial artefacts, alternative CMR techniques such as spoiled gradient-echo cine-sequences and wide-band inversion-recovery LGE (wb-LGE) sequences were applied.</AbstractText Successful CMR studies could be performed in all patients without any case of unexpected early termination or relevant technical complication other than permanent loss of the S-ICD system beeper volume in 52% of our patients. Assessment of cine-CMR images was predominantly impaired in the left ventricular (LV) anterior, lateral and inferior wall segments and a switch to spoiled gradient echo-based cine-CMR allowed an accurate assessment of cine-images in N&#x2009;=&#x2009;17 (74%) patients with only limited artefacts. Hyperintensity artefacts in conventional LGE-images were predominantly observed in the LV anterior, lateral and inferior wall segments and image optimisation by use of the wb-LGE was helpful in 15 (65%) cases. Aortic flow measurements and 3D-CMR angiography were assessable in all patients Perfusion imaging artefacts precluded a meaningful assessment in at least one half of the patients. A benefit in clinical-decision making was documented in 17 (74%) patients in the present study.</AbstractText Safe 1.5&#x2009;T CMR imaging was possible in all patients with an S-ICD, though the majority had permanent loss of the S-ICD beeper volume. Achieving good image quality may be challenging in some patients - particularly for perfusion imaging. Using spoiled gradient echo-based cine-sequences and wb-LGE sequences may help to reduce the extent of artefacts, thereby allowing accurate cardiac assessment. Thus, 1.5&#x2009;T CMR studies should not be withhold in patients with S-ICD for safety concerns and/or fear of extensive imaging artefacts precluding successful image analysis.</AbstractText
To determine whether it is feasible to use solely an accelerated 4D phase-contrast magnetic resonance imaging (4D-PC MRI) acquisition to quantify net and regurgitant flow volume through each of the cardiac valves.</AbstractText Accelerated, 4D-PC MRI examinations performed between March 2010 through June 2011 as part of routine MRI examinations for congenital, structural heart disease were retrospectively reviewed and analyzed using valve-tracking visualization and quantification algorithms developed in Java and OpenGL. Excluding patients with transposition or single ventricle physiology, a total of 34 consecutive pediatric patients (19 male, 15 female; mean age 6.9 years; age range 10 months to 15 years) were identified. 4D-PC flow measurements were compared at each valve and against routine measurements from conventional cardiac MRI using Bland-Altman and Pearson correlation analysis.</AbstractText Inlet and outlet valve net flow were highly correlated between all valves (P&#x2009;=&#x2009;0.940-0.985). The sum of forward flow at the outlet valve and regurgitant flow at the inlet valve were consistent with volumetric displacements in each ventricle (P&#x2009;=&#x2009;0.939-0.948). These were also highly consistent with conventional planar MRI measurements with net flow (P&#x2009;=&#x2009;0.923-0.935) and regurgitant fractions (P&#x2009;=&#x2009;0.917-0.972) at the outlet valve and ventricular volumes (P&#x2009;=&#x2009;0.925-0.965).</AbstractText It is possible to obtain consistent measurements of net and regurgitant blood flow across the inlet and outlet valves relying solely on accelerated 4D-PC. This may facilitate more efficient clinical quantification of valvular regurgitation.</AbstractText
Epstein-Barr virus (EBV) is an oncogenic human herpes virus that was discovered in 1964. Viral non-coding RNAs, such as <i
Clinical experience regarding safety and diagnostic value of cardiovascular magnetic resonance in patients with a subcutaneous implanted cardioverter/defibrillator (S-ICD) at 1.5 T. Cardiovascular magnetic resonance (CMR) studies in patients with implanted cardioverter/defibrillators (ICD) are increasingly required in daily clinical practice. However, the clinical experience regarding the feasibility as well as clinical value of CMR studies in patients with subcutaneous ICD (S-ICD) is still limited. Besides safety issues, image quality and analysis can be impaired primarily due the presence of image artefacts associated with the generator.</AbstractText Twenty-three patients with an implanted S-ICD (EMBLEM, Boston Scientific, Marlborough, Massachusetts, USA; MR-conditional) with suspected cardiomyopathy and/or myocarditis underwent multi-parametric CMR imaging. Studies were performed on a 1.5 T CMR scanner after device interrogation and comprised standard a) balanced steady state free precession cine, b) T2 weighted-edema, c) velocity-encoded cine flow, d) myocardial perfusion, e) late-gadolinium-enhancement (LGE)-imaging and f) 3D-CMR angiography of the aorta. In case of substantial artefacts, alternative CMR techniques such as spoiled gradient-echo cine-sequences and wide-band inversion-recovery LGE (wb-LGE) sequences were applied.</AbstractText Successful CMR studies could be performed in all patients without any case of unexpected early termination or relevant technical complication other than permanent loss of the S-ICD system beeper volume in 52% of our patients. Assessment of cine-CMR images was predominantly impaired in the left ventricular (LV) anterior, lateral and inferior wall segments and a switch to spoiled gradient echo-based cine-CMR allowed an accurate assessment of cine-images in N&#x2009;=&#x2009;17 (74%) patients with only limited artefacts. Hyperintensity artefacts in conventional LGE-images were predominantly observed in the LV anterior, lateral and inferior wall segments and image optimisation by use of the wb-LGE was helpful in 15 (65%) cases. Aortic flow measurements and 3D-CMR angiography were assessable in all patients Perfusion imaging artefacts precluded a meaningful assessment in at least one half of the patients. A benefit in clinical-decision making was documented in 17 (74%) patients in the present study.</AbstractText Safe 1.5&#x2009;T CMR imaging was possible in all patients with an S-ICD, though the majority had permanent loss of the S-ICD beeper volume. Achieving good image quality may be challenging in some patients - particularly for perfusion imaging. Using spoiled gradient echo-based cine-sequences and wb-LGE sequences may help to reduce the extent of artefacts, thereby allowing accurate cardiac assessment. Thus, 1.5&#x2009;T CMR studies should not be withhold in patients with S-ICD for safety concerns and/or fear of extensive imaging artefacts precluding successful image analysis.</AbstractText
Inlet and outlet valve flow and regurgitant volume may be directly and reliably quantified with accelerated, volumetric phase-contrast MRI. To determine whether it is feasible to use solely an accelerated 4D phase-contrast magnetic resonance imaging (4D-PC MRI) acquisition to quantify net and regurgitant flow volume through each of the cardiac valves.</AbstractText Accelerated, 4D-PC MRI examinations performed between March 2010 through June 2011 as part of routine MRI examinations for congenital, structural heart disease were retrospectively reviewed and analyzed using valve-tracking visualization and quantification algorithms developed in Java and OpenGL. Excluding patients with transposition or single ventricle physiology, a total of 34 consecutive pediatric patients (19 male, 15 female; mean age 6.9 years; age range 10 months to 15 years) were identified. 4D-PC flow measurements were compared at each valve and against routine measurements from conventional cardiac MRI using Bland-Altman and Pearson correlation analysis.</AbstractText Inlet and outlet valve net flow were highly correlated between all valves (P&#x2009;=&#x2009;0.940-0.985). The sum of forward flow at the outlet valve and regurgitant flow at the inlet valve were consistent with volumetric displacements in each ventricle (P&#x2009;=&#x2009;0.939-0.948). These were also highly consistent with conventional planar MRI measurements with net flow (P&#x2009;=&#x2009;0.923-0.935) and regurgitant fractions (P&#x2009;=&#x2009;0.917-0.972) at the outlet valve and ventricular volumes (P&#x2009;=&#x2009;0.925-0.965).</AbstractText It is possible to obtain consistent measurements of net and regurgitant blood flow across the inlet and outlet valves relying solely on accelerated 4D-PC. This may facilitate more efficient clinical quantification of valvular regurgitation.</AbstractText
Role of Viral and Host microRNAs in Immune Regulation of Epstein-Barr Virus-Associated Diseases. Epstein-Barr virus (EBV) is an oncogenic human herpes virus that was discovered in 1964. Viral non-coding RNAs, such as <i
26813856
21787167
27662495
Imaging Surrogates of Infiltration Obtained Via Multiparametric Imaging Pattern Analysis Predict Subsequent Location of Recurrence of Glioblastoma.
Emerging imaging tools for use with traumatic brain injury research.
Acupuncture Increases the Excitability of the Cortico-Spinal System in Patients with Chronic Disorders of Consciousness Following Traumatic Brain Injury.
Glioblastoma is an aggressive and highly infiltrative brain cancer. Standard surgical resection is guided by enhancement on postcontrast T1-weighted (T1) magnetic resonance imaging, which is insufficient for delineating surrounding infiltrating tumor.</AbstractText To develop imaging biomarkers that delineate areas of tumor infiltration and predict early recurrence in peritumoral tissue. Such markers would enable intensive, yet targeted, surgery and radiotherapy, thereby potentially delaying recurrence and prolonging survival.</AbstractText Preoperative multiparametric magnetic resonance images (T1, T1-gadolinium, T2-weighted, T2-weighted fluid-attenuated inversion recovery, diffusion tensor imaging, and dynamic susceptibility contrast-enhanced magnetic resonance images) from 31 patients were combined using machine learning methods, thereby creating predictive spatial maps of infiltrated peritumoral tissue. Cross-validation was used in the retrospective cohort to achieve generalizable biomarkers. Subsequently, the imaging signatures learned from the retrospective study were used in a replication cohort of 34 new patients. Spatial maps representing the likelihood of tumor infiltration and future early recurrence were compared with regions of recurrence on postresection follow-up studies with pathology confirmation.</AbstractText This technique produced predictions of early recurrence with a mean area under the curve of 0.84, sensitivity of 91%, specificity of 93%, and odds ratio estimates of 9.29 (99% confidence interval: 8.95-9.65) for tissue predicted to be heavily infiltrated in the replication study. Regions of tumor recurrence were found to have subtle, yet fairly distinctive multiparametric imaging signatures when analyzed quantitatively by pattern analysis and machine learning.</AbstractText Visually imperceptible imaging patterns discovered via multiparametric pattern analysis methods were found to estimate the extent of infiltration and location of future tumor recurrence, paving the way for improved targeted treatment.</AbstractText
This article identifies emerging neuroimaging measures considered by the inter-agency Pediatric Traumatic Brain Injury (TBI) Neuroimaging Workgroup. This article attempts to address some of the potential uses of more advanced forms of imaging in TBI as well as highlight some of the current considerations and unresolved challenges of using them. We summarize emerging elements likely to gain more widespread use in the coming years, because of 1) their utility in diagnosis, prognosis, and understanding the natural course of degeneration or recovery following TBI, and potential for evaluating treatment strategies; 2) the ability of many centers to acquire these data with scanners and equipment that are readily available in existing clinical and research settings; and 3) advances in software that provide more automated, readily available, and cost-effective analysis methods for large scale data image analysis. These include multi-slice CT, volumetric MRI analysis, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), arterial spin tag labeling (ASL), functional MRI (fMRI), including resting state and connectivity MRI, MR spectroscopy (MRS), and hyperpolarization scanning. However, we also include brief introductions to other specialized forms of advanced imaging that currently do require specialized equipment, for example, single photon emission computed tomography (SPECT), positron emission tomography (PET), encephalography (EEG), and magnetoencephalography (MEG)/magnetic source imaging (MSI). Finally, we identify some of the challenges that users of the emerging imaging CDEs may wish to consider, including quality control, performing multi-site and longitudinal imaging studies, and MR scanning in infants and children.</AbstractText
To evaluate the immediate effect of acupuncture on cortico spinal tract (CST) activity in patients with chronic disorders of consciousness (DOC) after traumatic brain injury (TBI) by measuring motor-evoked potential (MEP) using transcranial magnetic stimulation (TMS).</AbstractText Changes in several variables in the acupuncture session were compared with those in the control session without acupuncture in the same patients.</AbstractText Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, Gifu, Japan.</AbstractText Fourteen patients (mean age &#xb1; standard deviation, 39&#x2009;&#xb1;&#x2009;17 years; 12 men) with chronic DOC (5 in a vegetative state and 9 in a minimally conscious state) following severe TBI.</AbstractText Acupuncture treatment was performed at GV 26, Ex-HN 3, bilateral LI 4, and ST 36 for 10 minutes.</AbstractText Main outcome measure was MEP amplitude. MEP amplitude, measured by using TMS on the primary motor cortex, was recorded from the abductor pollicis brevis muscle. MEP recordings were performed before acupuncture (baseline), 10 minutes after needle insertion (phase 1), and 10 minutes after needle removal (phase 2). As a control, the same procedure without acupuncture was performed on another day with the order randomized. MEP amplitude and latency were calculated. Evoked F-wave measurements were also performed to calculate maximum M-wave amplitude (Mmax), M-wave latency, and F-wave latency in the same muscle. Central motor conduction time (CMCT) and MEP/Mmax ratio were also calculated from the MEP and F-wave measurement data.</AbstractText MEP amplitude and MEP/Mmax were increased significantly in the acupuncture session at phases 1 and 2 compared with the control session (p&#x2009;&lt;&#x2009;0.001, p&#x2009;&lt;&#x2009;0.001, p&#x2009;&lt;&#x2009;0.001, and p&#x2009;=&#x2009;0.001, respectively). CMCTs were reduced at phases 1 and 2 in the acupuncture session compared with the control session, and the change at phase 1 was statistically significant (P&#x2009;=&#x2009;0.002).</AbstractText Acupuncture treatment increased the CST activity of patients with chronic DOC after severe TBI.</AbstractText
Imaging Surrogates of Infiltration Obtained Via Multiparametric Imaging Pattern Analysis Predict Subsequent Location of Recurrence of Glioblastoma. Glioblastoma is an aggressive and highly infiltrative brain cancer. Standard surgical resection is guided by enhancement on postcontrast T1-weighted (T1) magnetic resonance imaging, which is insufficient for delineating surrounding infiltrating tumor.</AbstractText To develop imaging biomarkers that delineate areas of tumor infiltration and predict early recurrence in peritumoral tissue. Such markers would enable intensive, yet targeted, surgery and radiotherapy, thereby potentially delaying recurrence and prolonging survival.</AbstractText Preoperative multiparametric magnetic resonance images (T1, T1-gadolinium, T2-weighted, T2-weighted fluid-attenuated inversion recovery, diffusion tensor imaging, and dynamic susceptibility contrast-enhanced magnetic resonance images) from 31 patients were combined using machine learning methods, thereby creating predictive spatial maps of infiltrated peritumoral tissue. Cross-validation was used in the retrospective cohort to achieve generalizable biomarkers. Subsequently, the imaging signatures learned from the retrospective study were used in a replication cohort of 34 new patients. Spatial maps representing the likelihood of tumor infiltration and future early recurrence were compared with regions of recurrence on postresection follow-up studies with pathology confirmation.</AbstractText This technique produced predictions of early recurrence with a mean area under the curve of 0.84, sensitivity of 91%, specificity of 93%, and odds ratio estimates of 9.29 (99% confidence interval: 8.95-9.65) for tissue predicted to be heavily infiltrated in the replication study. Regions of tumor recurrence were found to have subtle, yet fairly distinctive multiparametric imaging signatures when analyzed quantitatively by pattern analysis and machine learning.</AbstractText Visually imperceptible imaging patterns discovered via multiparametric pattern analysis methods were found to estimate the extent of infiltration and location of future tumor recurrence, paving the way for improved targeted treatment.</AbstractText
Emerging imaging tools for use with traumatic brain injury research. This article identifies emerging neuroimaging measures considered by the inter-agency Pediatric Traumatic Brain Injury (TBI) Neuroimaging Workgroup. This article attempts to address some of the potential uses of more advanced forms of imaging in TBI as well as highlight some of the current considerations and unresolved challenges of using them. We summarize emerging elements likely to gain more widespread use in the coming years, because of 1) their utility in diagnosis, prognosis, and understanding the natural course of degeneration or recovery following TBI, and potential for evaluating treatment strategies; 2) the ability of many centers to acquire these data with scanners and equipment that are readily available in existing clinical and research settings; and 3) advances in software that provide more automated, readily available, and cost-effective analysis methods for large scale data image analysis. These include multi-slice CT, volumetric MRI analysis, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), arterial spin tag labeling (ASL), functional MRI (fMRI), including resting state and connectivity MRI, MR spectroscopy (MRS), and hyperpolarization scanning. However, we also include brief introductions to other specialized forms of advanced imaging that currently do require specialized equipment, for example, single photon emission computed tomography (SPECT), positron emission tomography (PET), encephalography (EEG), and magnetoencephalography (MEG)/magnetic source imaging (MSI). Finally, we identify some of the challenges that users of the emerging imaging CDEs may wish to consider, including quality control, performing multi-site and longitudinal imaging studies, and MR scanning in infants and children.</AbstractText
Acupuncture Increases the Excitability of the Cortico-Spinal System in Patients with Chronic Disorders of Consciousness Following Traumatic Brain Injury. To evaluate the immediate effect of acupuncture on cortico spinal tract (CST) activity in patients with chronic disorders of consciousness (DOC) after traumatic brain injury (TBI) by measuring motor-evoked potential (MEP) using transcranial magnetic stimulation (TMS).</AbstractText Changes in several variables in the acupuncture session were compared with those in the control session without acupuncture in the same patients.</AbstractText Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, Gifu, Japan.</AbstractText Fourteen patients (mean age &#xb1; standard deviation, 39&#x2009;&#xb1;&#x2009;17 years; 12 men) with chronic DOC (5 in a vegetative state and 9 in a minimally conscious state) following severe TBI.</AbstractText Acupuncture treatment was performed at GV 26, Ex-HN 3, bilateral LI 4, and ST 36 for 10 minutes.</AbstractText Main outcome measure was MEP amplitude. MEP amplitude, measured by using TMS on the primary motor cortex, was recorded from the abductor pollicis brevis muscle. MEP recordings were performed before acupuncture (baseline), 10 minutes after needle insertion (phase 1), and 10 minutes after needle removal (phase 2). As a control, the same procedure without acupuncture was performed on another day with the order randomized. MEP amplitude and latency were calculated. Evoked F-wave measurements were also performed to calculate maximum M-wave amplitude (Mmax), M-wave latency, and F-wave latency in the same muscle. Central motor conduction time (CMCT) and MEP/Mmax ratio were also calculated from the MEP and F-wave measurement data.</AbstractText MEP amplitude and MEP/Mmax were increased significantly in the acupuncture session at phases 1 and 2 compared with the control session (p&#x2009;&lt;&#x2009;0.001, p&#x2009;&lt;&#x2009;0.001, p&#x2009;&lt;&#x2009;0.001, and p&#x2009;=&#x2009;0.001, respectively). CMCTs were reduced at phases 1 and 2 in the acupuncture session compared with the control session, and the change at phase 1 was statistically significant (P&#x2009;=&#x2009;0.002).</AbstractText Acupuncture treatment increased the CST activity of patients with chronic DOC after severe TBI.</AbstractText
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37420235
An Overview of Adaptive Designs and Some of Their Challenges, Benefits, and Innovative Applications.
Conducting clinical trials-costs, impacts, and the value of clinical trials networks: A scoping review.
Change in activity patterns in the prefrontal cortex in different phases during the dual-task walking in older adults.
Adaptive designs are increasingly developed and used to improve all phases of clinical trials and in biomedical studies in various ways to address different statistical issues. We first present an overview of adaptive designs and note their numerous advantages over traditional clinical trials. In particular, we provide a concrete demonstration that shows how recent adaptive design strategies can further improve an adaptive trial implemented 13 years ago. Despite their usefulness, adaptive designs are still not widely implemented in clinical trials. We offer a few possible reasons and propose some ways to use them more broadly in practice, which include greater availability of software tools and interactive websites to generate optimal adaptive trials freely and effectively, including the use of metaheuristics to facilitate the search for an efficient trial design. To this end, we present several web-based tools for finding various adaptive and nonadaptive optimal designs and discuss nature-inspired metaheuristics. Metaheuristics are assumptions-free general purpose optimization algorithms widely used in computer science and engineering to tackle all kinds of challenging optimization problems, and their use in designing clinical trials is just emerging. We describe a few recent such applications and some of their capabilities for designing various complex trials. Particle swarm optimization is an exemplary nature-inspired algorithm, and similar to others, it has a simple definition but many moving parts, making it hard to study its properties analytically. We investigated one of its hitherto unstudied issues on how to bring back out-of-range candidates during the search for the optimum of the search domain and show that different strategies can impact the success and time of the search. We conclude with a few caveats on the use of metaheuristics for a successful search.</AbstractText
A significant barrier to conducting clinical trials is their high cost, which is driven primarily by the time and resources required to activate trials and reach accrual targets. The high cost of running trials has a substantial impact on their long-term feasibility and the type of clinical research undertaken.</AbstractText A scoping review of the empirical literature on the costs associated with conducting clinical trials was undertaken for the years 2001-2015. Five reference databases were consulted to elicit how trials costs are presented in the literature. A review instrument was developed to extract the content of in-scope papers. Findings were characterized by date and place of publication, clinical disease area, and network/cooperative group designation, when specified. Costs were captured and grouped by patient accrual and management, infrastructure, and the opportunity costs associated with industry funding for trials research. Cost impacts on translational research and health systems were also captured, as were recommendations to reduce trial expenditures. Since articles often cited multiple costs, multiple cost coding was used during data extraction to capture the range and frequency of costs.</AbstractText A total of 288 empirical articles were included. The distribution of reported costs was: patient management and accrual costs (132 articles), infrastructure costs (118 articles) and the opportunity costs of industry sponsorship (72 articles). 221 articles reported on the impact of undertaking costly trials on translational research and health systems; of these, the most frequently reported consequences were to research integrity (52% of articles), research capacity (36% of articles) and running low-value trials (34% of articles). 254 articles provided recommendations to reduce trial costs; of these, the most frequently reported recommendations related to improvements in: operational efficiencies (33% of articles); patient accrual (24% of articles); funding for trials and transparency in trials reporting (18% of articles, each).</AbstractText Key findings from the review are: 1) delayed trial activation has costs to budgets and research; 2) poor accrual leads to low-value trials and wasted resources; 3) the pharmaceutical industry can be a pragmatic, if problematic, partner in clinical research; 4) organizational know-how and successful research collaboration are benefits of network/cooperative groups; and 5) there are spillover benefits of clinical trials to healthcare systems, including better health outcomes, enhanced research capacity, and drug cost avoidance. There is a need for more economic evaluations of the benefits of clinical research, such as health system use (or avoidance) and health outcomes in cities and health authorities with institutions that conduct clinical research, to demonstrate the affordability of clinical trials, despite their high cost.</AbstractText
Studies using functional near-infrared spectroscopy (fNIRS) have shown that dual-task walking leads to greater prefrontal cortex (PFC) activation compared to the single-task walking task. However, evidence on age-related changes in PFC activity patterns is inconsistent. Therefore, this study aimed to explore the changes in the activation patterns of PFC subregions in different activation phases (early and late phases) during both single-task and dual-task walking in both older and younger adults.</AbstractText Overall, 20 older and 15 younger adults performed a walking task with and without a cognitive task. The activity of the PFC subregions in different phases (early and late phases) and task performance (gait and cognitive task) were evaluated using fNIRS and a gait analyzer.</AbstractText The gait (slower speed and lower cadence) and cognitive performance (lower total response, correct response and accuracy rate, and higher error rate) of older adults was poorer during the dual task than that of younger adults. Right dorsolateral PFC activity in the early period in older adults was higher than that in younger adults, which declined precipitously during the late period. Conversely, the activity level of the right orbitofrontal cortex in the dual-task for older adults was lower than for younger adults.</AbstractText These altered PFC subregion-specific activation patterns in older adults would indicate a decline in dual-task performance with aging.</AbstractText
An Overview of Adaptive Designs and Some of Their Challenges, Benefits, and Innovative Applications. Adaptive designs are increasingly developed and used to improve all phases of clinical trials and in biomedical studies in various ways to address different statistical issues. We first present an overview of adaptive designs and note their numerous advantages over traditional clinical trials. In particular, we provide a concrete demonstration that shows how recent adaptive design strategies can further improve an adaptive trial implemented 13 years ago. Despite their usefulness, adaptive designs are still not widely implemented in clinical trials. We offer a few possible reasons and propose some ways to use them more broadly in practice, which include greater availability of software tools and interactive websites to generate optimal adaptive trials freely and effectively, including the use of metaheuristics to facilitate the search for an efficient trial design. To this end, we present several web-based tools for finding various adaptive and nonadaptive optimal designs and discuss nature-inspired metaheuristics. Metaheuristics are assumptions-free general purpose optimization algorithms widely used in computer science and engineering to tackle all kinds of challenging optimization problems, and their use in designing clinical trials is just emerging. We describe a few recent such applications and some of their capabilities for designing various complex trials. Particle swarm optimization is an exemplary nature-inspired algorithm, and similar to others, it has a simple definition but many moving parts, making it hard to study its properties analytically. We investigated one of its hitherto unstudied issues on how to bring back out-of-range candidates during the search for the optimum of the search domain and show that different strategies can impact the success and time of the search. We conclude with a few caveats on the use of metaheuristics for a successful search.</AbstractText
Conducting clinical trials-costs, impacts, and the value of clinical trials networks: A scoping review. A significant barrier to conducting clinical trials is their high cost, which is driven primarily by the time and resources required to activate trials and reach accrual targets. The high cost of running trials has a substantial impact on their long-term feasibility and the type of clinical research undertaken.</AbstractText A scoping review of the empirical literature on the costs associated with conducting clinical trials was undertaken for the years 2001-2015. Five reference databases were consulted to elicit how trials costs are presented in the literature. A review instrument was developed to extract the content of in-scope papers. Findings were characterized by date and place of publication, clinical disease area, and network/cooperative group designation, when specified. Costs were captured and grouped by patient accrual and management, infrastructure, and the opportunity costs associated with industry funding for trials research. Cost impacts on translational research and health systems were also captured, as were recommendations to reduce trial expenditures. Since articles often cited multiple costs, multiple cost coding was used during data extraction to capture the range and frequency of costs.</AbstractText A total of 288 empirical articles were included. The distribution of reported costs was: patient management and accrual costs (132 articles), infrastructure costs (118 articles) and the opportunity costs of industry sponsorship (72 articles). 221 articles reported on the impact of undertaking costly trials on translational research and health systems; of these, the most frequently reported consequences were to research integrity (52% of articles), research capacity (36% of articles) and running low-value trials (34% of articles). 254 articles provided recommendations to reduce trial costs; of these, the most frequently reported recommendations related to improvements in: operational efficiencies (33% of articles); patient accrual (24% of articles); funding for trials and transparency in trials reporting (18% of articles, each).</AbstractText Key findings from the review are: 1) delayed trial activation has costs to budgets and research; 2) poor accrual leads to low-value trials and wasted resources; 3) the pharmaceutical industry can be a pragmatic, if problematic, partner in clinical research; 4) organizational know-how and successful research collaboration are benefits of network/cooperative groups; and 5) there are spillover benefits of clinical trials to healthcare systems, including better health outcomes, enhanced research capacity, and drug cost avoidance. There is a need for more economic evaluations of the benefits of clinical research, such as health system use (or avoidance) and health outcomes in cities and health authorities with institutions that conduct clinical research, to demonstrate the affordability of clinical trials, despite their high cost.</AbstractText
Change in activity patterns in the prefrontal cortex in different phases during the dual-task walking in older adults. Studies using functional near-infrared spectroscopy (fNIRS) have shown that dual-task walking leads to greater prefrontal cortex (PFC) activation compared to the single-task walking task. However, evidence on age-related changes in PFC activity patterns is inconsistent. Therefore, this study aimed to explore the changes in the activation patterns of PFC subregions in different activation phases (early and late phases) during both single-task and dual-task walking in both older and younger adults.</AbstractText Overall, 20 older and 15 younger adults performed a walking task with and without a cognitive task. The activity of the PFC subregions in different phases (early and late phases) and task performance (gait and cognitive task) were evaluated using fNIRS and a gait analyzer.</AbstractText The gait (slower speed and lower cadence) and cognitive performance (lower total response, correct response and accuracy rate, and higher error rate) of older adults was poorer during the dual task than that of younger adults. Right dorsolateral PFC activity in the early period in older adults was higher than that in younger adults, which declined precipitously during the late period. Conversely, the activity level of the right orbitofrontal cortex in the dual-task for older adults was lower than for younger adults.</AbstractText These altered PFC subregion-specific activation patterns in older adults would indicate a decline in dual-task performance with aging.</AbstractText
36261268
30003976
35112800
History of Previous Midlife Estradiol Treatment Permanently Alters Interactions of Brain Insulin-like Growth Factor-1 Signaling and Hippocampal Estrogen Synthesis to Enhance Cognitive Aging in a Rat Model of Menopause.
Saccade latency delays in young apolipoprotein E (APOE) epsilon 4 carriers.
Conductive Polymer Enabled Biostable Liquid Metal Electrodes for Bioelectronic Applications.
Across species, including humans, elevated levels of brain estrogen receptor (ER) &#x3b1; are associated with enhanced cognitive aging, even in the absence of circulating estrogens. In rodents, short-term estrogen treatment, such as that commonly used in the menopausal transition, results in long-term increases in ER&#x3b1; levels in the hippocampus, leading to enhanced memory long after termination of estrogen treatment. However, mechanisms by which increased levels of brain ER&#x3b1; enhances cognitive aging remain unclear. Here we demonstrate in aging female rats that insulin-like growth factor-1 (IGF-1), which can activate ER via ligand-independent mechanisms, requires concomitant synthesis of brain-derived neuroestrogens to phosphorylate ER&#x3b1; via MAPK signaling, ultimately resulting in enhanced memory. In a rat model of menopause involving long-term ovarian hormone deprivation, hippocampal neuroestrogen activity decreases, altering IGF-1 activity and resulting in impaired memory. However, this process is reversed by short-term estradiol treatment. Forty days of estradiol exposure following ovariectomy results in maintenance of neuroestrogen levels that persist beyond the period of hormone treatment, allowing for continued interactions between IGF-1 and neuroestrogen signaling, elevated levels of hippocampal ER&#x3b1;, and ultimately enhanced memory. Collectively, results demonstrate that short-term estradiol use following loss of ovarian function has long-lasting effects on hippocampal function and memory by dynamically regulating cellular mechanisms that promote activity of ER&#x3b1; in the absence of circulating estrogens. Translational impacts of these findings suggest lasting cognitive benefits of short-term estrogen use near menopause and highlight the importance of hippocampal ER&#x3b1;, independent from the role of circulating estrogens, in regulating memory in aging females.<b
The apolipoprotein E (APOE) epsilon 4 isoform has been associated with a significantly greater risk of developing late onset Alzheimer's disease (AD). However, the negative effects of APOE-&#x3b5;4 allele on cognitive function vary across the lifespan: reduced memory and executive function have been found in older individuals but, paradoxically, young APOE-&#x3b5;4 carriers perform better on cognitive tests and show higher neural efficiency. This study aimed to assess the association between APOE genotype and saccade latency using a prosaccade and antisaccade task in young individuals (N&#x202f;=&#x202f;97, age: 17-35 years). Results showed that prosaccade latency was significantly delayed in a group of &#x3b5;4 carriers in comparison to non-carriers, which was due to a lower rate of signal accumulation rather than a change in the criterion threshold. In contrast, there was no significant genotype difference for antisaccade latency in this young cohort. These results indicate that prosaccade latency may be useful in establishing the APOE behavioural phenotype, which could ultimately assist with distinguishing between normal and pathological aging.</AbstractText
Gallium (Ga)-based liquid metal materials have emerged as a promising material platform for soft bioelectronics. Unfortunately, Ga has limited biostability and electrochemical performance under physiological conditions, which can hinder the implementation of its use in bioelectronic devices. Here, an effective conductive polymer deposition strategy on the liquid metal surface to improve the biostability and electrochemical performance of Ga-based liquid metals for use under physiological conditions is demonstrated. The conductive polymer [poly(3,4-ethylene dioxythiophene):tetrafluoroborate]-modified liquid metal surface significantly outperforms the liquid metal.based electrode in mechanical, biological, and electrochemical studies. In vivo action potential recordings in behaving nonhuman primate and invertebrate models demonstrate the feasibility of using liquid metal electrodes for high-performance neural recording applications. This is the first demonstration of single-unit neural recording using Ga-based liquid metal bioelectronic devices to date. The results determine that the electrochemical deposition of conductive polymer over liquid metal can improve the material properties of liquid metal electrodes for use under physiological conditions and open numerous design opportunities for next-generation liquid metal-based bioelectronics.</AbstractText
History of Previous Midlife Estradiol Treatment Permanently Alters Interactions of Brain Insulin-like Growth Factor-1 Signaling and Hippocampal Estrogen Synthesis to Enhance Cognitive Aging in a Rat Model of Menopause. Across species, including humans, elevated levels of brain estrogen receptor (ER) &#x3b1; are associated with enhanced cognitive aging, even in the absence of circulating estrogens. In rodents, short-term estrogen treatment, such as that commonly used in the menopausal transition, results in long-term increases in ER&#x3b1; levels in the hippocampus, leading to enhanced memory long after termination of estrogen treatment. However, mechanisms by which increased levels of brain ER&#x3b1; enhances cognitive aging remain unclear. Here we demonstrate in aging female rats that insulin-like growth factor-1 (IGF-1), which can activate ER via ligand-independent mechanisms, requires concomitant synthesis of brain-derived neuroestrogens to phosphorylate ER&#x3b1; via MAPK signaling, ultimately resulting in enhanced memory. In a rat model of menopause involving long-term ovarian hormone deprivation, hippocampal neuroestrogen activity decreases, altering IGF-1 activity and resulting in impaired memory. However, this process is reversed by short-term estradiol treatment. Forty days of estradiol exposure following ovariectomy results in maintenance of neuroestrogen levels that persist beyond the period of hormone treatment, allowing for continued interactions between IGF-1 and neuroestrogen signaling, elevated levels of hippocampal ER&#x3b1;, and ultimately enhanced memory. Collectively, results demonstrate that short-term estradiol use following loss of ovarian function has long-lasting effects on hippocampal function and memory by dynamically regulating cellular mechanisms that promote activity of ER&#x3b1; in the absence of circulating estrogens. Translational impacts of these findings suggest lasting cognitive benefits of short-term estrogen use near menopause and highlight the importance of hippocampal ER&#x3b1;, independent from the role of circulating estrogens, in regulating memory in aging females.<b
Saccade latency delays in young apolipoprotein E (APOE) epsilon 4 carriers. The apolipoprotein E (APOE) epsilon 4 isoform has been associated with a significantly greater risk of developing late onset Alzheimer's disease (AD). However, the negative effects of APOE-&#x3b5;4 allele on cognitive function vary across the lifespan: reduced memory and executive function have been found in older individuals but, paradoxically, young APOE-&#x3b5;4 carriers perform better on cognitive tests and show higher neural efficiency. This study aimed to assess the association between APOE genotype and saccade latency using a prosaccade and antisaccade task in young individuals (N&#x202f;=&#x202f;97, age: 17-35 years). Results showed that prosaccade latency was significantly delayed in a group of &#x3b5;4 carriers in comparison to non-carriers, which was due to a lower rate of signal accumulation rather than a change in the criterion threshold. In contrast, there was no significant genotype difference for antisaccade latency in this young cohort. These results indicate that prosaccade latency may be useful in establishing the APOE behavioural phenotype, which could ultimately assist with distinguishing between normal and pathological aging.</AbstractText
Conductive Polymer Enabled Biostable Liquid Metal Electrodes for Bioelectronic Applications. Gallium (Ga)-based liquid metal materials have emerged as a promising material platform for soft bioelectronics. Unfortunately, Ga has limited biostability and electrochemical performance under physiological conditions, which can hinder the implementation of its use in bioelectronic devices. Here, an effective conductive polymer deposition strategy on the liquid metal surface to improve the biostability and electrochemical performance of Ga-based liquid metals for use under physiological conditions is demonstrated. The conductive polymer [poly(3,4-ethylene dioxythiophene):tetrafluoroborate]-modified liquid metal surface significantly outperforms the liquid metal.based electrode in mechanical, biological, and electrochemical studies. In vivo action potential recordings in behaving nonhuman primate and invertebrate models demonstrate the feasibility of using liquid metal electrodes for high-performance neural recording applications. This is the first demonstration of single-unit neural recording using Ga-based liquid metal bioelectronic devices to date. The results determine that the electrochemical deposition of conductive polymer over liquid metal can improve the material properties of liquid metal electrodes for use under physiological conditions and open numerous design opportunities for next-generation liquid metal-based bioelectronics.</AbstractText
32658148
19543222
32246286
Analgesic dorsal root ganglionic field stimulation blocks conduction of afferent impulse trains selectively in nociceptive sensory afferents.
Principles of neural ensemble physiology underlying the operation of brain-machine interfaces.
An in vivo proton magnetic resonance spectroscopy study with optimized echo-time technique for concurrent quantification and T2 measurement targeting glutamate in the rat brain.
Increased excitability of primary sensory neurons after peripheral nerve injury may cause hyperalgesia and allodynia. Dorsal root ganglion field stimulation (GFS) is effective in relieving clinical pain associated with nerve injury and neuropathic pain in animal models. However, its mechanism has not been determined. We examined effects of GFS on transmission of action potentials (APs) from the peripheral to central processes by in vivo single-unit recording from lumbar dorsal roots in sham injured rats and rats with tibial nerve injury (TNI) in fiber types defined by conduction velocity. Transmission of APs directly generated by GFS (20 Hz) in C-type units progressively abated over 20 seconds, whereas GFS-induced A&#x3b2; activity persisted unabated, while A&#x3b4; showed an intermediate pattern. Activity generated peripherally by electrical stimulation of the sciatic nerve and punctate mechanical stimulation of the receptive field (glabrous skin) was likewise fully blocked by GFS within 20 seconds in C-type units, whereas A&#x3b2; units were minimally affected and a subpopulation of A&#x3b4; units was blocked. After TNI, the threshold to induce AP firing by punctate mechanical stimulation (von Frey) was reduced, which was reversed to normal during GFS. These results also suggest that C-type fibers, not A&#x3b2;, mainly contribute to mechanical and thermal hypersensitivity (von Frey, brush, acetone) after injury. Ganglion field stimulation produces use-dependent blocking of afferent AP trains, consistent with enhanced filtering of APs at the sensory neuron T-junction, particularly in nociceptive units.</AbstractText
Research on brain-machine interfaces has been ongoing for at least a decade. During this period, simultaneous recordings of the extracellular electrical activity of hundreds of individual neurons have been used for direct, real-time control of various artificial devices. Brain-machine interfaces have also added greatly to our knowledge of the fundamental physiological principles governing the operation of large neural ensembles. Further understanding of these principles is likely to have a key role in the future development of neuroprosthetics for restoring mobility in severely paralysed patients.</AbstractText
The present study applied in vivo proton magnetic resonance spectroscopy (<sup 7T MRS scans of the OpQT2-Glu were acquired from the prefrontal cortex of five rats. The echo-time-(TE)-specific J-modulation of glutamate was investigated by spectral simulations and analyses for selecting the eight TEs appropriate for T2 estimation of glutamate. The OpQT2-Glu results were compared to those of the typical short-TE MRS and T2 measurements.</AbstractText No significant differences were observed between the OpQT2-Glu and typical short-TE MRS (p&#x2009;&gt;&#x2009;0.050). The estimated glutamate T2 (67.75&#xa0;ms) of the OpQT2-Glu was similar to the multiple TE MRS for the T2 measurement (71.58&#xa0;ms) with enhanced signal-to-noise ratio and reliability.</AbstractText The results revealed that the quantification reliability of the OpQT2-Glu was comparable to that of the single short-TE MRS and its estimation reliability for the T2 relaxation time of glutamate was enhanced compared to the multiple TE MRS for T2 measurement. Despite certain limitations, the quantification and T2 estimation of glutamate can be concurrently performed within an acceptable scan time via high-field in vivo <sup
Analgesic dorsal root ganglionic field stimulation blocks conduction of afferent impulse trains selectively in nociceptive sensory afferents. Increased excitability of primary sensory neurons after peripheral nerve injury may cause hyperalgesia and allodynia. Dorsal root ganglion field stimulation (GFS) is effective in relieving clinical pain associated with nerve injury and neuropathic pain in animal models. However, its mechanism has not been determined. We examined effects of GFS on transmission of action potentials (APs) from the peripheral to central processes by in vivo single-unit recording from lumbar dorsal roots in sham injured rats and rats with tibial nerve injury (TNI) in fiber types defined by conduction velocity. Transmission of APs directly generated by GFS (20 Hz) in C-type units progressively abated over 20 seconds, whereas GFS-induced A&#x3b2; activity persisted unabated, while A&#x3b4; showed an intermediate pattern. Activity generated peripherally by electrical stimulation of the sciatic nerve and punctate mechanical stimulation of the receptive field (glabrous skin) was likewise fully blocked by GFS within 20 seconds in C-type units, whereas A&#x3b2; units were minimally affected and a subpopulation of A&#x3b4; units was blocked. After TNI, the threshold to induce AP firing by punctate mechanical stimulation (von Frey) was reduced, which was reversed to normal during GFS. These results also suggest that C-type fibers, not A&#x3b2;, mainly contribute to mechanical and thermal hypersensitivity (von Frey, brush, acetone) after injury. Ganglion field stimulation produces use-dependent blocking of afferent AP trains, consistent with enhanced filtering of APs at the sensory neuron T-junction, particularly in nociceptive units.</AbstractText
Principles of neural ensemble physiology underlying the operation of brain-machine interfaces. Research on brain-machine interfaces has been ongoing for at least a decade. During this period, simultaneous recordings of the extracellular electrical activity of hundreds of individual neurons have been used for direct, real-time control of various artificial devices. Brain-machine interfaces have also added greatly to our knowledge of the fundamental physiological principles governing the operation of large neural ensembles. Further understanding of these principles is likely to have a key role in the future development of neuroprosthetics for restoring mobility in severely paralysed patients.</AbstractText
An in vivo proton magnetic resonance spectroscopy study with optimized echo-time technique for concurrent quantification and T2 measurement targeting glutamate in the rat brain. The present study applied in vivo proton magnetic resonance spectroscopy (<sup 7T MRS scans of the OpQT2-Glu were acquired from the prefrontal cortex of five rats. The echo-time-(TE)-specific J-modulation of glutamate was investigated by spectral simulations and analyses for selecting the eight TEs appropriate for T2 estimation of glutamate. The OpQT2-Glu results were compared to those of the typical short-TE MRS and T2 measurements.</AbstractText No significant differences were observed between the OpQT2-Glu and typical short-TE MRS (p&#x2009;&gt;&#x2009;0.050). The estimated glutamate T2 (67.75&#xa0;ms) of the OpQT2-Glu was similar to the multiple TE MRS for the T2 measurement (71.58&#xa0;ms) with enhanced signal-to-noise ratio and reliability.</AbstractText The results revealed that the quantification reliability of the OpQT2-Glu was comparable to that of the single short-TE MRS and its estimation reliability for the T2 relaxation time of glutamate was enhanced compared to the multiple TE MRS for T2 measurement. Despite certain limitations, the quantification and T2 estimation of glutamate can be concurrently performed within an acceptable scan time via high-field in vivo <sup
29044439
28859167
28835001
Liver Masses: What Physicians Need to Know About Ordering and Interpreting Liver Imaging.
Up to 52 administrations of macrocyclic ionic MR contrast agent are not associated with intracranial gadolinium deposition: Multifactorial analysis in 385 patients.
Maternal Age and Trajectories of Risky Alcohol Use: A Prospective Study.
This paper reviews diagnostic imaging techniques used to characterize liver masses and the imaging characteristics of the most common liver masses.</AbstractText The role of recently adopted ultrasound and magnetic resonance imaging contrast agents will be emphasized. Contrast-enhanced ultrasound is an inexpensive exam which can confirm benignity of certain liver masses without ionizing radiation. Magnetic resonance imaging using hepatocyte-specific gadolinium-based contrast agents can help confirm or narrow the differential diagnosis of liver masses.</AbstractText
To determine whether multiple repeated administrations of gadolinium-based macrocyclic ionic MR contrast agent (MICA) are associated with intracranial gadolinium deposition and identify the predisposing factors for deposition in various clinical situations.</AbstractText In this institutional review board-approved retrospective study, 385 consecutive patients who underwent MICA-enhanced MR imaging were enrolled. The dentate nucleus-to-pons (DN/P) and globus pallidus-to-thalamus (GP/Th) signal intensity (SI) ratios on unenhanced T1-weighted images were recorded by 2 independent readers and averaged. The mean DN/P and GP/Th SI ratio difference between the last and the first examinations were tested using the one-sample t-test. Student's t-test and stepwise regression analysis were used to identify the predisposing factors for deposition based on the number of administrations, time interval, hepatic and renal function, magnetic field strength, and chemo- or radiation therapy.</AbstractText The mean DN/P SI ratio difference was not different from zero (P = .697), even in patients with &#x2265;20 administrations (n = 33). Only patients with abnormal renal function showed an increase in the mean DN/P SI ratio difference (P = .019). The mean DN/P SI ratio difference was not associated with any predisposing factors. However, the mean GP/Th SI ratio difference showed decrease (P &lt; .001), which was associated with age (P = .007), number of administrations (P = .01) and number of radiation therapy sessions (P = .022) on multivariate analysis.</AbstractText Multiple repeated administrations of MICA were not associated with increased T1 signal intensity in deep brain nuclei suggestive of Gd deposition in patients with normal renal function.</AbstractText
No prospective study of maternal alcohol use has focused on age at transition to motherhood as a predictor of trajectories of risky drinking. The goal of this study was to examine the impact of maternal age at first birth on trajectories of alcohol use beyond recommended levels over a 17-year span.</AbstractText Pregnant women (N&#xa0;=&#xa0;456) were recruited at an urban prenatal clinic. The women (13 to 42&#xa0;years old; 64% African American, 36% White) were interviewed about alcohol use during pregnancy and at 6, 10, 14, and 16&#xa0;years postpartum. Growth mixture modeling (GMM) was used to identify trajectories of risky drinking. Maternal age at first birth was then regressed onto trajectory class membership.</AbstractText The GMM on maternal alcohol use identified 3 groups of mothers as a function of alcohol use before, during, and after the pregnancy. The majority of mothers (66%) were identified as having low-risk trajectories of alcohol use over the 17-year span. However, 2 groups were in the higher-risk categories, with 23% identified as being in a long-term high-risk trajectory, and 11% in a short-term high-risk trajectory group. Maternal age at first birth predicted membership in a high-risk group: Younger mothers were more likely to be classified into a long-term high-risk alcohol use group.</AbstractText Younger mothers were more likely to engage in risky drinking early in pregnancy, continuing 6 to 14&#xa0;years postpartum. These results can help physicians target mothers who are likely to exceed current NIAAA guidelines of abstinence during pregnancy, and no more than 7 drinks per week in the postpartum.</AbstractText
Liver Masses: What Physicians Need to Know About Ordering and Interpreting Liver Imaging. This paper reviews diagnostic imaging techniques used to characterize liver masses and the imaging characteristics of the most common liver masses.</AbstractText The role of recently adopted ultrasound and magnetic resonance imaging contrast agents will be emphasized. Contrast-enhanced ultrasound is an inexpensive exam which can confirm benignity of certain liver masses without ionizing radiation. Magnetic resonance imaging using hepatocyte-specific gadolinium-based contrast agents can help confirm or narrow the differential diagnosis of liver masses.</AbstractText
Up to 52 administrations of macrocyclic ionic MR contrast agent are not associated with intracranial gadolinium deposition: Multifactorial analysis in 385 patients. To determine whether multiple repeated administrations of gadolinium-based macrocyclic ionic MR contrast agent (MICA) are associated with intracranial gadolinium deposition and identify the predisposing factors for deposition in various clinical situations.</AbstractText In this institutional review board-approved retrospective study, 385 consecutive patients who underwent MICA-enhanced MR imaging were enrolled. The dentate nucleus-to-pons (DN/P) and globus pallidus-to-thalamus (GP/Th) signal intensity (SI) ratios on unenhanced T1-weighted images were recorded by 2 independent readers and averaged. The mean DN/P and GP/Th SI ratio difference between the last and the first examinations were tested using the one-sample t-test. Student's t-test and stepwise regression analysis were used to identify the predisposing factors for deposition based on the number of administrations, time interval, hepatic and renal function, magnetic field strength, and chemo- or radiation therapy.</AbstractText The mean DN/P SI ratio difference was not different from zero (P = .697), even in patients with &#x2265;20 administrations (n = 33). Only patients with abnormal renal function showed an increase in the mean DN/P SI ratio difference (P = .019). The mean DN/P SI ratio difference was not associated with any predisposing factors. However, the mean GP/Th SI ratio difference showed decrease (P &lt; .001), which was associated with age (P = .007), number of administrations (P = .01) and number of radiation therapy sessions (P = .022) on multivariate analysis.</AbstractText Multiple repeated administrations of MICA were not associated with increased T1 signal intensity in deep brain nuclei suggestive of Gd deposition in patients with normal renal function.</AbstractText
Maternal Age and Trajectories of Risky Alcohol Use: A Prospective Study. No prospective study of maternal alcohol use has focused on age at transition to motherhood as a predictor of trajectories of risky drinking. The goal of this study was to examine the impact of maternal age at first birth on trajectories of alcohol use beyond recommended levels over a 17-year span.</AbstractText Pregnant women (N&#xa0;=&#xa0;456) were recruited at an urban prenatal clinic. The women (13 to 42&#xa0;years old; 64% African American, 36% White) were interviewed about alcohol use during pregnancy and at 6, 10, 14, and 16&#xa0;years postpartum. Growth mixture modeling (GMM) was used to identify trajectories of risky drinking. Maternal age at first birth was then regressed onto trajectory class membership.</AbstractText The GMM on maternal alcohol use identified 3 groups of mothers as a function of alcohol use before, during, and after the pregnancy. The majority of mothers (66%) were identified as having low-risk trajectories of alcohol use over the 17-year span. However, 2 groups were in the higher-risk categories, with 23% identified as being in a long-term high-risk trajectory, and 11% in a short-term high-risk trajectory group. Maternal age at first birth predicted membership in a high-risk group: Younger mothers were more likely to be classified into a long-term high-risk alcohol use group.</AbstractText Younger mothers were more likely to engage in risky drinking early in pregnancy, continuing 6 to 14&#xa0;years postpartum. These results can help physicians target mothers who are likely to exceed current NIAAA guidelines of abstinence during pregnancy, and no more than 7 drinks per week in the postpartum.</AbstractText
40728843
40130013
40774209
Neurite density but not myelination of specific fiber tracts links polygenic scores to general intelligence.
Microbiota-Gut-Brain Axis in Psychiatry: Focus on Depressive Disorders.
Preparation of oat metal ion chelating peptides via froth floatation: Efficacy, molecular characteristics, and their anti-browning effects.
White matter is fundamental for efficient information transfer and thus crucial for intelligence. Previous studies demonstrated associations between fractional anisotropy and intelligence, but it remains unclear whether this relation is due to greater axon density, parallel, homogenous fiber orientation distributions, or greater myelination, as all influence fractional anisotropy. Using neurite orientation dispersion and density imaging and myelin water fraction imaging, we analyzed the microstructural architecture of intelligence in 500 healthy young adults. We were also interested whether specific white matter indices mediate the pathway linking genetic disposition for intelligence to phenotype. For the first time, we conducted mediation analyses investigating whether neurite density index, orientation dispersion index, and myelin water fraction of 64 white matter tracts mediate the effects of polygenic scores for intelligence on general intelligence (g). Our results showed that neurite density index, but not orientation dispersion index or myelin water fraction of white matter tracts, was significantly associated with g and that neurite density index of six fiber tracts mediated the relation between genetic variability and g. These findings are a crucial step toward decoding the neurogenetic underpinnings of general intelligence, as they identify that neurite density of specific fiber tracts relates polygenic variation to g, whereas orientation dispersion and myelination did not.</AbstractText
Gut microbiota contribute to several physiological processes in the host. The composition of the gut microbiome is associated with different neurological and neurodevelopmental diseases. In psychiatric disease, stress may be a major factor leading to gut microbiota alterations. Depressive disorders are the most prevalent mental health issues worldwide and patients often report gastrointestinal symptoms. Accordingly, evidence of gut microbial alterations in depressive disorders has been growing. Here we review current literature revealing links between the gut microbiome and brain function in the context of depression.</AbstractText The gut-brain axis could impact the behavioral manifestation of depression and the underlying neuropathology via multiple routes: the HPA axis, immune function, the enteric nervous system, and the vagus nerve. Furthermore, we explore possible therapeutic interventions including fecal microbiota transplant or probiotic supplementation in alleviating depressive symptoms.</AbstractText Understanding the mechanisms by which bidirectional communication along the gut-brain axis can be dysregulated in patients with depression could lead to the development of personalized, microbiome-targeted therapies for the treatment of this disorder.</AbstractText
Currently, the low purity and complex nature of metal ion chelating peptides (MPs) limit their application effectiveness. This study developed a novel method for the efficient preparation of MPs via zinc ion-chelating froth flotation, achieving a 19.2&#xa0;% yield of high-purity MPs. The chelating capacities for Cu<sup
Neurite density but not myelination of specific fiber tracts links polygenic scores to general intelligence. White matter is fundamental for efficient information transfer and thus crucial for intelligence. Previous studies demonstrated associations between fractional anisotropy and intelligence, but it remains unclear whether this relation is due to greater axon density, parallel, homogenous fiber orientation distributions, or greater myelination, as all influence fractional anisotropy. Using neurite orientation dispersion and density imaging and myelin water fraction imaging, we analyzed the microstructural architecture of intelligence in 500 healthy young adults. We were also interested whether specific white matter indices mediate the pathway linking genetic disposition for intelligence to phenotype. For the first time, we conducted mediation analyses investigating whether neurite density index, orientation dispersion index, and myelin water fraction of 64 white matter tracts mediate the effects of polygenic scores for intelligence on general intelligence (g). Our results showed that neurite density index, but not orientation dispersion index or myelin water fraction of white matter tracts, was significantly associated with g and that neurite density index of six fiber tracts mediated the relation between genetic variability and g. These findings are a crucial step toward decoding the neurogenetic underpinnings of general intelligence, as they identify that neurite density of specific fiber tracts relates polygenic variation to g, whereas orientation dispersion and myelination did not.</AbstractText
Microbiota-Gut-Brain Axis in Psychiatry: Focus on Depressive Disorders. Gut microbiota contribute to several physiological processes in the host. The composition of the gut microbiome is associated with different neurological and neurodevelopmental diseases. In psychiatric disease, stress may be a major factor leading to gut microbiota alterations. Depressive disorders are the most prevalent mental health issues worldwide and patients often report gastrointestinal symptoms. Accordingly, evidence of gut microbial alterations in depressive disorders has been growing. Here we review current literature revealing links between the gut microbiome and brain function in the context of depression.</AbstractText The gut-brain axis could impact the behavioral manifestation of depression and the underlying neuropathology via multiple routes: the HPA axis, immune function, the enteric nervous system, and the vagus nerve. Furthermore, we explore possible therapeutic interventions including fecal microbiota transplant or probiotic supplementation in alleviating depressive symptoms.</AbstractText Understanding the mechanisms by which bidirectional communication along the gut-brain axis can be dysregulated in patients with depression could lead to the development of personalized, microbiome-targeted therapies for the treatment of this disorder.</AbstractText
Preparation of oat metal ion chelating peptides via froth floatation: Efficacy, molecular characteristics, and their anti-browning effects. Currently, the low purity and complex nature of metal ion chelating peptides (MPs) limit their application effectiveness. This study developed a novel method for the efficient preparation of MPs via zinc ion-chelating froth flotation, achieving a 19.2&#xa0;% yield of high-purity MPs. The chelating capacities for Cu<sup
32430580
9345505
34028206
Kinetic modeling and parametric imaging with dynamic PET for oncological applications: general considerations, current clinical applications, and future perspectives.
Simplified reference tissue model for PET receptor studies.
Elucidating the nature of linguistic processing in insight.
Dynamic PET (dPET) studies have been used until now primarily within research purposes. Although it is generally accepted that the information provided by dPET is superior to that of conventional static PET acquisitions acquired usually 60&#xa0;min post injection of the radiotracer, the duration of dynamic protocols, the limited axial field of view (FOV) of current generation clinical PET systems covering a relatively small axial extent of the human body for a dynamic measurement, and the complexity of data evaluation have hampered its implementation into clinical routine. However, the development of new-generation PET/CT scanners with an extended FOV as well as of more sophisticated evaluation software packages that offer better segmentation algorithms, automatic retrieval of the arterial input function, and automatic calculation of parametric imaging, in combination with dedicated shorter dynamic protocols, will facilitate the wider use of dPET. This is expected to aid in oncological diagnostics and therapy assessment. The aim of this review is to present some general considerations about dPET analysis in oncology by means of kinetic modeling, based on compartmental and noncompartmental approaches, and parametric imaging. Moreover, the current clinical applications and future perspectives of the modality are outlined.</AbstractText
The reference tissue model allows for quantification of receptor kinetics without measuring the arterial input function, thus avoiding arterial cannulation and time-consuming metabolite measurements. The model contains four parameters, of which the binding potential (BP) is the parameter of interest. Although BP is robust, convergence rates are slow and the other parameters can have large standard errors. To overcome this problem, a simplified reference tissue containing only three parameters was developed. This new three-parameter model was compared with the previous four-parameter model using a variety of PET studies: [11C]SCH 23390 (D1 receptor) and [11C]raclopride (D2 receptor) in humans, and [11C]SCH 23390, [11C]raclopride and [11C]RTI-121 (dopamine transporter) in rats. The BP values obtained from both models were essentially the same for all cases. In addition, the three-parameter model was insensitive to starting values, produced stable results for the other parameters (small standard errors), and converged rapidly. In conclusion, for the ligands tested the three-parameter model is a better choice, combining increased convergence rate with increased stability.</AbstractText
The relationship between language and thinking has long been a matter of debate and a research focus in studies on thinking and problem solving, including creativity. Previous behavioral studies have found that verbalization of one's internal thoughts does not participate in or even interfere with the creative insight process, thus suggesting that insight may take place nonverbally. In contrast to this hypothesis, the present study proposes a new one. That is, given that the basic categories or fundamental functions of key concepts or objects are critically changed or expanded during insightful thinking, the linguistic processing accompanying insight can be reflected as category-related representation and recategorization processes, which can be critically mediated by the posterior middle temporal gyrus and the angular gyrus (pMTG/AG). Using constraint-relaxation insight riddles as materials in a guided-insight experimental design with external hints to trigger the insightful representational change, this preliminary neuroimaging study of 11 participants found the involvement of pMTG/AG during moments of induced insight, but did not find the activation of left ventral frontal areas which are typically involved in verbalizing of one's internal thoughts. Although this observation still cannot exclude the possibility of internal verbalization in insightful restructuring, it implies that linguistic processing in insight may take the more fundamental form of category-related processing.</AbstractText
Kinetic modeling and parametric imaging with dynamic PET for oncological applications: general considerations, current clinical applications, and future perspectives. Dynamic PET (dPET) studies have been used until now primarily within research purposes. Although it is generally accepted that the information provided by dPET is superior to that of conventional static PET acquisitions acquired usually 60&#xa0;min post injection of the radiotracer, the duration of dynamic protocols, the limited axial field of view (FOV) of current generation clinical PET systems covering a relatively small axial extent of the human body for a dynamic measurement, and the complexity of data evaluation have hampered its implementation into clinical routine. However, the development of new-generation PET/CT scanners with an extended FOV as well as of more sophisticated evaluation software packages that offer better segmentation algorithms, automatic retrieval of the arterial input function, and automatic calculation of parametric imaging, in combination with dedicated shorter dynamic protocols, will facilitate the wider use of dPET. This is expected to aid in oncological diagnostics and therapy assessment. The aim of this review is to present some general considerations about dPET analysis in oncology by means of kinetic modeling, based on compartmental and noncompartmental approaches, and parametric imaging. Moreover, the current clinical applications and future perspectives of the modality are outlined.</AbstractText
Simplified reference tissue model for PET receptor studies. The reference tissue model allows for quantification of receptor kinetics without measuring the arterial input function, thus avoiding arterial cannulation and time-consuming metabolite measurements. The model contains four parameters, of which the binding potential (BP) is the parameter of interest. Although BP is robust, convergence rates are slow and the other parameters can have large standard errors. To overcome this problem, a simplified reference tissue containing only three parameters was developed. This new three-parameter model was compared with the previous four-parameter model using a variety of PET studies: [11C]SCH 23390 (D1 receptor) and [11C]raclopride (D2 receptor) in humans, and [11C]SCH 23390, [11C]raclopride and [11C]RTI-121 (dopamine transporter) in rats. The BP values obtained from both models were essentially the same for all cases. In addition, the three-parameter model was insensitive to starting values, produced stable results for the other parameters (small standard errors), and converged rapidly. In conclusion, for the ligands tested the three-parameter model is a better choice, combining increased convergence rate with increased stability.</AbstractText
Elucidating the nature of linguistic processing in insight. The relationship between language and thinking has long been a matter of debate and a research focus in studies on thinking and problem solving, including creativity. Previous behavioral studies have found that verbalization of one's internal thoughts does not participate in or even interfere with the creative insight process, thus suggesting that insight may take place nonverbally. In contrast to this hypothesis, the present study proposes a new one. That is, given that the basic categories or fundamental functions of key concepts or objects are critically changed or expanded during insightful thinking, the linguistic processing accompanying insight can be reflected as category-related representation and recategorization processes, which can be critically mediated by the posterior middle temporal gyrus and the angular gyrus (pMTG/AG). Using constraint-relaxation insight riddles as materials in a guided-insight experimental design with external hints to trigger the insightful representational change, this preliminary neuroimaging study of 11 participants found the involvement of pMTG/AG during moments of induced insight, but did not find the activation of left ventral frontal areas which are typically involved in verbalizing of one's internal thoughts. Although this observation still cannot exclude the possibility of internal verbalization in insightful restructuring, it implies that linguistic processing in insight may take the more fundamental form of category-related processing.</AbstractText
39698610
37174039
37902591
Preoperatively predicting human epidermal growth factor receptor 2-low expression in breast cancer using neural network model based on multiparameter magnetic resonance imaging.
Artificial Intelligence in CT and MR Imaging for Oncological Applications.
The Impact of Linguistic Prediction Violations on Downstream Recognition Memory and Sentence Recall.
Preoperative prediction of human epidermal growth factor receptor 2 (HER2)-low expression using magnetic resonance imaging (MRI) can enhance the selection of clinical treatment strategies and enhance patient outcomes. Herein, we investigated the value of a neural network model constructed with multiparametric MRI in diagnosing HER2-low breast cancer.</AbstractText This retrospective study involved two different centers. A total of 895 breast cancer patients (903 lesions) were enrolled from the Second Hospital of Shandong University (known as "Center 1") between January 2015 to December 2022. They were allocated to the training set (626 cases/632 lesions) and the internal validation set (269 cases/271 lesions). The external validation set included 100 patients (100 lesions) from the Qilu Hospital of Shandong University (referred to as "Center 2") between June 2021 to December 2022. All patients were subgrouped into HER2-low and HER2-0 expression groups. We used t-tests, Wilcoxon rank sum tests, and Chi-squared tests or Fisher's exact test to compare the dynamic contrast-enhanced MRI features (morphological/hemodynamic features), and the apparent diffusion coefficient (ADC) values. A neural network model was constructed using the Neuralnet package in R, with the architecture specified as c(5,2) for the hidden layers. Bootstrapping was used for internal validation. The diagnostic performance in the training set was analyzed using receiver operating characteristic (ROC) curves. The clinical effectiveness of the model was validated using a decision curve analysis (DCA).</AbstractText HER2-low breast cancer lesions had irregular morphology, high early enhancement rate, and low ADC value compared to HER2-0 expressed lesions. The differences were significant (P&lt;0.05). We then constructed a neural network model using these significant variables. ROC analysis showed that the area under the ROC curve of the model for diagnosing HER2-low breast cancer in the training, internal validation, and external validation sets was 0.757 [95% confidence interval (CI): 0.712-0.802], 0.728 (95% CI: 0.658-0.798), and 0.791 (95% CI: 0.693-0.890), respectively. The DCA demonstrated that the net benefit of the model was significantly greater than zero at a predicted probability of 0.764.</AbstractText The neural network model based on MRI features is an effective tool in predicting HER2-low breast cancer, which may facilitate clinical treatment decision-making.</AbstractText
Cancer care increasingly relies on imaging for patient management. The two most common cross-sectional imaging modalities in oncology are computed tomography (CT) and magnetic resonance imaging (MRI), which provide high-resolution anatomic and physiological imaging. Herewith is a summary of recent applications of rapidly advancing artificial intelligence (AI) in CT and MRI oncological imaging that addresses the benefits and challenges of the resultant opportunities with examples. Major challenges remain, such as how best to integrate AI developments into clinical radiology practice, the vigorous assessment of quantitative CT and MR imaging data accuracy, and reliability for clinical utility and research integrity in oncology. Such challenges necessitate an evaluation of the robustness of imaging biomarkers to be included in AI developments, a culture of data sharing, and the cooperation of knowledgeable academics with vendor scientists and companies operating in radiology and oncology fields. Herein, we will illustrate a few challenges and solutions of these efforts using novel methods for synthesizing different contrast modality images, auto-segmentation, and image reconstruction with examples from lung CT as well as abdome, pelvis, and head and neck MRI. The imaging community must embrace the need for quantitative CT and MRI metrics beyond lesion size measurement. AI methods for the extraction and longitudinal tracking of imaging metrics from registered lesions and understanding the tumor environment will be invaluable for interpreting disease status and treatment efficacy. This is an exciting time to work together to move the imaging field forward with narrow AI-specific tasks. New AI developments using CT and MRI datasets will be used to improve the personalized management of cancer patients.</AbstractText
Predicting upcoming words during language comprehension not only affects processing in the moment but also has consequences for memory, although the source of these memory effects (e.g., whether driven by lingering pre-activations, re-analysis following prediction violations, or other mechanisms) remains underspecified. Here, we investigated downstream impacts of prediction on memory in two experiments. First, we recorded EEG as participants read strongly and weakly constraining sentences with expected, unexpected but plausible, or semantically anomalous endings ("He made a holster for his gun / father / train") and were tested on their recognition memory for the sentence endings. Participants showed similar rates of false alarms for predicted but never presented sentence endings whether the prediction violation was plausible or anomalous, suggesting that these arise from pre-activation of the expected words during reading. During sentence reading, especially in strongly constraining sentences, plausible prediction violations elicited an anterior positivity; anomalous endings instead elicited a posterior positivity, whose amplitude was predictive of later memory for those anomalous words. ERP patterns at the time of recognition differentiated plausible and anomalous sentence endings: Words that had been plausible prediction violations elicited enhanced late positive complex amplitudes, suggesting greater episodic recollection, whereas anomalous sentence endings elicited greater N1 amplitudes, suggesting attentional tagging. In a follow-up behavioral study, a separate group of participants read the same sentence stimuli and were tested for sentence-level recall. We found that recall of full sentences was impaired when sentences ended with a prediction violation. Taken together, the results suggest that prediction violations draw attention and affect encoding of the violating word, in a manner that depends on plausibility, and that this, in turn, may impair future memory of the gist of the sentence.</AbstractText
Preoperatively predicting human epidermal growth factor receptor 2-low expression in breast cancer using neural network model based on multiparameter magnetic resonance imaging. Preoperative prediction of human epidermal growth factor receptor 2 (HER2)-low expression using magnetic resonance imaging (MRI) can enhance the selection of clinical treatment strategies and enhance patient outcomes. Herein, we investigated the value of a neural network model constructed with multiparametric MRI in diagnosing HER2-low breast cancer.</AbstractText This retrospective study involved two different centers. A total of 895 breast cancer patients (903 lesions) were enrolled from the Second Hospital of Shandong University (known as "Center 1") between January 2015 to December 2022. They were allocated to the training set (626 cases/632 lesions) and the internal validation set (269 cases/271 lesions). The external validation set included 100 patients (100 lesions) from the Qilu Hospital of Shandong University (referred to as "Center 2") between June 2021 to December 2022. All patients were subgrouped into HER2-low and HER2-0 expression groups. We used t-tests, Wilcoxon rank sum tests, and Chi-squared tests or Fisher's exact test to compare the dynamic contrast-enhanced MRI features (morphological/hemodynamic features), and the apparent diffusion coefficient (ADC) values. A neural network model was constructed using the Neuralnet package in R, with the architecture specified as c(5,2) for the hidden layers. Bootstrapping was used for internal validation. The diagnostic performance in the training set was analyzed using receiver operating characteristic (ROC) curves. The clinical effectiveness of the model was validated using a decision curve analysis (DCA).</AbstractText HER2-low breast cancer lesions had irregular morphology, high early enhancement rate, and low ADC value compared to HER2-0 expressed lesions. The differences were significant (P&lt;0.05). We then constructed a neural network model using these significant variables. ROC analysis showed that the area under the ROC curve of the model for diagnosing HER2-low breast cancer in the training, internal validation, and external validation sets was 0.757 [95% confidence interval (CI): 0.712-0.802], 0.728 (95% CI: 0.658-0.798), and 0.791 (95% CI: 0.693-0.890), respectively. The DCA demonstrated that the net benefit of the model was significantly greater than zero at a predicted probability of 0.764.</AbstractText The neural network model based on MRI features is an effective tool in predicting HER2-low breast cancer, which may facilitate clinical treatment decision-making.</AbstractText
Artificial Intelligence in CT and MR Imaging for Oncological Applications. Cancer care increasingly relies on imaging for patient management. The two most common cross-sectional imaging modalities in oncology are computed tomography (CT) and magnetic resonance imaging (MRI), which provide high-resolution anatomic and physiological imaging. Herewith is a summary of recent applications of rapidly advancing artificial intelligence (AI) in CT and MRI oncological imaging that addresses the benefits and challenges of the resultant opportunities with examples. Major challenges remain, such as how best to integrate AI developments into clinical radiology practice, the vigorous assessment of quantitative CT and MR imaging data accuracy, and reliability for clinical utility and research integrity in oncology. Such challenges necessitate an evaluation of the robustness of imaging biomarkers to be included in AI developments, a culture of data sharing, and the cooperation of knowledgeable academics with vendor scientists and companies operating in radiology and oncology fields. Herein, we will illustrate a few challenges and solutions of these efforts using novel methods for synthesizing different contrast modality images, auto-segmentation, and image reconstruction with examples from lung CT as well as abdome, pelvis, and head and neck MRI. The imaging community must embrace the need for quantitative CT and MRI metrics beyond lesion size measurement. AI methods for the extraction and longitudinal tracking of imaging metrics from registered lesions and understanding the tumor environment will be invaluable for interpreting disease status and treatment efficacy. This is an exciting time to work together to move the imaging field forward with narrow AI-specific tasks. New AI developments using CT and MRI datasets will be used to improve the personalized management of cancer patients.</AbstractText
The Impact of Linguistic Prediction Violations on Downstream Recognition Memory and Sentence Recall. Predicting upcoming words during language comprehension not only affects processing in the moment but also has consequences for memory, although the source of these memory effects (e.g., whether driven by lingering pre-activations, re-analysis following prediction violations, or other mechanisms) remains underspecified. Here, we investigated downstream impacts of prediction on memory in two experiments. First, we recorded EEG as participants read strongly and weakly constraining sentences with expected, unexpected but plausible, or semantically anomalous endings ("He made a holster for his gun / father / train") and were tested on their recognition memory for the sentence endings. Participants showed similar rates of false alarms for predicted but never presented sentence endings whether the prediction violation was plausible or anomalous, suggesting that these arise from pre-activation of the expected words during reading. During sentence reading, especially in strongly constraining sentences, plausible prediction violations elicited an anterior positivity; anomalous endings instead elicited a posterior positivity, whose amplitude was predictive of later memory for those anomalous words. ERP patterns at the time of recognition differentiated plausible and anomalous sentence endings: Words that had been plausible prediction violations elicited enhanced late positive complex amplitudes, suggesting greater episodic recollection, whereas anomalous sentence endings elicited greater N1 amplitudes, suggesting attentional tagging. In a follow-up behavioral study, a separate group of participants read the same sentence stimuli and were tested for sentence-level recall. We found that recall of full sentences was impaired when sentences ended with a prediction violation. Taken together, the results suggest that prediction violations draw attention and affect encoding of the violating word, in a manner that depends on plausibility, and that this, in turn, may impair future memory of the gist of the sentence.</AbstractText
33882803
30054439
34670572
New Contemplation Upon Subjective Memory Complaints as a Self- Report Criterion for MCI Diagnosis.
CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease.
Endogenous assessment of myocardial injury with single-shot model-based non-rigid motion-corrected T1 rho mapping.
Subjective memory complaints are a key component in mild cognitive impairment (MCI) diagnosis. However, studies that examined memory awareness among MCI participants have published contradictory results. One possible explanation for the inconsistent findings could be the disregard from the multidimensional structure of subjective memory.</AbstractText The present study is directed at assessing subjective memory among healthy and MCI participants, referring to three main types of memory: episodic, semantic, and working memory.</AbstractText Participants were 123 adults (aged 50-90). They were divided into two groups, the MCI group, and the control group, according to their objective cognitive performance in RAVL or Mo- CA tests. All participants filled a subjective memory questionnaire, assessing their awareness of episodic, semantic, and working memory.</AbstractText MCI participants estimated their semantic memory as significantly lower in comparison to the estimation of the healthy controls. By contrast, MCI participants showed an overestimation of their episodic memory capabilities compared to the control group. No significant difference was found between groups (MCI and healthy controls) in evaluating their working memory. In addition, for both groups, Pearson's correlation revealed a significant negative correlation between age and semantic memory evaluation. Such correlation was not found for subjective episodic memory.</AbstractText Findings suggest that while people with MCI exhibit poor awareness of their episodic and working memory capabilities, their awareness of their decrease in semantic memory is apparently intact. Therefore, it is suggested that when using the self-report criterion for MCI diagnosis, clinicians should consider the patient's' semantic memory complaints.</AbstractText
To measure CSF levels of biomarkers reflecting microglia and astrocytes activation, neuroinflammation, and cerebrovascular changes and study their associations with the core biomarkers of Alzheimer disease (AD) pathology (&#x3b2;-amyloid [A&#x3b2;] and tau), structural imaging correlates, and clinical disease progression over time.</AbstractText The study included cognitively unimpaired elderly (n = 508), patients with mild cognitive impairment (MCI, n = 256), and patients with AD dementia (n = 57) from the longitudinal Swedish BioFINDER cohort. CSF samples were analyzed for YKL-40, interleukin (IL)-6, IL-7, IL-8, IL-15, IP-10, monocyte chemoattractant protein 1, intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), placental growth factor, and fms-related tyrosine kinase 1 (Flt-1). MRI data were available from 677 study participants. Longitudinal clinical assessments were conducted in control individuals and patients with MCI (mean follow-up 3 years, range 1-6 years).</AbstractText CSF levels of YKL-40, ICAM-1, VCAM-1, IL-15, and Flt-1 were increased during the preclinical, prodromal, and dementia stages of AD. High levels of these biomarkers were associated with increased CSF levels of total tau, with the associations, especially for YKL-40, being stronger in A&#x3b2;-positive individuals. The results were similar for associations between phosphorylated tau and YKL-40, ICAM-1, and VCAM-1. High levels of the biomarkers were also associated with cortical thinning (primarily in the precuneus and superior parietal regions) and with subsequent cognitive deterioration in patients without dementia as measured with Mini-Mental State Examination (YKL-40) and Clinical Dementia Rating Sum of Boxes (YKL-40, ICAM-1, VCAM-1 and IL-15). Finally, higher levels of CSF YKL-40, ICAM-1, and Flt-1 increased risk of development of AD dementia in patients without dementia.</AbstractText Neuroinflammation and cerebrovascular dysfunction are early events occurring already at presymptomatic stages of AD and contribute to disease progression.</AbstractText
Cardiovascular magnetic resonance T1&#x3c1;&#xa0;mapping may detect myocardial injuries without exogenous contrast agent. However, multiple co-registered acquisitions are required, and the lack of robust motion correction limits its clinical translation. We introduce a single breath-hold myocardial T1&#x3c1; mapping method that includes model-based non-rigid motion correction.</AbstractText A single-shot electrocardiogram (ECG)-triggered balanced steady state free precession (bSSFP) 2D adiabatic T1&#x3c1; mapping sequence that collects five T1&#x3c1;-weighted (T1&#x3c1;w) images with different spin lock times within a single breath-hold is proposed. To address the problem of residual respiratory motion, a unified optimization framework consisting of a joint T1&#x3c1; fitting and model-based non-rigid motion correction algorithm, insensitive to contrast change, was implemented inline for fast (~&#x2009;30&#xa0;s) and direct visualization of T1&#x3c1; maps. The proposed reconstruction was optimized on an ex vivo human heart placed on a motion-controlled platform. The technique was then tested in 8 healthy subjects and validated in 30 patients with suspected myocardial injury on a 1.5T CMR scanner. The Dice similarity coefficient (DSC) and maximum perpendicular distance (MPD) were used to quantify motion and evaluate motion correction. The quality of T1&#x3c1; maps was scored. In patients, T1&#x3c1; mapping was compared to cine imaging, T2 mapping and conventional post-contrast 2D late gadolinium enhancement (LGE). T1&#x3c1; values were assessed in remote and injured areas, using LGE as reference.</AbstractText Despite breath holds, respiratory motion throughout T1&#x3c1;w images was much larger in patients than in healthy subjects (5.1&#x2009;&#xb1;&#x2009;2.7&#xa0;mm vs. 0.5&#x2009;&#xb1;&#x2009;0.4&#xa0;mm, P&#x2009;&lt;&#x2009;0.01). In patients, the model-based non-rigid motion correction improved the alignment of T1&#x3c1;w images, with higher DSC (87.7&#x2009;&#xb1;&#x2009;5.3% vs. 82.2&#x2009;&#xb1;&#x2009;7.5%, P&#x2009;&lt;&#x2009;0.01), and lower MPD (3.5&#x2009;&#xb1;&#x2009;1.9&#xa0;mm vs. 5.1&#x2009;&#xb1;&#x2009;2.7&#xa0;mm, P&#x2009;&lt;&#x2009;0.01). This resulted in significantly improved quality of the T1&#x3c1; maps (3.6&#x2009;&#xb1;&#x2009;0.6 vs. 2.1&#x2009;&#xb1;&#x2009;0.9, P&#x2009;&lt;&#x2009;0.01). Using this approach, T1&#x3c1; mapping could be used to identify LGE in patients with 93% sensitivity and 89% specificity. T1&#x3c1; values in injured (LGE positive) areas were significantly higher than in the remote myocardium (68.4&#x2009;&#xb1;&#x2009;7.9&#xa0;ms vs. 48.8&#x2009;&#xb1;&#x2009;6.5&#xa0;ms, P&#x2009;&lt;&#x2009;0.01).</AbstractText The proposed motion-corrected T1&#x3c1; mapping framework enables a quantitative characterization of myocardial injuries with relatively low sensitivity to respiratory motion. This technique may be a robust and contrast-free adjunct to LGE for gaining new insight into myocardial structural disorders.</AbstractText
New Contemplation Upon Subjective Memory Complaints as a Self- Report Criterion for MCI Diagnosis. Subjective memory complaints are a key component in mild cognitive impairment (MCI) diagnosis. However, studies that examined memory awareness among MCI participants have published contradictory results. One possible explanation for the inconsistent findings could be the disregard from the multidimensional structure of subjective memory.</AbstractText The present study is directed at assessing subjective memory among healthy and MCI participants, referring to three main types of memory: episodic, semantic, and working memory.</AbstractText Participants were 123 adults (aged 50-90). They were divided into two groups, the MCI group, and the control group, according to their objective cognitive performance in RAVL or Mo- CA tests. All participants filled a subjective memory questionnaire, assessing their awareness of episodic, semantic, and working memory.</AbstractText MCI participants estimated their semantic memory as significantly lower in comparison to the estimation of the healthy controls. By contrast, MCI participants showed an overestimation of their episodic memory capabilities compared to the control group. No significant difference was found between groups (MCI and healthy controls) in evaluating their working memory. In addition, for both groups, Pearson's correlation revealed a significant negative correlation between age and semantic memory evaluation. Such correlation was not found for subjective episodic memory.</AbstractText Findings suggest that while people with MCI exhibit poor awareness of their episodic and working memory capabilities, their awareness of their decrease in semantic memory is apparently intact. Therefore, it is suggested that when using the self-report criterion for MCI diagnosis, clinicians should consider the patient's' semantic memory complaints.</AbstractText
CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease. To measure CSF levels of biomarkers reflecting microglia and astrocytes activation, neuroinflammation, and cerebrovascular changes and study their associations with the core biomarkers of Alzheimer disease (AD) pathology (&#x3b2;-amyloid [A&#x3b2;] and tau), structural imaging correlates, and clinical disease progression over time.</AbstractText The study included cognitively unimpaired elderly (n = 508), patients with mild cognitive impairment (MCI, n = 256), and patients with AD dementia (n = 57) from the longitudinal Swedish BioFINDER cohort. CSF samples were analyzed for YKL-40, interleukin (IL)-6, IL-7, IL-8, IL-15, IP-10, monocyte chemoattractant protein 1, intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), placental growth factor, and fms-related tyrosine kinase 1 (Flt-1). MRI data were available from 677 study participants. Longitudinal clinical assessments were conducted in control individuals and patients with MCI (mean follow-up 3 years, range 1-6 years).</AbstractText CSF levels of YKL-40, ICAM-1, VCAM-1, IL-15, and Flt-1 were increased during the preclinical, prodromal, and dementia stages of AD. High levels of these biomarkers were associated with increased CSF levels of total tau, with the associations, especially for YKL-40, being stronger in A&#x3b2;-positive individuals. The results were similar for associations between phosphorylated tau and YKL-40, ICAM-1, and VCAM-1. High levels of the biomarkers were also associated with cortical thinning (primarily in the precuneus and superior parietal regions) and with subsequent cognitive deterioration in patients without dementia as measured with Mini-Mental State Examination (YKL-40) and Clinical Dementia Rating Sum of Boxes (YKL-40, ICAM-1, VCAM-1 and IL-15). Finally, higher levels of CSF YKL-40, ICAM-1, and Flt-1 increased risk of development of AD dementia in patients without dementia.</AbstractText Neuroinflammation and cerebrovascular dysfunction are early events occurring already at presymptomatic stages of AD and contribute to disease progression.</AbstractText
Endogenous assessment of myocardial injury with single-shot model-based non-rigid motion-corrected T1 rho mapping. Cardiovascular magnetic resonance T1&#x3c1;&#xa0;mapping may detect myocardial injuries without exogenous contrast agent. However, multiple co-registered acquisitions are required, and the lack of robust motion correction limits its clinical translation. We introduce a single breath-hold myocardial T1&#x3c1; mapping method that includes model-based non-rigid motion correction.</AbstractText A single-shot electrocardiogram (ECG)-triggered balanced steady state free precession (bSSFP) 2D adiabatic T1&#x3c1; mapping sequence that collects five T1&#x3c1;-weighted (T1&#x3c1;w) images with different spin lock times within a single breath-hold is proposed. To address the problem of residual respiratory motion, a unified optimization framework consisting of a joint T1&#x3c1; fitting and model-based non-rigid motion correction algorithm, insensitive to contrast change, was implemented inline for fast (~&#x2009;30&#xa0;s) and direct visualization of T1&#x3c1; maps. The proposed reconstruction was optimized on an ex vivo human heart placed on a motion-controlled platform. The technique was then tested in 8 healthy subjects and validated in 30 patients with suspected myocardial injury on a 1.5T CMR scanner. The Dice similarity coefficient (DSC) and maximum perpendicular distance (MPD) were used to quantify motion and evaluate motion correction. The quality of T1&#x3c1; maps was scored. In patients, T1&#x3c1; mapping was compared to cine imaging, T2 mapping and conventional post-contrast 2D late gadolinium enhancement (LGE). T1&#x3c1; values were assessed in remote and injured areas, using LGE as reference.</AbstractText Despite breath holds, respiratory motion throughout T1&#x3c1;w images was much larger in patients than in healthy subjects (5.1&#x2009;&#xb1;&#x2009;2.7&#xa0;mm vs. 0.5&#x2009;&#xb1;&#x2009;0.4&#xa0;mm, P&#x2009;&lt;&#x2009;0.01). In patients, the model-based non-rigid motion correction improved the alignment of T1&#x3c1;w images, with higher DSC (87.7&#x2009;&#xb1;&#x2009;5.3% vs. 82.2&#x2009;&#xb1;&#x2009;7.5%, P&#x2009;&lt;&#x2009;0.01), and lower MPD (3.5&#x2009;&#xb1;&#x2009;1.9&#xa0;mm vs. 5.1&#x2009;&#xb1;&#x2009;2.7&#xa0;mm, P&#x2009;&lt;&#x2009;0.01). This resulted in significantly improved quality of the T1&#x3c1; maps (3.6&#x2009;&#xb1;&#x2009;0.6 vs. 2.1&#x2009;&#xb1;&#x2009;0.9, P&#x2009;&lt;&#x2009;0.01). Using this approach, T1&#x3c1; mapping could be used to identify LGE in patients with 93% sensitivity and 89% specificity. T1&#x3c1; values in injured (LGE positive) areas were significantly higher than in the remote myocardium (68.4&#x2009;&#xb1;&#x2009;7.9&#xa0;ms vs. 48.8&#x2009;&#xb1;&#x2009;6.5&#xa0;ms, P&#x2009;&lt;&#x2009;0.01).</AbstractText The proposed motion-corrected T1&#x3c1; mapping framework enables a quantitative characterization of myocardial injuries with relatively low sensitivity to respiratory motion. This technique may be a robust and contrast-free adjunct to LGE for gaining new insight into myocardial structural disorders.</AbstractText
33395972
28173729
32534385
Topological reorganization of brain functional networks in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes.
Structural and Functional Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder: A Focus on Subgenual Anterior Cingulate Cortex.
Avoiding iatrogenic injuries to the vertebral artery: A morphometric study of the vertebral artery-free dissection area.
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare maternally inherited genetic disease; however, little is known about its underlying brain basis. Furthermore, the topological organization of brain functional network in MELAS has not been explored. Here, 45 patients with MELAS (22 at acute stage, 23 at chronic stage) and 22 normal controls were studied using resting- state functional magnetic resonance imaging and graph theory analysis approaches. Topological properties of brain functional networks including global and nodal metrics, rich club organization and modularity were analyzed. At the global level, MELAS patients exhibited reduced clustering coefficient, normalized clustering coefficient, normalized characteristic path length and local network efficiency compared with the controls. At the nodal level, several nodes with abnormal degree centrality and nodal efficiency were detected in MELAS patients, and the distribution of these nodes was partly consistent with the stroke-like lesions. For rich club organization, rich club nodes were reorganized and the connections among them were decreased in MELAS patients. Modularity analysis revealed that MELAS patents had altered intra- or inter-modular connections in default mode network, fronto-parietal network, sensorimotor network, occipital network and cerebellum network. Notably, the patients at acute stage showed more obvious changes in these topological properties than the patients at chronic stage. These findings indicated that MELAS patients, particularly those at acute stage, exhibited topological reorganization of the whole-brain functional network. This study may help us to understand the neuropathological mechanisms of MELAS.</AbstractText
Attention-deficit/hyperactivity disorder (ADHD), characterized by developmentally inappropriate inattention, hyperactivity/impulsivity, or a combination of both, is a major public health problem. Neuroimaging studies have revealed associations of these cognitive impairments with structural and functional deficits all over the brain. Existing findings are not fully consistent because of the heterogeneity of study samples and diversity of research techniques. In this study, we propose to utilize a multimodal magnetic resonance imaging (MRI) approach to study the structural and functional brain networks in children with ADHD-combined type (ADHD-C) with a focus on the subgenual anterior cingulate cortex (sgACC). Diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) data from 32 children with ADHD-C and 32 group-matched controls were involved. Network-based statistic analysis of the rs-fMRI data revealed a disconnected functional network between the sgACC and multiple regions in the occipital lobe and cerebellum, whereas the DTI data showed disrupted white matter integrity in the subgenual cingulum bundle (sgCB). Post hoc region of interest (ROI)-based analyses showed significantly increased fluctuation of the spontaneous brain activity in the sgACC and higher radial diffusivity in the sgCB in the ADHD group. Both the rs-fMRI and DTI ROI-based measures were significantly correlated with clinical measures that examine behavioral capacities of attention and inhibitory control. Findings of this study suggest that functional alterations in the sgACC and white matter under development in the sgCB may impact each other, and together contribute to impaired attention and inhibitory control function in children with ADHD.</AbstractText
To determine the area of a safety window that excludes the vertebral artery for the safe access of the occipital condyle screws during occipitocervical fixation.</AbstractText This study included 138 cervical computed tomography angiograms. Six measurements per side were made in each imaging study. These measurements are from the vertebral artery to (A) the mastoid process, (B) the mastoid incisura, (C) the posterior condylar fossa, (D) the occipital condyle in its midline, and (E) the medial border of the condyle. We also measured from the tip of the mastoid process to the lower border of the occipital condyle on its lateral side (F).</AbstractText A total of 276 areas from 138 individuals were included, of which 51.4 % were men. The mean age was 54.2&#x202f;&#xb1;&#x202f;18.63 years. The mean variable measurements (mm) for all the population were 21&#x202f;&#xb1;&#x202f;4, 16&#x202f;&#xb1;&#x202f;3, 6&#x202f;&#xb1;&#x202f;2, 3&#x202f;&#xb1;&#x202f;2, 2&#x202f;&#xb1;&#x202f;1 and 35&#x202f;&#xb1;&#x202f;4 for variables A-F, respectively. We found significant differences between sex when we compared measurements A (p&#x202f;=&#x202f;0.003), C (p&#x202f;=&#x202f;0.001), D (p&#x202f;=&#x202f;0.000) and F (p&#x202f;=&#x202f;0.000). The incidence rate of dominance for the vertebral artery was 18.8 % and 30.4 % for right and left respectively.</AbstractText Women had significantly smaller measures than men. This could indicate a higher risk of iatrogenic injury secondary to a smaller vertebral artery-free area. Results may guide surgeons in the pre-surgical planning aiming to reduce the risk of iatrogenic injuries to the vertebral artery.</AbstractText
Topological reorganization of brain functional networks in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare maternally inherited genetic disease; however, little is known about its underlying brain basis. Furthermore, the topological organization of brain functional network in MELAS has not been explored. Here, 45 patients with MELAS (22 at acute stage, 23 at chronic stage) and 22 normal controls were studied using resting- state functional magnetic resonance imaging and graph theory analysis approaches. Topological properties of brain functional networks including global and nodal metrics, rich club organization and modularity were analyzed. At the global level, MELAS patients exhibited reduced clustering coefficient, normalized clustering coefficient, normalized characteristic path length and local network efficiency compared with the controls. At the nodal level, several nodes with abnormal degree centrality and nodal efficiency were detected in MELAS patients, and the distribution of these nodes was partly consistent with the stroke-like lesions. For rich club organization, rich club nodes were reorganized and the connections among them were decreased in MELAS patients. Modularity analysis revealed that MELAS patents had altered intra- or inter-modular connections in default mode network, fronto-parietal network, sensorimotor network, occipital network and cerebellum network. Notably, the patients at acute stage showed more obvious changes in these topological properties than the patients at chronic stage. These findings indicated that MELAS patients, particularly those at acute stage, exhibited topological reorganization of the whole-brain functional network. This study may help us to understand the neuropathological mechanisms of MELAS.</AbstractText
Structural and Functional Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder: A Focus on Subgenual Anterior Cingulate Cortex. Attention-deficit/hyperactivity disorder (ADHD), characterized by developmentally inappropriate inattention, hyperactivity/impulsivity, or a combination of both, is a major public health problem. Neuroimaging studies have revealed associations of these cognitive impairments with structural and functional deficits all over the brain. Existing findings are not fully consistent because of the heterogeneity of study samples and diversity of research techniques. In this study, we propose to utilize a multimodal magnetic resonance imaging (MRI) approach to study the structural and functional brain networks in children with ADHD-combined type (ADHD-C) with a focus on the subgenual anterior cingulate cortex (sgACC). Diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) data from 32 children with ADHD-C and 32 group-matched controls were involved. Network-based statistic analysis of the rs-fMRI data revealed a disconnected functional network between the sgACC and multiple regions in the occipital lobe and cerebellum, whereas the DTI data showed disrupted white matter integrity in the subgenual cingulum bundle (sgCB). Post hoc region of interest (ROI)-based analyses showed significantly increased fluctuation of the spontaneous brain activity in the sgACC and higher radial diffusivity in the sgCB in the ADHD group. Both the rs-fMRI and DTI ROI-based measures were significantly correlated with clinical measures that examine behavioral capacities of attention and inhibitory control. Findings of this study suggest that functional alterations in the sgACC and white matter under development in the sgCB may impact each other, and together contribute to impaired attention and inhibitory control function in children with ADHD.</AbstractText
Avoiding iatrogenic injuries to the vertebral artery: A morphometric study of the vertebral artery-free dissection area. To determine the area of a safety window that excludes the vertebral artery for the safe access of the occipital condyle screws during occipitocervical fixation.</AbstractText This study included 138 cervical computed tomography angiograms. Six measurements per side were made in each imaging study. These measurements are from the vertebral artery to (A) the mastoid process, (B) the mastoid incisura, (C) the posterior condylar fossa, (D) the occipital condyle in its midline, and (E) the medial border of the condyle. We also measured from the tip of the mastoid process to the lower border of the occipital condyle on its lateral side (F).</AbstractText A total of 276 areas from 138 individuals were included, of which 51.4 % were men. The mean age was 54.2&#x202f;&#xb1;&#x202f;18.63 years. The mean variable measurements (mm) for all the population were 21&#x202f;&#xb1;&#x202f;4, 16&#x202f;&#xb1;&#x202f;3, 6&#x202f;&#xb1;&#x202f;2, 3&#x202f;&#xb1;&#x202f;2, 2&#x202f;&#xb1;&#x202f;1 and 35&#x202f;&#xb1;&#x202f;4 for variables A-F, respectively. We found significant differences between sex when we compared measurements A (p&#x202f;=&#x202f;0.003), C (p&#x202f;=&#x202f;0.001), D (p&#x202f;=&#x202f;0.000) and F (p&#x202f;=&#x202f;0.000). The incidence rate of dominance for the vertebral artery was 18.8 % and 30.4 % for right and left respectively.</AbstractText Women had significantly smaller measures than men. This could indicate a higher risk of iatrogenic injury secondary to a smaller vertebral artery-free area. Results may guide surgeons in the pre-surgical planning aiming to reduce the risk of iatrogenic injuries to the vertebral artery.</AbstractText
38409462
28916181
38942709
Neuroticism and openness exhibit an anti-correlation pattern to dissociable default mode network: using resting connectivity and structural equation modeling analysis.
Replicability of time-varying connectivity patterns in large resting state fMRI samples.
Epidemiological study on pediatric-onset dystonia in Japan: A questionnaire-based survey.
The default mode network (DMN) can be subdivided into ventral and dorsal subsystems, which serve affective cognition and mental sense construction, respectively. An internally dissociated pattern of anti-correlations was observed between these two subsystems. Although numerous studies on neuroticism and openness have demonstrated the neurological functions of the DMN, little is known about whether different subsystems and hubs regions within the network are engaged in different functions in response to the two traits. We recruited 223 healthy volunteers in this study and collected their resting-state functional magnetic resonance imaging (fMRI) and NEO Five-Factor Inventory scores. We used independent component analysis (ICA) to obtain the DMN, before further decomposing it into the ventral and dorsal subsystems. Then, the network coherence of hubs regions within subsystems was extracted to construct two structural equation models (SEM) to explore the relationship between neuroticism and openness traits and DMN. We observed that the ventral DMN could significantly predict positive openness and negative neuroticism. The dorsal DMN was diametrically opposed. Additionally, the medial prefrontal cortex (mPFC) and middle temporal gyrus (MTG), both of which are core hubs of the subnetworks within the DMN, are significantly positively correlated with neuroticism and openness. These findings may point to a biological basis that neuroticism and openness are engaged in opposite mechanisms and support the hypothesis about the functional dissociation of the DMN.</AbstractText
The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain's inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7&#xa0;500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance.</AbstractText
This study aimed to investigate the clinical characteristics of pediatric-onset dystonia in Japan, addressing the diagnostic challenges arising from symptom variations and etiological diversity.</AbstractText From 2020 to 2022, questionnaires were distributed to 1218 board certified child neurologists (BCCNs) by Japanese Society of Child Neurology. In the primary survey, participants were asked to report the number of patients with pediatric-onset dystonia under their care. Subsequently, the follow-up secondary survey sought additional information on the clinical characteristics of these patients.</AbstractText The primary survey obtained 550 responses (response rate: 45&#xa0;%) from BCCNs for their 736 patients with dystonia. The predominant etiologies included inherited cases (with DYT10 &#xa0;&lt;PxMD-PRRT2&gt; being the most prevalent, followed by DYT5 &lt;DYT/PARK-GCH1&gt; and ATP1A3-related neurologic disorders), acquired cases (with perinatal abnormalities being the most common), and idiopathic cases. The secondary survey provided clinical insights into 308 cases from 82 BCCNs. Infancy-onset dystonia presented as persistent and generalized with diverse symptoms, primarily linked to ATP1A3-related neurologic disorders and other genetic disorders resembling acquired dystonia. Conversely, childhood/adolescent-onset dystonia showed paroxysmal, fluctuating courses, predominantly affecting limbs. The most common etiologies were DYT5 &lt;DYT/PARK-GCH1&gt; and DYT10 &lt;PxMD-PRRT2&gt;, leading to therapeutic diagnoses.</AbstractText Pediatric-onset dystonia in Japan was treated by 28&#xa0;% of BCCNs. The majority of cases were inherited, with high prevalence rates of DYT5 &lt;DYT/PARK-GCH1&gt; and DYT10 &lt;PxMD-PRRT2&gt;. Infancy-onset dystonia exhibits diverse etiologies and symptoms, emphasizing the utility of various examinations, including genetic testing. These findings significantly contribute to our understanding of pediatric-onset dystonia in Japan, although this study has the limitation of questionnaire survey.</AbstractText
Neuroticism and openness exhibit an anti-correlation pattern to dissociable default mode network: using resting connectivity and structural equation modeling analysis. The default mode network (DMN) can be subdivided into ventral and dorsal subsystems, which serve affective cognition and mental sense construction, respectively. An internally dissociated pattern of anti-correlations was observed between these two subsystems. Although numerous studies on neuroticism and openness have demonstrated the neurological functions of the DMN, little is known about whether different subsystems and hubs regions within the network are engaged in different functions in response to the two traits. We recruited 223 healthy volunteers in this study and collected their resting-state functional magnetic resonance imaging (fMRI) and NEO Five-Factor Inventory scores. We used independent component analysis (ICA) to obtain the DMN, before further decomposing it into the ventral and dorsal subsystems. Then, the network coherence of hubs regions within subsystems was extracted to construct two structural equation models (SEM) to explore the relationship between neuroticism and openness traits and DMN. We observed that the ventral DMN could significantly predict positive openness and negative neuroticism. The dorsal DMN was diametrically opposed. Additionally, the medial prefrontal cortex (mPFC) and middle temporal gyrus (MTG), both of which are core hubs of the subnetworks within the DMN, are significantly positively correlated with neuroticism and openness. These findings may point to a biological basis that neuroticism and openness are engaged in opposite mechanisms and support the hypothesis about the functional dissociation of the DMN.</AbstractText
Replicability of time-varying connectivity patterns in large resting state fMRI samples. The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain's inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7&#xa0;500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance.</AbstractText
Epidemiological study on pediatric-onset dystonia in Japan: A questionnaire-based survey. This study aimed to investigate the clinical characteristics of pediatric-onset dystonia in Japan, addressing the diagnostic challenges arising from symptom variations and etiological diversity.</AbstractText From 2020 to 2022, questionnaires were distributed to 1218 board certified child neurologists (BCCNs) by Japanese Society of Child Neurology. In the primary survey, participants were asked to report the number of patients with pediatric-onset dystonia under their care. Subsequently, the follow-up secondary survey sought additional information on the clinical characteristics of these patients.</AbstractText The primary survey obtained 550 responses (response rate: 45&#xa0;%) from BCCNs for their 736 patients with dystonia. The predominant etiologies included inherited cases (with DYT10 &#xa0;&lt;PxMD-PRRT2&gt; being the most prevalent, followed by DYT5 &lt;DYT/PARK-GCH1&gt; and ATP1A3-related neurologic disorders), acquired cases (with perinatal abnormalities being the most common), and idiopathic cases. The secondary survey provided clinical insights into 308 cases from 82 BCCNs. Infancy-onset dystonia presented as persistent and generalized with diverse symptoms, primarily linked to ATP1A3-related neurologic disorders and other genetic disorders resembling acquired dystonia. Conversely, childhood/adolescent-onset dystonia showed paroxysmal, fluctuating courses, predominantly affecting limbs. The most common etiologies were DYT5 &lt;DYT/PARK-GCH1&gt; and DYT10 &lt;PxMD-PRRT2&gt;, leading to therapeutic diagnoses.</AbstractText Pediatric-onset dystonia in Japan was treated by 28&#xa0;% of BCCNs. The majority of cases were inherited, with high prevalence rates of DYT5 &lt;DYT/PARK-GCH1&gt; and DYT10 &lt;PxMD-PRRT2&gt;. Infancy-onset dystonia exhibits diverse etiologies and symptoms, emphasizing the utility of various examinations, including genetic testing. These findings significantly contribute to our understanding of pediatric-onset dystonia in Japan, although this study has the limitation of questionnaire survey.</AbstractText
33651680
31866116
34252392
A 16-Channel (13)C Array Coil for Magnetic Resonance Spectroscopy of the Breast at 7T.
Comparison of optimized intensity correction methods for (23)Na MRI of the human brain using a 32-channel phased array coil at 7 Tesla.
Molecular mechanism involved in epithelial to mesenchymal transition.
Considering the reported elevation of &#x3c9;-6/&#x3c9;-3 fatty acid ratios in breast neoplasms, one particularly important application of <sup This work presents a unilateral breast 16-channel <sup Bench measurements showed receive coil matching better than -17 dB and average preamplifier decoupling of 16.2 dB with no evident peak splitting. Phantom MRS studies show better than a three-fold increase in average SNR over the entirety of the breast region compared to volume coil reception alone as well as an ability for individual array elements to be used for coarse metabolite localization without the use of single-voxel or spectroscopic imaging methods.</AbstractText Our current study has shown the benefits of the array. Future in vivo lipidomics studies can be pursued.</AbstractText Development of the 16-channel breast array coil opens possibilities of in vivo lipidomics studies to elucidate the link between breast cancer incidence and lipid metabolics.</AbstractText
To correct for the non-homogeneous receive profile of a phased array head coil in sodium magnetic resonance imaging (<sup <sup Phantom measurements show the correction of the intensity profile applying the given methods. Compared to the uncorrected phased array image (NRMSE = 0.46, CSF<sub Acquiring a birdcage image as reference image to correct for the receive profile demonstrates the best performance. However, when aiming to reduce acquisition time or for measurements without existing birdcage coil, methods that use a support region as reference image, a universal or a pre-scanned sensitivity map provide good alternatives for correction of the receive profile.</AbstractText
Epithelial to mesenchymal transition (EMT) is a biological process that plays an important role during embryonic development. During this process, the epithelial cells lose their polarity and acquire mesenchymal properties. In addition to embryonic development, EMT is also well-known to participate in tissue repair, inflammation, fibrosis, and tumor metastasis. In the present review, we address the basics of epithelial to mesenchymal transition during both development and disease conditions and emphasize the role of various transcription factors and miRNAs involved in the process.</AbstractText
A 16-Channel (13)C Array Coil for Magnetic Resonance Spectroscopy of the Breast at 7T. Considering the reported elevation of &#x3c9;-6/&#x3c9;-3 fatty acid ratios in breast neoplasms, one particularly important application of <sup This work presents a unilateral breast 16-channel <sup Bench measurements showed receive coil matching better than -17 dB and average preamplifier decoupling of 16.2 dB with no evident peak splitting. Phantom MRS studies show better than a three-fold increase in average SNR over the entirety of the breast region compared to volume coil reception alone as well as an ability for individual array elements to be used for coarse metabolite localization without the use of single-voxel or spectroscopic imaging methods.</AbstractText Our current study has shown the benefits of the array. Future in vivo lipidomics studies can be pursued.</AbstractText Development of the 16-channel breast array coil opens possibilities of in vivo lipidomics studies to elucidate the link between breast cancer incidence and lipid metabolics.</AbstractText
Comparison of optimized intensity correction methods for (23)Na MRI of the human brain using a 32-channel phased array coil at 7 Tesla. To correct for the non-homogeneous receive profile of a phased array head coil in sodium magnetic resonance imaging (<sup <sup Phantom measurements show the correction of the intensity profile applying the given methods. Compared to the uncorrected phased array image (NRMSE = 0.46, CSF<sub Acquiring a birdcage image as reference image to correct for the receive profile demonstrates the best performance. However, when aiming to reduce acquisition time or for measurements without existing birdcage coil, methods that use a support region as reference image, a universal or a pre-scanned sensitivity map provide good alternatives for correction of the receive profile.</AbstractText
Molecular mechanism involved in epithelial to mesenchymal transition. Epithelial to mesenchymal transition (EMT) is a biological process that plays an important role during embryonic development. During this process, the epithelial cells lose their polarity and acquire mesenchymal properties. In addition to embryonic development, EMT is also well-known to participate in tissue repair, inflammation, fibrosis, and tumor metastasis. In the present review, we address the basics of epithelial to mesenchymal transition during both development and disease conditions and emphasize the role of various transcription factors and miRNAs involved in the process.</AbstractText
34900176
31682262
34291517
A RFID Authentication Protocol for Epidemic Prevention and Epidemic Emergency Management Systems.
A governance model for the application of AI in health care.
Volumetric coronary endothelial function assessment: a feasibility study exploiting stack-of-stars 3D cine MRI and image-based respiratory self-gating.
The outbreak of the novel coronavirus has exposed many problems in the auxiliary information system for epidemic prevention and control, which needs to be resolved by using methods such as the antitampering of logistics data and the management and control of epidemic materials. This article discusses the introduction of emerging technologies such as Radio Frequency Identification (RFID), which support privacy protection into the auxiliary information system for epidemic prevention and control. Recently, this paper found that Khwaja et al.'s protocol (RAPUS protocol) is susceptible to database impersonation attacks and reader impersonation attacks. Therefore, this article proposes the enhanced protocol, which not only perfectly solves the problems of the abovementioned protocols but also comprehensively compares multiple protocols. The enhanced protocol has higher efficiency and security. The security of the proposed protocol (RAPUS&#x2009;+&#x2009;protocol) is analyzed by GNY logic and the AVISPA model. The designed scheme can help realize the safety and traceability of epidemic prevention materials and improve the automation and decision-making efficiency of the epidemic prevention.</AbstractText
As the efficacy of artificial intelligence (AI) in improving aspects of healthcare delivery is increasingly becoming evident, it becomes likely that AI will be incorporated in routine clinical care in the near future. This promise has led to growing focus and investment in AI medical applications both from governmental organizations and technological companies. However, concern has been expressed about the ethical and regulatory aspects of the application of AI in health care. These concerns include the possibility of biases, lack of transparency with certain AI algorithms, privacy concerns with the data used for training AI models, and safety and liability issues with AI application in clinical environments. While there has been extensive discussion about the ethics of AI in health care, there has been little dialogue or recommendations as to how to practically address these concerns in health care. In this article, we propose a governance model that aims to not only address the ethical and regulatory issues that arise out of the application of AI in health care, but also stimulate further discussion about governance of AI in health care.</AbstractText
Abnormal coronary endothelial function (CEF), manifesting as depressed vasoreactive responses to endothelial-specific stressors, occurs early in atherosclerosis, independently predicts cardiovascular events, and responds to cardioprotective interventions. CEF is spatially heterogeneous along a coronary artery in patients with atherosclerosis, and thus recently developed and tested non-invasive 2D MRI techniques to measure CEF may not capture the extent of changes in CEF in a given coronary artery. The purpose of this study was to develop and test the first volumetric coronary 3D MRI cine method for assessing CEF along the proximal and mid-coronary arteries with isotropic spatial resolution and in free-breathing. This approach, called 3D-Stars, combines a 6 min continuous, untriggered golden-angle stack-of-stars acquisition with a novel image-based respiratory self-gating method and cardiac and respiratory motion-resolved reconstruction. The proposed respiratory self-gating method agreed well with respiratory bellows and center-of-k-space methods. In healthy subjects, 3D-Stars vessel sharpness was non-significantly different from that by conventional 2D radial in proximal segments, albeit lower in mid-portions. Importantly, 3D-Stars detected normal vasodilatation of the right coronary artery in response to endothelial-dependent isometric handgrip stress in healthy subjects. Coronary artery cross-sectional areas measured using 3D-Stars were similar to those from 2D radial MRI when similar thresholding was used. In conclusion, 3D-Stars offers good image quality and shows feasibility for non-invasively studying vasoreactivity-related lumen area changes along the proximal coronary artery in 3D during free-breathing.</AbstractText
A RFID Authentication Protocol for Epidemic Prevention and Epidemic Emergency Management Systems. The outbreak of the novel coronavirus has exposed many problems in the auxiliary information system for epidemic prevention and control, which needs to be resolved by using methods such as the antitampering of logistics data and the management and control of epidemic materials. This article discusses the introduction of emerging technologies such as Radio Frequency Identification (RFID), which support privacy protection into the auxiliary information system for epidemic prevention and control. Recently, this paper found that Khwaja et al.'s protocol (RAPUS protocol) is susceptible to database impersonation attacks and reader impersonation attacks. Therefore, this article proposes the enhanced protocol, which not only perfectly solves the problems of the abovementioned protocols but also comprehensively compares multiple protocols. The enhanced protocol has higher efficiency and security. The security of the proposed protocol (RAPUS&#x2009;+&#x2009;protocol) is analyzed by GNY logic and the AVISPA model. The designed scheme can help realize the safety and traceability of epidemic prevention materials and improve the automation and decision-making efficiency of the epidemic prevention.</AbstractText
A governance model for the application of AI in health care. As the efficacy of artificial intelligence (AI) in improving aspects of healthcare delivery is increasingly becoming evident, it becomes likely that AI will be incorporated in routine clinical care in the near future. This promise has led to growing focus and investment in AI medical applications both from governmental organizations and technological companies. However, concern has been expressed about the ethical and regulatory aspects of the application of AI in health care. These concerns include the possibility of biases, lack of transparency with certain AI algorithms, privacy concerns with the data used for training AI models, and safety and liability issues with AI application in clinical environments. While there has been extensive discussion about the ethics of AI in health care, there has been little dialogue or recommendations as to how to practically address these concerns in health care. In this article, we propose a governance model that aims to not only address the ethical and regulatory issues that arise out of the application of AI in health care, but also stimulate further discussion about governance of AI in health care.</AbstractText
Volumetric coronary endothelial function assessment: a feasibility study exploiting stack-of-stars 3D cine MRI and image-based respiratory self-gating. Abnormal coronary endothelial function (CEF), manifesting as depressed vasoreactive responses to endothelial-specific stressors, occurs early in atherosclerosis, independently predicts cardiovascular events, and responds to cardioprotective interventions. CEF is spatially heterogeneous along a coronary artery in patients with atherosclerosis, and thus recently developed and tested non-invasive 2D MRI techniques to measure CEF may not capture the extent of changes in CEF in a given coronary artery. The purpose of this study was to develop and test the first volumetric coronary 3D MRI cine method for assessing CEF along the proximal and mid-coronary arteries with isotropic spatial resolution and in free-breathing. This approach, called 3D-Stars, combines a 6 min continuous, untriggered golden-angle stack-of-stars acquisition with a novel image-based respiratory self-gating method and cardiac and respiratory motion-resolved reconstruction. The proposed respiratory self-gating method agreed well with respiratory bellows and center-of-k-space methods. In healthy subjects, 3D-Stars vessel sharpness was non-significantly different from that by conventional 2D radial in proximal segments, albeit lower in mid-portions. Importantly, 3D-Stars detected normal vasodilatation of the right coronary artery in response to endothelial-dependent isometric handgrip stress in healthy subjects. Coronary artery cross-sectional areas measured using 3D-Stars were similar to those from 2D radial MRI when similar thresholding was used. In conclusion, 3D-Stars offers good image quality and shows feasibility for non-invasively studying vasoreactivity-related lumen area changes along the proximal coronary artery in 3D during free-breathing.</AbstractText
39592434
32848645
38960101
Exploring neurofeedback as a therapeutic intervention for subjective cognitive decline.
A Critical Analysis on Characterizing the Meditation Experience Through the Electroencephalogram.
Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus.
This study addresses the pressing issue of subjective cognitive decline in aging populations by investigating neurofeedback (NFB) as a potential early therapeutic intervention. By evaluating the efficacy of individualised NFB training compared to standard protocols, tailored to each participant's EEG profile, it provides novel insights into personalised treatment approaches. The incorporation of innovative elements and rigorous analytical techniques contributes to advancing our understanding of NFB's modulatory effects on EEG frequencies and cognitive function in aging individuals.</AbstractText In the context of an aging population, concerns surrounding memory function become increasingly prevalent, particularly as individuals transition into middle age and beyond. This study investigated neurofeedback (NFB) as a potential early therapeutic intervention to address subjective cognitive decline (SCD) in aging populations. NFB, a biofeedback technique utilising a brain-computer interface, has demonstrated promise in the treatment of various neurological and psychological conditions. Here, we evaluated the efficacy of individualised NFB training, tailored to each participant's EEG profile, compared to a standard NFB training protocol aimed at increasing peak alpha frequency power, in enhancing cognitive function among individuals experiencing SCD. Our NFB protocol incorporated innovative elements, including the implementation of a criterion for learning success to ensure consistent achievement levels by the conclusion of the training sessions. Additionally, we introduced a non-learner group to account for individuals who do not demonstrate the expected proficiency in NFB regulation. Analysis of electroencephalographic (EEG) signals during NFB sessions, as well as before and after training, provides insights into the modulatory effects of NFB on EEG frequencies. Contrary to expectations, our rigorous analysis revealed that the ability of individuals with SCD to modulate EEG signal power and duration at specific frequencies was not exclusive to the intended frequency target. Furthermore, examination of EEG signals recorded using a high-density EEG showed no discernible alteration in signal power between pre- and post-NFB training sessions. Similarly, no significant effects were observed on questionnaire scores when comparing pre- and post-NFB training assessments.</AbstractText
Meditation practices, originated from ancient traditions, have increasingly received attention due to their potential benefits to mental and physical health. The scientific community invests efforts into scrutinizing and quantifying the effects of these practices, especially on the brain. There are methodological challenges in describing the neural correlates of the subjective experience of meditation. We noticed, however, that technical considerations on signal processing also don't follow standardized approaches, which may hinder generalizations. Therefore, in this article, we discuss the usage of the electroencephalogram (EEG) as a tool to study meditation experiences in healthy individuals. We describe the main EEG signal processing techniques and how they have been translated to the meditation field until April 2020. Moreover, we examine in detail the limitations/assumptions of these techniques and highlight some good practices, further discussing how technical specifications may impact the interpretation of the outcomes. By shedding light on technical features, this article contributes to more rigorous approaches to evaluate the construct of meditation.</AbstractText
Clinical and preclinical evidence has demonstrated an increased risk for neuropsychiatric disorders following prenatal cannabinoid exposure. However, given the phytochemical complexity of cannabis, there is a need to understand how specific components of cannabis may contribute to these neurodevelopmental risks later in life. To investigate this, a rat model of prenatal cannabinoid exposure was utilized to examine the impacts of specific cannabis constituents (&#x394;9-tetrahydrocannabinol [THC]; cannabidiol [CBD]) alone and in combination on future neuropsychiatric liability in male and female offspring. Prenatal THC and CBD exposure were associated with low birth weight. At adolescence, offspring displayed sex-specific behavioural changes in anxiety, temporal order and social cognition, and sensorimotor gating. These phenotypes were associated with sex and treatment-specific neuronal and gene transcriptional alterations in the prefrontal cortex, and ventral hippocampus, regions where the endocannabinoid system is implicated in affective and cognitive development. Electrophysiology and RT-qPCR analysis in these regions implicated dysregulation of the endocannabinoid system and balance of excitatory and inhibitory signalling in the developmental consequences of prenatal cannabinoids. These findings reveal critical insights into how specific cannabinoids can differentially impact the developing fetal brains of males and females to enhance subsequent neuropsychiatric risk.</AbstractText
Exploring neurofeedback as a therapeutic intervention for subjective cognitive decline. This study addresses the pressing issue of subjective cognitive decline in aging populations by investigating neurofeedback (NFB) as a potential early therapeutic intervention. By evaluating the efficacy of individualised NFB training compared to standard protocols, tailored to each participant's EEG profile, it provides novel insights into personalised treatment approaches. The incorporation of innovative elements and rigorous analytical techniques contributes to advancing our understanding of NFB's modulatory effects on EEG frequencies and cognitive function in aging individuals.</AbstractText In the context of an aging population, concerns surrounding memory function become increasingly prevalent, particularly as individuals transition into middle age and beyond. This study investigated neurofeedback (NFB) as a potential early therapeutic intervention to address subjective cognitive decline (SCD) in aging populations. NFB, a biofeedback technique utilising a brain-computer interface, has demonstrated promise in the treatment of various neurological and psychological conditions. Here, we evaluated the efficacy of individualised NFB training, tailored to each participant's EEG profile, compared to a standard NFB training protocol aimed at increasing peak alpha frequency power, in enhancing cognitive function among individuals experiencing SCD. Our NFB protocol incorporated innovative elements, including the implementation of a criterion for learning success to ensure consistent achievement levels by the conclusion of the training sessions. Additionally, we introduced a non-learner group to account for individuals who do not demonstrate the expected proficiency in NFB regulation. Analysis of electroencephalographic (EEG) signals during NFB sessions, as well as before and after training, provides insights into the modulatory effects of NFB on EEG frequencies. Contrary to expectations, our rigorous analysis revealed that the ability of individuals with SCD to modulate EEG signal power and duration at specific frequencies was not exclusive to the intended frequency target. Furthermore, examination of EEG signals recorded using a high-density EEG showed no discernible alteration in signal power between pre- and post-NFB training sessions. Similarly, no significant effects were observed on questionnaire scores when comparing pre- and post-NFB training assessments.</AbstractText
A Critical Analysis on Characterizing the Meditation Experience Through the Electroencephalogram. Meditation practices, originated from ancient traditions, have increasingly received attention due to their potential benefits to mental and physical health. The scientific community invests efforts into scrutinizing and quantifying the effects of these practices, especially on the brain. There are methodological challenges in describing the neural correlates of the subjective experience of meditation. We noticed, however, that technical considerations on signal processing also don't follow standardized approaches, which may hinder generalizations. Therefore, in this article, we discuss the usage of the electroencephalogram (EEG) as a tool to study meditation experiences in healthy individuals. We describe the main EEG signal processing techniques and how they have been translated to the meditation field until April 2020. Moreover, we examine in detail the limitations/assumptions of these techniques and highlight some good practices, further discussing how technical specifications may impact the interpretation of the outcomes. By shedding light on technical features, this article contributes to more rigorous approaches to evaluate the construct of meditation.</AbstractText
Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus. Clinical and preclinical evidence has demonstrated an increased risk for neuropsychiatric disorders following prenatal cannabinoid exposure. However, given the phytochemical complexity of cannabis, there is a need to understand how specific components of cannabis may contribute to these neurodevelopmental risks later in life. To investigate this, a rat model of prenatal cannabinoid exposure was utilized to examine the impacts of specific cannabis constituents (&#x394;9-tetrahydrocannabinol [THC]; cannabidiol [CBD]) alone and in combination on future neuropsychiatric liability in male and female offspring. Prenatal THC and CBD exposure were associated with low birth weight. At adolescence, offspring displayed sex-specific behavioural changes in anxiety, temporal order and social cognition, and sensorimotor gating. These phenotypes were associated with sex and treatment-specific neuronal and gene transcriptional alterations in the prefrontal cortex, and ventral hippocampus, regions where the endocannabinoid system is implicated in affective and cognitive development. Electrophysiology and RT-qPCR analysis in these regions implicated dysregulation of the endocannabinoid system and balance of excitatory and inhibitory signalling in the developmental consequences of prenatal cannabinoids. These findings reveal critical insights into how specific cannabinoids can differentially impact the developing fetal brains of males and females to enhance subsequent neuropsychiatric risk.</AbstractText
20815456
17132081
21311625
The time course of cochlear gain reduction measured using a more efficient psychophysical technique.
Induced visual fading of complex images.
Lipomatosis of the trigeminal nerve causing trigeminal neuralgia: case report and literature review.
In a previous study it was shown that an on-frequency precursor intended to activate the medial olivocochlear reflex (MOCR) at the signal frequency reduces the gain estimated from growth-of-masking (GOM) functions. This is called the temporal effect (TE). In Expt. 1 a shorter method of measuring this change in gain is established. GOM functions were measured with an on- and off-frequency precursor presented before the masker and signal, and used to estimate Input/Output functions. The change in gain estimated in this way was very similar to that estimated from comparing two points measured with a single fixed masker level on the lower legs of the GOM functions. In Expt. 2, the TE was measured as a function of precursor duration and signal delay. For short precursor durations and short delays the TE increased (buildup) or remained constant as delay increased, then decreased. The TE also increased with precursor duration for the shortest delay. The results were fitted with a model based on the time course of the MOCR. The model fitted the data well, and predicted the buildup. This buildup is not consistent with exponential decay predicted by neural adaptation or persistence of excitation.</AbstractText
Visual stimuli fade from awareness under retinal stabilization or careful fixation, a phenomenon documented by Troxler more than 200 years ago. Research on visual fading during normal visual fixation typically has been restricted to discrete, simple, low-contrast shapes presented peripherally against a uniform or textured background. In four experiments, we document a striking new visual fading effect in which entire photographs of scenes fade to a uniform luminance and hue during normal visual fixation. Critically, this "scene fading" can be induced almost instantaneously by some types of visual transients but not by others. These induced fading effects are sufficiently robust that they can be experienced by most observers in a single trial. Taken as a whole, the effects are inconsistent with simple contrast adaptation, gradual Troxler fading, or transient-induced fading. They are, however, consistent with the idea that small contrast decrements can induce fading of entire scenes. The methods provide a robust tool for the exploration of visual fading, and the results could have important implications for the role of filling-in and neural adaptation in our visual awareness of natural scenes and other complex stimuli.</AbstractText
Cerebellopontine angle lipomas are rare and attempts at surgical excision are associated with significant morbidity. Lipomatosis of nerve, the fatty infiltration of nerves, is a distinct entity. We present a case of intractible trigeminal neuralgia caused by lipomatosis of the trigeminal nerve.</AbstractText A 25-year-old male presented with severe right-sided trigeminal neuralgia. Imaging showed a lesion involving the trigeminal nerve with signal characteristics of fat. At surgery the lesion was found to be a fatty infiltration of the nerve itself. Surgery was therefore limited to arachnoid adhesiolysis. The patient remains symptom-free and neurologically intact to date. Correctly identifying these lesions as lipomatosis of nerve rather than lipoma of the cerebellopontine angle make it clear that even partial surgical excision will inevitably result in neurological deficit and should not be attempted. However, in the case of intractable trigeminal neuralgia we demonstrate that surgery can still play a role.</AbstractText
The time course of cochlear gain reduction measured using a more efficient psychophysical technique. In a previous study it was shown that an on-frequency precursor intended to activate the medial olivocochlear reflex (MOCR) at the signal frequency reduces the gain estimated from growth-of-masking (GOM) functions. This is called the temporal effect (TE). In Expt. 1 a shorter method of measuring this change in gain is established. GOM functions were measured with an on- and off-frequency precursor presented before the masker and signal, and used to estimate Input/Output functions. The change in gain estimated in this way was very similar to that estimated from comparing two points measured with a single fixed masker level on the lower legs of the GOM functions. In Expt. 2, the TE was measured as a function of precursor duration and signal delay. For short precursor durations and short delays the TE increased (buildup) or remained constant as delay increased, then decreased. The TE also increased with precursor duration for the shortest delay. The results were fitted with a model based on the time course of the MOCR. The model fitted the data well, and predicted the buildup. This buildup is not consistent with exponential decay predicted by neural adaptation or persistence of excitation.</AbstractText
Induced visual fading of complex images. Visual stimuli fade from awareness under retinal stabilization or careful fixation, a phenomenon documented by Troxler more than 200 years ago. Research on visual fading during normal visual fixation typically has been restricted to discrete, simple, low-contrast shapes presented peripherally against a uniform or textured background. In four experiments, we document a striking new visual fading effect in which entire photographs of scenes fade to a uniform luminance and hue during normal visual fixation. Critically, this "scene fading" can be induced almost instantaneously by some types of visual transients but not by others. These induced fading effects are sufficiently robust that they can be experienced by most observers in a single trial. Taken as a whole, the effects are inconsistent with simple contrast adaptation, gradual Troxler fading, or transient-induced fading. They are, however, consistent with the idea that small contrast decrements can induce fading of entire scenes. The methods provide a robust tool for the exploration of visual fading, and the results could have important implications for the role of filling-in and neural adaptation in our visual awareness of natural scenes and other complex stimuli.</AbstractText
Lipomatosis of the trigeminal nerve causing trigeminal neuralgia: case report and literature review. Cerebellopontine angle lipomas are rare and attempts at surgical excision are associated with significant morbidity. Lipomatosis of nerve, the fatty infiltration of nerves, is a distinct entity. We present a case of intractible trigeminal neuralgia caused by lipomatosis of the trigeminal nerve.</AbstractText A 25-year-old male presented with severe right-sided trigeminal neuralgia. Imaging showed a lesion involving the trigeminal nerve with signal characteristics of fat. At surgery the lesion was found to be a fatty infiltration of the nerve itself. Surgery was therefore limited to arachnoid adhesiolysis. The patient remains symptom-free and neurologically intact to date. Correctly identifying these lesions as lipomatosis of nerve rather than lipoma of the cerebellopontine angle make it clear that even partial surgical excision will inevitably result in neurological deficit and should not be attempted. However, in the case of intractable trigeminal neuralgia we demonstrate that surgery can still play a role.</AbstractText
40147368
34193257
40692645
In situ engineering of a glutathione-derived hydrophobic layer for durable and dendrite-free Zn anodes.
Neurite orientation dispersion and density imaging reveals white matter microstructural alterations in adults with autism.
Moving through migrant psychiatry: asylum seeking in Europe, forced mobility, and anthropology as interdisciplinary intervention.
Aqueous Zn-ion batteries (AZIBs) are gaining increasing attention for large-scale energy storage due to their cost-effectiveness, safety, and high volumetric energy density. However, their practical application is still hindered by challenges such as uncontrolled growth of Zn dendrites and unwanted side reactions. In this study, we introduce an interfacial engineering strategy by applying a glutathione (GSH) functional layer on the surface of the Zn anode (GSH@Zn). The GSH layer not only mitigates corrosion by increasing the hydrophobicity of Zn anodes but also guides uniform Zn deposition. Moreover, the native oxides on Zn anodes are etched by glutathione, resulting in an increased electrochemical active area and reduced interfacial impedance, which improves reaction kinetics. Therefore, the GSH@Zn anode demonstrates stable, long-term plating/stripping cycling, operating dendrite-free for 4500&#xa0;h at 1&#xa0;mA cm<sup
Evidences suggesting the association between behavioral anomalies in autism and white matter (WM) microstructural alterations are increasing. Diffusion tensor imaging (DTI) is widely used to infer tissue microstructure. However, due to its lack of specificity, the underlying pathology of reported differences in DTI measures in autism remains poorly understood. Herein, we applied neurite orientation dispersion and density imaging (NODDI) to quantify and define more specific causes of WM microstructural changes associated with autism in adults.</AbstractText NODDI (neurite density index [NDI], orientation dispersion index, and isotropic volume fraction [ISOVF]) and DTI (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity [RD]) measures were compared between autism (N&#x2009;=&#x2009;26; 19 males&#xa0;and 7&#xa0;females; 32.93&#x2009;&#xb1;&#x2009;9.24&#xa0;years old) and age- and sex-matched typically developing (TD; N&#x2009;=&#x2009;25; 17 males&#xa0;and 8&#xa0;females; 34.43&#x2009;&#xb1;&#x2009;9.02&#xa0;years old) groups using tract-based spatial statistics and region-of-interest analyses. Linear discriminant analysis using leave-one-out cross-validation (LDA-LOOCV) was also performed to assess the discriminative power of diffusion measures in autism and TD.</AbstractText Significantly lower NDI and higher ISOVF, suggestive of decreased neurite density and increased extracellular free-water, respectively, were demonstrated in the autism group compared with the TD group, mainly in commissural and long-range association tracts, but with distinct predominant sides. Consistent with previous reports, the autism group showed lower FA and higher MD and RD when compared with TD group. Notably, LDA-LOOCV suggests that NDI and ISOVF have relatively higher accuracy (82%) and specificity (NDI, 84%; ISOVF, 88%) compared with that of FA, MD, and RD (accuracy, 67-73%; specificity, 68-80%).</AbstractText The absence of histopathological confirmation limit the interpretation of our findings.</AbstractText Our results suggest that NODDI measures might be useful as imaging biomarkers to diagnose autism in adults and assess its behavioral characteristics. Furthermore, NODDI allows interpretation of previous findings on changes in WM diffusion tensor metrics in individuals with autism.</AbstractText
This perspective reflects on the relationship between migrant psychiatry and asylum seeking in Europe, drawing on anthropological fieldwork in a public migrant psychiatry clinic and mobile psychiatry teams serving asylum seekers, refused asylum seekers, and homeless migrants in France. Restrictive EU migration policies have produced protracted forms of "wandering" that may last for years; a sedentarist emphasis in national migrant services has generally not kept pace. Calls by international agencies to protect the mental health of refugees and displaced people are conflicting with a hostile policy backlash by national governments, delimiting a contradictory situation. This perspective discusses ways movements of migrants across countries and discontinuous and uneven healthcare and asylum infrastructures are shaping clinical expressions of illness and intervention and the asylum clinic as a critical site of inquiry. It develops on anthropology as an interdisciplinary intervention that can more roundly align ways in which migrant patients, clinical services, and professionals move across sectoral boundaries, account for contested political fields and multiple registers of interpretation, and answer some questions arising at their juncture.</AbstractText
In situ engineering of a glutathione-derived hydrophobic layer for durable and dendrite-free Zn anodes. Aqueous Zn-ion batteries (AZIBs) are gaining increasing attention for large-scale energy storage due to their cost-effectiveness, safety, and high volumetric energy density. However, their practical application is still hindered by challenges such as uncontrolled growth of Zn dendrites and unwanted side reactions. In this study, we introduce an interfacial engineering strategy by applying a glutathione (GSH) functional layer on the surface of the Zn anode (GSH@Zn). The GSH layer not only mitigates corrosion by increasing the hydrophobicity of Zn anodes but also guides uniform Zn deposition. Moreover, the native oxides on Zn anodes are etched by glutathione, resulting in an increased electrochemical active area and reduced interfacial impedance, which improves reaction kinetics. Therefore, the GSH@Zn anode demonstrates stable, long-term plating/stripping cycling, operating dendrite-free for 4500&#xa0;h at 1&#xa0;mA cm<sup
Neurite orientation dispersion and density imaging reveals white matter microstructural alterations in adults with autism. Evidences suggesting the association between behavioral anomalies in autism and white matter (WM) microstructural alterations are increasing. Diffusion tensor imaging (DTI) is widely used to infer tissue microstructure. However, due to its lack of specificity, the underlying pathology of reported differences in DTI measures in autism remains poorly understood. Herein, we applied neurite orientation dispersion and density imaging (NODDI) to quantify and define more specific causes of WM microstructural changes associated with autism in adults.</AbstractText NODDI (neurite density index [NDI], orientation dispersion index, and isotropic volume fraction [ISOVF]) and DTI (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity [RD]) measures were compared between autism (N&#x2009;=&#x2009;26; 19 males&#xa0;and 7&#xa0;females; 32.93&#x2009;&#xb1;&#x2009;9.24&#xa0;years old) and age- and sex-matched typically developing (TD; N&#x2009;=&#x2009;25; 17 males&#xa0;and 8&#xa0;females; 34.43&#x2009;&#xb1;&#x2009;9.02&#xa0;years old) groups using tract-based spatial statistics and region-of-interest analyses. Linear discriminant analysis using leave-one-out cross-validation (LDA-LOOCV) was also performed to assess the discriminative power of diffusion measures in autism and TD.</AbstractText Significantly lower NDI and higher ISOVF, suggestive of decreased neurite density and increased extracellular free-water, respectively, were demonstrated in the autism group compared with the TD group, mainly in commissural and long-range association tracts, but with distinct predominant sides. Consistent with previous reports, the autism group showed lower FA and higher MD and RD when compared with TD group. Notably, LDA-LOOCV suggests that NDI and ISOVF have relatively higher accuracy (82%) and specificity (NDI, 84%; ISOVF, 88%) compared with that of FA, MD, and RD (accuracy, 67-73%; specificity, 68-80%).</AbstractText The absence of histopathological confirmation limit the interpretation of our findings.</AbstractText Our results suggest that NODDI measures might be useful as imaging biomarkers to diagnose autism in adults and assess its behavioral characteristics. Furthermore, NODDI allows interpretation of previous findings on changes in WM diffusion tensor metrics in individuals with autism.</AbstractText
Moving through migrant psychiatry: asylum seeking in Europe, forced mobility, and anthropology as interdisciplinary intervention. This perspective reflects on the relationship between migrant psychiatry and asylum seeking in Europe, drawing on anthropological fieldwork in a public migrant psychiatry clinic and mobile psychiatry teams serving asylum seekers, refused asylum seekers, and homeless migrants in France. Restrictive EU migration policies have produced protracted forms of "wandering" that may last for years; a sedentarist emphasis in national migrant services has generally not kept pace. Calls by international agencies to protect the mental health of refugees and displaced people are conflicting with a hostile policy backlash by national governments, delimiting a contradictory situation. This perspective discusses ways movements of migrants across countries and discontinuous and uneven healthcare and asylum infrastructures are shaping clinical expressions of illness and intervention and the asylum clinic as a critical site of inquiry. It develops on anthropology as an interdisciplinary intervention that can more roundly align ways in which migrant patients, clinical services, and professionals move across sectoral boundaries, account for contested political fields and multiple registers of interpretation, and answer some questions arising at their juncture.</AbstractText
34954409
26101377
36226083
The neuroendocrinology of stress: Glucocorticoid signaling mechanisms.
60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-prolactin axis.
Effect of head-down tilt on clinical outcome and cerebral perfusion in ischemic stroke patients: A case series.
Glucocorticoid signaling plays major roles in energy homeostasis and adaptation to adversity, and dysregulation of this process is linked to systemic and psychological pathology. Over the last several decades, new work has challenged many of the long-standing assumptions regarding regulation of glucocorticoid secretion and glucocorticoid signaling mechanisms, revealing an exquisite complexity that accompanies the important and perhaps global role of these hormones in physiological and psychological regulation. New findings have included discovery of membrane signaling, direct neural control of the adrenal, a role for pulsatile glucocorticoid release in glucocorticoid receptor signaling, marked sex differences in brain glucocorticoid biology, and salutary as well as deleterious roles for glucocorticoids in long- and short-term adaptations to stress. This review covers some of the major lessons learned in the area of mechanisms of glucocorticoid signaling, and discusses how these may inform the field moving forward.</AbstractText
The hypothalamic control of prolactin secretion is different from other anterior pituitary hormones, in that it is predominantly inhibitory, by means of dopamine from the tuberoinfundibular dopamine neurons. In addition, prolactin does not have an endocrine target tissue, and therefore lacks the classical feedback pathway to regulate its secretion. Instead, it is regulated by short loop feedback, whereby prolactin itself acts in the brain to stimulate production of dopamine and thereby inhibit its own secretion. Finally, despite its relatively simple name, prolactin has a broad range of functions in the body, in addition to its defining role in promoting lactation. As such, the hypothalamo-prolactin axis has many characteristics that are quite distinct from other hypothalamo-pituitary systems. This review will provide a brief overview of our current understanding of the neuroendocrine control of prolactin secretion, in particular focusing on the plasticity evident in this system, which keeps prolactin secretion at low levels most of the time, but enables extended periods of hyperprolactinemia when necessary for lactation. Key prolactin functions beyond milk production will be discussed, particularly focusing on the role of prolactin in inducing adaptive responses in multiple different systems to facilitate lactation, and the consequences if prolactin action is impaired. A feature of this pleiotropic activity is that functions that may be adaptive in the lactating state might be maladaptive if prolactin levels are elevated inappropriately. Overall, my goal is to give a flavour of both the history and current state of the field of prolactin neuroendocrinology, and identify some exciting new areas of research development.</AbstractText
The effect of head position on stroke is not clear. The current study aimed to observe the effect of head-down tilt on acute ischemic stroke (AIS) patients with large vessel occlusion.</AbstractText We observed the influence of head-down tilt position on clinical outcomes, myocardial enzymogram and N-terminal pro b-type Natriuretic Peptide in 4 AIS patients who suffered early neurological deterioration (END). Cerebral perfusion imaging was performed in 3 patients using arterial spin labeling.</AbstractText In series of AIS patients with END, head down tilt (-20&#xb0;) prevented further neurological deterioration and improved clinical outcomes. An increase in cerebral blood flow was observed by arterial spin labeling after head down tilt treatment. No obvious adverse events occurred.</AbstractText The case series suggest that head-down tilt may improve clinical outcome in AIS patients through increasing the cerebral perfusion with no obvious adverse events. The finding needs to be confirmed in future clinical trials.</AbstractText
The neuroendocrinology of stress: Glucocorticoid signaling mechanisms. Glucocorticoid signaling plays major roles in energy homeostasis and adaptation to adversity, and dysregulation of this process is linked to systemic and psychological pathology. Over the last several decades, new work has challenged many of the long-standing assumptions regarding regulation of glucocorticoid secretion and glucocorticoid signaling mechanisms, revealing an exquisite complexity that accompanies the important and perhaps global role of these hormones in physiological and psychological regulation. New findings have included discovery of membrane signaling, direct neural control of the adrenal, a role for pulsatile glucocorticoid release in glucocorticoid receptor signaling, marked sex differences in brain glucocorticoid biology, and salutary as well as deleterious roles for glucocorticoids in long- and short-term adaptations to stress. This review covers some of the major lessons learned in the area of mechanisms of glucocorticoid signaling, and discusses how these may inform the field moving forward.</AbstractText
60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-prolactin axis. The hypothalamic control of prolactin secretion is different from other anterior pituitary hormones, in that it is predominantly inhibitory, by means of dopamine from the tuberoinfundibular dopamine neurons. In addition, prolactin does not have an endocrine target tissue, and therefore lacks the classical feedback pathway to regulate its secretion. Instead, it is regulated by short loop feedback, whereby prolactin itself acts in the brain to stimulate production of dopamine and thereby inhibit its own secretion. Finally, despite its relatively simple name, prolactin has a broad range of functions in the body, in addition to its defining role in promoting lactation. As such, the hypothalamo-prolactin axis has many characteristics that are quite distinct from other hypothalamo-pituitary systems. This review will provide a brief overview of our current understanding of the neuroendocrine control of prolactin secretion, in particular focusing on the plasticity evident in this system, which keeps prolactin secretion at low levels most of the time, but enables extended periods of hyperprolactinemia when necessary for lactation. Key prolactin functions beyond milk production will be discussed, particularly focusing on the role of prolactin in inducing adaptive responses in multiple different systems to facilitate lactation, and the consequences if prolactin action is impaired. A feature of this pleiotropic activity is that functions that may be adaptive in the lactating state might be maladaptive if prolactin levels are elevated inappropriately. Overall, my goal is to give a flavour of both the history and current state of the field of prolactin neuroendocrinology, and identify some exciting new areas of research development.</AbstractText
Effect of head-down tilt on clinical outcome and cerebral perfusion in ischemic stroke patients: A case series. The effect of head position on stroke is not clear. The current study aimed to observe the effect of head-down tilt on acute ischemic stroke (AIS) patients with large vessel occlusion.</AbstractText We observed the influence of head-down tilt position on clinical outcomes, myocardial enzymogram and N-terminal pro b-type Natriuretic Peptide in 4 AIS patients who suffered early neurological deterioration (END). Cerebral perfusion imaging was performed in 3 patients using arterial spin labeling.</AbstractText In series of AIS patients with END, head down tilt (-20&#xb0;) prevented further neurological deterioration and improved clinical outcomes. An increase in cerebral blood flow was observed by arterial spin labeling after head down tilt treatment. No obvious adverse events occurred.</AbstractText The case series suggest that head-down tilt may improve clinical outcome in AIS patients through increasing the cerebral perfusion with no obvious adverse events. The finding needs to be confirmed in future clinical trials.</AbstractText
33581311
25266616
34207224
The ALOXE3 gene variants from patients with Dravet syndrome decrease gene expression and enzyme activity.
Adjunctive levetiracetam treatment in pediatric Lennox-Gastaut syndrome.
Novel Cyclophilin Inhibitor Decreases Cell Proliferation and Tumor Growth in Models of Hepatocellular Carcinoma.
Aberrant expression or dysfunction of a number of genes in the brain contributes to epilepsy, a common neurological disorder characterized by recurrent seizures. Local overexpression of arachidonate lipoxygenase 3 (ALOXE3), a key enzyme for arachidonic acid (AA) metabolic pathway, alleviates seizure severities. However, the relationship between the ALOXE3 gene mutation and epilepsy has not been reported until now. Here we firstly characterized the promoter of human ALOXE3 gene and found that the ALOXE3 promoter could drive luciferase gene expression in the human HEK-293 and SH-SY5Y cells. We then screened the ALOXE3 promoter region and all coding exons from those patients with Dravet syndrome and identified 5 variants c.-163T&#x2009;&gt;&#x2009;C, c.-50C&#x2009;&gt;&#x2009;G, c.-37G&#x2009;&gt;&#x2009;A, c.&#x2009;+&#x2009;228G&#x2009;&gt;&#x2009;A and c.&#x2009;+&#x2009;290G&#x2009;&gt;&#x2009;T in the promoter region and one missense variant c.1939A&#x2009;&gt;&#x2009;G (p.I647&#x2009;V) in the exon. Of these variants in the promoter region, only -50C&#x2009;&gt;&#x2009;G was a novel variant located on the transcriptional factor NFII-I binding element. Luciferase reporter gene analyses indicated that the c.-50C&#x2009;&gt;&#x2009;G could decrease gene expression by preventing the TFII-I's binding. In addition, the variant p.I647&#x2009;V was conserved among all analyzed species and located within the ALOXE3 functional domain for catalyzing its substrate. In cultured cell lines, overexpression of ALOXE3 significantly decreased the cellular AA levels and overexpression of ALOXE3-I647&#x2009;V could restore the AA levels, suggesting that the p.I647&#x2009;V mutant led to a decrease in enzyme activity. Taken together, the present study proposes that the identified ALOXE3 variants potentially contribute to the AA-pathway-mediated epileptogenesis, which should provide a novel avenue for clinical diagnosis of epilepsy.</AbstractText
Our aim was to investigate the efficacy and tolerability of levetiracetam as an add-on treatment in pediatric patients with Lennox-Gastaut syndrome.</AbstractText The study was an open-label, multicenter, observational clinical trial of levetiracetam as an add-on treatment in Lennox-Gastaut syndrome. Fifty-five patients aged 1.1-18.6 years (mean, 10.0 years) were enrolled. The study included a 4-8-week titration period and an 8-week maintenance period. The maintenance dose of levetiracetam was 20-80 mg/kg/day, according to its effectiveness and tolerability. The primary end point was reduction in seizure frequency, and related variables were also evaluated.</AbstractText Among 55 patents, 51 patients (92.7%) completed the study. Thirty-two patients (58.2%) experienced a more than 50% reduction in seizure frequency, and 15 patients (27.3%) became seizure free. A reduction in seizure frequency of more than 50% was observed in 21 of 36 patients (58.3%) with convulsive seizures, 7 of 12 patients (58.3%) with drop attacks, 2 of 4 patients (50.0%) with myoclonic seizures, and 2 of 3 patients (66.7%) with epileptic spasms. Overall, 34.5% of patients reported adverse events. None of the adverse events were life threatening, and the most common adverse event was hyperactivity (12.7%).</AbstractText This study suggests that levetiracetam is a safe and effective treatment in pediatric patients with Lennox-Gastaut syndrome.</AbstractText
Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed in its late state. Tyrosine kinase inhibitors such as sorafenib and regorafenib are one of the few treatment options approved for advanced HCC and only prolong the patient's life expectancy by a few months. Therefore, there is a need for novel effective treatments. Cyclophilins are intracellular proteins that catalyze the cis/trans isomerization of peptide bonds at proline residues. Cyclophilins are known to be overexpressed in HCC, affecting therapy resistance and cell proliferation. In the present study, we explored the potential of cyclophilin inhibitors as new therapeutic options for HCC in vitro and in vivo. Our results showed that the novel cyclophilin inhibitor, NV651, was able to significantly decrease proliferation in a diverse set of HCC cell lines. The exposure of HCC cells to NV651 caused an accumulation of cells during mitosis and consequent accumulation in the G<sub
The ALOXE3 gene variants from patients with Dravet syndrome decrease gene expression and enzyme activity. Aberrant expression or dysfunction of a number of genes in the brain contributes to epilepsy, a common neurological disorder characterized by recurrent seizures. Local overexpression of arachidonate lipoxygenase 3 (ALOXE3), a key enzyme for arachidonic acid (AA) metabolic pathway, alleviates seizure severities. However, the relationship between the ALOXE3 gene mutation and epilepsy has not been reported until now. Here we firstly characterized the promoter of human ALOXE3 gene and found that the ALOXE3 promoter could drive luciferase gene expression in the human HEK-293 and SH-SY5Y cells. We then screened the ALOXE3 promoter region and all coding exons from those patients with Dravet syndrome and identified 5 variants c.-163T&#x2009;&gt;&#x2009;C, c.-50C&#x2009;&gt;&#x2009;G, c.-37G&#x2009;&gt;&#x2009;A, c.&#x2009;+&#x2009;228G&#x2009;&gt;&#x2009;A and c.&#x2009;+&#x2009;290G&#x2009;&gt;&#x2009;T in the promoter region and one missense variant c.1939A&#x2009;&gt;&#x2009;G (p.I647&#x2009;V) in the exon. Of these variants in the promoter region, only -50C&#x2009;&gt;&#x2009;G was a novel variant located on the transcriptional factor NFII-I binding element. Luciferase reporter gene analyses indicated that the c.-50C&#x2009;&gt;&#x2009;G could decrease gene expression by preventing the TFII-I's binding. In addition, the variant p.I647&#x2009;V was conserved among all analyzed species and located within the ALOXE3 functional domain for catalyzing its substrate. In cultured cell lines, overexpression of ALOXE3 significantly decreased the cellular AA levels and overexpression of ALOXE3-I647&#x2009;V could restore the AA levels, suggesting that the p.I647&#x2009;V mutant led to a decrease in enzyme activity. Taken together, the present study proposes that the identified ALOXE3 variants potentially contribute to the AA-pathway-mediated epileptogenesis, which should provide a novel avenue for clinical diagnosis of epilepsy.</AbstractText
Adjunctive levetiracetam treatment in pediatric Lennox-Gastaut syndrome. Our aim was to investigate the efficacy and tolerability of levetiracetam as an add-on treatment in pediatric patients with Lennox-Gastaut syndrome.</AbstractText The study was an open-label, multicenter, observational clinical trial of levetiracetam as an add-on treatment in Lennox-Gastaut syndrome. Fifty-five patients aged 1.1-18.6 years (mean, 10.0 years) were enrolled. The study included a 4-8-week titration period and an 8-week maintenance period. The maintenance dose of levetiracetam was 20-80 mg/kg/day, according to its effectiveness and tolerability. The primary end point was reduction in seizure frequency, and related variables were also evaluated.</AbstractText Among 55 patents, 51 patients (92.7%) completed the study. Thirty-two patients (58.2%) experienced a more than 50% reduction in seizure frequency, and 15 patients (27.3%) became seizure free. A reduction in seizure frequency of more than 50% was observed in 21 of 36 patients (58.3%) with convulsive seizures, 7 of 12 patients (58.3%) with drop attacks, 2 of 4 patients (50.0%) with myoclonic seizures, and 2 of 3 patients (66.7%) with epileptic spasms. Overall, 34.5% of patients reported adverse events. None of the adverse events were life threatening, and the most common adverse event was hyperactivity (12.7%).</AbstractText This study suggests that levetiracetam is a safe and effective treatment in pediatric patients with Lennox-Gastaut syndrome.</AbstractText
Novel Cyclophilin Inhibitor Decreases Cell Proliferation and Tumor Growth in Models of Hepatocellular Carcinoma. Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed in its late state. Tyrosine kinase inhibitors such as sorafenib and regorafenib are one of the few treatment options approved for advanced HCC and only prolong the patient's life expectancy by a few months. Therefore, there is a need for novel effective treatments. Cyclophilins are intracellular proteins that catalyze the cis/trans isomerization of peptide bonds at proline residues. Cyclophilins are known to be overexpressed in HCC, affecting therapy resistance and cell proliferation. In the present study, we explored the potential of cyclophilin inhibitors as new therapeutic options for HCC in vitro and in vivo. Our results showed that the novel cyclophilin inhibitor, NV651, was able to significantly decrease proliferation in a diverse set of HCC cell lines. The exposure of HCC cells to NV651 caused an accumulation of cells during mitosis and consequent accumulation in the G<sub
20132897
15518940
20597593
The neural implementation of task rule activation in the task-cuing paradigm: an event-related fMRI study.
Errors without conflict: implications for performance monitoring theories of anterior cingulate cortex.
Defining neuromarketing: practices and professional challenges.
To isolate the neural correlates for task rule activation from those related to general task preparation, the effect of a cue explicitly specifying the S-R correspondences (rule-cue) was contrasted with the effects of a cue specifying only the task to performed (task-cue). While the task-cue provides merely information about the type of task, the rule-cue is explicit about both the task type and the task rule (i.e., the set of S-R correspondences). The rule-cue was expected to activate the task rule more efficiently in the preparation period (prior to target presentation); by contrast, in the task-cue condition, part of the task rule activation was expected to be postponed into the task execution period (following the presentation of the target). In an event-related fMRI experiment, we found the right anterior and middle parts of the middle frontal and superior frontal gyri, the right inferior frontal junction, the pre-SMA, as well as the right superior and inferior parietal lobes to show larger activation elicited by the rule-cue than by the task-cue prior to target presentation. Conversely, the results revealed larger activations in these regions in the task-cue than in the rule-cue condition during the task execution period. In summary, this study identified some of the neural correlates of task rule activation and showed that these are a subset of the general task preparation network.</AbstractText
Recent theories of the neural basis of performance monitoring have emphasized a central role for the anterior cingulate cortex (ACC). Replicating an earlier event-related potential (ERP) study, which showed an error feedback negativity that was modeled as having an ACC generator, we used event-related fMRI to investigate whether the ACC would differentiate between correct and incorrect feedback stimuli in a time estimation task. The design controlled for response conflict and frequency and expectancy effects. Although participants in the current study adjusted their performance following error feedback, we did not observe error feedback-evoked ACC activity. In contrast, we did observe ACC activity while the same subjects performed the Stroop task, in which an area of the ACC activated during both conflict and error trials. These findings are inconsistent with previous dipole models of the error feedback negativity, and suggest the ACC may not be involved in the generation of this ERP component. These results question involvement of the ACC in the detection of errors per se when controlling for conflict.</AbstractText
Neuromarketing has recently generated controversies concerning the involvement of medical professionals, and many key questions remain-ones that have potentially important implications for the field of psychiatry. Conflicting definitions of neuromarketing have been proposed, and little is known about the actual practices of companies, physicians, and scientists involved in its practice. This article reviews the history of neuromarketing and uses an exploratory survey of neuromarketing Web sites to illustrate ethical issues raised by this new field. Neuromarketing, as currently practiced, is heterogeneous, as companies are offering a variety of technologies. Many companies employ academicians and professionals, but few list their clients or fees. Media coverage of neuromarketing appears disproportionately high compared to the paucity of peer-reviewed reports in the field. Companies may be making premature claims about the power of neuroscience to predict consumer behavior. Overall, neuromarketing has important implications for academic-industrial partnerships, the responsible conduct of research, and the public understanding of the brain. We explore these themes to uncover issues relevant to professional ethics, research, and policy. Of particular relevance to psychiatry, neuromarketing may be seen as an extension of the search for quantification and certainty in previously indefinite aspects of human behavior.</AbstractText
The neural implementation of task rule activation in the task-cuing paradigm: an event-related fMRI study. To isolate the neural correlates for task rule activation from those related to general task preparation, the effect of a cue explicitly specifying the S-R correspondences (rule-cue) was contrasted with the effects of a cue specifying only the task to performed (task-cue). While the task-cue provides merely information about the type of task, the rule-cue is explicit about both the task type and the task rule (i.e., the set of S-R correspondences). The rule-cue was expected to activate the task rule more efficiently in the preparation period (prior to target presentation); by contrast, in the task-cue condition, part of the task rule activation was expected to be postponed into the task execution period (following the presentation of the target). In an event-related fMRI experiment, we found the right anterior and middle parts of the middle frontal and superior frontal gyri, the right inferior frontal junction, the pre-SMA, as well as the right superior and inferior parietal lobes to show larger activation elicited by the rule-cue than by the task-cue prior to target presentation. Conversely, the results revealed larger activations in these regions in the task-cue than in the rule-cue condition during the task execution period. In summary, this study identified some of the neural correlates of task rule activation and showed that these are a subset of the general task preparation network.</AbstractText
Errors without conflict: implications for performance monitoring theories of anterior cingulate cortex. Recent theories of the neural basis of performance monitoring have emphasized a central role for the anterior cingulate cortex (ACC). Replicating an earlier event-related potential (ERP) study, which showed an error feedback negativity that was modeled as having an ACC generator, we used event-related fMRI to investigate whether the ACC would differentiate between correct and incorrect feedback stimuli in a time estimation task. The design controlled for response conflict and frequency and expectancy effects. Although participants in the current study adjusted their performance following error feedback, we did not observe error feedback-evoked ACC activity. In contrast, we did observe ACC activity while the same subjects performed the Stroop task, in which an area of the ACC activated during both conflict and error trials. These findings are inconsistent with previous dipole models of the error feedback negativity, and suggest the ACC may not be involved in the generation of this ERP component. These results question involvement of the ACC in the detection of errors per se when controlling for conflict.</AbstractText
Defining neuromarketing: practices and professional challenges. Neuromarketing has recently generated controversies concerning the involvement of medical professionals, and many key questions remain-ones that have potentially important implications for the field of psychiatry. Conflicting definitions of neuromarketing have been proposed, and little is known about the actual practices of companies, physicians, and scientists involved in its practice. This article reviews the history of neuromarketing and uses an exploratory survey of neuromarketing Web sites to illustrate ethical issues raised by this new field. Neuromarketing, as currently practiced, is heterogeneous, as companies are offering a variety of technologies. Many companies employ academicians and professionals, but few list their clients or fees. Media coverage of neuromarketing appears disproportionately high compared to the paucity of peer-reviewed reports in the field. Companies may be making premature claims about the power of neuroscience to predict consumer behavior. Overall, neuromarketing has important implications for academic-industrial partnerships, the responsible conduct of research, and the public understanding of the brain. We explore these themes to uncover issues relevant to professional ethics, research, and policy. Of particular relevance to psychiatry, neuromarketing may be seen as an extension of the search for quantification and certainty in previously indefinite aspects of human behavior.</AbstractText
12151781
15313521
11888279
Habituation of attentional networks during emotion processing.
Functional MRI mapping of brain activation during visually guided saccades and antisaccades: cortical and subcortical networks.
Biophysical properties of camelid V(HH) domains compared to those of human V(H)3 domains.
Dysfunctional emotion processing is a key aspect of many neuropsychiatric disorders. This dysfunction may be due to an abnormal magnitude of neural substrate activation during emotion processing or due to an altered time course of the neural substrate response. To better understand the temporal characteristics of the neural substrate activation underlying implicit emotion processing, nine healthy female controls were repeatedly exposed to pictures of affective faces while performing a gender identification task in an fMRI. As the salience of the stimuli decreased with repeated exposure, brain areas implicated in a right hemispheric spatial attention network (including the posterior parietal cortex (BA 40) and the frontal eye fields (BA 6)) habituated while brain areas lateralized to the left hemisphere (including the angular gyrus (BA 39), posterior superior temporal gyrus (BA 39) and insula (BA 13)) sensitized. These results provide strong evidence that the time course of activation is a critical component when assessing the function of neural substrates underlying emotion processing (specifically whether habituation is altered) in neuro-psychiatric patients.</AbstractText
Antisaccade tasks require a subject to inhibit a saccade toward a briefly appearing peripheral target and instead to immediately generate a saccade to an equivalent point in the opposite hemifield. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks required to inhibit reflexive saccades and to voluntarily generate saccades. The results demonstrated that saccade and antisaccade tasks often bilaterally activate frontal, parietal and supplementary eye fields, lenticular nuclei and occipital cortex. Additional activation of bilateral dorsolateral prefrontal cortices, supramarginal gyri, anterior cingulate cortices and thalamus was observed during antisaccade tasks. These results indicate that fronto-parietal and fronto-striato-thalamo-cortical circuits are involved in antisaccade tasks. The fronto-parietal circuit is thought to be related to the planning of saccadic eye movements that involve attentional control, while the fronto-striato-thalamo-cortical circuits connect to cortical region as a feedback network. We speculate that the abnormalities in spatial attention and eye movement control observed in schizophrenia stem from dysfunctions in the fronto-parietal and fronto-striato-thalamo-cortical circuits.</AbstractText
Camelidae possess an unusual form of antibodies lacking the light chains. The variable domain of these heavy chain antibodies (V(HH)) is not paired, while the V(H) domain of all other antibodies forms a heterodimer with the variable domain of the light chain (V(L)), held together by a hydrophobic interface. Here, we analyzed the biophysical properties of four camelid V(HH) fragments (H14, AMD9, RN05, and CA05) and two human consensus V(H)3 domains with different CDR3 loops to gain insight into factors determining stability and aggregation of immunoglobulin domains. We show by denaturant-induced unfolding equilibria that the free energies of unfolding of V(HH) fragments are characterized by Delta G(N-U) values between 21.1 and 35.0 kJ/mol and thus lie in the upper range of values for V(H) fragments from murine and human antibodies. Nevertheless, the V(HH) fragments studied here did not reach the high values between 39.7 and 52.7 kJ/mol of the human consensus V(H)3 domains with which they share the highest degree of sequence similarity. Temperature-induced unfolding of the V(HH) fragments that were studied proved to be reversible, and the binding affinity after cooling was fully retained. The melting temperatures were determined to be between 60.1 and 66.7 degrees C. In contrast, the studied V(H)3 domains aggregated during temperature-induced denaturation at 63-65 degrees C. In summary, the camelid V(HH) fragments are characterized by a favorable but not unusually high stability. Their hallmark is the ability to reversibly melt without aggregation, probably mediated by the surface mutations characterizing the V(HH) domains, which allow them to regain binding activity after heat renaturation.</AbstractText
Habituation of attentional networks during emotion processing. Dysfunctional emotion processing is a key aspect of many neuropsychiatric disorders. This dysfunction may be due to an abnormal magnitude of neural substrate activation during emotion processing or due to an altered time course of the neural substrate response. To better understand the temporal characteristics of the neural substrate activation underlying implicit emotion processing, nine healthy female controls were repeatedly exposed to pictures of affective faces while performing a gender identification task in an fMRI. As the salience of the stimuli decreased with repeated exposure, brain areas implicated in a right hemispheric spatial attention network (including the posterior parietal cortex (BA 40) and the frontal eye fields (BA 6)) habituated while brain areas lateralized to the left hemisphere (including the angular gyrus (BA 39), posterior superior temporal gyrus (BA 39) and insula (BA 13)) sensitized. These results provide strong evidence that the time course of activation is a critical component when assessing the function of neural substrates underlying emotion processing (specifically whether habituation is altered) in neuro-psychiatric patients.</AbstractText
Functional MRI mapping of brain activation during visually guided saccades and antisaccades: cortical and subcortical networks. Antisaccade tasks require a subject to inhibit a saccade toward a briefly appearing peripheral target and instead to immediately generate a saccade to an equivalent point in the opposite hemifield. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks required to inhibit reflexive saccades and to voluntarily generate saccades. The results demonstrated that saccade and antisaccade tasks often bilaterally activate frontal, parietal and supplementary eye fields, lenticular nuclei and occipital cortex. Additional activation of bilateral dorsolateral prefrontal cortices, supramarginal gyri, anterior cingulate cortices and thalamus was observed during antisaccade tasks. These results indicate that fronto-parietal and fronto-striato-thalamo-cortical circuits are involved in antisaccade tasks. The fronto-parietal circuit is thought to be related to the planning of saccadic eye movements that involve attentional control, while the fronto-striato-thalamo-cortical circuits connect to cortical region as a feedback network. We speculate that the abnormalities in spatial attention and eye movement control observed in schizophrenia stem from dysfunctions in the fronto-parietal and fronto-striato-thalamo-cortical circuits.</AbstractText
Biophysical properties of camelid V(HH) domains compared to those of human V(H)3 domains. Camelidae possess an unusual form of antibodies lacking the light chains. The variable domain of these heavy chain antibodies (V(HH)) is not paired, while the V(H) domain of all other antibodies forms a heterodimer with the variable domain of the light chain (V(L)), held together by a hydrophobic interface. Here, we analyzed the biophysical properties of four camelid V(HH) fragments (H14, AMD9, RN05, and CA05) and two human consensus V(H)3 domains with different CDR3 loops to gain insight into factors determining stability and aggregation of immunoglobulin domains. We show by denaturant-induced unfolding equilibria that the free energies of unfolding of V(HH) fragments are characterized by Delta G(N-U) values between 21.1 and 35.0 kJ/mol and thus lie in the upper range of values for V(H) fragments from murine and human antibodies. Nevertheless, the V(HH) fragments studied here did not reach the high values between 39.7 and 52.7 kJ/mol of the human consensus V(H)3 domains with which they share the highest degree of sequence similarity. Temperature-induced unfolding of the V(HH) fragments that were studied proved to be reversible, and the binding affinity after cooling was fully retained. The melting temperatures were determined to be between 60.1 and 66.7 degrees C. In contrast, the studied V(H)3 domains aggregated during temperature-induced denaturation at 63-65 degrees C. In summary, the camelid V(HH) fragments are characterized by a favorable but not unusually high stability. Their hallmark is the ability to reversibly melt without aggregation, probably mediated by the surface mutations characterizing the V(HH) domains, which allow them to regain binding activity after heat renaturation.</AbstractText
33607346
23767923
34766498
Preference for locomotion-compatible curved paths and forward direction of self-motion in somatomotor and visual areas.
Stimulating the brain's language network: syntactic ambiguity resolution after TMS to the inferior frontal gyrus and middle temporal gyrus.
One-Step Biosynthesis of Soft Magnetic Bacterial Cellulose Spheres with Localized Nanoparticle Functionalization.
During locomotion, leg movements define the direction of walking (forward or backward) and the path one is taking (straight or curved). These aspects of locomotion produce characteristic visual motion patterns during movement. Here, we tested whether cortical regions responding to either egomotion-compatible visual motion, or leg movements, or both, are sensitive to these locomotion-relevant aspects of visual motion. We compared a curved path (typically the visual feedback of a changing direction of movement in the environment) to a linear path for simulated forward and backward motion in an event-related fMRI experiment. We used an individual surface-based approach and two functional localizers to define (1) six egomotion-related areas (V6+, V3A, intraparietal motion area [IPSmot], cingulate sulcus visual area [CSv], posterior cingulate area [pCi], posterior insular cortex [PIC]) using the flow field stimulus and (2) three leg-related cortical regions (human PEc [hPEc], human PE [hPE] and primary somatosensory cortex [S-I]) using a somatomotor task. Then, we extracted the response from all these regions with respect to the main event-related fMRI experiment, consisting of passive viewing of an optic flow stimulus, simulating a forward or backward direction of self-motion in either linear or curved path. Results showed that some regions have a significant preference for the curved path motion (hPEc, hPE, S-I, IPSmot) or a preference for the forward motion (V3A), while other regions have both a significant preference for the curved path motion and for the forward compared to backward motion (V6+, CSv, pCi). We did not find any significant effects of the present stimuli in PIC. Since controlling locomotion mainly means controlling changes of walking direction in the environment during forward self-motion, such a differential functional profile among these cortical regions suggests that they play a differentiated role in the visual guidance of locomotion.</AbstractText
The posterior middle temporal gyrus (MTG) and inferior frontal gyrus (IFG) are two critical nodes of the brain's language network. Previous neuroimaging evidence has supported a dissociation in language comprehension in which parts of the MTG are involved in the retrieval of lexical syntactic information and the IFG in unification operations that maintain, select, and integrate multiple sources of information over time. In the present investigation, we tested for causal evidence of this dissociation by modulating activity in IFG and MTG using an offline TMS procedure: continuous theta-burst stimulation. Lexical-syntactic retrieval was manipulated by using sentences with and without a temporarily word-class (noun/verb) ambiguity (e.g., run). In one group of participants, TMS was applied to the IFG and MTG, and in a control group, no TMS was applied. Eye movements were recorded and quantified at two critical sentence regions: a temporarily ambiguous region and a disambiguating region. Results show that stimulation of the IFG led to a modulation of the ambiguity effect (ambiguous-unambiguous) at the disambiguating sentence region in three measures: first fixation durations, total reading times, and regressive eye movements into the region. Both IFG and MTG stimulation modulated the ambiguity effect for total reading times in the temporarily ambiguous sentence region relative to the control group. The current results demonstrate that an offline repetitive TMS protocol can have influences at a different point in time during online processing and provide causal evidence for IFG involvement in unification operations during sentence comprehension.</AbstractText
Actuated structures are becoming relevant in medical fields; however, they call for flexible/soft-base materials that comply with biological tissues and can be synthesized in simple fabrication steps. In this work, we extend the palette of techniques to afford soft, actuable spherical structures taking advantage of the biosynthesis process of bacterial cellulose. Bacterial cellulose spheres (BCS) with localized magnetic nanoparticles (NPs) have been biosynthesized using two different one-pot processes: in agitation and on hydrophobic surface-supported static culture, achieving core-shell or hollow spheres, respectively. Magnetic actuability is conferred by superparamagnetic iron oxide NPs (SPIONs), and their location within the structure was finely tuned with high precision. The size, structure, flexibility and magnetic response of the spheres have been characterized. In addition, the versatility of the methodology allows us to produce actuated spherical structures adding other NPs (Au and Pt) in specific locations, creating Janus structures. The combination of Pt NPs and SPIONs provides moving composite structures driven both by a magnetic field and a H<sub
Preference for locomotion-compatible curved paths and forward direction of self-motion in somatomotor and visual areas. During locomotion, leg movements define the direction of walking (forward or backward) and the path one is taking (straight or curved). These aspects of locomotion produce characteristic visual motion patterns during movement. Here, we tested whether cortical regions responding to either egomotion-compatible visual motion, or leg movements, or both, are sensitive to these locomotion-relevant aspects of visual motion. We compared a curved path (typically the visual feedback of a changing direction of movement in the environment) to a linear path for simulated forward and backward motion in an event-related fMRI experiment. We used an individual surface-based approach and two functional localizers to define (1) six egomotion-related areas (V6+, V3A, intraparietal motion area [IPSmot], cingulate sulcus visual area [CSv], posterior cingulate area [pCi], posterior insular cortex [PIC]) using the flow field stimulus and (2) three leg-related cortical regions (human PEc [hPEc], human PE [hPE] and primary somatosensory cortex [S-I]) using a somatomotor task. Then, we extracted the response from all these regions with respect to the main event-related fMRI experiment, consisting of passive viewing of an optic flow stimulus, simulating a forward or backward direction of self-motion in either linear or curved path. Results showed that some regions have a significant preference for the curved path motion (hPEc, hPE, S-I, IPSmot) or a preference for the forward motion (V3A), while other regions have both a significant preference for the curved path motion and for the forward compared to backward motion (V6+, CSv, pCi). We did not find any significant effects of the present stimuli in PIC. Since controlling locomotion mainly means controlling changes of walking direction in the environment during forward self-motion, such a differential functional profile among these cortical regions suggests that they play a differentiated role in the visual guidance of locomotion.</AbstractText
Stimulating the brain's language network: syntactic ambiguity resolution after TMS to the inferior frontal gyrus and middle temporal gyrus. The posterior middle temporal gyrus (MTG) and inferior frontal gyrus (IFG) are two critical nodes of the brain's language network. Previous neuroimaging evidence has supported a dissociation in language comprehension in which parts of the MTG are involved in the retrieval of lexical syntactic information and the IFG in unification operations that maintain, select, and integrate multiple sources of information over time. In the present investigation, we tested for causal evidence of this dissociation by modulating activity in IFG and MTG using an offline TMS procedure: continuous theta-burst stimulation. Lexical-syntactic retrieval was manipulated by using sentences with and without a temporarily word-class (noun/verb) ambiguity (e.g., run). In one group of participants, TMS was applied to the IFG and MTG, and in a control group, no TMS was applied. Eye movements were recorded and quantified at two critical sentence regions: a temporarily ambiguous region and a disambiguating region. Results show that stimulation of the IFG led to a modulation of the ambiguity effect (ambiguous-unambiguous) at the disambiguating sentence region in three measures: first fixation durations, total reading times, and regressive eye movements into the region. Both IFG and MTG stimulation modulated the ambiguity effect for total reading times in the temporarily ambiguous sentence region relative to the control group. The current results demonstrate that an offline repetitive TMS protocol can have influences at a different point in time during online processing and provide causal evidence for IFG involvement in unification operations during sentence comprehension.</AbstractText
One-Step Biosynthesis of Soft Magnetic Bacterial Cellulose Spheres with Localized Nanoparticle Functionalization. Actuated structures are becoming relevant in medical fields; however, they call for flexible/soft-base materials that comply with biological tissues and can be synthesized in simple fabrication steps. In this work, we extend the palette of techniques to afford soft, actuable spherical structures taking advantage of the biosynthesis process of bacterial cellulose. Bacterial cellulose spheres (BCS) with localized magnetic nanoparticles (NPs) have been biosynthesized using two different one-pot processes: in agitation and on hydrophobic surface-supported static culture, achieving core-shell or hollow spheres, respectively. Magnetic actuability is conferred by superparamagnetic iron oxide NPs (SPIONs), and their location within the structure was finely tuned with high precision. The size, structure, flexibility and magnetic response of the spheres have been characterized. In addition, the versatility of the methodology allows us to produce actuated spherical structures adding other NPs (Au and Pt) in specific locations, creating Janus structures. The combination of Pt NPs and SPIONs provides moving composite structures driven both by a magnetic field and a H<sub
40211007
33749402
40640637
Towards quantitative assessment of cerebrovascular autoregulation in human neonates using ultrafast ultrasound imaging.
Cerebral blood flow changes during aging process and in cognitive disorders: A review.
Twin differences in the Minnesota Trust Game relate to neural mechanisms of suspiciousness.
Newborns with congenital heart diseases requiring cardiopulmonary bypass (CPB) are at risk of neurodevelopmental impairment. The impact of deep hypothermia cardiopulmonary bypass (DH-CPB) on cerebrovascular autoregulation (CAR) that controls brain perfusion in the presence of blood pressure variation is not well understood. Recently, ultrafast power Doppler (UPD) showed potential to study CAR in neonates based on cerebral blood volume (CBV). However, since CAR relies mainly on arterial vasoconstriction/vasodilation, monitoring of brain perfusion variation based on CBV requires the discrimination of arterial from venous CBV. This study aims to use UPD combined with an algorithm for the discrimination of arteries and veins to monitor CAR during DH-CPB in neonates. Transfontanellar ultrafast power Doppler was performed in two groups of newborns: those undergoing deep hypothermic cardiopulmonary bypass with circulatory arrest (18-20 &#xb0;C, n&#x2009;=&#x2009;6, "DH group") and those undergoing full-flow CPB at mild hypothermia (32-34 &#xb0;C, n&#x2009;=&#x2009;6, "non-DH group"). Blood flow directionality was used to differentiate arterial compartments of CBV from venous CBV in specific brain regions where arterial and venous flows exhibit opposite directions. To study CAR, a linear mixed effect model was used to find the association between arterial CBV and mean arterial blood pressure (MAP). In the "non-DH group", we found a negative association between arterial CBV and MAP, indicating that an increase in MAP is associated with a decrease in arterial CBV (slope = -0.020 [Formula: see text], p&#x2009;=&#x2009;0.047). Conversely, in the "DH group" no significant association was found such that arterial CBV remained stable as MAP increased (p&#x2009;=&#x2009;0.314). We interpret the reduction in arterial CBV with increasing MAP in the "non-DH group" as an active arterial vasoconstriction triggered by CAR, whereas the lack of variation of arterial CBV in the DH group suggests impaired CAR response. Our findings highlight the potential of ultrafast ultrasound imaging for intra-operative CAR monitoring, paving the way for a better understanding of the impact of different types of CPB on cerebral perfusion.</AbstractText
We aimed to summarize the available evidence on cerebral blood flow (CBF) changes in normal aging and common cognitive disorders. We searched PubMed for studies on CBF changes in normal aging and cognitive disorders up to 1 January 2019. We summarized the milestones in the history of CBF assessment and reviewed the current evidence on the association between CBF and cognitive changes in normal aging, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). There is promising evidence regarding the utility of CBF studies in cognition research. Age-related CBF changes could be related to a progressive neuronal loss or diminished activity and synaptic density of neurons in the brain. While a similar cause or outcome theory applies to VCI and AD, it is possible that CBF reduction might precede cognitive decline. Despite the diversity of CBF research findings, its measurement could help early detection of cognitive disorders and also understanding their underlying etiology.</AbstractText
Spite sensitivity, or the fear that a person is willing to intentionally take a loss to ensure that another person will as well, may be a key component in understanding persecutory ideation (the belief that others want to harm you). We implemented a co-twin control design to examine potentially causal relationships among persecutory ideation, spite sensitivity, and neural activity and connectivity. Sixty-nine participants (23 monozygotic twin pairs and an additional 23 unpaired monozygotic twins) completed the Minnesota Trust Game-a social decision-making game played asynchronously with an anonymous partner that targets spite sensitivity by varying the incentives of the partner. Participants with more self-reported persecutory ideation (relative to those with lower persecutory ideation) trusted less even when the partner was incentivized to be fair. Similarly, computational modeling showed that increased persecutory ideation was associated with greater beliefs of a partner's spitefulness. Twins with greater beliefs of a partner's spitefulness (relative to their co-twins) also reported higher persecution. In addition, twin differences in left lateral OFC activation during the task were associated with spite sensitivity. These results point towards a potentially causal role of the lateral OFC on spite sensitivity, and in turn effects of spite sensitivity on persecutory ideation.</AbstractText
Towards quantitative assessment of cerebrovascular autoregulation in human neonates using ultrafast ultrasound imaging. Newborns with congenital heart diseases requiring cardiopulmonary bypass (CPB) are at risk of neurodevelopmental impairment. The impact of deep hypothermia cardiopulmonary bypass (DH-CPB) on cerebrovascular autoregulation (CAR) that controls brain perfusion in the presence of blood pressure variation is not well understood. Recently, ultrafast power Doppler (UPD) showed potential to study CAR in neonates based on cerebral blood volume (CBV). However, since CAR relies mainly on arterial vasoconstriction/vasodilation, monitoring of brain perfusion variation based on CBV requires the discrimination of arterial from venous CBV. This study aims to use UPD combined with an algorithm for the discrimination of arteries and veins to monitor CAR during DH-CPB in neonates. Transfontanellar ultrafast power Doppler was performed in two groups of newborns: those undergoing deep hypothermic cardiopulmonary bypass with circulatory arrest (18-20 &#xb0;C, n&#x2009;=&#x2009;6, "DH group") and those undergoing full-flow CPB at mild hypothermia (32-34 &#xb0;C, n&#x2009;=&#x2009;6, "non-DH group"). Blood flow directionality was used to differentiate arterial compartments of CBV from venous CBV in specific brain regions where arterial and venous flows exhibit opposite directions. To study CAR, a linear mixed effect model was used to find the association between arterial CBV and mean arterial blood pressure (MAP). In the "non-DH group", we found a negative association between arterial CBV and MAP, indicating that an increase in MAP is associated with a decrease in arterial CBV (slope = -0.020 [Formula: see text], p&#x2009;=&#x2009;0.047). Conversely, in the "DH group" no significant association was found such that arterial CBV remained stable as MAP increased (p&#x2009;=&#x2009;0.314). We interpret the reduction in arterial CBV with increasing MAP in the "non-DH group" as an active arterial vasoconstriction triggered by CAR, whereas the lack of variation of arterial CBV in the DH group suggests impaired CAR response. Our findings highlight the potential of ultrafast ultrasound imaging for intra-operative CAR monitoring, paving the way for a better understanding of the impact of different types of CPB on cerebral perfusion.</AbstractText
Cerebral blood flow changes during aging process and in cognitive disorders: A review. We aimed to summarize the available evidence on cerebral blood flow (CBF) changes in normal aging and common cognitive disorders. We searched PubMed for studies on CBF changes in normal aging and cognitive disorders up to 1 January 2019. We summarized the milestones in the history of CBF assessment and reviewed the current evidence on the association between CBF and cognitive changes in normal aging, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). There is promising evidence regarding the utility of CBF studies in cognition research. Age-related CBF changes could be related to a progressive neuronal loss or diminished activity and synaptic density of neurons in the brain. While a similar cause or outcome theory applies to VCI and AD, it is possible that CBF reduction might precede cognitive decline. Despite the diversity of CBF research findings, its measurement could help early detection of cognitive disorders and also understanding their underlying etiology.</AbstractText
Twin differences in the Minnesota Trust Game relate to neural mechanisms of suspiciousness. Spite sensitivity, or the fear that a person is willing to intentionally take a loss to ensure that another person will as well, may be a key component in understanding persecutory ideation (the belief that others want to harm you). We implemented a co-twin control design to examine potentially causal relationships among persecutory ideation, spite sensitivity, and neural activity and connectivity. Sixty-nine participants (23 monozygotic twin pairs and an additional 23 unpaired monozygotic twins) completed the Minnesota Trust Game-a social decision-making game played asynchronously with an anonymous partner that targets spite sensitivity by varying the incentives of the partner. Participants with more self-reported persecutory ideation (relative to those with lower persecutory ideation) trusted less even when the partner was incentivized to be fair. Similarly, computational modeling showed that increased persecutory ideation was associated with greater beliefs of a partner's spitefulness. Twins with greater beliefs of a partner's spitefulness (relative to their co-twins) also reported higher persecution. In addition, twin differences in left lateral OFC activation during the task were associated with spite sensitivity. These results point towards a potentially causal role of the lateral OFC on spite sensitivity, and in turn effects of spite sensitivity on persecutory ideation.</AbstractText
33799582
31461679
37701914
Disrupted Pallido-Thalamo-Cortical Functional Connectivity in Chronic Disorders of Consciousness.
Imaging the spontaneous flow of thought: Distinct periods of cognition contribute to dynamic functional connectivity during rest.
Real-Time Mapping of Tissue Properties for Magnetic Resonance Fingerprinting.
Chronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals.</AbstractText
Brain functional connectivity (FC) changes have been measured across seconds using fMRI. This is true for both rest and task scenarios. Moreover, it is well accepted that task engagement alters FC, and that dynamic estimates of FC during and before task events can help predict their nature and performance. Yet, when it comes to dynamic FC (dFC) during rest, there is no consensus about its origin or significance. Some argue that rest dFC reflects fluctuations in on-going cognition, or is a manifestation of intrinsic brain maintenance mechanisms, which could have predictive clinical value. Conversely, others have concluded that rest dFC is mostly the result of sampling variability, head motion or fluctuating sleep states. Here, we present novel analyses suggesting that rest dFC is influenced by short periods of spontaneous cognitive-task-like processes, and that the cognitive nature of such mental processes can be inferred blindly from the data. As such, several different behaviorally relevant whole-brain FC configurations may occur during a single rest scan even when subjects were continuously awake and displayed minimal motion. In addition, using low dimensional embeddings as visualization aids, we show how FC states-commonly used to summarize and interpret resting dFC-can accurately and robustly reveal periods of externally imposed tasks; however, they may be less effective in capturing periods of distinct cognition during rest.</AbstractText
Magnetic resonance fingerprinting (MRF) is a relatively new multi-parametric quantitative imaging method that involves a two-step process: (i) reconstructing a series of time frames from highly-undersampled non-Cartesian spiral k-space data and (ii) pattern matching using the time frames to infer tissue properties (e.g., <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
Disrupted Pallido-Thalamo-Cortical Functional Connectivity in Chronic Disorders of Consciousness. Chronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals.</AbstractText
Imaging the spontaneous flow of thought: Distinct periods of cognition contribute to dynamic functional connectivity during rest. Brain functional connectivity (FC) changes have been measured across seconds using fMRI. This is true for both rest and task scenarios. Moreover, it is well accepted that task engagement alters FC, and that dynamic estimates of FC during and before task events can help predict their nature and performance. Yet, when it comes to dynamic FC (dFC) during rest, there is no consensus about its origin or significance. Some argue that rest dFC reflects fluctuations in on-going cognition, or is a manifestation of intrinsic brain maintenance mechanisms, which could have predictive clinical value. Conversely, others have concluded that rest dFC is mostly the result of sampling variability, head motion or fluctuating sleep states. Here, we present novel analyses suggesting that rest dFC is influenced by short periods of spontaneous cognitive-task-like processes, and that the cognitive nature of such mental processes can be inferred blindly from the data. As such, several different behaviorally relevant whole-brain FC configurations may occur during a single rest scan even when subjects were continuously awake and displayed minimal motion. In addition, using low dimensional embeddings as visualization aids, we show how FC states-commonly used to summarize and interpret resting dFC-can accurately and robustly reveal periods of externally imposed tasks; however, they may be less effective in capturing periods of distinct cognition during rest.</AbstractText
Real-Time Mapping of Tissue Properties for Magnetic Resonance Fingerprinting. Magnetic resonance fingerprinting (MRF) is a relatively new multi-parametric quantitative imaging method that involves a two-step process: (i) reconstructing a series of time frames from highly-undersampled non-Cartesian spiral k-space data and (ii) pattern matching using the time frames to infer tissue properties (e.g., <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
33091822
36348265
33941231
Intraindividual reaction time variability as an index of attentional control acts as a moderator of the longitudinal relationships between marital quality and children's externalizing problems.
Negative and positive templates: Two forms of cued attentional control.
Pyroptosis: a new paradigm of cell death for fighting against cancer.
The current study investigated whether trial-to-trial intraindividual reaction time variability (IIRTV), which serves as an index of attentional control fluctuations, moderates the effect of marital quality at 7&#xa0;years of age on the development of children's externalizing problems from 7 to 9&#xa0;years of age (N&#xa0;=&#xa0;197). At the first assessment (T1), a flanker task was administered to children for assessing their IIRTV. The Chinese version of a marital quality questionnaire (Evaluating and Nurturing Relationship Issues, Communication, and Happiness [ENRICH]) and the Chinese version of the Child Behavior Checklist (CBCL) were completed by children's mothers to assess marital quality and children's externalizing problems. At the second and third assessments (T2 and T3), children's externalizing problems were reassessed by their mothers. Growth curve analyses showed that boys' externalizing problems were relatively high and significantly decreased over time, whereas girls' externalizing problems were relatively low and stable. Importantly, the results indicated that boys' IIRTV (but not girls' IIRTV) and parental marital quality interactively predict the concurrent and developmental trajectories of externalizing problems. Specifically, boys with greater IIRTV were found to exhibit a relatively persistent high level of externalizing problems in the context of poor parental marital quality, whereas boys with lower IIRTV were found to exhibit a relatively low level of externalizing problems over time regardless of their parental marital quality. The findings suggest that poorer attentional control indexed by greater IIRTV is a robust predictor of boys' externalizing problems and that better attentional control indexed by lower IIRTV may buffer the negative impact of adverse family environment on the development of boys' externalizing problems.</AbstractText
Our ability to control our attention to focus on goal-relevant information is critical for functioning in daily life. In addition to the typical attentional control driven by target enhancement described in most theories of attention, recent research has focused on our ability to use information about distractions maintained in working memory to direct our attention away from known distractors. Using these negative templates can improve the efficiency of attention, much in the same way as enhancing information matching search targets. However, these effects only occur for specific tasks or in specific circumstances. In this review, I will focus on our emerging understanding of the relationship between distractor ignoring from negative templates and target enhancement from positive templates. I will also highlight key remaining questions for further study.</AbstractText
Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer.</AbstractText Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1&#x3b2; (IL-1&#x3b2;) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1&#x3b2;, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies.</AbstractText In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy.</AbstractText
Intraindividual reaction time variability as an index of attentional control acts as a moderator of the longitudinal relationships between marital quality and children's externalizing problems. The current study investigated whether trial-to-trial intraindividual reaction time variability (IIRTV), which serves as an index of attentional control fluctuations, moderates the effect of marital quality at 7&#xa0;years of age on the development of children's externalizing problems from 7 to 9&#xa0;years of age (N&#xa0;=&#xa0;197). At the first assessment (T1), a flanker task was administered to children for assessing their IIRTV. The Chinese version of a marital quality questionnaire (Evaluating and Nurturing Relationship Issues, Communication, and Happiness [ENRICH]) and the Chinese version of the Child Behavior Checklist (CBCL) were completed by children's mothers to assess marital quality and children's externalizing problems. At the second and third assessments (T2 and T3), children's externalizing problems were reassessed by their mothers. Growth curve analyses showed that boys' externalizing problems were relatively high and significantly decreased over time, whereas girls' externalizing problems were relatively low and stable. Importantly, the results indicated that boys' IIRTV (but not girls' IIRTV) and parental marital quality interactively predict the concurrent and developmental trajectories of externalizing problems. Specifically, boys with greater IIRTV were found to exhibit a relatively persistent high level of externalizing problems in the context of poor parental marital quality, whereas boys with lower IIRTV were found to exhibit a relatively low level of externalizing problems over time regardless of their parental marital quality. The findings suggest that poorer attentional control indexed by greater IIRTV is a robust predictor of boys' externalizing problems and that better attentional control indexed by lower IIRTV may buffer the negative impact of adverse family environment on the development of boys' externalizing problems.</AbstractText
Negative and positive templates: Two forms of cued attentional control. Our ability to control our attention to focus on goal-relevant information is critical for functioning in daily life. In addition to the typical attentional control driven by target enhancement described in most theories of attention, recent research has focused on our ability to use information about distractions maintained in working memory to direct our attention away from known distractors. Using these negative templates can improve the efficiency of attention, much in the same way as enhancing information matching search targets. However, these effects only occur for specific tasks or in specific circumstances. In this review, I will focus on our emerging understanding of the relationship between distractor ignoring from negative templates and target enhancement from positive templates. I will also highlight key remaining questions for further study.</AbstractText
Pyroptosis: a new paradigm of cell death for fighting against cancer. Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer.</AbstractText Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1&#x3b2; (IL-1&#x3b2;) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1&#x3b2;, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies.</AbstractText In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy.</AbstractText
40195499
28394483
40595826
The selenocysteine-containing protein SELENOT maintains dopamine signaling in the midbrain to protect mice from hyperactivity disorder.
Corticobulbar projections from distinct motor cortical areas to the reticular formation in macaque monkeys.
Effect of bonding characteristics of major constituents of mineral filler-based glass fiber reinforced with epoxy composites.
Dopaminergic neuron dysfunction has been implicated in multiple neurological and psychiatric disorders. SELENOT is a selenocysteine-containing protein of the ER membrane with antioxidant and neuroprotective activities, but its pathophysiological role in dopaminergic neurons remains unclear. In this study we show that male mice with SELENOT-deficient dopaminergic neurons exhibit attention deficit/hyperactivity disorder (ADHD)-like symptoms, including hyperlocomotion, recognition memory deficits, repetitive movements, and impulsivity. Dopamine metabolism, extrasynaptic dopamine levels, spontaneous excitatory postsynaptic currents in the striatum, and electroencephalography theta power are all enhanced in these animals, while dopaminergic neurons in the substantia nigra are slightly reduced but with normal firing and cellular stress levels. Our results also indicate that the expression of dopamine transporter (DAT) is significantly reduced in the absence of SELENOT. Both the development of ADHD-like phenotypes and DAT downregulation are also observed when SELENOT is absent from the whole brain, but not when its conditional knockout is restricted to astrocytes. Mechanistically, we show that SELENOT downregulates DAT expression via interaction with SERCA2 of the ER -but not with IP3R or RYR- to regulate the ER-cytosol Ca<sup
Corticospinal and corticobulbar descending pathways act in parallel with brainstem systems, such as the reticulospinal tract, to ensure the control of voluntary movements via direct or indirect influences onto spinal motoneurons. The aim of this study was to investigate the corticobulbar projections from distinct motor cortical areas onto different nuclei of the reticular formation. Seven adult macaque monkeys were analysed for the location of corticobulbar axonal boutons, and one monkey for reticulospinal neurons' location. The anterograde tracer BDA was injected in the premotor cortex (PM), in the primary motor cortex (M1) or in the supplementary motor area (SMA), in 3, 3 and 1 monkeys respectively. BDA anterograde labelling of corticobulbar axons were analysed on brainstem histological sections and overlapped with adjacent Nissl-stained sections for cytoarchitecture. One adult monkey was analysed for retrograde CB tracer injected in C5-C8 hemispinal cord to visualise reticulospinal neurons. The corticobulbar axons formed bilateral terminal fields with boutons terminaux and en passant, which were quantified in various nuclei belonging to the Ponto-Medullary Reticular Formation (PMRF). The corticobulbar projections from both PM and SMA tended to end mainly ipsilaterally in PMRF, but contralaterally when originating from M1. Furthermore, the corticobulbar projection was less dense when originating from M1 than from non-primary motor areas (PM, SMA). The main nuclei of bouton terminals corresponded to the regions where reticulospinal neurons were located with CB retrograde tracing. In conclusion, the corticobulbar projection differs according to the motor cortical area of origin in density and laterality.</AbstractText
In the present study, attempt has been made in understanding the bonding behaviour of mineral filler when it is introduced with epoxy matrix structured with e-glass fibre at molecular level. Firstly, filler content in GFRP composite was analysed through Fourier Transform infrared spectroscopy (FTIR). Here, Silicon dioxide has been chosen as a representative for E-glass fibre as Silicon dioxide holds major part in the composition of an E-glass fibre. DFT simulation techniques has been employed to study the reaction in between them. In order to increase the binding capability, wollastonite has been introduced into the system and many possible configurations were modelled for study. Out of all the models, the model with the highest dipole moment and stability has been considered. Spectral studies such as NMR, VCD and IR studies has been done to witness the oxygen atoms in the glass fibre acted as the connecting bridge in between the silicon atoms of the glass fibre and the carbon atoms of the epoxy resin. But these alone were not enough to obtain a stable structure that was described above. The calcium atoms in the wollastonite acted as better electron bridges and support for the complex. This work majorly focusses on the interactions between epoxy resin(ly556) and SiO<sub
The selenocysteine-containing protein SELENOT maintains dopamine signaling in the midbrain to protect mice from hyperactivity disorder. Dopaminergic neuron dysfunction has been implicated in multiple neurological and psychiatric disorders. SELENOT is a selenocysteine-containing protein of the ER membrane with antioxidant and neuroprotective activities, but its pathophysiological role in dopaminergic neurons remains unclear. In this study we show that male mice with SELENOT-deficient dopaminergic neurons exhibit attention deficit/hyperactivity disorder (ADHD)-like symptoms, including hyperlocomotion, recognition memory deficits, repetitive movements, and impulsivity. Dopamine metabolism, extrasynaptic dopamine levels, spontaneous excitatory postsynaptic currents in the striatum, and electroencephalography theta power are all enhanced in these animals, while dopaminergic neurons in the substantia nigra are slightly reduced but with normal firing and cellular stress levels. Our results also indicate that the expression of dopamine transporter (DAT) is significantly reduced in the absence of SELENOT. Both the development of ADHD-like phenotypes and DAT downregulation are also observed when SELENOT is absent from the whole brain, but not when its conditional knockout is restricted to astrocytes. Mechanistically, we show that SELENOT downregulates DAT expression via interaction with SERCA2 of the ER -but not with IP3R or RYR- to regulate the ER-cytosol Ca<sup
Corticobulbar projections from distinct motor cortical areas to the reticular formation in macaque monkeys. Corticospinal and corticobulbar descending pathways act in parallel with brainstem systems, such as the reticulospinal tract, to ensure the control of voluntary movements via direct or indirect influences onto spinal motoneurons. The aim of this study was to investigate the corticobulbar projections from distinct motor cortical areas onto different nuclei of the reticular formation. Seven adult macaque monkeys were analysed for the location of corticobulbar axonal boutons, and one monkey for reticulospinal neurons' location. The anterograde tracer BDA was injected in the premotor cortex (PM), in the primary motor cortex (M1) or in the supplementary motor area (SMA), in 3, 3 and 1 monkeys respectively. BDA anterograde labelling of corticobulbar axons were analysed on brainstem histological sections and overlapped with adjacent Nissl-stained sections for cytoarchitecture. One adult monkey was analysed for retrograde CB tracer injected in C5-C8 hemispinal cord to visualise reticulospinal neurons. The corticobulbar axons formed bilateral terminal fields with boutons terminaux and en passant, which were quantified in various nuclei belonging to the Ponto-Medullary Reticular Formation (PMRF). The corticobulbar projections from both PM and SMA tended to end mainly ipsilaterally in PMRF, but contralaterally when originating from M1. Furthermore, the corticobulbar projection was less dense when originating from M1 than from non-primary motor areas (PM, SMA). The main nuclei of bouton terminals corresponded to the regions where reticulospinal neurons were located with CB retrograde tracing. In conclusion, the corticobulbar projection differs according to the motor cortical area of origin in density and laterality.</AbstractText
Effect of bonding characteristics of major constituents of mineral filler-based glass fiber reinforced with epoxy composites. In the present study, attempt has been made in understanding the bonding behaviour of mineral filler when it is introduced with epoxy matrix structured with e-glass fibre at molecular level. Firstly, filler content in GFRP composite was analysed through Fourier Transform infrared spectroscopy (FTIR). Here, Silicon dioxide has been chosen as a representative for E-glass fibre as Silicon dioxide holds major part in the composition of an E-glass fibre. DFT simulation techniques has been employed to study the reaction in between them. In order to increase the binding capability, wollastonite has been introduced into the system and many possible configurations were modelled for study. Out of all the models, the model with the highest dipole moment and stability has been considered. Spectral studies such as NMR, VCD and IR studies has been done to witness the oxygen atoms in the glass fibre acted as the connecting bridge in between the silicon atoms of the glass fibre and the carbon atoms of the epoxy resin. But these alone were not enough to obtain a stable structure that was described above. The calcium atoms in the wollastonite acted as better electron bridges and support for the complex. This work majorly focusses on the interactions between epoxy resin(ly556) and SiO<sub
39715777
29079522
38787475
Response to clozapine in treatment resistant schizophrenia is related to alterations in regional cerebral blood flow.
Image processing and Quality Control for the first 10,000 brain imaging datasets from UK Biobank.
Reshaping energy horizon of Iran: investigating economic sanctions, export diversification, and environmental resilience.
PET and SPECT studies in treatment-resistant schizophrenia (TRS) have revealed significant alterations in regional cerebral blood flow (CBF) during clozapine treatment, which may vary according to the clinical response. Here, we used the more recent MRI approach of arterial spin labelling (ASL) to evaluate regional CBF in participants with TRS (N&#x2009;=&#x2009;36) before starting treatment with clozapine compared to in healthy volunteers (N&#x2009;=&#x2009;16). We then compared CBF in the TRS group, before and after 12 weeks of treatment with clozapine (N&#x2009;=&#x2009;24); and examined the relationship of those differences against changes in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores over the treatment period. We observed widespread reductions in CBF in TRS compared to in healthy volunteers (p&#x2009;&lt;&#x2009;0.05). After covarying for global CBF and age, lower CBF in frontal and parietal regions was still evident (p&#x2009;&lt;&#x2009;0.05, FWE corrected). Clozapine treatment was associated with longitudinal decreases in CBF in the anterior cingulate cortex (ACC) (p&#x2009;&lt;&#x2009;0.05). Higher striatal CBF at baseline was associated with greater improvement in total and general symptoms following clozapine, and higher hippocampal CBF was associated with greater improvement in total and positive symptoms. Longitudinal reductions in CBF in the ACC and thalamus were associated with less improvement in negative (ACC), positive (thalamus), and total (thalamus) symptoms. These findings suggest that changes in CBF on clozapine administration in TRS may accompany symptomatic improvement, and that CBF prior to clozapine initiation may determine the degree of clinical response.</AbstractText
UK Biobank is a large-scale prospective epidemiological study with all data accessible to researchers worldwide. It is currently in the process of bringing back 100,000 of the original participants for brain, heart and body MRI, carotid ultrasound and low-dose bone/fat x-ray. The brain imaging component covers 6 modalities (T1, T2 FLAIR, susceptibility weighted MRI, Resting fMRI, Task fMRI and Diffusion MRI). Raw and processed data from the first 10,000 imaged subjects has recently been released for general research access. To help convert this data into useful summary information we have developed an automated processing and QC (Quality Control) pipeline that is available for use by other researchers. In this paper we describe the pipeline in detail, following a brief overview of UK Biobank brain imaging and the acquisition protocol. We also describe several quantitative investigations carried out as part of the development of both the imaging protocol and the processing pipeline.</AbstractText
Employing robust methodologies, including principal component analysis, autoregressive moving average, Fourier bootstrap dynamic autoregressive distributed lag, error correction model, and the Breitung-Candelon spectral Granger causality test, this study scrutinizes the impact of export diversification (EXD) on Iran's ecological footprint (EF) from 1997 to 2020, considering economic sanctions (ESI), trade openness (TOP), energy consumption per capita (ECpc), globalization (KOF), and real GDP per capita (RGDPpc). Findings consistently affirm a positive environmental impact of EXD, revealing a nuanced temporal pattern. Notably, the short-term impact (-&#x2009;0.645) is more pronounced than its long-term counterpart (-&#x2009;.020). Increased industrial activities due to globalization (10% rise) lead to 4.26% and 1.64% EF degradation in the long and short term. Conversely, due to Iran's heavy reliance on fossil fuels, a 10% rise in ECpc correlates with 1.63% and 3.81% long- and short-term environmental quality reduction. ESI demonstrates a dual impact, improving short-term environmental quality but contributing to long-term degradation. Frequency-domain causality analysis highlights EXD and KOF as short- and long-term causes of EF, ESI, and TOP as medium- to long-term causes and RGDPpc as a long-term cause. These findings emphasize the need for sustainable policies, stringent environmental standards, and a balanced approach to fostering economic growth while preserving the environment.</AbstractText
Response to clozapine in treatment resistant schizophrenia is related to alterations in regional cerebral blood flow. PET and SPECT studies in treatment-resistant schizophrenia (TRS) have revealed significant alterations in regional cerebral blood flow (CBF) during clozapine treatment, which may vary according to the clinical response. Here, we used the more recent MRI approach of arterial spin labelling (ASL) to evaluate regional CBF in participants with TRS (N&#x2009;=&#x2009;36) before starting treatment with clozapine compared to in healthy volunteers (N&#x2009;=&#x2009;16). We then compared CBF in the TRS group, before and after 12 weeks of treatment with clozapine (N&#x2009;=&#x2009;24); and examined the relationship of those differences against changes in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores over the treatment period. We observed widespread reductions in CBF in TRS compared to in healthy volunteers (p&#x2009;&lt;&#x2009;0.05). After covarying for global CBF and age, lower CBF in frontal and parietal regions was still evident (p&#x2009;&lt;&#x2009;0.05, FWE corrected). Clozapine treatment was associated with longitudinal decreases in CBF in the anterior cingulate cortex (ACC) (p&#x2009;&lt;&#x2009;0.05). Higher striatal CBF at baseline was associated with greater improvement in total and general symptoms following clozapine, and higher hippocampal CBF was associated with greater improvement in total and positive symptoms. Longitudinal reductions in CBF in the ACC and thalamus were associated with less improvement in negative (ACC), positive (thalamus), and total (thalamus) symptoms. These findings suggest that changes in CBF on clozapine administration in TRS may accompany symptomatic improvement, and that CBF prior to clozapine initiation may determine the degree of clinical response.</AbstractText
Image processing and Quality Control for the first 10,000 brain imaging datasets from UK Biobank. UK Biobank is a large-scale prospective epidemiological study with all data accessible to researchers worldwide. It is currently in the process of bringing back 100,000 of the original participants for brain, heart and body MRI, carotid ultrasound and low-dose bone/fat x-ray. The brain imaging component covers 6 modalities (T1, T2 FLAIR, susceptibility weighted MRI, Resting fMRI, Task fMRI and Diffusion MRI). Raw and processed data from the first 10,000 imaged subjects has recently been released for general research access. To help convert this data into useful summary information we have developed an automated processing and QC (Quality Control) pipeline that is available for use by other researchers. In this paper we describe the pipeline in detail, following a brief overview of UK Biobank brain imaging and the acquisition protocol. We also describe several quantitative investigations carried out as part of the development of both the imaging protocol and the processing pipeline.</AbstractText
Reshaping energy horizon of Iran: investigating economic sanctions, export diversification, and environmental resilience. Employing robust methodologies, including principal component analysis, autoregressive moving average, Fourier bootstrap dynamic autoregressive distributed lag, error correction model, and the Breitung-Candelon spectral Granger causality test, this study scrutinizes the impact of export diversification (EXD) on Iran's ecological footprint (EF) from 1997 to 2020, considering economic sanctions (ESI), trade openness (TOP), energy consumption per capita (ECpc), globalization (KOF), and real GDP per capita (RGDPpc). Findings consistently affirm a positive environmental impact of EXD, revealing a nuanced temporal pattern. Notably, the short-term impact (-&#x2009;0.645) is more pronounced than its long-term counterpart (-&#x2009;.020). Increased industrial activities due to globalization (10% rise) lead to 4.26% and 1.64% EF degradation in the long and short term. Conversely, due to Iran's heavy reliance on fossil fuels, a 10% rise in ECpc correlates with 1.63% and 3.81% long- and short-term environmental quality reduction. ESI demonstrates a dual impact, improving short-term environmental quality but contributing to long-term degradation. Frequency-domain causality analysis highlights EXD and KOF as short- and long-term causes of EF, ESI, and TOP as medium- to long-term causes and RGDPpc as a long-term cause. These findings emphasize the need for sustainable policies, stringent environmental standards, and a balanced approach to fostering economic growth while preserving the environment.</AbstractText
40761606
35702648
39993666
Cervical, Breast, and Colorectal Cancer Screening Rates Among Sexual and Gender Minority Women in Japan: Using a Nationwide Online Survey.
Assessment of association between smoking and all-cause mortality among Malaysian adult population: Findings from a retrospective cohort study.
Event-Related Spectral Perturbations differences analyzed in standard-deviant tone sequences presented in passive and active conditions.
Owing to the high mortality rates associated with cervical and breast cancers, increasing screening uptake is a priority. However, the current policy lacks consideration for sexual and gender minorities (SGMs). This study aimed to examine whether SGM women have lower take-up rates of these female-organ-specific cancers than non-SGM women by investigating the difference in screening frequency between them. Additionally, colorectal cancer screening was used as another outcome to determine whether the results were unique to female-organ-specific cancers.</AbstractText This cross-sectional study was conducted using a nationwide online survey in 2023. Information from women aged 20-69 years was used, with a sample size of 12,305, including 1371 SGM and 10,934 non-SGM individuals. As an outcome variable, the careening take-up of cervical and breast cancers was used, sex-specific cancer and being screened in Obstetrics and Gynecology, colorectal cancer, which is non-sex specific, and the screening is conducted at home.</AbstractText Considering demographic characteristics and socioeconomic status as constants, a lower likelihood of screening for cervical and breast cancer was observed in SGM women than in non-SGM women (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.69-0.88 for cervical cancer, and OR 0.77; 95% CI 0.64-0.93 for breast cancer). No difference was found between SGM and non-SGM women in colorectal cancer screening (OR 0.96; 95% CI 0.80-1.16).</AbstractText This study highlights the sexual orientation and gender identity gap in the frequency of cervical and breast cancer screenings but not in colorectal cancer screenings. This study highlights the potential barriers faced by SGM women, emphasizing the importance of raising awareness of the unique healthcare challenges, particularly concerning female-organ-specific cancers.</AbstractText
Smoking is a known risk factor for many chronic diseases. Illness and death due to smoking are a significant public health burden in many countries. This study aims to address the information gap in smoking-related mortality in Malaysia by estimating the risk of cardiovascular disease and all-cause mortalities due to smoking among Malaysian adults.</AbstractText We analyzed data on 2525 respondents, aged 24-64 years, of the Malaysian Non-Communicable Disease Surveillance survey conducted September 2005 to February 2006. Mortality records from the Malaysian National Registration Department were linked to the MYNCDS-1 data to determine respondents' mortality status over 12 years from 2006 to 2018. Associations between smoking and all-cause mortalities were assessed using Cox proportional hazards regression with adjustments for non-communicable disease and sociodemographic and lifestyle factors.</AbstractText The prevalence of daily smoking was 21.2% (95% CI: 19.0-23.7). During the 31668 person-years follow-up, 213 deaths from all causes occurred, where 68 deaths were among smokers (13.2%), and 452 were among non-smokers (6.3%). Smoking was associated with a significantly increased risk of all-cause mortality (adjusted hazard ration, AHR=1.79; 95% CI: 1.12- 2.97). These associations remained significant after excluding mortalities in the first two years of follow-up.</AbstractText Daily smoking is associated with a significantly higher risk of all-cause death. Behavioral and pharmacological smoking cessation interventions should be intensified among smokers to reduce the risk of mortality.</AbstractText
The predictive coding theory, although a well-supported framework for understanding brain processing, remains elusive regarding how different brain rhythms contribute to error prediction and modify the a priori probabilities of predictive events. This study addresses this issue by analyzing Event-Related Spectral Perturbations (ERSP) generated during an auditory oddball paradigm presented in both a passive and active condition. The design involved sequences of four tones, where the last tone was either predictable (standard, S), completing the scale, or less predictable (deviant, D) when the first tone was occasionally repeated. In the passive condition, participants were instructed to ignore the sounds, whereas, in the active condition, they were asked to press the up or down arrow on a keyboard depending on whether the last tone of the sequence presented a higher or lower frequency than the previous one. This experimental design aimed to bias cognitive processing towards predictable (S) or unpredictable scenarios (D) in two different conditions: passive and attentional. EEG data from 13 channels were analyzed with Morlet wavelets, revealing event-related synchronization (ERS) and desynchronization (ERD) induced by the stimuli. Early theta activity was key in computing prediction errors and updating next-trial expectations. In the active condition, theta responses were higher in D than in S trials, indicating enhanced prediction error processing with attention. Early beta activity also increased during D, likely reflecting motor adjustments. These findings emphasize the critical role of early theta rhythms and the amplifying effect of attention on prediction error processing.</AbstractText
Cervical, Breast, and Colorectal Cancer Screening Rates Among Sexual and Gender Minority Women in Japan: Using a Nationwide Online Survey. Owing to the high mortality rates associated with cervical and breast cancers, increasing screening uptake is a priority. However, the current policy lacks consideration for sexual and gender minorities (SGMs). This study aimed to examine whether SGM women have lower take-up rates of these female-organ-specific cancers than non-SGM women by investigating the difference in screening frequency between them. Additionally, colorectal cancer screening was used as another outcome to determine whether the results were unique to female-organ-specific cancers.</AbstractText This cross-sectional study was conducted using a nationwide online survey in 2023. Information from women aged 20-69 years was used, with a sample size of 12,305, including 1371 SGM and 10,934 non-SGM individuals. As an outcome variable, the careening take-up of cervical and breast cancers was used, sex-specific cancer and being screened in Obstetrics and Gynecology, colorectal cancer, which is non-sex specific, and the screening is conducted at home.</AbstractText Considering demographic characteristics and socioeconomic status as constants, a lower likelihood of screening for cervical and breast cancer was observed in SGM women than in non-SGM women (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.69-0.88 for cervical cancer, and OR 0.77; 95% CI 0.64-0.93 for breast cancer). No difference was found between SGM and non-SGM women in colorectal cancer screening (OR 0.96; 95% CI 0.80-1.16).</AbstractText This study highlights the sexual orientation and gender identity gap in the frequency of cervical and breast cancer screenings but not in colorectal cancer screenings. This study highlights the potential barriers faced by SGM women, emphasizing the importance of raising awareness of the unique healthcare challenges, particularly concerning female-organ-specific cancers.</AbstractText
Assessment of association between smoking and all-cause mortality among Malaysian adult population: Findings from a retrospective cohort study. Smoking is a known risk factor for many chronic diseases. Illness and death due to smoking are a significant public health burden in many countries. This study aims to address the information gap in smoking-related mortality in Malaysia by estimating the risk of cardiovascular disease and all-cause mortalities due to smoking among Malaysian adults.</AbstractText We analyzed data on 2525 respondents, aged 24-64 years, of the Malaysian Non-Communicable Disease Surveillance survey conducted September 2005 to February 2006. Mortality records from the Malaysian National Registration Department were linked to the MYNCDS-1 data to determine respondents' mortality status over 12 years from 2006 to 2018. Associations between smoking and all-cause mortalities were assessed using Cox proportional hazards regression with adjustments for non-communicable disease and sociodemographic and lifestyle factors.</AbstractText The prevalence of daily smoking was 21.2% (95% CI: 19.0-23.7). During the 31668 person-years follow-up, 213 deaths from all causes occurred, where 68 deaths were among smokers (13.2%), and 452 were among non-smokers (6.3%). Smoking was associated with a significantly increased risk of all-cause mortality (adjusted hazard ration, AHR=1.79; 95% CI: 1.12- 2.97). These associations remained significant after excluding mortalities in the first two years of follow-up.</AbstractText Daily smoking is associated with a significantly higher risk of all-cause death. Behavioral and pharmacological smoking cessation interventions should be intensified among smokers to reduce the risk of mortality.</AbstractText
Event-Related Spectral Perturbations differences analyzed in standard-deviant tone sequences presented in passive and active conditions. The predictive coding theory, although a well-supported framework for understanding brain processing, remains elusive regarding how different brain rhythms contribute to error prediction and modify the a priori probabilities of predictive events. This study addresses this issue by analyzing Event-Related Spectral Perturbations (ERSP) generated during an auditory oddball paradigm presented in both a passive and active condition. The design involved sequences of four tones, where the last tone was either predictable (standard, S), completing the scale, or less predictable (deviant, D) when the first tone was occasionally repeated. In the passive condition, participants were instructed to ignore the sounds, whereas, in the active condition, they were asked to press the up or down arrow on a keyboard depending on whether the last tone of the sequence presented a higher or lower frequency than the previous one. This experimental design aimed to bias cognitive processing towards predictable (S) or unpredictable scenarios (D) in two different conditions: passive and attentional. EEG data from 13 channels were analyzed with Morlet wavelets, revealing event-related synchronization (ERS) and desynchronization (ERD) induced by the stimuli. Early theta activity was key in computing prediction errors and updating next-trial expectations. In the active condition, theta responses were higher in D than in S trials, indicating enhanced prediction error processing with attention. Early beta activity also increased during D, likely reflecting motor adjustments. These findings emphasize the critical role of early theta rhythms and the amplifying effect of attention on prediction error processing.</AbstractText
36217831
31849148
35408042
Rates of rare copy number variants in different circumstances among patients with genetic developmental and epileptic encephalopathy.
Dynamic changes of amplitude of low-frequency fluctuations in patients with generalized anxiety disorder.
Joint Error Estimation and Calibration Method of Memory Nonlinear Mismatch for a Four-Channel 16-Bit TIADC System.
Most patients with developmental and epileptic encephalopathy (DEE) have genetic etiology, which has been uncovered with different methods. Although chromosomal microarray analysis (CMA) has been broadly used in patients with DEE, data is still limited.</AbstractText Among 560 children (&lt;18 years) who underwent CMA in our hospital between January 2013 and June 2021, 146 patients with developmental delay and recurrent seizures were screened. Patients with major brain abnormalities, metabolic abnormalities, and specific syndromes were excluded. The rate of rare copy number variants (CNVs) was estimated in total and according to seizure-onset age, relation to first seizure with the diagnosis of developmental delay, epilepsy syndromes, and organ anomalies.</AbstractText Among the 110 patients enrolled, the rate of rare CNVs was 16.4%, varying by seizure-onset age: 33.3% in three neonates, 21.2% in 33 infants, 13.3% in 45 early childhood patients, 5.3% in 19 late childhood patients, and 30.0% in 10 adolescents. In relation to the first seizure with the diagnosis of developmental delay, the rates were 3.7%, 22.2%, and 12.5% in "before", "after", and "concurrent" subclasses, respectively. The rates of rare CNVs were 16.7% in "other predominantly focal or multifocal epilepsy", 28.6% in "other predominantly generalized epilepsy (PGE)", and 15.4% in West syndrome. The rates were 27.8% in minor brain anomalies, 37.5% in facial dysmorphism, and 22.2%, 20.0%, and 57.1% in endocrine, genitourinary and cardiovascular anomalies, respectively.</AbstractText The rate of rare CNVs in patients with genetic DEE was 16.4% in total, which was higher in seizures occurring below the infantile period or after the diagnosis of developmental delay, in PGE, and in the presence of facial dysmorphism or cardiovascular anomalies.</AbstractText
Previous neuroimaging studies have mainly focused on alterations of static and dynamic functional connectivity in patients with generalized anxiety disorder (GAD). However, the characteristics of local brain activity over time in GAD are poorly understood. This study aimed to investigate the abnormal time-varying local brain activity of GAD by using the amplitude of low-frequency fluctuation (ALFF) method combined with sliding-window approach. Group comparison results showed that compared with healthy controls (HCs), patients with GAD exhibited increased dynamic ALFF (dALFF) variability in widespread regions, including the bilateral dorsomedial prefrontal cortex, hippocampus, thalamus, striatum; and left orbital frontal gyrus, inferior parietal lobule, temporal pole, inferior temporal gyrus, and fusiform gyrus. The abnormal dALFF could be used to distinguish between patients with GAD and HCs. Increased dALFF variability values in the striatum were positively correlated with GAD symptom severity. These findings suggest that GAD patients are associated with abnormal temporal variability of local brain activity in regions implicated in executive, emotional, and social function. This study provides insight into the brain dysfunction of GAD from the perspective of dynamic local brain activity, highlighting the important role of dALFF variability in understanding neurophysiological mechanisms and potentially informing the diagnosis of GAD.</AbstractText
Memory nonlinear error greatly reduces the performance of analog-to-digital converters (ADCs), and this effect is more serious in a time-interleaved analog-to-digital converter (TIADC) system. In this study, the sinusoidal wave fitting method was adopted and a joint error estimation method was proposed to address the memory nonlinear mismatch problem of the current TIADC system. This method divides the nonlinear error estimation method into two steps: the nonlinear mismatch error is coarsely estimated offline using the least squares (LS) method, and then accurately estimated online using the recursive least squares (RLS) method. After the estimation, digital post-compensation method is adopted. The obtained error parameters are used to reconstruct the error and then the reconstructed error is reduced at the output. This study used a four-channel 16-bit TIADC system with an effective number of bits (ENOB) value of 10.06 bits after the introduction of a memory nonlinearity error, which was increased to 15.42 bits after calibration by the joint error estimation method. As a result, the spurious-free dynamic range (SFDR) increased by 36.22 dB. This error estimation method can improve the error estimation accuracy and reduce the hardware complexity of implementing the error estimation system using a field programmable gate array (FPGA).</AbstractText
Rates of rare copy number variants in different circumstances among patients with genetic developmental and epileptic encephalopathy. Most patients with developmental and epileptic encephalopathy (DEE) have genetic etiology, which has been uncovered with different methods. Although chromosomal microarray analysis (CMA) has been broadly used in patients with DEE, data is still limited.</AbstractText Among 560 children (&lt;18 years) who underwent CMA in our hospital between January 2013 and June 2021, 146 patients with developmental delay and recurrent seizures were screened. Patients with major brain abnormalities, metabolic abnormalities, and specific syndromes were excluded. The rate of rare copy number variants (CNVs) was estimated in total and according to seizure-onset age, relation to first seizure with the diagnosis of developmental delay, epilepsy syndromes, and organ anomalies.</AbstractText Among the 110 patients enrolled, the rate of rare CNVs was 16.4%, varying by seizure-onset age: 33.3% in three neonates, 21.2% in 33 infants, 13.3% in 45 early childhood patients, 5.3% in 19 late childhood patients, and 30.0% in 10 adolescents. In relation to the first seizure with the diagnosis of developmental delay, the rates were 3.7%, 22.2%, and 12.5% in "before", "after", and "concurrent" subclasses, respectively. The rates of rare CNVs were 16.7% in "other predominantly focal or multifocal epilepsy", 28.6% in "other predominantly generalized epilepsy (PGE)", and 15.4% in West syndrome. The rates were 27.8% in minor brain anomalies, 37.5% in facial dysmorphism, and 22.2%, 20.0%, and 57.1% in endocrine, genitourinary and cardiovascular anomalies, respectively.</AbstractText The rate of rare CNVs in patients with genetic DEE was 16.4% in total, which was higher in seizures occurring below the infantile period or after the diagnosis of developmental delay, in PGE, and in the presence of facial dysmorphism or cardiovascular anomalies.</AbstractText
Dynamic changes of amplitude of low-frequency fluctuations in patients with generalized anxiety disorder. Previous neuroimaging studies have mainly focused on alterations of static and dynamic functional connectivity in patients with generalized anxiety disorder (GAD). However, the characteristics of local brain activity over time in GAD are poorly understood. This study aimed to investigate the abnormal time-varying local brain activity of GAD by using the amplitude of low-frequency fluctuation (ALFF) method combined with sliding-window approach. Group comparison results showed that compared with healthy controls (HCs), patients with GAD exhibited increased dynamic ALFF (dALFF) variability in widespread regions, including the bilateral dorsomedial prefrontal cortex, hippocampus, thalamus, striatum; and left orbital frontal gyrus, inferior parietal lobule, temporal pole, inferior temporal gyrus, and fusiform gyrus. The abnormal dALFF could be used to distinguish between patients with GAD and HCs. Increased dALFF variability values in the striatum were positively correlated with GAD symptom severity. These findings suggest that GAD patients are associated with abnormal temporal variability of local brain activity in regions implicated in executive, emotional, and social function. This study provides insight into the brain dysfunction of GAD from the perspective of dynamic local brain activity, highlighting the important role of dALFF variability in understanding neurophysiological mechanisms and potentially informing the diagnosis of GAD.</AbstractText
Joint Error Estimation and Calibration Method of Memory Nonlinear Mismatch for a Four-Channel 16-Bit TIADC System. Memory nonlinear error greatly reduces the performance of analog-to-digital converters (ADCs), and this effect is more serious in a time-interleaved analog-to-digital converter (TIADC) system. In this study, the sinusoidal wave fitting method was adopted and a joint error estimation method was proposed to address the memory nonlinear mismatch problem of the current TIADC system. This method divides the nonlinear error estimation method into two steps: the nonlinear mismatch error is coarsely estimated offline using the least squares (LS) method, and then accurately estimated online using the recursive least squares (RLS) method. After the estimation, digital post-compensation method is adopted. The obtained error parameters are used to reconstruct the error and then the reconstructed error is reduced at the output. This study used a four-channel 16-bit TIADC system with an effective number of bits (ENOB) value of 10.06 bits after the introduction of a memory nonlinearity error, which was increased to 15.42 bits after calibration by the joint error estimation method. As a result, the spurious-free dynamic range (SFDR) increased by 36.22 dB. This error estimation method can improve the error estimation accuracy and reduce the hardware complexity of implementing the error estimation system using a field programmable gate array (FPGA).</AbstractText
38167418
26899433
38683407
Fully endoscopic far-lateral supracerebellar infratentorial approach for trigeminal neuralgia: illustrative case reports.
Reduced volume of gray matter in patients with trigeminal neuralgia.
Assessing the possible association between MTHFR (rs1801133) and GPx-1 (rs1050450) polymorphisms with the risk of type 2 diabetes, diabetic neuropathy, and diabetic retinopathy.
Trigeminal neuralgia (TN) is a common cause of craniofacial pain. The retrosigmoid approach is usually used to treat TN, but no cases of endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) were used to undergo operation for TN.</AbstractText Two patients were presented with severe facial pain and preliminary diagnosis was TN. Preoperative magnetic resonance imaging revealed that a superior cerebellar artery (SCA) compressed the trigeminal nerve in case 1, and a tumor located in the petrous apex extending into the Meckel's cave compressed the trigeminal nerve in case 2. Operations were achieved through the EF-SCITA. The pain was totally relieved with no postsurgical complications in both cases.</AbstractText We present the first two case reports of EF-SCITA to relieve classical and secondary TN successfully. The EF-SCITA can be a promising approach for treating TN.</AbstractText
Accumulating evidence from brain structural imaging studies has supported that chronic pain could induce changes in brain gray matter volume. However, few studies have focused on the gray matter alterations of Trigeminal neuralgia (TN). In this study, twenty-eight TN patients (thirteen females; mean age, 45.86&#xa0;years &#xb1;11.17) and 28 healthy controls (HC; thirteen females; mean age, 44.89&#xa0;years &#xb1;7.67) were included. Using voxel-based morphometry (VBM), we detected abnormalities in gray matter volume in the TN patients. Based on a voxel-wise analysis, the TN group showed significantly decreased gray matter volume in the bilateral superior/middle temporal gyrus (STG/MTG), bilateral parahippocampus, left anterior cingulate cortex (ACC), caudate nucleus, right fusiform gyrus, and right cerebellum compared with the HC. In addition, we found that the gray matter volume in the bilateral STG/MTG was negatively correlated with the duration of TN. These results provide compelling evidence for gray matter abnormalities in TN and suggest that the duration of TN may be a critical factor associated with brain alterations.</AbstractText
Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications.</AbstractText In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n&#x2009;=&#x2009;100), with neuropathy(n&#x2009;=&#x2009;100), and without complication (n&#x2009;=&#x2009;100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods.</AbstractText Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8&#x2009;&#xb1;&#x2009;4.5; P&#x2009;&lt;&#x2009;0.001), GPx activity (39.5&#x2009;&#xb1;&#x2009;8.5; P&#x2009;&lt;&#x2009;0.001), and TAC (703.1&#x2009;&#xb1;&#x2009;129.1; P&#x2009;=&#x2009;0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2&#x2009;&#xb1;&#x2009;2.4; p&#x2009;=&#x2009;0.02) and TAC (793.4&#x2009;&#xb1;&#x2009;124.6; P&#x2009;&lt;&#x2009;0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5&#x2009;&#xb1;&#x2009;1.1; P&#x2009;&lt;&#x2009;0.001) and OSI (0.0050&#x2009;&#xb1;&#x2009;0.001; P&#x2009;&lt;&#x2009;0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8&#x2009;&#xb1;&#x2009;2.5; P&#x2009;=&#x2009;0.02) and lower levels of TOS (3.7&#x2009;&#xb1;&#x2009;1.6; P&#x2009;&lt;&#x2009;0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P&#x2009;=&#x2009;0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR&#x2009;=&#x2009;2.7 (95% CI&#x2009;=&#x2009;1.38-5.44; P&#x2009;=&#x2009;0.0039)].</AbstractText The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.</AbstractText
Fully endoscopic far-lateral supracerebellar infratentorial approach for trigeminal neuralgia: illustrative case reports. Trigeminal neuralgia (TN) is a common cause of craniofacial pain. The retrosigmoid approach is usually used to treat TN, but no cases of endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) were used to undergo operation for TN.</AbstractText Two patients were presented with severe facial pain and preliminary diagnosis was TN. Preoperative magnetic resonance imaging revealed that a superior cerebellar artery (SCA) compressed the trigeminal nerve in case 1, and a tumor located in the petrous apex extending into the Meckel's cave compressed the trigeminal nerve in case 2. Operations were achieved through the EF-SCITA. The pain was totally relieved with no postsurgical complications in both cases.</AbstractText We present the first two case reports of EF-SCITA to relieve classical and secondary TN successfully. The EF-SCITA can be a promising approach for treating TN.</AbstractText
Reduced volume of gray matter in patients with trigeminal neuralgia. Accumulating evidence from brain structural imaging studies has supported that chronic pain could induce changes in brain gray matter volume. However, few studies have focused on the gray matter alterations of Trigeminal neuralgia (TN). In this study, twenty-eight TN patients (thirteen females; mean age, 45.86&#xa0;years &#xb1;11.17) and 28 healthy controls (HC; thirteen females; mean age, 44.89&#xa0;years &#xb1;7.67) were included. Using voxel-based morphometry (VBM), we detected abnormalities in gray matter volume in the TN patients. Based on a voxel-wise analysis, the TN group showed significantly decreased gray matter volume in the bilateral superior/middle temporal gyrus (STG/MTG), bilateral parahippocampus, left anterior cingulate cortex (ACC), caudate nucleus, right fusiform gyrus, and right cerebellum compared with the HC. In addition, we found that the gray matter volume in the bilateral STG/MTG was negatively correlated with the duration of TN. These results provide compelling evidence for gray matter abnormalities in TN and suggest that the duration of TN may be a critical factor associated with brain alterations.</AbstractText
Assessing the possible association between MTHFR (rs1801133) and GPx-1 (rs1050450) polymorphisms with the risk of type 2 diabetes, diabetic neuropathy, and diabetic retinopathy. Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications.</AbstractText In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n&#x2009;=&#x2009;100), with neuropathy(n&#x2009;=&#x2009;100), and without complication (n&#x2009;=&#x2009;100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods.</AbstractText Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8&#x2009;&#xb1;&#x2009;4.5; P&#x2009;&lt;&#x2009;0.001), GPx activity (39.5&#x2009;&#xb1;&#x2009;8.5; P&#x2009;&lt;&#x2009;0.001), and TAC (703.1&#x2009;&#xb1;&#x2009;129.1; P&#x2009;=&#x2009;0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2&#x2009;&#xb1;&#x2009;2.4; p&#x2009;=&#x2009;0.02) and TAC (793.4&#x2009;&#xb1;&#x2009;124.6; P&#x2009;&lt;&#x2009;0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5&#x2009;&#xb1;&#x2009;1.1; P&#x2009;&lt;&#x2009;0.001) and OSI (0.0050&#x2009;&#xb1;&#x2009;0.001; P&#x2009;&lt;&#x2009;0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8&#x2009;&#xb1;&#x2009;2.5; P&#x2009;=&#x2009;0.02) and lower levels of TOS (3.7&#x2009;&#xb1;&#x2009;1.6; P&#x2009;&lt;&#x2009;0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P&#x2009;=&#x2009;0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR&#x2009;=&#x2009;2.7 (95% CI&#x2009;=&#x2009;1.38-5.44; P&#x2009;=&#x2009;0.0039)].</AbstractText The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.</AbstractText
39452003
33017963
38746526
Efficient Neural Decoding Based on Multimodal Training.
Potential pitfalls of widely used implementations of common spatial patterns.
The profile of epilepsy and its characteristics in children with neurocutaneous syndromes.
Neural decoding methods are often limited by the performance of brain encoders, which map complex brain signals into a latent representation space of perception information. These brain encoders are constrained by the limited amount of paired brain and stimuli data available for training, making it challenging to learn rich neural representations.</AbstractText To address this limitation, we present a novel multimodal training approach using paired image and functional magnetic resonance imaging (fMRI) data to establish a brain masked autoencoder that learns the interactions between images and brain activities. Subsequently, we employ a diffusion model conditioned on brain data to decode realistic images.</AbstractText Our method achieves high-quality decoding results in semantic contents and low-level visual attributes, outperforming previous methods both qualitatively and quantitatively, while maintaining computational efficiency. Additionally, our method is applied to decode artificial patterns across region of interests (ROIs) to explore their functional properties. We not only validate existing knowledge concerning ROIs but also unveil new insights, such as the synergy between early visual cortex and higher-level scene ROIs, as well as the competition within the higher-level scene ROIs.</AbstractText These findings provide valuable insights for future directions in the field of neural decoding.</AbstractText
We have uncovered serious flaws in handling EEG signals with a decreased rank in implementations of the common spatial patterns (CSP). The CSP algorithm assumes covariance matrices of the signal to have full rank. However, preprocessing techniques, such as artifact removal using independent component analysis, may decrease the rank of the signal, leading to potential errors in the CSP decomposition. We inspect what could go wrong when CSP implementations do not take this into consideration on a binary motor imagery classification task. We review CSP implementations in open-source toolboxes for EEG signal analysis (FieldTrip, BBCI Toolbox, BioSig, EEGLAB, BCILAB, and MNE). We show that unprotected implementations decreased mean classification accuracy by up to 32%, with spatial filters resulting in complex numbers, for which corresponding spatial patterns do not have a clear interpretation. We encourage researchers to check their implementations and analysis pipelines.</AbstractText
The profile of seizures in neurocutaneous syndromes is variable. We aimed to define the characteristics of epilepsy in children with neurocutaneous syndromes.</AbstractText Cross-sectional study over 18 months at a tertiary care pediatric hospital, including children with neurocutaneous syndromes aged between 1 and 15 years, using the 2017-International League Against Epilepsy classification.</AbstractText In 119 children with neurocutaneous syndromes, 94 (79%) had epilepsy. In eight children with neurofibromatosis one with epilepsy, 5 (62.5%) had generalized motor tonic-clonic seizures, 1 (12.5%) had generalized motor epileptic spasms, 1 (12.5%) had generalized motor automatism, and 1 (12.5%) had a focal seizure. In 69 children with tuberous sclerosis complex with epilepsy, 30 (43.5%) had generalized motor epileptic spasms, 23 (33.3%) had focal seizures, and nine (13.0%) had generalized motor tonic-clonic seizures. In 14 children with Sturge-Weber syndrome with epilepsy, 13 (92.8%) had focal seizures, and 1 (7.2%) had generalized motor tonic seizures. Statistically significant associations were found between epilepsy and intellectual disability (<i Profiling seizures in children with neurocutaneous syndromes are paramount in devising target-specific treatments as the epileptogenesis in each syndrome differs in the molecular pathways leading to the hyperexcitability state. Further multicentric studies are required to unravel better insights into the epilepsy profile of neurocutaneous syndromes.</AbstractText
Efficient Neural Decoding Based on Multimodal Training. Neural decoding methods are often limited by the performance of brain encoders, which map complex brain signals into a latent representation space of perception information. These brain encoders are constrained by the limited amount of paired brain and stimuli data available for training, making it challenging to learn rich neural representations.</AbstractText To address this limitation, we present a novel multimodal training approach using paired image and functional magnetic resonance imaging (fMRI) data to establish a brain masked autoencoder that learns the interactions between images and brain activities. Subsequently, we employ a diffusion model conditioned on brain data to decode realistic images.</AbstractText Our method achieves high-quality decoding results in semantic contents and low-level visual attributes, outperforming previous methods both qualitatively and quantitatively, while maintaining computational efficiency. Additionally, our method is applied to decode artificial patterns across region of interests (ROIs) to explore their functional properties. We not only validate existing knowledge concerning ROIs but also unveil new insights, such as the synergy between early visual cortex and higher-level scene ROIs, as well as the competition within the higher-level scene ROIs.</AbstractText These findings provide valuable insights for future directions in the field of neural decoding.</AbstractText
Potential pitfalls of widely used implementations of common spatial patterns. We have uncovered serious flaws in handling EEG signals with a decreased rank in implementations of the common spatial patterns (CSP). The CSP algorithm assumes covariance matrices of the signal to have full rank. However, preprocessing techniques, such as artifact removal using independent component analysis, may decrease the rank of the signal, leading to potential errors in the CSP decomposition. We inspect what could go wrong when CSP implementations do not take this into consideration on a binary motor imagery classification task. We review CSP implementations in open-source toolboxes for EEG signal analysis (FieldTrip, BBCI Toolbox, BioSig, EEGLAB, BCILAB, and MNE). We show that unprotected implementations decreased mean classification accuracy by up to 32%, with spatial filters resulting in complex numbers, for which corresponding spatial patterns do not have a clear interpretation. We encourage researchers to check their implementations and analysis pipelines.</AbstractText
The profile of epilepsy and its characteristics in children with neurocutaneous syndromes. The profile of seizures in neurocutaneous syndromes is variable. We aimed to define the characteristics of epilepsy in children with neurocutaneous syndromes.</AbstractText Cross-sectional study over 18 months at a tertiary care pediatric hospital, including children with neurocutaneous syndromes aged between 1 and 15 years, using the 2017-International League Against Epilepsy classification.</AbstractText In 119 children with neurocutaneous syndromes, 94 (79%) had epilepsy. In eight children with neurofibromatosis one with epilepsy, 5 (62.5%) had generalized motor tonic-clonic seizures, 1 (12.5%) had generalized motor epileptic spasms, 1 (12.5%) had generalized motor automatism, and 1 (12.5%) had a focal seizure. In 69 children with tuberous sclerosis complex with epilepsy, 30 (43.5%) had generalized motor epileptic spasms, 23 (33.3%) had focal seizures, and nine (13.0%) had generalized motor tonic-clonic seizures. In 14 children with Sturge-Weber syndrome with epilepsy, 13 (92.8%) had focal seizures, and 1 (7.2%) had generalized motor tonic seizures. Statistically significant associations were found between epilepsy and intellectual disability (<i Profiling seizures in children with neurocutaneous syndromes are paramount in devising target-specific treatments as the epileptogenesis in each syndrome differs in the molecular pathways leading to the hyperexcitability state. Further multicentric studies are required to unravel better insights into the epilepsy profile of neurocutaneous syndromes.</AbstractText
40747570
40430848
40460399
Peanut butter confirmed as the source in a case of infant botulism, United Kingdom, 2024.
Transforming Pharmacogenomics and CRISPR Gene Editing with the Power of Artificial Intelligence for Precision Medicine.
Construct Validity of the Amyotrophic Lateral Sclerosis Bulbar Dysfunction Index-Remote.
A 6-month-old infant was hospitalised with suspected infant botulism after being given peanut butter to reduce their risk of developing peanut allergy. <i
<b
The Amyotrophic Lateral Sclerosis Bulbar Dysfunction Index-Remote (ALSBDI-R) is a clinician-administered tool designed to assess bulbar dysfunction remotely in patients with amyotrophic lateral sclerosis (ALS). This study aimed to evaluate the construct validity of the ALSBDI-R by examining its correlation with established clinical measures and its ability to discriminate among different bulbar disease severities.</AbstractText A total of 92 patients with ALS were recruited from two multidisciplinary clinics. Participants were assessed using the ALSBDI-R, the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), the Center for Neurologic Study Bulbar Function Scale (CNS-BFS), the Sentence Intelligibility Test, and the Eating Assessment Tool (EAT-10). Construct validity was established through Spearman correlations and comparison of ALSBDI-R scores across bulbar severity groups (asymptomatic, mild, moderate, severe).</AbstractText Strong correlations were found between ALSBDI-R total scores and bulbar-specific measures such as ALSFRS-R bulbar subscore (<i The ALSBDI-R is a valid tool for remotely assessing bulbar dysfunction in patients with ALS. Despite several limitations, its ability to capture varying degrees of severity makes it valuable for clinical use and research, offering a standardized approach to monitor disease progression remotely.</AbstractText
Peanut butter confirmed as the source in a case of infant botulism, United Kingdom, 2024. A 6-month-old infant was hospitalised with suspected infant botulism after being given peanut butter to reduce their risk of developing peanut allergy. <i
Transforming Pharmacogenomics and CRISPR Gene Editing with the Power of Artificial Intelligence for Precision Medicine. <b
Construct Validity of the Amyotrophic Lateral Sclerosis Bulbar Dysfunction Index-Remote. The Amyotrophic Lateral Sclerosis Bulbar Dysfunction Index-Remote (ALSBDI-R) is a clinician-administered tool designed to assess bulbar dysfunction remotely in patients with amyotrophic lateral sclerosis (ALS). This study aimed to evaluate the construct validity of the ALSBDI-R by examining its correlation with established clinical measures and its ability to discriminate among different bulbar disease severities.</AbstractText A total of 92 patients with ALS were recruited from two multidisciplinary clinics. Participants were assessed using the ALSBDI-R, the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), the Center for Neurologic Study Bulbar Function Scale (CNS-BFS), the Sentence Intelligibility Test, and the Eating Assessment Tool (EAT-10). Construct validity was established through Spearman correlations and comparison of ALSBDI-R scores across bulbar severity groups (asymptomatic, mild, moderate, severe).</AbstractText Strong correlations were found between ALSBDI-R total scores and bulbar-specific measures such as ALSFRS-R bulbar subscore (<i The ALSBDI-R is a valid tool for remotely assessing bulbar dysfunction in patients with ALS. Despite several limitations, its ability to capture varying degrees of severity makes it valuable for clinical use and research, offering a standardized approach to monitor disease progression remotely.</AbstractText
19449788
15082333
18705579
Equifinality, multifinality, and the rediscovery of the importance of early experiences: pathways from early adversity to psychiatric and (functional) somatic disorders.
Current directions in social cognitive neuroscience.
Subcutaneous linea alba fasciotomy: a less morbid treatment for abdominal compartment syndrome.
Most current mainstream research, diagnostic assessment, and treatment strategies focus on specific psychiatric disorders--on diagnoses that are based on manifest symptoms within a categorical, atheoretical approach. This disorder-centered approach has been antithetical to psychoanalytic views, which are fundamentally person centered, focusing on the dynamics of individual lives. Growing realization of the high comorbidity among psychiatric disorders has led to the need to include developmental considerations and hierarchical models in the classification and treatment of psychopathology. In addition, this realization has led to a renewed interest in the principles of equifinality and multifinality--that a given end state can be the result of different developmental paths and that similar developmental factors may lead to dissimilar outcomes. In this chapter these developments are illustrated by research on the impact of early adversity, a central domain in psychoanalytic thought. Findings from various strands of research in the neurosciences and genetic research, in particular, suggest that early adversity leads to vulnerability for a wide variety of both psychiatric and (functional) somatic disorders. These findings have contributed to the rediscovery of the importance of early experiences more generally and to the need for a broad developmental perspective. In this context, we also discuss the danger of reductionism associated with the growing influence and popularity of affective neuroscience and genetics as well as the vital role a psychoanalytic perspective might play in countering this reductionism by reestablishing the importance of meaning and meaning making in understanding and treating patients with a history of early adversity. In particular, we focus on the importance of narrative and mental representations in the development of the capacity for mentalization in these patients.</AbstractText
Social cognitive neuroscience is an emerging discipline that seeks to explain the psychological and neural bases of socioemotional experience and behavior. Although research in some areas is already well developed (e.g. perception of nonverbal social cues) investigation in other areas has only just begun (e.g. social interaction). Current studies are elucidating; the role of the amygdala in a variety of evaluative and social judgment processes, the role of medial prefrontal cortex in mental state attribution, how frontally mediated controlled processes can regulate perception and experience, and the way in which these and other systems are recruited during social interaction. Future progress will depend upon the development of programmatic lines of research that integrate contemporary social cognitive research with cognitive neuroscience theory and methodology.</AbstractText
Abdominal compartment syndrome is a cause of significant morbidity and mortality among surgical patients. It has traditionally been treated by abdominal decompression with the associated risks of chronic incisional hernia and enteroatmospheric fistula. Subcutaneous linea alba fasciotomy has recently been described as a new surgical technique for the treatment of abdominal compartment syndrome secondary to acute pancreatitis. This technique reduces intraabdominal pressure and restores organ function while maintaining the skin and peritoneum intact for visceral protection. We describe the application of subcutaneous linea alba fasciotomy as a safe and effective alternative for the surgical management of abdominal compartment syndrome in a traumatically injured patient refractory to comprehensive medical interventions.</AbstractText
Equifinality, multifinality, and the rediscovery of the importance of early experiences: pathways from early adversity to psychiatric and (functional) somatic disorders. Most current mainstream research, diagnostic assessment, and treatment strategies focus on specific psychiatric disorders--on diagnoses that are based on manifest symptoms within a categorical, atheoretical approach. This disorder-centered approach has been antithetical to psychoanalytic views, which are fundamentally person centered, focusing on the dynamics of individual lives. Growing realization of the high comorbidity among psychiatric disorders has led to the need to include developmental considerations and hierarchical models in the classification and treatment of psychopathology. In addition, this realization has led to a renewed interest in the principles of equifinality and multifinality--that a given end state can be the result of different developmental paths and that similar developmental factors may lead to dissimilar outcomes. In this chapter these developments are illustrated by research on the impact of early adversity, a central domain in psychoanalytic thought. Findings from various strands of research in the neurosciences and genetic research, in particular, suggest that early adversity leads to vulnerability for a wide variety of both psychiatric and (functional) somatic disorders. These findings have contributed to the rediscovery of the importance of early experiences more generally and to the need for a broad developmental perspective. In this context, we also discuss the danger of reductionism associated with the growing influence and popularity of affective neuroscience and genetics as well as the vital role a psychoanalytic perspective might play in countering this reductionism by reestablishing the importance of meaning and meaning making in understanding and treating patients with a history of early adversity. In particular, we focus on the importance of narrative and mental representations in the development of the capacity for mentalization in these patients.</AbstractText
Current directions in social cognitive neuroscience. Social cognitive neuroscience is an emerging discipline that seeks to explain the psychological and neural bases of socioemotional experience and behavior. Although research in some areas is already well developed (e.g. perception of nonverbal social cues) investigation in other areas has only just begun (e.g. social interaction). Current studies are elucidating; the role of the amygdala in a variety of evaluative and social judgment processes, the role of medial prefrontal cortex in mental state attribution, how frontally mediated controlled processes can regulate perception and experience, and the way in which these and other systems are recruited during social interaction. Future progress will depend upon the development of programmatic lines of research that integrate contemporary social cognitive research with cognitive neuroscience theory and methodology.</AbstractText
Subcutaneous linea alba fasciotomy: a less morbid treatment for abdominal compartment syndrome. Abdominal compartment syndrome is a cause of significant morbidity and mortality among surgical patients. It has traditionally been treated by abdominal decompression with the associated risks of chronic incisional hernia and enteroatmospheric fistula. Subcutaneous linea alba fasciotomy has recently been described as a new surgical technique for the treatment of abdominal compartment syndrome secondary to acute pancreatitis. This technique reduces intraabdominal pressure and restores organ function while maintaining the skin and peritoneum intact for visceral protection. We describe the application of subcutaneous linea alba fasciotomy as a safe and effective alternative for the surgical management of abdominal compartment syndrome in a traumatically injured patient refractory to comprehensive medical interventions.</AbstractText
25496724
18828447
26223371
Stereochemistry and neuropharmacology of a 'bath salt' cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates.
A BOLD-fMRI study of cerebral activation induced by injection of algesic chemical substances into the anesthetized rat forepaw.
Quantitative MR Imaging of Brain Tissue and Brain Pathologies.
Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100-1000 &#x3bc;M) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 &#x3bc;M) and racemate (100 &#x3bc;M) produced EPC, but S-MEPH was ineffective at all concentrations (10-100 &#x3bc;M). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 &#x3bc;M) produced EPC that was abolished when S-MEPH (100 &#x3bc;M) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 &#x3bc;M) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10-250 &#x3bc;M). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own.</AbstractText
This study was performed to examine whether the brain activities induced by noxious algesic chemical substances in anesthetized animals could be detected by blood oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI). Multislice gradient echo images of the primary somatosensory cortex were obtained using a 7.05 T superconducting system and a one-turned surface coil centered over the primary somatosensory cortex of the 1.0%-isoflurane-anesthetized rat. The Z-score t-map of BOLD signals and its time-course analysis revealed that subcutaneous injection of formalin into the left forepaw immediately induced an early response in the contralateral primary sensory cortex lasting for a few minutes, followed by a late response until 20 min after stimulation. In contrast, injection of capsaicin into the left forepaw evoked only the early response. Furthermore, pretreatment with morphine completely abolished these responses induced by the chemical algesic substances. Thus BOLD-fMRI is a useful method to analyze the brain activities of painful stimulation in anesthetized animals.</AbstractText
Measurement of basic quantitative magnetic resonance (MR) parameters (e.g., relaxation times T1, T2*, T2 or respective rates R (1/T)) corrected for radiofrequency (RF) coil bias yields different conventional and new tissue contrasts as well as volumes for tissue segmentation. This approach also provides quantitative measures of microstructural and functional tissue changes. We herein demonstrate some prospects of quantitative MR imaging in neurological diagnostics and science.</AbstractText
Stereochemistry and neuropharmacology of a 'bath salt' cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates. Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100-1000 &#x3bc;M) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 &#x3bc;M) and racemate (100 &#x3bc;M) produced EPC, but S-MEPH was ineffective at all concentrations (10-100 &#x3bc;M). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 &#x3bc;M) produced EPC that was abolished when S-MEPH (100 &#x3bc;M) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 &#x3bc;M) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10-250 &#x3bc;M). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own.</AbstractText
A BOLD-fMRI study of cerebral activation induced by injection of algesic chemical substances into the anesthetized rat forepaw. This study was performed to examine whether the brain activities induced by noxious algesic chemical substances in anesthetized animals could be detected by blood oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI). Multislice gradient echo images of the primary somatosensory cortex were obtained using a 7.05 T superconducting system and a one-turned surface coil centered over the primary somatosensory cortex of the 1.0%-isoflurane-anesthetized rat. The Z-score t-map of BOLD signals and its time-course analysis revealed that subcutaneous injection of formalin into the left forepaw immediately induced an early response in the contralateral primary sensory cortex lasting for a few minutes, followed by a late response until 20 min after stimulation. In contrast, injection of capsaicin into the left forepaw evoked only the early response. Furthermore, pretreatment with morphine completely abolished these responses induced by the chemical algesic substances. Thus BOLD-fMRI is a useful method to analyze the brain activities of painful stimulation in anesthetized animals.</AbstractText
Quantitative MR Imaging of Brain Tissue and Brain Pathologies. Measurement of basic quantitative magnetic resonance (MR) parameters (e.g., relaxation times T1, T2*, T2 or respective rates R (1/T)) corrected for radiofrequency (RF) coil bias yields different conventional and new tissue contrasts as well as volumes for tissue segmentation. This approach also provides quantitative measures of microstructural and functional tissue changes. We herein demonstrate some prospects of quantitative MR imaging in neurological diagnostics and science.</AbstractText
39504933
22484410
40768103
The Impact of Cognitive Behavioral Therapy for Insomnia on Neurofilament Light and Phosphorylated Tau in Individuals with a Concussion.
NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain.
Agree to Disagree? Fertility Intentions Among Mixed Couples in Sweden.
Concussions damage neurologic tissue, increasing release of intercellular proteins including phosphorylated Tau (pTau) and neurofilament light (NfL). Disrupted sleep from a concussion negatively impacts the ability of the glymphatic system to remove cellular waste from the brain.</AbstractText The purpose of this study was to determine if enhancing sleep using Cognitive Behavioral Therapy for Insomnia (CBT-I) impacts pTau and NFL levels following a concussion.</AbstractText This is pre/post intervention analysis of a larger wait-list control study. Participants had their blood sampled pre/post the CBT-I intervention which was analyzed using SIMOA analytics. Paired sampling statistics and linear regression models were used to examine how insomnia severity impacts pTau181 and NfL.</AbstractText Twenty-eight participants were enrolled in this study. Age and baseline protein level were significantly associated with post-intervention protein levels, but post-intervention insomnia severity was not associated with post-intervention protein levels. About 50% of participants that had clinically meaningful change in insomnia and had a reduction in their NfL and pTau181 values.</AbstractText Post-intervention insomnia was not associated with post-intervention NfL or pTau. Yet, on an individual level, ~50% of participants had a clinically meaningful change in insomnia and reduced level of NfL and pTau 18.1.</AbstractText NCT04885205 https://clinicaltrials.gov.</AbstractText
This paper introduces neurite orientation dispersion and density imaging (NODDI), a practical diffusion MRI technique for estimating the microstructural complexity of dendrites and axons in vivo on clinical MRI scanners. Such indices of neurites relate more directly to and provide more specific markers of brain tissue microstructure than standard indices from diffusion tensor imaging, such as fractional anisotropy (FA). Mapping these indices over the whole brain on clinical scanners presents new opportunities for understanding brain development and disorders. The proposed technique enables such mapping by combining a three-compartment tissue model with a two-shell high-angular-resolution diffusion imaging (HARDI) protocol optimized for clinical feasibility. An index of orientation dispersion is defined to characterize angular variation of neurites. We evaluate the method both in simulation and on a live human brain using a clinical 3T scanner. Results demonstrate that NODDI provides sensible neurite density and orientation dispersion estimates, thereby disentangling two key contributing factors to FA and enabling the analysis of each factor individually. We additionally show that while orientation dispersion can be estimated with just a single HARDI shell, neurite density requires at least two shells and can be estimated more accurately with the optimized two-shell protocol than with alternative two-shell protocols. The optimized protocol takes about 30 min to acquire, making it feasible for inclusion in a typical clinical setting. We further show that sampling fewer orientations in each shell can reduce the acquisition time to just 10 min with minimal impact on the accuracy of the estimates. This demonstrates the feasibility of NODDI even for the most time-sensitive clinical applications, such as neonatal and dementia imaging.</AbstractText
Whether couples agree on having a(nother) child is crucial for both individuals and society. While fertility research has long focused on women, recent studies emphasize the need to incorporate both partners' perspectives. However, analyses that jointly consider men's and women's fertility intentions remain scarce. This focus on women has been partly driven by homogamy-the tendency for individuals to select partners with similar traits and values. Given that couples with mixed backgrounds have higher dissolution rates, they may also be less likely to share family-related beliefs. This study examines how agreement on fertility intentions varies among mixed and homogamous couples in Sweden. Using the 2021 Swedish Generation and Gender Survey (GGS) and stratifying by respondents' gender, we find that most couples agree not to have a(nother) child, reflecting recent fertility declines. Couples where both partners are migrants exhibit the highest agreement, while mixed couples show the most disagreement and the strongest gender asymmetries in reported intentions. However, these differences are small and vary by the gender of the reporting partner. The higher disagreement among mixed couples aligns with broader research on their elevated dissolution risks. However, reverse causality is possible-value differences may be linked to other stressors, making childbearing less desirable. By highlighting the role of couple composition in fertility decision-making, our findings contribute to understanding how family formation dynamics vary across different couple types.</AbstractText
The Impact of Cognitive Behavioral Therapy for Insomnia on Neurofilament Light and Phosphorylated Tau in Individuals with a Concussion. Concussions damage neurologic tissue, increasing release of intercellular proteins including phosphorylated Tau (pTau) and neurofilament light (NfL). Disrupted sleep from a concussion negatively impacts the ability of the glymphatic system to remove cellular waste from the brain.</AbstractText The purpose of this study was to determine if enhancing sleep using Cognitive Behavioral Therapy for Insomnia (CBT-I) impacts pTau and NFL levels following a concussion.</AbstractText This is pre/post intervention analysis of a larger wait-list control study. Participants had their blood sampled pre/post the CBT-I intervention which was analyzed using SIMOA analytics. Paired sampling statistics and linear regression models were used to examine how insomnia severity impacts pTau181 and NfL.</AbstractText Twenty-eight participants were enrolled in this study. Age and baseline protein level were significantly associated with post-intervention protein levels, but post-intervention insomnia severity was not associated with post-intervention protein levels. About 50% of participants that had clinically meaningful change in insomnia and had a reduction in their NfL and pTau181 values.</AbstractText Post-intervention insomnia was not associated with post-intervention NfL or pTau. Yet, on an individual level, ~50% of participants had a clinically meaningful change in insomnia and reduced level of NfL and pTau 18.1.</AbstractText NCT04885205 https://clinicaltrials.gov.</AbstractText
NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain. This paper introduces neurite orientation dispersion and density imaging (NODDI), a practical diffusion MRI technique for estimating the microstructural complexity of dendrites and axons in vivo on clinical MRI scanners. Such indices of neurites relate more directly to and provide more specific markers of brain tissue microstructure than standard indices from diffusion tensor imaging, such as fractional anisotropy (FA). Mapping these indices over the whole brain on clinical scanners presents new opportunities for understanding brain development and disorders. The proposed technique enables such mapping by combining a three-compartment tissue model with a two-shell high-angular-resolution diffusion imaging (HARDI) protocol optimized for clinical feasibility. An index of orientation dispersion is defined to characterize angular variation of neurites. We evaluate the method both in simulation and on a live human brain using a clinical 3T scanner. Results demonstrate that NODDI provides sensible neurite density and orientation dispersion estimates, thereby disentangling two key contributing factors to FA and enabling the analysis of each factor individually. We additionally show that while orientation dispersion can be estimated with just a single HARDI shell, neurite density requires at least two shells and can be estimated more accurately with the optimized two-shell protocol than with alternative two-shell protocols. The optimized protocol takes about 30 min to acquire, making it feasible for inclusion in a typical clinical setting. We further show that sampling fewer orientations in each shell can reduce the acquisition time to just 10 min with minimal impact on the accuracy of the estimates. This demonstrates the feasibility of NODDI even for the most time-sensitive clinical applications, such as neonatal and dementia imaging.</AbstractText
Agree to Disagree? Fertility Intentions Among Mixed Couples in Sweden. Whether couples agree on having a(nother) child is crucial for both individuals and society. While fertility research has long focused on women, recent studies emphasize the need to incorporate both partners' perspectives. However, analyses that jointly consider men's and women's fertility intentions remain scarce. This focus on women has been partly driven by homogamy-the tendency for individuals to select partners with similar traits and values. Given that couples with mixed backgrounds have higher dissolution rates, they may also be less likely to share family-related beliefs. This study examines how agreement on fertility intentions varies among mixed and homogamous couples in Sweden. Using the 2021 Swedish Generation and Gender Survey (GGS) and stratifying by respondents' gender, we find that most couples agree not to have a(nother) child, reflecting recent fertility declines. Couples where both partners are migrants exhibit the highest agreement, while mixed couples show the most disagreement and the strongest gender asymmetries in reported intentions. However, these differences are small and vary by the gender of the reporting partner. The higher disagreement among mixed couples aligns with broader research on their elevated dissolution risks. However, reverse causality is possible-value differences may be linked to other stressors, making childbearing less desirable. By highlighting the role of couple composition in fertility decision-making, our findings contribute to understanding how family formation dynamics vary across different couple types.</AbstractText
37778691
30125269
39552574
Extracellular Vesicles from Neural Stem Cells Carry microRNA-16-5p to Reduce Corticosterone-induced Neuronal Injury in Depression Rats.
A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells.
Magnetic colloidal single particles and dumbbells on a tilted washboard moiré pattern in a precessing external field.
Depression is a common mental illness. Neural stem cell-derived extracellular vesicles (NSC-EVs) are involved in repairing neuronal injury. We estimated the mechanism of miR-16-5p in depression rats.</AbstractText EVs were extracted from NSCs. The depression rat model was established by corticosterone (CORT) induction and treated with NSC-EVs. The depression behavioral/pathological changes in rats were assessed using forced swimming test, open field test, sucrose consumption test and western blotting. The neuronal apoptosis in hippocampal tissue were detected. CORT-induced PC12 cell model was established. EV uptake by PC12 cells was measured and PC12 cell apoptosis was detected. The downstream targets of miR-16-5p were predicted and verified. The expressions of miR-16-5p and MYB in rats, PC12 cells, and EVs were measured. Functional rescue experiments were conducted to verify the role of miR-16-5p and MYB in PC12 cell apoptosis.</AbstractText CORT induction increased neuronal apoptosis in hippocampal tissue and induced depression-like behaviors in rats, while NSC-EV treatment improved depression-like behaviors and apoptosis in rats. In PC12 cells, NSC-EVs decreased CORT-induced PC12 cell apoptosis. NSC-EVs carried miR-16-5p into PC12 cells. miR-16-5p knockdown in EVs partially reversed the inhibitory effects of NSC-EVs on CORT-induced PC12 cell apoptosis. miR-16-5p targeted to inhibit MYB to repress CORT-induced PC12 cell apoptosis. In vivo experiments further verified that NSC-EVs reduced neuronal injury in CORT-induced depression rats via the miR-16-5p/MYB axis.</AbstractText NSC-EVs-mediated alleviation on neuronal injury by carrying miR-16-5p to target MYB was highly likely one of the mechanisms by which NSC-EVs mediated miR-16-5p in neuroprotection of depression rats.</AbstractText
The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contributions of each cell type. Here we model the human NVU using microfluidic organ chips, allowing analysis of the roles of individual cell types in NVU functions. Three coupled chips model influx across the blood-brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. We used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. Thus, the NVU system offers an in vitro approach for probing transport, efficacy, mechanism of action and toxicity of neuroactive drugs.</AbstractText
We measure the dynamical behavior of colloidal singlets and dumbbells on an inclined magnetic moir&#xe9; pattern, subject to a precessing external homogeneous magnetic field. At low external field strength single colloidal particles and dumbbells move everywhere on the pattern: at stronger external field strengths colloidal singlets and dumbbells are localized in generic locations. There are however nongeneric locations of flat channels that cross the moir&#xe9; Wigner Seitz cell. In the flat channels we find gravitational driven translational and non-translational dynamic phase behavior of the colloidal singlets and dumbbells depending on the external field strength and the precession angle of the external homogeneous magnetic field.</AbstractText
Extracellular Vesicles from Neural Stem Cells Carry microRNA-16-5p to Reduce Corticosterone-induced Neuronal Injury in Depression Rats. Depression is a common mental illness. Neural stem cell-derived extracellular vesicles (NSC-EVs) are involved in repairing neuronal injury. We estimated the mechanism of miR-16-5p in depression rats.</AbstractText EVs were extracted from NSCs. The depression rat model was established by corticosterone (CORT) induction and treated with NSC-EVs. The depression behavioral/pathological changes in rats were assessed using forced swimming test, open field test, sucrose consumption test and western blotting. The neuronal apoptosis in hippocampal tissue were detected. CORT-induced PC12 cell model was established. EV uptake by PC12 cells was measured and PC12 cell apoptosis was detected. The downstream targets of miR-16-5p were predicted and verified. The expressions of miR-16-5p and MYB in rats, PC12 cells, and EVs were measured. Functional rescue experiments were conducted to verify the role of miR-16-5p and MYB in PC12 cell apoptosis.</AbstractText CORT induction increased neuronal apoptosis in hippocampal tissue and induced depression-like behaviors in rats, while NSC-EV treatment improved depression-like behaviors and apoptosis in rats. In PC12 cells, NSC-EVs decreased CORT-induced PC12 cell apoptosis. NSC-EVs carried miR-16-5p into PC12 cells. miR-16-5p knockdown in EVs partially reversed the inhibitory effects of NSC-EVs on CORT-induced PC12 cell apoptosis. miR-16-5p targeted to inhibit MYB to repress CORT-induced PC12 cell apoptosis. In vivo experiments further verified that NSC-EVs reduced neuronal injury in CORT-induced depression rats via the miR-16-5p/MYB axis.</AbstractText NSC-EVs-mediated alleviation on neuronal injury by carrying miR-16-5p to target MYB was highly likely one of the mechanisms by which NSC-EVs mediated miR-16-5p in neuroprotection of depression rats.</AbstractText
A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells. The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contributions of each cell type. Here we model the human NVU using microfluidic organ chips, allowing analysis of the roles of individual cell types in NVU functions. Three coupled chips model influx across the blood-brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. We used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. Thus, the NVU system offers an in vitro approach for probing transport, efficacy, mechanism of action and toxicity of neuroactive drugs.</AbstractText
Magnetic colloidal single particles and dumbbells on a tilted washboard moiré pattern in a precessing external field. We measure the dynamical behavior of colloidal singlets and dumbbells on an inclined magnetic moir&#xe9; pattern, subject to a precessing external homogeneous magnetic field. At low external field strength single colloidal particles and dumbbells move everywhere on the pattern: at stronger external field strengths colloidal singlets and dumbbells are localized in generic locations. There are however nongeneric locations of flat channels that cross the moir&#xe9; Wigner Seitz cell. In the flat channels we find gravitational driven translational and non-translational dynamic phase behavior of the colloidal singlets and dumbbells depending on the external field strength and the precession angle of the external homogeneous magnetic field.</AbstractText
40039940
33980303
38890688
A Regression Framework for Predicting Cognitive Decline in Frontotemporal Dementia using Recurrent Neural Networks.
Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer's disease.
Repetition suppression between monetary loss and social pain.
Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder with a diverse range of symptoms, including personality changes, behavioral disturbances, language deficits, and impaired executive functions. FTD has three main subtypes: behavioral variant FTD, non-fluent variant primary progressive aphasia, and semantic variant primary progressive aphasia. While there has been extensive research on detecting FTD, there is a limited exploration of the progression of FTD severity in patients over time. FTD typically manifests at a younger age, occurring between 40 and 65 years, than any other dementia forms. Therefore, detecting specific FTD subtypes early on becomes more feasible when assessing disease severity in the initial stages. This study aims to forecast an individual's future cognitive status using their neuropsychiatric inventory. This inventory consists solely of neuropsychological test scores related to FTD markers collected from one or more time points. We proposed and applied a regression framework with Encoder-Decoder Long-Short-Term-Memory (ED-LSTM) model to the data from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI/NIFD) comprising longitudinal data of 288 participant's 918 instances. This study represents the first comprehensive exploration of forecasting individuals' FTD markers (cognitive scores) over four years into the future. We compared the performance of the proposed model with two baseline recurrent neural network models (LSTM and Simple RNN). The results indicate that the suggested model outperforms other implemented models when considering mean absolute error and root mean square error performance metrics.Clinical relevance- This study aims to provide valuable insights into the early identification and prognosis of cognitive decline in individuals with FTD. This could contribute to more timely and targeted interventions, improving patient outcomes and enhancing the overall management of FTD.</AbstractText
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer's disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.</AbstractText
The relationship between monetary loss and pain has been a recent research focus. Prior studies found similarities in the network representation patterns of monetary loss and pain, particularly social pain. However, the neural level evidence was lacking. To address this, we conducted an ERP experiment to investigate whether there is a repetitive suppression effect of monetary loss on the neural activity of social pain, aiming to understand if they engage overlapping neuronal populations. The results revealed that FRN amplitudes showed repetitive suppression effects of monetary loss on the neural activity of social pain. Our study suggests that monetary loss and social pain share common neural bases, indicating that they might involve shared neural modules related to cognitive conflict and affective appraisal.</AbstractText
A Regression Framework for Predicting Cognitive Decline in Frontotemporal Dementia using Recurrent Neural Networks. Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder with a diverse range of symptoms, including personality changes, behavioral disturbances, language deficits, and impaired executive functions. FTD has three main subtypes: behavioral variant FTD, non-fluent variant primary progressive aphasia, and semantic variant primary progressive aphasia. While there has been extensive research on detecting FTD, there is a limited exploration of the progression of FTD severity in patients over time. FTD typically manifests at a younger age, occurring between 40 and 65 years, than any other dementia forms. Therefore, detecting specific FTD subtypes early on becomes more feasible when assessing disease severity in the initial stages. This study aims to forecast an individual's future cognitive status using their neuropsychiatric inventory. This inventory consists solely of neuropsychological test scores related to FTD markers collected from one or more time points. We proposed and applied a regression framework with Encoder-Decoder Long-Short-Term-Memory (ED-LSTM) model to the data from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI/NIFD) comprising longitudinal data of 288 participant's 918 instances. This study represents the first comprehensive exploration of forecasting individuals' FTD markers (cognitive scores) over four years into the future. We compared the performance of the proposed model with two baseline recurrent neural network models (LSTM and Simple RNN). The results indicate that the suggested model outperforms other implemented models when considering mean absolute error and root mean square error performance metrics.Clinical relevance- This study aims to provide valuable insights into the early identification and prognosis of cognitive decline in individuals with FTD. This could contribute to more timely and targeted interventions, improving patient outcomes and enhancing the overall management of FTD.</AbstractText
Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer's disease. Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer's disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.</AbstractText
Repetition suppression between monetary loss and social pain. The relationship between monetary loss and pain has been a recent research focus. Prior studies found similarities in the network representation patterns of monetary loss and pain, particularly social pain. However, the neural level evidence was lacking. To address this, we conducted an ERP experiment to investigate whether there is a repetitive suppression effect of monetary loss on the neural activity of social pain, aiming to understand if they engage overlapping neuronal populations. The results revealed that FRN amplitudes showed repetitive suppression effects of monetary loss on the neural activity of social pain. Our study suggests that monetary loss and social pain share common neural bases, indicating that they might involve shared neural modules related to cognitive conflict and affective appraisal.</AbstractText
32004658
27069668
32692725
Error-monitoring across social and affective processing contexts.
Beauty is in the efficient coding of the beholder.
Flexible numerical simulation framework for dynamic PET-MR data.
The error-related negativity (ERN) is one of the most researched event-related potentials in the study of cognitive control, and it is thought to capture preconscious error-monitoring. ERN amplitude is known to be modulated by trait and state differences in affect, yet most ERN studies use 'cold' cognitive tasks that do not directly target affective processes involved in cognitive control. For example, speeded response-time tasks that elicit the ERN typically use neutral stimuli (e.g., letters, arrows), yet these paradigms are also flexible enough such that affective or social stimuli can readily be incorporated to target the role of affect in error-monitoring. In this project, the commonly-used arrow flanker task was modified to examine whether the expected behavioral and psychophysiological indices of error-monitoring would be observed using affective and social stimuli. Specifically, four different flanker tasks were administered using a within-subjects design with the following stimuli: arrows, neutral faces, unpleasant images, and pleasant images. Analyses indicated that the flanker tasks using arrows and faces elicited expected behavioral patterns (e.g., lower accuracy and slower reaction time on incongruent versus congruent trials) and ERN modulation by error versus correct trials. Although flanker tasks using unpleasant and pleasant stimuli also modulated the ERN, flanker effects on behavioral performance were not as consistent as the other tasks. Further, within incongruent trials, the ERN was larger when affective stimuli needed to be suppressed for a correct response. The correlations of the ERN and behavioral measures across tasks indicated some consistent individual differences in the ERN across tasks as well as substantial task-specific variances. This project lays the foundation for modifying classic error-monitoring tasks in a manner that may better target social and affective constructs that are of interest to clinical researchers.</AbstractText
Sexual ornaments are often assumed to be indicators of mate quality. Yet it remains poorly known how certain ornaments are chosen before any coevolutionary race makes them indicative. Perceptual biases have been proposed to play this role, but known biases are mostly restricted to a specific taxon, which precludes evaluating their general importance in sexual selection. Here we identify a potentially universal perceptual bias in mate choice. We used an algorithm that models the sparseness of the activity of simple cells in the primary visual cortex (or V1) of humans when coding images of female faces. Sparseness was found positively correlated with attractiveness as rated by men and explained up to 17% of variance in attractiveness. Because V1 is adapted to process signals from natural scenes, in general, not faces specifically, our results indicate that attractiveness for female faces is influenced by a visual bias. Sparseness and more generally efficient neural coding are ubiquitous, occurring in various animals and sensory modalities, suggesting that the influence of efficient coding on mate choice can be widespread in animals.</AbstractText
This paper presents a simulation framework for dynamic PET-MR. The main focus of this framework is to provide motion-resolved MR and PET data and ground truth motion information. This can be used in the optimisation and quantitative evaluation of image registration and in assessing the error propagation due to inaccuracies in motion estimation in complex motion-compensated reconstruction algorithms. Contrast and tracer kinetics can also be simulated and are available as ground truth information. To closely emulate medical examination, input and output of the simulation are files in standardised open-source raw data formats. This enables the use of existing raw data as a template input and ensures seamless integration of the output into existing reconstruction pipelines. The proposed framework was validated in PET-MR and image registration applications. It was used to simulate a FDG-PET-MR scan with cardiac and respiratory motion. Ground truth motion information could be utilised to optimise parameters for PET and synergistic PET-MR image registration. In addition, a free-breathing dynamic contrast enhancement (DCE) abdominal scan of a patient with hepatic lesions was simulated. In order to correct for breathing motion, a motion-corrected image reconstruction scheme was used and a Toft's model was fit to the DCE data to obtain quantitative DCE-MRI parameters. Utilising the ground truth motion information, the dependency of quantitative DCE-MR images on the accuracy of the motion estimation was evaluated. We demonstrated that respiratory motion had to be available with an average accuracy of at least the spatial resolution of the DCE-MR images in order to ensure an improvement in lesions visualisation and quantification compared to no motion correction. The proposed framework provides a valuable tool with a wide range of scientific PET and MR applications and will be available as part of the open-source project Synergistic Image Reconstruction Framework (SIRF).</AbstractText
Error-monitoring across social and affective processing contexts. The error-related negativity (ERN) is one of the most researched event-related potentials in the study of cognitive control, and it is thought to capture preconscious error-monitoring. ERN amplitude is known to be modulated by trait and state differences in affect, yet most ERN studies use 'cold' cognitive tasks that do not directly target affective processes involved in cognitive control. For example, speeded response-time tasks that elicit the ERN typically use neutral stimuli (e.g., letters, arrows), yet these paradigms are also flexible enough such that affective or social stimuli can readily be incorporated to target the role of affect in error-monitoring. In this project, the commonly-used arrow flanker task was modified to examine whether the expected behavioral and psychophysiological indices of error-monitoring would be observed using affective and social stimuli. Specifically, four different flanker tasks were administered using a within-subjects design with the following stimuli: arrows, neutral faces, unpleasant images, and pleasant images. Analyses indicated that the flanker tasks using arrows and faces elicited expected behavioral patterns (e.g., lower accuracy and slower reaction time on incongruent versus congruent trials) and ERN modulation by error versus correct trials. Although flanker tasks using unpleasant and pleasant stimuli also modulated the ERN, flanker effects on behavioral performance were not as consistent as the other tasks. Further, within incongruent trials, the ERN was larger when affective stimuli needed to be suppressed for a correct response. The correlations of the ERN and behavioral measures across tasks indicated some consistent individual differences in the ERN across tasks as well as substantial task-specific variances. This project lays the foundation for modifying classic error-monitoring tasks in a manner that may better target social and affective constructs that are of interest to clinical researchers.</AbstractText
Beauty is in the efficient coding of the beholder. Sexual ornaments are often assumed to be indicators of mate quality. Yet it remains poorly known how certain ornaments are chosen before any coevolutionary race makes them indicative. Perceptual biases have been proposed to play this role, but known biases are mostly restricted to a specific taxon, which precludes evaluating their general importance in sexual selection. Here we identify a potentially universal perceptual bias in mate choice. We used an algorithm that models the sparseness of the activity of simple cells in the primary visual cortex (or V1) of humans when coding images of female faces. Sparseness was found positively correlated with attractiveness as rated by men and explained up to 17% of variance in attractiveness. Because V1 is adapted to process signals from natural scenes, in general, not faces specifically, our results indicate that attractiveness for female faces is influenced by a visual bias. Sparseness and more generally efficient neural coding are ubiquitous, occurring in various animals and sensory modalities, suggesting that the influence of efficient coding on mate choice can be widespread in animals.</AbstractText
Flexible numerical simulation framework for dynamic PET-MR data. This paper presents a simulation framework for dynamic PET-MR. The main focus of this framework is to provide motion-resolved MR and PET data and ground truth motion information. This can be used in the optimisation and quantitative evaluation of image registration and in assessing the error propagation due to inaccuracies in motion estimation in complex motion-compensated reconstruction algorithms. Contrast and tracer kinetics can also be simulated and are available as ground truth information. To closely emulate medical examination, input and output of the simulation are files in standardised open-source raw data formats. This enables the use of existing raw data as a template input and ensures seamless integration of the output into existing reconstruction pipelines. The proposed framework was validated in PET-MR and image registration applications. It was used to simulate a FDG-PET-MR scan with cardiac and respiratory motion. Ground truth motion information could be utilised to optimise parameters for PET and synergistic PET-MR image registration. In addition, a free-breathing dynamic contrast enhancement (DCE) abdominal scan of a patient with hepatic lesions was simulated. In order to correct for breathing motion, a motion-corrected image reconstruction scheme was used and a Toft's model was fit to the DCE data to obtain quantitative DCE-MRI parameters. Utilising the ground truth motion information, the dependency of quantitative DCE-MR images on the accuracy of the motion estimation was evaluated. We demonstrated that respiratory motion had to be available with an average accuracy of at least the spatial resolution of the DCE-MR images in order to ensure an improvement in lesions visualisation and quantification compared to no motion correction. The proposed framework provides a valuable tool with a wide range of scientific PET and MR applications and will be available as part of the open-source project Synergistic Image Reconstruction Framework (SIRF).</AbstractText
35784805
31402880
36180710
Toward Detecting the Zone of Elite Tennis Players Through Wearable Technology.
"Telling me not to worry…" Hyperscanning and Neural Dynamics of Emotion Processing During Guided Imagery and Music.
Olfaction and Melatonin: The Use of the Olfactory Discrimination Test.
Wearable devices fall short in providing information other than physiological metrics despite athletes' demand for psychological feedback. To address this, we introduce a preliminary exploration to track psychological states of athletes based on commercial wearable devices, coach observations and machine learning. Our system collects Inertial Measuring Unit data from tennis players, while their coaches provide labels on their psychological states. A recurrent neural network is then trained to predict coach labels from sensor data. We test our approach by predicting being in the zone, a psychological state of optimal performance. We conduct two experimental games with two elite coaches and four professional players for evaluation. Our learned models achieve above 85% test accuracy, implying that our approach could be utilized to predict the zone at relatively low cost. Based on these findings, we discuss design implications and feasibility of this approach by contextualizing it in a real-life scenario.</AbstractText
To analyze how emotions and imagery are shared, processed and recognized in Guided Imagery and Music, we measured the brain activity of an experienced therapist ("Guide") and client ("Traveler") with dual-EEG in a real therapy session about potential death of family members. Synchronously with the EEG, the session was video-taped and then micro-analyzed. Four raters identified therapeutically important moments of interest (MOI) and no-interest (MONI) which were transcribed and annotated. Several indices of emotion- and imagery-related processing were analyzed: frontal and parietal alpha asymmetry, frontal midline theta, and occipital alpha activity. Session ratings showed overlaps across all raters, confirming the importance of these MOIs, which showed different cortical activity in visual areas compared to resting-state. MOI 1 was a pivotal moment including an important imagery with a message of hope from a close family member, while in the second MOI the Traveler sent a message to an unborn baby. Generally, results seemed to indicate that the emotions of Traveler and Guide during important moments were not positive, pleasurably or relaxed when compared to resting-state, confirming both were dealing with negative emotions and anxiety that had to be contained in the interpersonal process. However, the temporal dynamics of emotion-related markers suggested shifts in emotional valence and intensity during these important, personally meaningful moments; for example, during receiving the message of hope, an increase of frontal alpha asymmetry was observed, reflecting increased positive emotional processing. EEG source localization during the message suggested a peak activation in left middle temporal gyrus. Interestingly, peaks in emotional markers in the Guide partly paralleled the Traveler's peaks; for example, during the Guide's strong feeling of mutuality in MOI 2, the time series of frontal alpha asymmetries showed a significant cross-correlation, indicating similar emotional processing in Traveler and Guide. Investigating the moment-to-moment interaction in music therapy showed how asymmetry peaks align with the situated cognition of Traveler and Guide along the emotional contour of the music, representing the highs and lows during the therapy process. Combining dual-EEG with detailed audiovisual and qualitative data seems to be a promising approach for further research into music therapy.</AbstractText
In order to investigate the role of melatonin in olfactory function, we present the olfactory discrimination test as a simple and low-cost behavioral assessment. The test consists in evaluating the time that each rat spent in two compartments: one has a familiar odor (sawdust with the smell from the animal) and the other one with an unfamiliar odor (clean sawdust). Animals with the normal olfactory functions will discriminate between these two odors and will spend more time in the familiar compartment. We used the olfactory discrimination test to evaluate the role of melatonin receptors expressed in the olfactory bulb of rats. In a previous study, our results have successfully detected an olfactory modulation, by mean of the olfactory discrimination test, promoted by the infusion of melatonin receptor ligands into the olfactory bulb of rats.</AbstractText
Toward Detecting the Zone of Elite Tennis Players Through Wearable Technology. Wearable devices fall short in providing information other than physiological metrics despite athletes' demand for psychological feedback. To address this, we introduce a preliminary exploration to track psychological states of athletes based on commercial wearable devices, coach observations and machine learning. Our system collects Inertial Measuring Unit data from tennis players, while their coaches provide labels on their psychological states. A recurrent neural network is then trained to predict coach labels from sensor data. We test our approach by predicting being in the zone, a psychological state of optimal performance. We conduct two experimental games with two elite coaches and four professional players for evaluation. Our learned models achieve above 85% test accuracy, implying that our approach could be utilized to predict the zone at relatively low cost. Based on these findings, we discuss design implications and feasibility of this approach by contextualizing it in a real-life scenario.</AbstractText
"Telling me not to worry…" Hyperscanning and Neural Dynamics of Emotion Processing During Guided Imagery and Music. To analyze how emotions and imagery are shared, processed and recognized in Guided Imagery and Music, we measured the brain activity of an experienced therapist ("Guide") and client ("Traveler") with dual-EEG in a real therapy session about potential death of family members. Synchronously with the EEG, the session was video-taped and then micro-analyzed. Four raters identified therapeutically important moments of interest (MOI) and no-interest (MONI) which were transcribed and annotated. Several indices of emotion- and imagery-related processing were analyzed: frontal and parietal alpha asymmetry, frontal midline theta, and occipital alpha activity. Session ratings showed overlaps across all raters, confirming the importance of these MOIs, which showed different cortical activity in visual areas compared to resting-state. MOI 1 was a pivotal moment including an important imagery with a message of hope from a close family member, while in the second MOI the Traveler sent a message to an unborn baby. Generally, results seemed to indicate that the emotions of Traveler and Guide during important moments were not positive, pleasurably or relaxed when compared to resting-state, confirming both were dealing with negative emotions and anxiety that had to be contained in the interpersonal process. However, the temporal dynamics of emotion-related markers suggested shifts in emotional valence and intensity during these important, personally meaningful moments; for example, during receiving the message of hope, an increase of frontal alpha asymmetry was observed, reflecting increased positive emotional processing. EEG source localization during the message suggested a peak activation in left middle temporal gyrus. Interestingly, peaks in emotional markers in the Guide partly paralleled the Traveler's peaks; for example, during the Guide's strong feeling of mutuality in MOI 2, the time series of frontal alpha asymmetries showed a significant cross-correlation, indicating similar emotional processing in Traveler and Guide. Investigating the moment-to-moment interaction in music therapy showed how asymmetry peaks align with the situated cognition of Traveler and Guide along the emotional contour of the music, representing the highs and lows during the therapy process. Combining dual-EEG with detailed audiovisual and qualitative data seems to be a promising approach for further research into music therapy.</AbstractText
Olfaction and Melatonin: The Use of the Olfactory Discrimination Test. In order to investigate the role of melatonin in olfactory function, we present the olfactory discrimination test as a simple and low-cost behavioral assessment. The test consists in evaluating the time that each rat spent in two compartments: one has a familiar odor (sawdust with the smell from the animal) and the other one with an unfamiliar odor (clean sawdust). Animals with the normal olfactory functions will discriminate between these two odors and will spend more time in the familiar compartment. We used the olfactory discrimination test to evaluate the role of melatonin receptors expressed in the olfactory bulb of rats. In a previous study, our results have successfully detected an olfactory modulation, by mean of the olfactory discrimination test, promoted by the infusion of melatonin receptor ligands into the olfactory bulb of rats.</AbstractText
35259650
36833190
36206398
Focused ultrasound and other lesioning in the treatment of tremor.
Phenotypes and Genotypes of Inherited Disorders of Biogenic Amine Neurotransmitter Metabolism.
Sex is predicted by spatial memory multivariate activation patterns.
There has been a long history of lesioning procedures to treat tremor associated with both essential tremor (ET) and Parkinson's disease (PD). These include radiofrequency (RF) thalamotomy, gamma knife radiosurgical (GKRS) thalamotomy, and magnetic resonance-guided focused ultrasound (MRgFUS). In this review, we summarize the clinical studies of lesioning procedures for tremor focusing on these ablative therapies for ET and tremor-predominant PD (TDPD). We then consider clinical treatment variables that influence decision-making regarding ablative therapies versus consideration of deep brain stimulation (DBS) and conclude with ongoing and future studies. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.</AbstractText
Inherited disorders of biogenic amine metabolism are genetically determined conditions resulting in dysfunctions or lack of enzymes involved in the synthesis, degradation, or transport of dopamine, serotonin, adrenaline/noradrenaline, and their metabolites or defects of their cofactor or chaperone biosynthesis. They represent a group of treatable diseases presenting with complex patterns of movement disorders (dystonia, oculogyric crises, severe/hypokinetic syndrome, myoclonic jerks, and tremors) associated with a delay in the emergence of postural reactions, global development delay, and autonomic dysregulation. The earlier the disease manifests, the more severe and widespread the impaired motor functions. Diagnosis mainly depends on measuring neurotransmitter metabolites in cerebrospinal fluid that may address the genetic confirmation. Correlations between the severity of phenotypes and genotypes may vary remarkably among the different diseases. Traditional pharmacological strategies are not disease-modifying in most cases. Gene therapy has provided promising results in patients with DYT-DDC and in vitro models of DYT/PARK-SLC6A3. The rarity of these diseases, combined with limited knowledge of their clinical, biochemical, and molecular genetic features, frequently leads to misdiagnosis or significant diagnostic delays. This review provides updates on these aspects with a final outlook on future perspectives.</AbstractText
Whether sex differences exist in the brain at the macroscopic level, as measured with magnetic resonance imaging (MRI), is a topic of debate. The present spatial long-term memory functional MRI (fMRI) study predicted sex based on event-related patterns of brain activity. Within spatial memory regions of interest, patterns of activity associated with females and males were used to predict the sex of each member of left-out female-male pairs at above-chance accuracy. The current results provide evidence for sex differences in the brain processes underlying spatial long-term memory. This is the first time that sex has been predicted using event-related fMRI activation patterns. The present findings contribute to a growing body of evidence that there are functional and anatomic sex differences in the brain and, more broadly, question the widespread practice of collapsing across sex in the field of cognitive neuroscience.</AbstractText
Focused ultrasound and other lesioning in the treatment of tremor. There has been a long history of lesioning procedures to treat tremor associated with both essential tremor (ET) and Parkinson's disease (PD). These include radiofrequency (RF) thalamotomy, gamma knife radiosurgical (GKRS) thalamotomy, and magnetic resonance-guided focused ultrasound (MRgFUS). In this review, we summarize the clinical studies of lesioning procedures for tremor focusing on these ablative therapies for ET and tremor-predominant PD (TDPD). We then consider clinical treatment variables that influence decision-making regarding ablative therapies versus consideration of deep brain stimulation (DBS) and conclude with ongoing and future studies. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.</AbstractText
Phenotypes and Genotypes of Inherited Disorders of Biogenic Amine Neurotransmitter Metabolism. Inherited disorders of biogenic amine metabolism are genetically determined conditions resulting in dysfunctions or lack of enzymes involved in the synthesis, degradation, or transport of dopamine, serotonin, adrenaline/noradrenaline, and their metabolites or defects of their cofactor or chaperone biosynthesis. They represent a group of treatable diseases presenting with complex patterns of movement disorders (dystonia, oculogyric crises, severe/hypokinetic syndrome, myoclonic jerks, and tremors) associated with a delay in the emergence of postural reactions, global development delay, and autonomic dysregulation. The earlier the disease manifests, the more severe and widespread the impaired motor functions. Diagnosis mainly depends on measuring neurotransmitter metabolites in cerebrospinal fluid that may address the genetic confirmation. Correlations between the severity of phenotypes and genotypes may vary remarkably among the different diseases. Traditional pharmacological strategies are not disease-modifying in most cases. Gene therapy has provided promising results in patients with DYT-DDC and in vitro models of DYT/PARK-SLC6A3. The rarity of these diseases, combined with limited knowledge of their clinical, biochemical, and molecular genetic features, frequently leads to misdiagnosis or significant diagnostic delays. This review provides updates on these aspects with a final outlook on future perspectives.</AbstractText
Sex is predicted by spatial memory multivariate activation patterns. Whether sex differences exist in the brain at the macroscopic level, as measured with magnetic resonance imaging (MRI), is a topic of debate. The present spatial long-term memory functional MRI (fMRI) study predicted sex based on event-related patterns of brain activity. Within spatial memory regions of interest, patterns of activity associated with females and males were used to predict the sex of each member of left-out female-male pairs at above-chance accuracy. The current results provide evidence for sex differences in the brain processes underlying spatial long-term memory. This is the first time that sex has been predicted using event-related fMRI activation patterns. The present findings contribute to a growing body of evidence that there are functional and anatomic sex differences in the brain and, more broadly, question the widespread practice of collapsing across sex in the field of cognitive neuroscience.</AbstractText
24711999
24120558
22865642
Optogenetic activation of the excitatory neurons expressing CaMKIIα in the ventral tegmental area upregulates the locomotor activity of free behaving rats.
Transfer of information by BMI.
Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds.
The ventral tegmental area (VTA) plays an important role in motivation and motor activity of mammals. Previous studies have reported that electrical stimulations of the VTA's neuronal projections were able to upregulate the locomotor activity of behaving rats. However, which types of neurons in the VTA that take part in the activation remain elusive. In this paper we employed optogenetic technique to selectively activate the excitatory neurons expressing CaMKII&#x3b1; in the VTA region and induced a higher locomotor activity for free behaving rats. Further behavioral studies indicated that reward learning mediated in the enhancement of the rat locomotor activity. Finally the immunohistochemistry studies explored that the excitatory neurons under the optogenetic activation in VTA were partly dopaminergic that may participate as a vital role in the optogenetic activation of the locomotor activity. In total, our study provided an optogenetic approach to selectively upregulate the locomotor activity of free behaving rats, thus facilitating both neuroscience researches and neural engineering such as animal robotics in the future.</AbstractText
Brain machine interfaces (BMI) have become important in systems neuroscience with the goal to restore motor function in paralyzed patients. We assess the current ability of BMI devices to move objects. The topics discussed include: (1) the bits of information generated by a BMI signal, (2) the limitations of including more neurons for generating a BMI signal, (3) the superiority of a BMI signal using single cells versus electroencephalography, (4) plasticity and BMI, (5) the selection of a neural code for generating BMI, (6) the suppression of body movements during BMI, and (7) the role of vision in BMI. We conclude that further research on understanding how the brain generates movement is necessary before BMI can become a reasonable option for paralyzed patients.</AbstractText
Degeneration of intervertebral discs (IVDs) occurs frequently and is often associated with lower back pain. Recent treatment options are limited and treat the symptoms rather than regenerate the degenerated disc. Cell-free, freeze-dried resorbable polyglycolic acid (PGA)-hyaluronan implants were used in an ovine IVD degeneration model. The nucleus pulposus of the IVD was partially removed, endoscopically. PGA-hyaluronan implants were immersed in autologous sheep serum and implanted into the disc defect. Animals with nucleotomy only served as controls. The T2-weighted/fat suppression sequence signal intensity index of the operated discs, as assessed by magnetic resonance imaging (MRI), showed that implantation of the PGA-hyaluronan implant improved (p = 0.0066) the MRI signal compared to controls at 6 months after surgery. Histological analysis by haematoxylin and eosin and safranin O staining showed the ingrowth of cells with typical chondrocytic morphology, even cell distribution, and extracellular matrix rich in proteoglycan. Histomorphometric analyses confirmed that the implantation of the PGA-hyaluronan scaffolds improved (p = 0.027) the formation of regenerated tissue after nucleotomy. Disc heights remained stable in discs with nucleotomy only as well as after implantation of the implant. In conclusion, implantation of cell-free polymer-based implants after nucleotomy induces nucleus pulposus tissue regeneration and improves disc water content in the ovine model.</AbstractText
Optogenetic activation of the excitatory neurons expressing CaMKIIα in the ventral tegmental area upregulates the locomotor activity of free behaving rats. The ventral tegmental area (VTA) plays an important role in motivation and motor activity of mammals. Previous studies have reported that electrical stimulations of the VTA's neuronal projections were able to upregulate the locomotor activity of behaving rats. However, which types of neurons in the VTA that take part in the activation remain elusive. In this paper we employed optogenetic technique to selectively activate the excitatory neurons expressing CaMKII&#x3b1; in the VTA region and induced a higher locomotor activity for free behaving rats. Further behavioral studies indicated that reward learning mediated in the enhancement of the rat locomotor activity. Finally the immunohistochemistry studies explored that the excitatory neurons under the optogenetic activation in VTA were partly dopaminergic that may participate as a vital role in the optogenetic activation of the locomotor activity. In total, our study provided an optogenetic approach to selectively upregulate the locomotor activity of free behaving rats, thus facilitating both neuroscience researches and neural engineering such as animal robotics in the future.</AbstractText
Transfer of information by BMI. Brain machine interfaces (BMI) have become important in systems neuroscience with the goal to restore motor function in paralyzed patients. We assess the current ability of BMI devices to move objects. The topics discussed include: (1) the bits of information generated by a BMI signal, (2) the limitations of including more neurons for generating a BMI signal, (3) the superiority of a BMI signal using single cells versus electroencephalography, (4) plasticity and BMI, (5) the selection of a neural code for generating BMI, (6) the suppression of body movements during BMI, and (7) the role of vision in BMI. We conclude that further research on understanding how the brain generates movement is necessary before BMI can become a reasonable option for paralyzed patients.</AbstractText
Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds. Degeneration of intervertebral discs (IVDs) occurs frequently and is often associated with lower back pain. Recent treatment options are limited and treat the symptoms rather than regenerate the degenerated disc. Cell-free, freeze-dried resorbable polyglycolic acid (PGA)-hyaluronan implants were used in an ovine IVD degeneration model. The nucleus pulposus of the IVD was partially removed, endoscopically. PGA-hyaluronan implants were immersed in autologous sheep serum and implanted into the disc defect. Animals with nucleotomy only served as controls. The T2-weighted/fat suppression sequence signal intensity index of the operated discs, as assessed by magnetic resonance imaging (MRI), showed that implantation of the PGA-hyaluronan implant improved (p = 0.0066) the MRI signal compared to controls at 6 months after surgery. Histological analysis by haematoxylin and eosin and safranin O staining showed the ingrowth of cells with typical chondrocytic morphology, even cell distribution, and extracellular matrix rich in proteoglycan. Histomorphometric analyses confirmed that the implantation of the PGA-hyaluronan scaffolds improved (p = 0.027) the formation of regenerated tissue after nucleotomy. Disc heights remained stable in discs with nucleotomy only as well as after implantation of the implant. In conclusion, implantation of cell-free polymer-based implants after nucleotomy induces nucleus pulposus tissue regeneration and improves disc water content in the ovine model.</AbstractText
39436288
38357240
38991131
Feasibility and Clinical Application of 5-T Noncontrast Dixon Whole-Heart Coronary MR Angiography: A Prospective Study.
Diagnostic algorithm for glioma grading using dynamic susceptibility contrast‑enhanced magnetic resonance perfusion and proton magnetic resonance spectroscopy.
Is That You I Hear? Speaker Familiarity Modulates Neural Signatures of Lexical-semantic Activation in 18-month-old Infants.
Background Coronary MR angiography (CMRA) at 3 T offers higher signal to noise ratio and contrast to noise ratio compared with 1.5 T. CMRA at 5 T may provide better diagnostic performance. Purpose To assess the feasibility and clinical application of 5-T noncontrast whole-heart CMRA and compare 5-T acquisition with 3-T acquisition. Materials and Methods From September 2023 to April 2024, patients scheduled for coronary CT angiography (CCTA) and volunteers were prospectively recruited. CCTA served as the reference standard in patients. CMRA was performed using a 3-T spectral attenuated inversion-recovery (3T<sub
The present retrospective study aimed to investigate the diagnostic capacity of and design a diagnostic algorithm for dynamic susceptibility contrast-enhanced MRI (DSCE-MRI) and proton magnetic resonance spectroscopy (<sup
Developmental language studies have shown that lexical-semantic organization develops between 18 and 24 months of age in monolingual infants. In the present study, we aimed to examine whether voice familiarity facilitates lexical-semantic activation in the infant brain. We recorded the brain activity of 18-month-old, French-learning infants using EEG while they listened to taxonomically related and unrelated spoken word pairs by one voice with which they were familiarized with before the experiment, and one voice with which they were not familiarized. The ERPs were measured in response to related and unrelated target words. Our results showed an N400 effect (greater amplitudes for unrelated as opposed to related target words) over the left hemisphere, only for the familiar voice, suggesting that the voice familiarity facilitated lexical-semantic activation. For unfamiliar voices, we observed an earlier congruence effect (greater amplitudes for related than for unrelated target words). This suggests that although 18-month-olds process lexical-semantic information from unfamiliar speakers, their neural signatures of lexical-semantic processing are less mature. Our results show that even in the absence of personal relation with a speaker, familiarity with a voice augments infant lexical-semantic processing. This supports the idea that extralinguistic information plays a role in infant lexical-semantic activation.</AbstractText
Feasibility and Clinical Application of 5-T Noncontrast Dixon Whole-Heart Coronary MR Angiography: A Prospective Study. Background Coronary MR angiography (CMRA) at 3 T offers higher signal to noise ratio and contrast to noise ratio compared with 1.5 T. CMRA at 5 T may provide better diagnostic performance. Purpose To assess the feasibility and clinical application of 5-T noncontrast whole-heart CMRA and compare 5-T acquisition with 3-T acquisition. Materials and Methods From September 2023 to April 2024, patients scheduled for coronary CT angiography (CCTA) and volunteers were prospectively recruited. CCTA served as the reference standard in patients. CMRA was performed using a 3-T spectral attenuated inversion-recovery (3T<sub
Diagnostic algorithm for glioma grading using dynamic susceptibility contrast‑enhanced magnetic resonance perfusion and proton magnetic resonance spectroscopy. The present retrospective study aimed to investigate the diagnostic capacity of and design a diagnostic algorithm for dynamic susceptibility contrast-enhanced MRI (DSCE-MRI) and proton magnetic resonance spectroscopy (<sup
Is That You I Hear? Speaker Familiarity Modulates Neural Signatures of Lexical-semantic Activation in 18-month-old Infants. Developmental language studies have shown that lexical-semantic organization develops between 18 and 24 months of age in monolingual infants. In the present study, we aimed to examine whether voice familiarity facilitates lexical-semantic activation in the infant brain. We recorded the brain activity of 18-month-old, French-learning infants using EEG while they listened to taxonomically related and unrelated spoken word pairs by one voice with which they were familiarized with before the experiment, and one voice with which they were not familiarized. The ERPs were measured in response to related and unrelated target words. Our results showed an N400 effect (greater amplitudes for unrelated as opposed to related target words) over the left hemisphere, only for the familiar voice, suggesting that the voice familiarity facilitated lexical-semantic activation. For unfamiliar voices, we observed an earlier congruence effect (greater amplitudes for related than for unrelated target words). This suggests that although 18-month-olds process lexical-semantic information from unfamiliar speakers, their neural signatures of lexical-semantic processing are less mature. Our results show that even in the absence of personal relation with a speaker, familiarity with a voice augments infant lexical-semantic processing. This supports the idea that extralinguistic information plays a role in infant lexical-semantic activation.</AbstractText
40417590
34220474
39197189
Toward Large Language Models as a Therapeutic Tool: Comparing Prompting Techniques to Improve GPT-Delivered Problem-Solving Therapy.
Naturalistic Stimuli in Affective Neuroimaging: A Review.
Rosemary extract activates oligodendrogenesis genes in mouse brain and improves learning and memory ability.
While Large Language Models (LLMs) are being quickly adapted to many domains, including healthcare, their strengths and pitfalls remain under-explored. In our study, we examine the effects of prompt engineering to guide Large Language Models (LLMs) in delivering parts of a Problem-Solving Therapy (PST) session via text, particularly during the symptom identification and assessment phase for personalized goal setting. We present evaluation results of the models' performances by automatic metrics and experienced medical professionals. We demonstrate that the models' capability to deliver protocolized therapy can be improved with the proper use of prompt engineering methods, albeit with limitations. To our knowledge, this study is among the first to assess the effects of various prompting techniques in enhancing a generalist model's ability to deliver psychotherapy, focusing on overall quality, consistency, and empathy. Exploring LLMs' potential in delivering psychotherapy holds promise with the current shortage of mental health professionals amid significant needs, enhancing the potential utility of AI-based and AI-enhanced care services.</AbstractText
Naturalistic stimuli such as movies, music, and spoken and written stories elicit strong emotions and allow brain imaging of emotions in close-to-real-life conditions. Emotions are multi-component phenomena: relevant stimuli lead to automatic changes in multiple functional components including perception, physiology, behavior, and conscious experiences. Brain activity during naturalistic stimuli reflects all these changes, suggesting that parsing emotion-related processing during such complex stimulation is not a straightforward task. Here, I review affective neuroimaging studies that have employed naturalistic stimuli to study emotional processing, focusing especially on experienced emotions. I argue that to investigate emotions with naturalistic stimuli, we need to define and extract <i
Rosemary (Rosmarinus officinalis L.) is a rich source of dietary bioactive compounds such as rosmarinic acid and carnosol with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. In the present study, we investigated rosemary as a potential new therapeutic agent for cognitive function and other symptoms of aging. In this present study, we have aimed to investigate the effects of oral administration of rosemary extract (RME) on learning and memory in the context of other biomarkers-related cognitive function and neurotransmitter levels in senescent accelerated prone 8 (SAMP8) mouse, a model of accelerating aging and Alzheimer's disease. The Morris water maze (MWM) test showed improved spatial learning and memory behavior in RME treated SAMP8 mouse. Moreover, RME decreased A&#x3b2;<sub
Toward Large Language Models as a Therapeutic Tool: Comparing Prompting Techniques to Improve GPT-Delivered Problem-Solving Therapy. While Large Language Models (LLMs) are being quickly adapted to many domains, including healthcare, their strengths and pitfalls remain under-explored. In our study, we examine the effects of prompt engineering to guide Large Language Models (LLMs) in delivering parts of a Problem-Solving Therapy (PST) session via text, particularly during the symptom identification and assessment phase for personalized goal setting. We present evaluation results of the models' performances by automatic metrics and experienced medical professionals. We demonstrate that the models' capability to deliver protocolized therapy can be improved with the proper use of prompt engineering methods, albeit with limitations. To our knowledge, this study is among the first to assess the effects of various prompting techniques in enhancing a generalist model's ability to deliver psychotherapy, focusing on overall quality, consistency, and empathy. Exploring LLMs' potential in delivering psychotherapy holds promise with the current shortage of mental health professionals amid significant needs, enhancing the potential utility of AI-based and AI-enhanced care services.</AbstractText
Naturalistic Stimuli in Affective Neuroimaging: A Review. Naturalistic stimuli such as movies, music, and spoken and written stories elicit strong emotions and allow brain imaging of emotions in close-to-real-life conditions. Emotions are multi-component phenomena: relevant stimuli lead to automatic changes in multiple functional components including perception, physiology, behavior, and conscious experiences. Brain activity during naturalistic stimuli reflects all these changes, suggesting that parsing emotion-related processing during such complex stimulation is not a straightforward task. Here, I review affective neuroimaging studies that have employed naturalistic stimuli to study emotional processing, focusing especially on experienced emotions. I argue that to investigate emotions with naturalistic stimuli, we need to define and extract <i
Rosemary extract activates oligodendrogenesis genes in mouse brain and improves learning and memory ability. Rosemary (Rosmarinus officinalis L.) is a rich source of dietary bioactive compounds such as rosmarinic acid and carnosol with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. In the present study, we investigated rosemary as a potential new therapeutic agent for cognitive function and other symptoms of aging. In this present study, we have aimed to investigate the effects of oral administration of rosemary extract (RME) on learning and memory in the context of other biomarkers-related cognitive function and neurotransmitter levels in senescent accelerated prone 8 (SAMP8) mouse, a model of accelerating aging and Alzheimer's disease. The Morris water maze (MWM) test showed improved spatial learning and memory behavior in RME treated SAMP8 mouse. Moreover, RME decreased A&#x3b2;<sub
25596109
35377841
26080049
Optimizing 4-dimensional magnetic resonance imaging data sampling for respiratory motion analysis of pancreatic tumors.
Accelerated MRI Reconstruction With Separable and Enhanced Low-Rank Hankel Regularization.
Multi-level discriminative dictionary learning with application to large scale image classification.
To determine the optimum sampling strategy for retrospective reconstruction of 4-dimensional (4D) MR data for nonrigid motion characterization of tumor and organs at risk for radiation therapy purposes.</AbstractText For optimization, we compared 2 surrogate signals (external respiratory bellows and internal MRI navigators) and 2 MR sampling strategies (Cartesian and radial) in terms of image quality and robustness. Using the optimized protocol, 6 pancreatic cancer patients were scanned to calculate the 4D motion. Region of interest analysis was performed to characterize the respiratory-induced motion of the tumor and organs at risk simultaneously.</AbstractText The MRI navigator was found to be a more reliable surrogate for pancreatic motion than the respiratory bellows signal. Radial sampling is most benign for undersampling artifacts and intraview motion. Motion characterization revealed interorgan and interpatient variation, as well as heterogeneity within the tumor.</AbstractText A robust 4D-MRI method, based on clinically available protocols, is presented and successfully applied to characterize the abdominal motion in a small number of pancreatic cancer patients.</AbstractText
Magnetic resonance imaging serves as an essential tool for clinical diagnosis, however, suffers from a long acquisition time. Sparse sampling effectively saves this time but images need to be faithfully reconstructed from undersampled data. Among the existing reconstruction methods, the structured low-rank methods have advantages in robustness to the sampling patterns and lower error. However, the structured low-rank methods use the 2D or higher dimension k-space data to build a huge block Hankel matrix, leading to considerable time and memory consumption. To reduce the size of the Hankel matrix, we proposed to separably construct multiple small Hankel matrices from rows and columns of the k-space and then constrain the low-rankness on these small matrices. This separable model can significantly reduce the computational time but ignores the correlation existed in inter- and intra-row or column, resulting in increased reconstruction error. To improve the reconstructed image without obviously increasing the computation, we further introduced the self-consistency of k-space and virtual coil prior. Besides, the proposed separable model can be extended into other imaging scenarios which hold exponential characteristics in the parameter dimension. The in vivo experimental results demonstrated that the proposed method permits the lowest reconstruction error with a fast reconstruction. The proposed approach requires only 4% of the state-of-the-art STDLR-SPIRiT runtime for parallel imaging reconstruction, and achieves the fastest computational speed in parameter imaging reconstruction.</AbstractText
The sparse coding technique has shown flexibility and capability in image representation and analysis. It is a powerful tool in many visual applications. Some recent work has shown that incorporating the properties of task (such as discrimination for classification task) into dictionary learning is effective for improving the accuracy. However, the traditional supervised dictionary learning methods suffer from high computation complexity when dealing with large number of categories, making them less satisfactory in large scale applications. In this paper, we propose a novel multi-level discriminative dictionary learning method and apply it to large scale image classification. Our method takes advantage of hierarchical category correlation to encode multi-level discriminative information. Each internal node of the category hierarchy is associated with a discriminative dictionary and a classification model. The dictionaries at different layers are learnt to capture the information of different scales. Moreover, each node at lower layers also inherits the dictionary of its parent, so that the categories at lower layers can be described with multi-scale information. The learning of dictionaries and associated classification models is jointly conducted by minimizing an overall tree loss. The experimental results on challenging data sets demonstrate that our approach achieves excellent accuracy and competitive computation cost compared with other sparse coding methods for large scale image classification.</AbstractText
Optimizing 4-dimensional magnetic resonance imaging data sampling for respiratory motion analysis of pancreatic tumors. To determine the optimum sampling strategy for retrospective reconstruction of 4-dimensional (4D) MR data for nonrigid motion characterization of tumor and organs at risk for radiation therapy purposes.</AbstractText For optimization, we compared 2 surrogate signals (external respiratory bellows and internal MRI navigators) and 2 MR sampling strategies (Cartesian and radial) in terms of image quality and robustness. Using the optimized protocol, 6 pancreatic cancer patients were scanned to calculate the 4D motion. Region of interest analysis was performed to characterize the respiratory-induced motion of the tumor and organs at risk simultaneously.</AbstractText The MRI navigator was found to be a more reliable surrogate for pancreatic motion than the respiratory bellows signal. Radial sampling is most benign for undersampling artifacts and intraview motion. Motion characterization revealed interorgan and interpatient variation, as well as heterogeneity within the tumor.</AbstractText A robust 4D-MRI method, based on clinically available protocols, is presented and successfully applied to characterize the abdominal motion in a small number of pancreatic cancer patients.</AbstractText
Accelerated MRI Reconstruction With Separable and Enhanced Low-Rank Hankel Regularization. Magnetic resonance imaging serves as an essential tool for clinical diagnosis, however, suffers from a long acquisition time. Sparse sampling effectively saves this time but images need to be faithfully reconstructed from undersampled data. Among the existing reconstruction methods, the structured low-rank methods have advantages in robustness to the sampling patterns and lower error. However, the structured low-rank methods use the 2D or higher dimension k-space data to build a huge block Hankel matrix, leading to considerable time and memory consumption. To reduce the size of the Hankel matrix, we proposed to separably construct multiple small Hankel matrices from rows and columns of the k-space and then constrain the low-rankness on these small matrices. This separable model can significantly reduce the computational time but ignores the correlation existed in inter- and intra-row or column, resulting in increased reconstruction error. To improve the reconstructed image without obviously increasing the computation, we further introduced the self-consistency of k-space and virtual coil prior. Besides, the proposed separable model can be extended into other imaging scenarios which hold exponential characteristics in the parameter dimension. The in vivo experimental results demonstrated that the proposed method permits the lowest reconstruction error with a fast reconstruction. The proposed approach requires only 4% of the state-of-the-art STDLR-SPIRiT runtime for parallel imaging reconstruction, and achieves the fastest computational speed in parameter imaging reconstruction.</AbstractText
Multi-level discriminative dictionary learning with application to large scale image classification. The sparse coding technique has shown flexibility and capability in image representation and analysis. It is a powerful tool in many visual applications. Some recent work has shown that incorporating the properties of task (such as discrimination for classification task) into dictionary learning is effective for improving the accuracy. However, the traditional supervised dictionary learning methods suffer from high computation complexity when dealing with large number of categories, making them less satisfactory in large scale applications. In this paper, we propose a novel multi-level discriminative dictionary learning method and apply it to large scale image classification. Our method takes advantage of hierarchical category correlation to encode multi-level discriminative information. Each internal node of the category hierarchy is associated with a discriminative dictionary and a classification model. The dictionaries at different layers are learnt to capture the information of different scales. Moreover, each node at lower layers also inherits the dictionary of its parent, so that the categories at lower layers can be described with multi-scale information. The learning of dictionaries and associated classification models is jointly conducted by minimizing an overall tree loss. The experimental results on challenging data sets demonstrate that our approach achieves excellent accuracy and competitive computation cost compared with other sparse coding methods for large scale image classification.</AbstractText
24326314
23739174
24778691
Digital pulse processing and optimization of the front-end electronics for nuclear instrumentation.
Application and experimental validation of an integral method for simulation of gradient-induced eddy currents on conducting surfaces during magnetic resonance imaging.
Evidence for adverse effect of perinatal glucocorticoid use on the developing brain.
This article describes an algorithm developed for the digital processing of signals provided by a high-efficiency well-type NaI(Tl) detector used to apply the 4&#x3c0;&#x3b3; technique. In order to achieve a low-energy threshold, a new front-end electronics has been specifically designed to optimize the coupling to an analog-to-digital converter (14 bit, 125 MHz) connected to a digital development kit produced by Altera(&#xae;). The digital pulse processing is based on an IIR (Infinite Impulse Response) approximation of the Gaussian filter (and its derivatives) that can be applied to the real-time processing of digitized signals. Based on measurements obtained with the photon emissions generated by an (241)Am source, the energy threshold is estimated to be equal to ~2 keV corresponding to the physical threshold of the NaI(Tl) detector. An algorithm developed for a Silicon Drift Detector used for low-energy x-ray spectrometry is also described. In that case, the digital pulse processing is specifically designed for signals provided by a reset-type preamplifier ((55)Fe source).</AbstractText
The time-varying magnetic fields created by the gradient coils in magnetic resonance imaging can produce negative effects on image quality and the system itself. Additionally, they can be a limiting factor to the introduction of non-MR devices such as cardiac pacemakers, orthopedic implants, and surgical robotics. The ability to model the induced currents produced by the switching gradient fields is key to developing methods for reducing these unwanted interactions. In this work, a framework for the calculation of induced currents on conducting surface geometries is summarized. This procedure is then compared to two separate experiments: (1) the analysis of the decay of currents induced upon a conducting cylinder by an insert gradient set within a head only 7 T MR scanner; and (2) analysis of the heat deposited into a small conductor by a uniform switching magnetic field at multiple frequencies and two distinct conductor thicknesses. The method was shown to allow the accurate modeling of the induced time-varying field decay in the first case, and was able to provide accurate estimation of the rise in temperature in the second experiment to within 30% when the skin depth was greater than or equal to the thickness of the conductor.</AbstractText
The use of glucocorticoids (GCs) in the perinatal period is suspected of being associated with adverse effects on long-term neurodevelopmental outcomes for preterm infants. Repeated administration of antenatal GCs to mothers at risk of preterm birth may adversely affect fetal growth and head circumference. Fetal exposure to excess GCs during critical periods of brain development may profoundly modify the limbic system (primarily the hippocampus), resulting in long-term effects on cognition, behavior, memory, co-ordination of the autonomic nervous system, and regulation of the endocrine system later in adult life. Postnatal GC treatment for chronic lung disease in premature infants, particularly involving the use of dexamethasone, has been shown to induce neurodevelopmental impairment and increases the risk of cerebral palsy. In contrast to studies involving postnatal dexamethasone, long-term follow-up studies for hydrocortisone therapy have not revealed adverse effects on neurodevelopmental outcomes. In experimental studies on animals, GCs has been shown to impair neurogenesis, and induce neuronal apoptosis in the immature brains of newborn animals. A recent study has demonstrated that dexamethasone-induced hypomyelination may result from the apoptotic degeneration of oligodendrocyte progenitors in the immature brain. Thus, based on clinical and experimental studies, there is enough evidence to advice caution regarding the use of GCs in the perinatal period; and moreover, the potential long-term effects of GCs on brain development need to be determined.</AbstractText
Digital pulse processing and optimization of the front-end electronics for nuclear instrumentation. This article describes an algorithm developed for the digital processing of signals provided by a high-efficiency well-type NaI(Tl) detector used to apply the 4&#x3c0;&#x3b3; technique. In order to achieve a low-energy threshold, a new front-end electronics has been specifically designed to optimize the coupling to an analog-to-digital converter (14 bit, 125 MHz) connected to a digital development kit produced by Altera(&#xae;). The digital pulse processing is based on an IIR (Infinite Impulse Response) approximation of the Gaussian filter (and its derivatives) that can be applied to the real-time processing of digitized signals. Based on measurements obtained with the photon emissions generated by an (241)Am source, the energy threshold is estimated to be equal to ~2 keV corresponding to the physical threshold of the NaI(Tl) detector. An algorithm developed for a Silicon Drift Detector used for low-energy x-ray spectrometry is also described. In that case, the digital pulse processing is specifically designed for signals provided by a reset-type preamplifier ((55)Fe source).</AbstractText
Application and experimental validation of an integral method for simulation of gradient-induced eddy currents on conducting surfaces during magnetic resonance imaging. The time-varying magnetic fields created by the gradient coils in magnetic resonance imaging can produce negative effects on image quality and the system itself. Additionally, they can be a limiting factor to the introduction of non-MR devices such as cardiac pacemakers, orthopedic implants, and surgical robotics. The ability to model the induced currents produced by the switching gradient fields is key to developing methods for reducing these unwanted interactions. In this work, a framework for the calculation of induced currents on conducting surface geometries is summarized. This procedure is then compared to two separate experiments: (1) the analysis of the decay of currents induced upon a conducting cylinder by an insert gradient set within a head only 7 T MR scanner; and (2) analysis of the heat deposited into a small conductor by a uniform switching magnetic field at multiple frequencies and two distinct conductor thicknesses. The method was shown to allow the accurate modeling of the induced time-varying field decay in the first case, and was able to provide accurate estimation of the rise in temperature in the second experiment to within 30% when the skin depth was greater than or equal to the thickness of the conductor.</AbstractText
Evidence for adverse effect of perinatal glucocorticoid use on the developing brain. The use of glucocorticoids (GCs) in the perinatal period is suspected of being associated with adverse effects on long-term neurodevelopmental outcomes for preterm infants. Repeated administration of antenatal GCs to mothers at risk of preterm birth may adversely affect fetal growth and head circumference. Fetal exposure to excess GCs during critical periods of brain development may profoundly modify the limbic system (primarily the hippocampus), resulting in long-term effects on cognition, behavior, memory, co-ordination of the autonomic nervous system, and regulation of the endocrine system later in adult life. Postnatal GC treatment for chronic lung disease in premature infants, particularly involving the use of dexamethasone, has been shown to induce neurodevelopmental impairment and increases the risk of cerebral palsy. In contrast to studies involving postnatal dexamethasone, long-term follow-up studies for hydrocortisone therapy have not revealed adverse effects on neurodevelopmental outcomes. In experimental studies on animals, GCs has been shown to impair neurogenesis, and induce neuronal apoptosis in the immature brains of newborn animals. A recent study has demonstrated that dexamethasone-induced hypomyelination may result from the apoptotic degeneration of oligodendrocyte progenitors in the immature brain. Thus, based on clinical and experimental studies, there is enough evidence to advice caution regarding the use of GCs in the perinatal period; and moreover, the potential long-term effects of GCs on brain development need to be determined.</AbstractText
27191912
23092697
28718550
A methodological study of locus coeruleus degeneration in dementing disorders.
Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation.
Upper And Lower Limbs Disability And Personality Traits.
Degeneration of the locus coeruleus (LC) of the brain stem is a recognized phenomenon in Alzheimer's disease (AD), in dementia with Lewy bodies (DLB), and in Parkinson's disease with dementia (PDD). Prior studies have suggested that LC degeneration can be used to differentiate various dementing disorders histologically, but the paucity of methodological data may hamper systematic research on this nucleus.</AbstractText The purpose of this study was to evaluate various approaches to quantifying LC degeneration in dementing disorders, and to inform future decisions regarding the most appropriate method for diagnostics and research.</AbstractText 105 LCs from brains of demented individuals with AD, DLB/PDD, vascular dementia (VaD), mixed dementia (AD+VaD), or frontotemporal lobar degeneration (FTLD) were examined, and the extent of LC degeneration was assessed using macroscopic evaluation, cell counting, and two degeneration scales. Scores were compared across diagnostic categories; diagnostic utility and intra- and interobserver reliability were assessed.</AbstractText AD and DLB/PDD were associated with greater LC damage using either assessment method, significantly different from VaD and FTLD. Macroscopic appearance was informative, but cell counting was more sensitive and specific. The degeneration scales did not add significant diagnostic value over cell counting and were associated with greater observer variability.</AbstractText The LC degenerates in certain dementia subtypes, especially in AD and DLB/PDD. Macroscopic assessment of the LC postmortem can be used to differentiate between disorders associated with degeneration (AD, DLB/PDD) or sparing (VaD) of the LC, but counting LC cells in a representative pontine section is the most appropriate method by which to assess LC degeneration.</AbstractText
Degraded social function, disinhibition, and stereotypy are defining characteristics of frontotemporal dementia (FTD), manifesting in both the behavioral variant of frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Recent neuroimaging research also associates FTD with alterations in the brain's intrinsic connectivity networks. The present study explored the relationship between neural network connectivity and specific behavioral symptoms in FTD.</AbstractText Resting-state functional magnetic resonance imaging was employed to investigate neural network changes in bvFTD and SD. We used independent components analysis (ICA) to examine changes in frontolimbic network connectivity, as well as several metrics of local network strength, such as the fractional amplitude of low-frequency fluctuations, regional homogeneity, and seed-based functional connectivity. For each analysis, we compared each FTD subgroup to healthy controls, characterizing general and subtype-unique network changes. The relationship between abnormal connectivity in FTD and behavior disturbances was explored.</AbstractText Across multiple analytic approaches, both bvFTD and SD were associated with disrupted frontolimbic connectivity and elevated local connectivity within the prefrontal cortex. Even after controlling for structural atrophy, prefrontal hyperconnectivity was robustly associated with apathy scores. Frontolimbic disconnection was associated with lower disinhibition scores, suggesting that abnormal frontolimbic connectivity contributes to positive symptoms in dementia. Unique to bvFTD, stereotypy was associated with elevated default network connectivity in the right angular gyrus. The behavioral variant was also associated with marginally higher apathy scores and a more diffuse pattern of prefrontal hyperconnectivity than SD.</AbstractText The present findings support a theory of FTD as a disorder of frontolimbic disconnection leading to unconstrained prefrontal connectivity. Prefrontal hyperconnectivity may represent a compensatory response to the absence of affective feedback during the planning and execution of behavior. Increased reliance upon prefrontal processes in isolation from subcortical structures appears to be maladaptive and may drive behavioral withdrawal that is commonly observed in later phases of neurodegeneration.</AbstractText
It is believed that the study of personality has the potentials to enhance our prognostic abilities and can better to expose the etiology of mental illness through the relationship of revealed mechanisms. The focus of this study was to investigate and compare the habitual patterns of behavior, thought and emotions of upper and lower limb physically disabled students in terms of personality traits.</AbstractText This cross sectional study consisted of 100 upper limbs and lower limbs disabled students taken from Kingston school Inclusive Education System Abottabad, Mashal special education system Haripur, Syed Ahmed Shaheed special education center Abottabad, Al-Munir Foundation Mansehra and Hera Special Education System Haripur and 100 normal students taken from Islamic International School Abottabad, Falcon Public School Haripur, Iqra Academy Mansehra and Alhamd International School Haripur of Hazara Division by purposive sampling technique. This study was conducted during the month of June 2013 to May 2014. Goldberg five big personality scale was used for measuring personality traits of physically disabled and normal students.</AbstractText The significant difference of personality traits scores between physically disabled students (M = 139.2, SD=12.0) and normal students (M=184.5, SD=13.2), t (198) =25.3, p&lt;.05 was observed.</AbstractText Normal students have high scores as compared to physically disabled students on big five traits, i.e., Extraversion, Agreeableness, Conscientiousness, Emotional Stability and Openness to Experience.</AbstractText
A methodological study of locus coeruleus degeneration in dementing disorders. Degeneration of the locus coeruleus (LC) of the brain stem is a recognized phenomenon in Alzheimer's disease (AD), in dementia with Lewy bodies (DLB), and in Parkinson's disease with dementia (PDD). Prior studies have suggested that LC degeneration can be used to differentiate various dementing disorders histologically, but the paucity of methodological data may hamper systematic research on this nucleus.</AbstractText The purpose of this study was to evaluate various approaches to quantifying LC degeneration in dementing disorders, and to inform future decisions regarding the most appropriate method for diagnostics and research.</AbstractText 105 LCs from brains of demented individuals with AD, DLB/PDD, vascular dementia (VaD), mixed dementia (AD+VaD), or frontotemporal lobar degeneration (FTLD) were examined, and the extent of LC degeneration was assessed using macroscopic evaluation, cell counting, and two degeneration scales. Scores were compared across diagnostic categories; diagnostic utility and intra- and interobserver reliability were assessed.</AbstractText AD and DLB/PDD were associated with greater LC damage using either assessment method, significantly different from VaD and FTLD. Macroscopic appearance was informative, but cell counting was more sensitive and specific. The degeneration scales did not add significant diagnostic value over cell counting and were associated with greater observer variability.</AbstractText The LC degenerates in certain dementia subtypes, especially in AD and DLB/PDD. Macroscopic assessment of the LC postmortem can be used to differentiate between disorders associated with degeneration (AD, DLB/PDD) or sparing (VaD) of the LC, but counting LC cells in a representative pontine section is the most appropriate method by which to assess LC degeneration.</AbstractText
Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation. Degraded social function, disinhibition, and stereotypy are defining characteristics of frontotemporal dementia (FTD), manifesting in both the behavioral variant of frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Recent neuroimaging research also associates FTD with alterations in the brain's intrinsic connectivity networks. The present study explored the relationship between neural network connectivity and specific behavioral symptoms in FTD.</AbstractText Resting-state functional magnetic resonance imaging was employed to investigate neural network changes in bvFTD and SD. We used independent components analysis (ICA) to examine changes in frontolimbic network connectivity, as well as several metrics of local network strength, such as the fractional amplitude of low-frequency fluctuations, regional homogeneity, and seed-based functional connectivity. For each analysis, we compared each FTD subgroup to healthy controls, characterizing general and subtype-unique network changes. The relationship between abnormal connectivity in FTD and behavior disturbances was explored.</AbstractText Across multiple analytic approaches, both bvFTD and SD were associated with disrupted frontolimbic connectivity and elevated local connectivity within the prefrontal cortex. Even after controlling for structural atrophy, prefrontal hyperconnectivity was robustly associated with apathy scores. Frontolimbic disconnection was associated with lower disinhibition scores, suggesting that abnormal frontolimbic connectivity contributes to positive symptoms in dementia. Unique to bvFTD, stereotypy was associated with elevated default network connectivity in the right angular gyrus. The behavioral variant was also associated with marginally higher apathy scores and a more diffuse pattern of prefrontal hyperconnectivity than SD.</AbstractText The present findings support a theory of FTD as a disorder of frontolimbic disconnection leading to unconstrained prefrontal connectivity. Prefrontal hyperconnectivity may represent a compensatory response to the absence of affective feedback during the planning and execution of behavior. Increased reliance upon prefrontal processes in isolation from subcortical structures appears to be maladaptive and may drive behavioral withdrawal that is commonly observed in later phases of neurodegeneration.</AbstractText
Upper And Lower Limbs Disability And Personality Traits. It is believed that the study of personality has the potentials to enhance our prognostic abilities and can better to expose the etiology of mental illness through the relationship of revealed mechanisms. The focus of this study was to investigate and compare the habitual patterns of behavior, thought and emotions of upper and lower limb physically disabled students in terms of personality traits.</AbstractText This cross sectional study consisted of 100 upper limbs and lower limbs disabled students taken from Kingston school Inclusive Education System Abottabad, Mashal special education system Haripur, Syed Ahmed Shaheed special education center Abottabad, Al-Munir Foundation Mansehra and Hera Special Education System Haripur and 100 normal students taken from Islamic International School Abottabad, Falcon Public School Haripur, Iqra Academy Mansehra and Alhamd International School Haripur of Hazara Division by purposive sampling technique. This study was conducted during the month of June 2013 to May 2014. Goldberg five big personality scale was used for measuring personality traits of physically disabled and normal students.</AbstractText The significant difference of personality traits scores between physically disabled students (M = 139.2, SD=12.0) and normal students (M=184.5, SD=13.2), t (198) =25.3, p&lt;.05 was observed.</AbstractText Normal students have high scores as compared to physically disabled students on big five traits, i.e., Extraversion, Agreeableness, Conscientiousness, Emotional Stability and Openness to Experience.</AbstractText
33705760
22356937
34369204
Exploring dynamics and network analysis of spike glycoprotein of SARS-COV-2.
The organization of physiological brain networks.
Renal Denervation by Noninvasive Stereotactic Radiotherapy Induces Persistent Reduction of Sympathetic Activity in a Hypertensive Swine Model.
The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 continues to rage with devastating consequences on human health and global economy. The spike glycoprotein on the surface of coronavirus mediates its entry into host cells and is the target of all current antibody design efforts to neutralize the virus. The glycan shield of the spike helps the virus to evade the human immune response by providing a thick sugar-coated barrier against any antibody. To study the dynamic motion of glycans in the spike protein, we performed microsecond-long molecular dynamics simulation in two different states that correspond to the receptor binding domain in open or closed conformations. Analysis of this microsecond-long simulation revealed a scissoring motion on the N-terminal domain of neighboring monomers in the spike trimer. The roles of multiple glycans in shielding of spike protein in different regions were uncovered by a network analysis, in which the high betweenness centrality of glycans at the apex revealed their importance and function in the glycan shield. Microdomains of glycans were identified featuring a high degree of intracommunication in these microdomains. An antibody overlap analysis revealed the glycan microdomains as well as individual glycans that inhibit access to the antibody epitopes on the spike protein. Overall, the results of this study provide detailed understanding of the spike glycan shield, which may be utilized for therapeutic efforts against this crisis.</AbstractText
One of the central questions in neuroscience is how communication in the brain is organized under normal conditions and how this architecture breaks down in neurological disease. It has become clear that simple activation studies are no longer sufficient. There is an urgent need to understand the brain as a complex structural and functional network. Interest in brain network studies has increased strongly with the advent of modern network theory and increasingly powerful investigative techniques such as "high-density EEG", MEG, functional and structural MRI. Modern network studies of the brain have demonstrated that healthy brains self-organize towards so-called "small-world networks" characterized by a combination of dense local connectivity and critical long-distance connections. In addition, normal brain networks display hierarchical modularity, and a connectivity backbone that consists of interconnected hub nodes. This complex architecture is believed to arise under genetic control and to underlie cognition and intelligence. Optimal brain network organization becomes disrupted in neurological disease in characteristic ways. This review gives an overview of modern network theory and its applications to healthy brain function and neurological disease, in particular using techniques from clinical neurophysiology, such as EEG and MEG.</AbstractText
Background We have previously reported the feasibility of noninvasive stereotactic body radiotherapy (SBRT) as a novel approach for renal denervation. Methods and Results Herein, from a translational point of view, we assessed the antihypertensive effect and chronological evolution of SBRT-induced renal nerve injury within 6&#xa0;months in a hypertensive swine model. Hypertension was induced in swine by subcutaneous implantation of deoxycorticosterone acetate pellets in combination with a high-salt diet. A single dose of 25&#xa0;Gy with SBRT was delivered for renal denervation in 9 swine within 3.4&#xb1;1.0&#xa0;minutes. Blood pressure levels at baseline and 1 and 6&#xa0;months post-SBRT were comparable to control (n=5), whereas renal norepinephrine was significantly lower at 6&#xa0;months (<i
Exploring dynamics and network analysis of spike glycoprotein of SARS-COV-2. The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 continues to rage with devastating consequences on human health and global economy. The spike glycoprotein on the surface of coronavirus mediates its entry into host cells and is the target of all current antibody design efforts to neutralize the virus. The glycan shield of the spike helps the virus to evade the human immune response by providing a thick sugar-coated barrier against any antibody. To study the dynamic motion of glycans in the spike protein, we performed microsecond-long molecular dynamics simulation in two different states that correspond to the receptor binding domain in open or closed conformations. Analysis of this microsecond-long simulation revealed a scissoring motion on the N-terminal domain of neighboring monomers in the spike trimer. The roles of multiple glycans in shielding of spike protein in different regions were uncovered by a network analysis, in which the high betweenness centrality of glycans at the apex revealed their importance and function in the glycan shield. Microdomains of glycans were identified featuring a high degree of intracommunication in these microdomains. An antibody overlap analysis revealed the glycan microdomains as well as individual glycans that inhibit access to the antibody epitopes on the spike protein. Overall, the results of this study provide detailed understanding of the spike glycan shield, which may be utilized for therapeutic efforts against this crisis.</AbstractText
The organization of physiological brain networks. One of the central questions in neuroscience is how communication in the brain is organized under normal conditions and how this architecture breaks down in neurological disease. It has become clear that simple activation studies are no longer sufficient. There is an urgent need to understand the brain as a complex structural and functional network. Interest in brain network studies has increased strongly with the advent of modern network theory and increasingly powerful investigative techniques such as "high-density EEG", MEG, functional and structural MRI. Modern network studies of the brain have demonstrated that healthy brains self-organize towards so-called "small-world networks" characterized by a combination of dense local connectivity and critical long-distance connections. In addition, normal brain networks display hierarchical modularity, and a connectivity backbone that consists of interconnected hub nodes. This complex architecture is believed to arise under genetic control and to underlie cognition and intelligence. Optimal brain network organization becomes disrupted in neurological disease in characteristic ways. This review gives an overview of modern network theory and its applications to healthy brain function and neurological disease, in particular using techniques from clinical neurophysiology, such as EEG and MEG.</AbstractText
Renal Denervation by Noninvasive Stereotactic Radiotherapy Induces Persistent Reduction of Sympathetic Activity in a Hypertensive Swine Model. Background We have previously reported the feasibility of noninvasive stereotactic body radiotherapy (SBRT) as a novel approach for renal denervation. Methods and Results Herein, from a translational point of view, we assessed the antihypertensive effect and chronological evolution of SBRT-induced renal nerve injury within 6&#xa0;months in a hypertensive swine model. Hypertension was induced in swine by subcutaneous implantation of deoxycorticosterone acetate pellets in combination with a high-salt diet. A single dose of 25&#xa0;Gy with SBRT was delivered for renal denervation in 9 swine within 3.4&#xb1;1.0&#xa0;minutes. Blood pressure levels at baseline and 1 and 6&#xa0;months post-SBRT were comparable to control (n=5), whereas renal norepinephrine was significantly lower at 6&#xa0;months (<i
40234288
34545240
39036973
Microbiome Gut-Brain-Axis: Impact on Brain Development and Mental Health.
Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS.
Schizophrenia Quality of Life Scale and Schizophrenia Quality of Life Scale Revision 4: A Systematic Review of Measurement Properties.
The current discovery that the gut microbiome, which contains roughly 100 trillion microbes, affects health and disease has catalyzed a boom in multidisciplinary research efforts focused on understanding this relationship. Also, it is commonly demonstrated that the gut and the CNS are closely related in a bidirectional pathway. A balanced gut microbiome is essential for regular brain activities and emotional responses. On the other hand, the CNS regulates the majority of GI physiology. Any disruption in this bidirectional pathway led to a progression of health problems in both directions, neurological and gastrointestinal diseases. In this review, we hope to shed light on the complicated connections of the microbiome-gut-brain axis and the critical roles of gut microbiome in the early development of the brain in order to get a deeper knowledge of microbiome-mediated pathological conditions and management options through rebalancing of gut microbiome.</AbstractText
Almost 60 years have passed since the initial discovery by Hubel and Wiesel that changes in neuronal activity can elicit developmental rewiring of the central nervous system (CNS). Over this period, we have gained a more comprehensive picture of how both spontaneous neural activity and sensory experience-induced changes in neuronal activity guide CNS circuit development. Here we review activity-dependent synaptic pruning in the mammalian CNS, which we define as the removal of a subset of synapses, while others are maintained, in response to changes in neural activity in the developing nervous system. We discuss the mounting evidence that immune and cell-death molecules are important mechanistic links by which changes in neural activity guide the pruning of specific synapses, emphasizing the role of glial cells in this process. Finally, we discuss how these developmental pruning programmes may go awry in neurodevelopmental disorders of the human CNS, focusing on autism spectrum disorder and schizophrenia. Together, our aim is to give an overview of how the field of activity-dependent pruning research has evolved, led to exciting new questions and guided the identification of new, therapeutically relevant mechanisms that result in aberrant circuit development in neurodevelopmental disorders.</AbstractText
Schizophrenia is a severe mental disorder that has a significant impact on quality of life (QOL). Measuring QOL can offer insights into treatment efficacy and areas of intervention, highlighting the importance of valid tools assessing QOL in people with schizophrenia.</AbstractText We employed the COSMIN systematic review guideline to assess the psychometric properties of the schizophrenia quality of life scale (SQLS) and its 4th revision, the schizophrenia quality of life scale revision 4 (SQLS-R4), as patient-reported outcome measures (PROMs).</AbstractText The search yielded 455 papers, 16 were included, 7 for the SQLS and 9 for the SQLS-R4. Both scales demonstrated good results in risk of bias assessment for internal consistency and convergent validity, the SQLS-R4 additionally for known-groups validity. For the SQLS, PROM development, structural validity, and reliability were suboptimal. The SQLS-R4 showed suboptimality regarding structural validity and reliability and inadequacy for cross-cultural validity and responsiveness. The updated criteria for good measurement properties indicated good convergent validity for the SQLS and good internal consistency, reliability, and convergent validity for the SQLS-R4. The SQLS showed suboptimal results for reliability and known-groups validity, while the SQLS-R4 demonstrated suboptimality in structural validity and known-groups validity. The SQLS had indeterminate structural validity and internal consistency; the SQLS-R4 showed indeterminate responsiveness, and insufficient cross-cultural validity. When using the updated GRADE approach of the COSMIN group, both scales received a very low grade.</AbstractText The SQLS and SQLS-R4 hold the potential for recommendation in rating QOL. Identified weaknesses necessitate further validations.</AbstractText
Microbiome Gut-Brain-Axis: Impact on Brain Development and Mental Health. The current discovery that the gut microbiome, which contains roughly 100 trillion microbes, affects health and disease has catalyzed a boom in multidisciplinary research efforts focused on understanding this relationship. Also, it is commonly demonstrated that the gut and the CNS are closely related in a bidirectional pathway. A balanced gut microbiome is essential for regular brain activities and emotional responses. On the other hand, the CNS regulates the majority of GI physiology. Any disruption in this bidirectional pathway led to a progression of health problems in both directions, neurological and gastrointestinal diseases. In this review, we hope to shed light on the complicated connections of the microbiome-gut-brain axis and the critical roles of gut microbiome in the early development of the brain in order to get a deeper knowledge of microbiome-mediated pathological conditions and management options through rebalancing of gut microbiome.</AbstractText
Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS. Almost 60 years have passed since the initial discovery by Hubel and Wiesel that changes in neuronal activity can elicit developmental rewiring of the central nervous system (CNS). Over this period, we have gained a more comprehensive picture of how both spontaneous neural activity and sensory experience-induced changes in neuronal activity guide CNS circuit development. Here we review activity-dependent synaptic pruning in the mammalian CNS, which we define as the removal of a subset of synapses, while others are maintained, in response to changes in neural activity in the developing nervous system. We discuss the mounting evidence that immune and cell-death molecules are important mechanistic links by which changes in neural activity guide the pruning of specific synapses, emphasizing the role of glial cells in this process. Finally, we discuss how these developmental pruning programmes may go awry in neurodevelopmental disorders of the human CNS, focusing on autism spectrum disorder and schizophrenia. Together, our aim is to give an overview of how the field of activity-dependent pruning research has evolved, led to exciting new questions and guided the identification of new, therapeutically relevant mechanisms that result in aberrant circuit development in neurodevelopmental disorders.</AbstractText
Schizophrenia Quality of Life Scale and Schizophrenia Quality of Life Scale Revision 4: A Systematic Review of Measurement Properties. Schizophrenia is a severe mental disorder that has a significant impact on quality of life (QOL). Measuring QOL can offer insights into treatment efficacy and areas of intervention, highlighting the importance of valid tools assessing QOL in people with schizophrenia.</AbstractText We employed the COSMIN systematic review guideline to assess the psychometric properties of the schizophrenia quality of life scale (SQLS) and its 4th revision, the schizophrenia quality of life scale revision 4 (SQLS-R4), as patient-reported outcome measures (PROMs).</AbstractText The search yielded 455 papers, 16 were included, 7 for the SQLS and 9 for the SQLS-R4. Both scales demonstrated good results in risk of bias assessment for internal consistency and convergent validity, the SQLS-R4 additionally for known-groups validity. For the SQLS, PROM development, structural validity, and reliability were suboptimal. The SQLS-R4 showed suboptimality regarding structural validity and reliability and inadequacy for cross-cultural validity and responsiveness. The updated criteria for good measurement properties indicated good convergent validity for the SQLS and good internal consistency, reliability, and convergent validity for the SQLS-R4. The SQLS showed suboptimal results for reliability and known-groups validity, while the SQLS-R4 demonstrated suboptimality in structural validity and known-groups validity. The SQLS had indeterminate structural validity and internal consistency; the SQLS-R4 showed indeterminate responsiveness, and insufficient cross-cultural validity. When using the updated GRADE approach of the COSMIN group, both scales received a very low grade.</AbstractText The SQLS and SQLS-R4 hold the potential for recommendation in rating QOL. Identified weaknesses necessitate further validations.</AbstractText
39926376
35840061
39985392
Modeling the determinants of attrition in a two-stage epilepsy prevalence survey in Nairobi using machine learning.
A novel machine learning model based on sparse structure learning with adaptive graph regularization for predicting drug side effects.
Enabling Solid-Electrolyte Interphase Formation Prior to Water Reduction in Aqueous Zinc Batteries by Mild Protic Chemistry.
Attrition is a challenge in parameter estimation in both longitudinal and multi-stage cross-sectional studies. Here, we examine utility of machine learning to predict attrition and identify associated factors in a two-stage population-based epilepsy prevalence study in Nairobi.</AbstractText All individuals in the Nairobi Urban Health and Demographic Surveillance System (NUHDSS) (Korogocho and Viwandani) were screened for epilepsy in two stages. Attrition was defined as probable epilepsy cases identified at stage-I but who did not attend stage-II (neurologist assessment). Categorical variables were one-hot encoded, class imbalance was addressed using synthetic minority over-sampling technique (SMOTE) and numeric variables were scaled and centered. The dataset was split into training and testing sets (7:3 ratio), and seven machine learning models, including the ensemble Super Learner, were trained. Hyperparameters were tuned using 10-fold cross-validation, and model performance evaluated using metrics like Area under the curve (AUC), accuracy, Brier score and F1 score over 500 bootstrap samples of the test data.</AbstractText Random forest (AUC&#x202f;=&#x202f;0.98, accuracy&#x202f;=&#x202f;0.95, Brier score&#x202f;=&#x202f;0.06, and F1&#x202f;=&#x202f;0.94), extreme gradient boost (XGB) (AUC&#x202f;=&#x202f;0.96, accuracy&#x202f;=&#x202f;0.91, Brier score&#x202f;=&#x202f;0.08, F1&#x202f;=&#x202f;0.90) and support vector machine (SVM) (AUC&#x202f;=&#x202f;0.93, accuracy&#x202f;=&#x202f;0.93, Brier score&#x202f;=&#x202f;0.07, F1&#x202f;=&#x202f;0.92) were the best performing models (base learners). Ensemble Super Learner had similarly high performance. Important predictors of attrition included proximity to industrial areas, male gender, employment, education, smaller households, and a history of complex partial seizures.</AbstractText These findings can aid researchers plan targeted mobilization for scheduled clinical appointments to improve follow-up rates. These findings will inform development of a web-based algorithm to predict attrition risk and aid in targeted follow-up efforts in similar studies.</AbstractText
Drug side effects are closely related to the success and failure of drug development. Here we present a novel machine learning method for side effect prediction. The proposed method treats side effect prediction as a multi-label learning problem and uses sparse structure learning to model the relationships between side effects. Additionally, the proposed method adopts the adaptive graph regularization strategy to explore the local structure in drug data and fuse multiple types of drug features. An alternating optimization algorithm is proposed to solve the optimization problem. We collected chemical structures and biological pathway features of drugs as the inputs of our method to predict drug side effects. The results of the cross-validation experiment showed that our method could significantly improve the prediction performance compared to the other state-of-the-art methods. Besides, our model is highly interpretable. It could learn the drug neighbourhood relationships, side effect relationships, and drug features related to side effects. We systematically validated the information extracted by the model with independent data. Some prediction results could also be supported by literature reports. The proposed method could be applied to integrate both chemical and biological data to predict side effects and helps improve drug safety.</AbstractText
Challenges like hydrogen evolution reaction (HER) and dendrite formation on zinc anodes hinder the practical application of aqueous zinc batteries (AZBs), primarily due to the lack of an exceptional passivating solid-electrolyte interphase (SEI). To effectively prevent water decomposition, it is essential to in situ construct SEI prior to water reduction. This study shifts the focus from aprotic to protic SEI chemistry and predicts reduction potentials of mild protic compounds using thermodynamics. Based on this insight, mild protic 2-mercapto-1-methylimidazole (MMI) is introduced and found to be reduced prior to water at higher electrode potentials, as MMI exhibits slightly higher proton activity than water due to its thiol group. The reduction of MMI produces isothiocyanate species via a proposed electrocatalytic ring cleavage mechanism, which deposit on zinc anodes to form an SEI predominantly composed of organic compounds supplemented with Zn(OH)<sub
Modeling the determinants of attrition in a two-stage epilepsy prevalence survey in Nairobi using machine learning. Attrition is a challenge in parameter estimation in both longitudinal and multi-stage cross-sectional studies. Here, we examine utility of machine learning to predict attrition and identify associated factors in a two-stage population-based epilepsy prevalence study in Nairobi.</AbstractText All individuals in the Nairobi Urban Health and Demographic Surveillance System (NUHDSS) (Korogocho and Viwandani) were screened for epilepsy in two stages. Attrition was defined as probable epilepsy cases identified at stage-I but who did not attend stage-II (neurologist assessment). Categorical variables were one-hot encoded, class imbalance was addressed using synthetic minority over-sampling technique (SMOTE) and numeric variables were scaled and centered. The dataset was split into training and testing sets (7:3 ratio), and seven machine learning models, including the ensemble Super Learner, were trained. Hyperparameters were tuned using 10-fold cross-validation, and model performance evaluated using metrics like Area under the curve (AUC), accuracy, Brier score and F1 score over 500 bootstrap samples of the test data.</AbstractText Random forest (AUC&#x202f;=&#x202f;0.98, accuracy&#x202f;=&#x202f;0.95, Brier score&#x202f;=&#x202f;0.06, and F1&#x202f;=&#x202f;0.94), extreme gradient boost (XGB) (AUC&#x202f;=&#x202f;0.96, accuracy&#x202f;=&#x202f;0.91, Brier score&#x202f;=&#x202f;0.08, F1&#x202f;=&#x202f;0.90) and support vector machine (SVM) (AUC&#x202f;=&#x202f;0.93, accuracy&#x202f;=&#x202f;0.93, Brier score&#x202f;=&#x202f;0.07, F1&#x202f;=&#x202f;0.92) were the best performing models (base learners). Ensemble Super Learner had similarly high performance. Important predictors of attrition included proximity to industrial areas, male gender, employment, education, smaller households, and a history of complex partial seizures.</AbstractText These findings can aid researchers plan targeted mobilization for scheduled clinical appointments to improve follow-up rates. These findings will inform development of a web-based algorithm to predict attrition risk and aid in targeted follow-up efforts in similar studies.</AbstractText
A novel machine learning model based on sparse structure learning with adaptive graph regularization for predicting drug side effects. Drug side effects are closely related to the success and failure of drug development. Here we present a novel machine learning method for side effect prediction. The proposed method treats side effect prediction as a multi-label learning problem and uses sparse structure learning to model the relationships between side effects. Additionally, the proposed method adopts the adaptive graph regularization strategy to explore the local structure in drug data and fuse multiple types of drug features. An alternating optimization algorithm is proposed to solve the optimization problem. We collected chemical structures and biological pathway features of drugs as the inputs of our method to predict drug side effects. The results of the cross-validation experiment showed that our method could significantly improve the prediction performance compared to the other state-of-the-art methods. Besides, our model is highly interpretable. It could learn the drug neighbourhood relationships, side effect relationships, and drug features related to side effects. We systematically validated the information extracted by the model with independent data. Some prediction results could also be supported by literature reports. The proposed method could be applied to integrate both chemical and biological data to predict side effects and helps improve drug safety.</AbstractText
Enabling Solid-Electrolyte Interphase Formation Prior to Water Reduction in Aqueous Zinc Batteries by Mild Protic Chemistry. Challenges like hydrogen evolution reaction (HER) and dendrite formation on zinc anodes hinder the practical application of aqueous zinc batteries (AZBs), primarily due to the lack of an exceptional passivating solid-electrolyte interphase (SEI). To effectively prevent water decomposition, it is essential to in situ construct SEI prior to water reduction. This study shifts the focus from aprotic to protic SEI chemistry and predicts reduction potentials of mild protic compounds using thermodynamics. Based on this insight, mild protic 2-mercapto-1-methylimidazole (MMI) is introduced and found to be reduced prior to water at higher electrode potentials, as MMI exhibits slightly higher proton activity than water due to its thiol group. The reduction of MMI produces isothiocyanate species via a proposed electrocatalytic ring cleavage mechanism, which deposit on zinc anodes to form an SEI predominantly composed of organic compounds supplemented with Zn(OH)<sub
27664824
26663615
39449736
Perceived social isolation is associated with altered functional connectivity in neural networks associated with tonic alertness and executive control.
Presurgical brain mapping of the language network in patients with brain tumors using resting-state fMRI: Comparison with task fMRI.
Extrapolative Scaling Expression: A Fitting Equation for Extrapolating Full Ic(B, T, ε) Data Matrixes From Limited Data.
Perceived social isolation (PSI), colloquially known as loneliness, is associated with selectively altered attentional, cognitive, and affective processes in humans, but the neural mechanisms underlying these adjustments remain largely unexplored. Behavioral, eye tracking, and neuroimaging research has identified associations between PSI and implicit hypervigilance for social threats. Additionally, selective executive dysfunction has been evidenced by reduced prepotent response inhibition in social Stroop and dichotic listening tasks. Given that PSI is associated with pre-attentional processes, PSI may also be related to altered resting-state functional connectivity (FC) in the brain. Therefore, we conducted the first resting-state fMRI FC study of PSI in healthy young adults. Five-minute resting-state scans were obtained from 55 participants (31 females). Analyses revealed robust associations between PSI and increased brain-wide FC in areas encompassing the right central operculum and right supramarginal gyrus, and these associations were not explained by depressive symptomatology, objective isolation, or demographics. Further analyses revealed that PSI was associated with increased FC between several nodes of the cingulo-opercular network, a network known to underlie the maintenance of tonic alertness. These regions encompassed the bilateral insula/frontoparietal opercula and ACC/pre-SMA. In contrast, FC between the cingulo-opercular network and right middle/superior frontal gyrus was reduced, a finding associated with diminished executive function in prior literature. We suggest that, in PSI, increased within-network cingulo-opercular FC may be associated with hypervigilance to social threat, whereas reduced right middle/superior frontal gyrus FC to the cingulo-opercular network may be associated with diminished impulse control.</AbstractText
To compare language networks derived from resting-state fMRI (rs-fMRI) with task-fMRI in patients with brain tumors and investigate variables that affect rs-fMRI vs task-fMRI concordance.</AbstractText Independent component analysis (ICA) of rs-fMRI was performed with 20, 30, 40, and 50 target components (ICA20 to ICA50) and language networks identified for patients presenting for presurgical fMRI mapping between 1/1/2009 and 7/1/2015. 49 patients were analyzed fulfilling criteria for presence of brain tumors, no prior brain surgery, and adequate task-fMRI performance. Rs-vs-task-fMRI concordance was measured using Dice coefficients across varying fMRI thresholds before and after noise removal. Multi-thresholded Dice coefficient volume under the surface (DiceVUS) and maximum Dice coefficient (MaxDice) were calculated. One-way Analysis of Variance (ANOVA) was performed to determine significance of DiceVUS and MaxDice between the four ICA order groups. Age, Sex, Handedness, Tumor Side, Tumor Size, WHO Grade, number of scrubbed volumes, image intensity root mean square (iRMS), and mean framewise displacement (FD) were used as predictors for VUS in a linear regression.</AbstractText Artificial elevation of rs-fMRI vs task-fMRI concordance is seen at low thresholds due to noise. Noise-removed group-mean DiceVUS and MaxDice improved as ICA order increased, however ANOVA demonstrated no statistically significant difference between the four groups. Linear regression demonstrated an association between iRMS and DiceVUS for ICA30-50, and iRMS and MaxDice for ICA50.</AbstractText Overall there is moderate group level rs-vs-task fMRI language network concordance, however substantial subject-level variability exists; iRMS may be used to determine reliability of rs-fMRI derived language networks.</AbstractText
Scaling analysis of several thousand Nb<sub
Perceived social isolation is associated with altered functional connectivity in neural networks associated with tonic alertness and executive control. Perceived social isolation (PSI), colloquially known as loneliness, is associated with selectively altered attentional, cognitive, and affective processes in humans, but the neural mechanisms underlying these adjustments remain largely unexplored. Behavioral, eye tracking, and neuroimaging research has identified associations between PSI and implicit hypervigilance for social threats. Additionally, selective executive dysfunction has been evidenced by reduced prepotent response inhibition in social Stroop and dichotic listening tasks. Given that PSI is associated with pre-attentional processes, PSI may also be related to altered resting-state functional connectivity (FC) in the brain. Therefore, we conducted the first resting-state fMRI FC study of PSI in healthy young adults. Five-minute resting-state scans were obtained from 55 participants (31 females). Analyses revealed robust associations between PSI and increased brain-wide FC in areas encompassing the right central operculum and right supramarginal gyrus, and these associations were not explained by depressive symptomatology, objective isolation, or demographics. Further analyses revealed that PSI was associated with increased FC between several nodes of the cingulo-opercular network, a network known to underlie the maintenance of tonic alertness. These regions encompassed the bilateral insula/frontoparietal opercula and ACC/pre-SMA. In contrast, FC between the cingulo-opercular network and right middle/superior frontal gyrus was reduced, a finding associated with diminished executive function in prior literature. We suggest that, in PSI, increased within-network cingulo-opercular FC may be associated with hypervigilance to social threat, whereas reduced right middle/superior frontal gyrus FC to the cingulo-opercular network may be associated with diminished impulse control.</AbstractText
Presurgical brain mapping of the language network in patients with brain tumors using resting-state fMRI: Comparison with task fMRI. To compare language networks derived from resting-state fMRI (rs-fMRI) with task-fMRI in patients with brain tumors and investigate variables that affect rs-fMRI vs task-fMRI concordance.</AbstractText Independent component analysis (ICA) of rs-fMRI was performed with 20, 30, 40, and 50 target components (ICA20 to ICA50) and language networks identified for patients presenting for presurgical fMRI mapping between 1/1/2009 and 7/1/2015. 49 patients were analyzed fulfilling criteria for presence of brain tumors, no prior brain surgery, and adequate task-fMRI performance. Rs-vs-task-fMRI concordance was measured using Dice coefficients across varying fMRI thresholds before and after noise removal. Multi-thresholded Dice coefficient volume under the surface (DiceVUS) and maximum Dice coefficient (MaxDice) were calculated. One-way Analysis of Variance (ANOVA) was performed to determine significance of DiceVUS and MaxDice between the four ICA order groups. Age, Sex, Handedness, Tumor Side, Tumor Size, WHO Grade, number of scrubbed volumes, image intensity root mean square (iRMS), and mean framewise displacement (FD) were used as predictors for VUS in a linear regression.</AbstractText Artificial elevation of rs-fMRI vs task-fMRI concordance is seen at low thresholds due to noise. Noise-removed group-mean DiceVUS and MaxDice improved as ICA order increased, however ANOVA demonstrated no statistically significant difference between the four groups. Linear regression demonstrated an association between iRMS and DiceVUS for ICA30-50, and iRMS and MaxDice for ICA50.</AbstractText Overall there is moderate group level rs-vs-task fMRI language network concordance, however substantial subject-level variability exists; iRMS may be used to determine reliability of rs-fMRI derived language networks.</AbstractText
Extrapolative Scaling Expression: A Fitting Equation for Extrapolating Full Ic(B, T, ε) Data Matrixes From Limited Data. Scaling analysis of several thousand Nb<sub
37799087
20665790
38221864
HyperSLICE: HyperBand optimized spiral for low-latency interactive cardiac examination.
SPIRiT: Iterative self-consistent parallel imaging reconstruction from arbitrary k-space.
The effect of age on executive functions in adults is not sex specific.
Interactive cardiac MRI is used for fast scan planning and MR-guided interventions. However, the requirement for real-time acquisition and near-real-time visualization constrains the achievable spatio-temporal resolution. This study aims to improve interactive imaging resolution through optimization of undersampled spiral sampling and leveraging of deep learning for low-latency reconstruction (deep artifact suppression).</AbstractText A variable density spiral trajectory was parametrized and optimized via HyperBand to provide the best candidate trajectory for rapid deep artifact suppression. Training data consisted of 692 breath-held CINEs. The developed interactive sequence was tested in simulations and prospectively in 13 subjects (10 for image evaluation, 2 during catheterization, 1 during exercise). In the prospective study, the optimized framework-HyperSLICE- was compared with conventional Cartesian real-time and breath-hold CINE imaging in terms quantitative and qualitative image metrics. Statistical differences were tested using Friedman chi-squared tests with post hoc Nemenyi test (p&#x2009;&lt;&#x2009;0.05).</AbstractText In simulations the normalized RMS error, peak SNR, structural similarity, and Laplacian energy were all statistically significantly higher using optimized spiral compared to radial and uniform spiral sampling, particularly after scan plan changes (structural similarity: 0.71 vs. 0.45 and 0.43). Prospectively, HyperSLICE enabled a higher spatial and temporal resolution than conventional Cartesian real-time imaging. The pipeline was demonstrated in patients during catheter pull back, showing sufficiently fast reconstruction for interactive imaging.</AbstractText HyperSLICE enables high spatial and temporal resolution interactive imaging. Optimizing the spiral sampling enabled better overall image quality and superior handling of image transitions compared with radial and uniform spiral trajectories.</AbstractText
A new approach to autocalibrating, coil-by-coil parallel imaging reconstruction, is presented. It is a generalized reconstruction framework based on self-consistency. The reconstruction problem is formulated as an optimization that yields the most consistent solution with the calibration and acquisition data. The approach is general and can accurately reconstruct images from arbitrary k-space sampling patterns. The formulation can flexibly incorporate additional image priors such as off-resonance correction and regularization terms that appear in compressed sensing. Several iterative strategies to solve the posed reconstruction problem in both image and k-space domain are presented. These are based on a projection over convex sets and conjugate gradient algorithms. Phantom and in vivo studies demonstrate efficient reconstructions from undersampled Cartesian and spiral trajectories. Reconstructions that include off-resonance correction and nonlinear l(1)-wavelet regularization are also demonstrated.</AbstractText
Numerous studies have shown a decrease in executive functions (EF) associated with aging. However, few investigations examined whether this decrease is similar between sexes throughout adulthood. The present study investigated if age-related decline in EF differs between men and women from early to late adulthood.</AbstractText A total of 302 participants (181 women) aged between 18 and 78 years old completed four computer-based cognitive tasks at home: an arrow-based Flanker task, a letter-based Visual search task, the Trail Making Test, and the Corsi task. These tasks measured inhibition, attention, cognitive flexibility, and working memory, respectively. To investigate the potential effects of age, sex, and their interaction on specific EF and a global EF score, we divided the sample population into five age groups (i.e., 18-30, 31-44, 45-54, 55-64, 65-78) and conducted analyses of covariance (MANCOVA and ANCOVA) with education and pointing device as control variables.</AbstractText Sex did not significantly affect EF performance across age groups. However, in every task, participants from the three youngest groups (&lt; 55 y/o) outperformed the ones from the two oldest. Results from the global score also suggest that an EF decrease is distinctly noticeable from 55 years old onward.</AbstractText Our results suggest that age-related decline in EF, including inhibition, attention, cognitive flexibility, and working memory, becomes apparent around the age of 55 and does not differ between sexes at any age. This study provides additional data regarding the effects of age and sex on EF across adulthood, filling a significant gap in the existing literature.</AbstractText
HyperSLICE: HyperBand optimized spiral for low-latency interactive cardiac examination. Interactive cardiac MRI is used for fast scan planning and MR-guided interventions. However, the requirement for real-time acquisition and near-real-time visualization constrains the achievable spatio-temporal resolution. This study aims to improve interactive imaging resolution through optimization of undersampled spiral sampling and leveraging of deep learning for low-latency reconstruction (deep artifact suppression).</AbstractText A variable density spiral trajectory was parametrized and optimized via HyperBand to provide the best candidate trajectory for rapid deep artifact suppression. Training data consisted of 692 breath-held CINEs. The developed interactive sequence was tested in simulations and prospectively in 13 subjects (10 for image evaluation, 2 during catheterization, 1 during exercise). In the prospective study, the optimized framework-HyperSLICE- was compared with conventional Cartesian real-time and breath-hold CINE imaging in terms quantitative and qualitative image metrics. Statistical differences were tested using Friedman chi-squared tests with post hoc Nemenyi test (p&#x2009;&lt;&#x2009;0.05).</AbstractText In simulations the normalized RMS error, peak SNR, structural similarity, and Laplacian energy were all statistically significantly higher using optimized spiral compared to radial and uniform spiral sampling, particularly after scan plan changes (structural similarity: 0.71 vs. 0.45 and 0.43). Prospectively, HyperSLICE enabled a higher spatial and temporal resolution than conventional Cartesian real-time imaging. The pipeline was demonstrated in patients during catheter pull back, showing sufficiently fast reconstruction for interactive imaging.</AbstractText HyperSLICE enables high spatial and temporal resolution interactive imaging. Optimizing the spiral sampling enabled better overall image quality and superior handling of image transitions compared with radial and uniform spiral trajectories.</AbstractText
SPIRiT: Iterative self-consistent parallel imaging reconstruction from arbitrary k-space. A new approach to autocalibrating, coil-by-coil parallel imaging reconstruction, is presented. It is a generalized reconstruction framework based on self-consistency. The reconstruction problem is formulated as an optimization that yields the most consistent solution with the calibration and acquisition data. The approach is general and can accurately reconstruct images from arbitrary k-space sampling patterns. The formulation can flexibly incorporate additional image priors such as off-resonance correction and regularization terms that appear in compressed sensing. Several iterative strategies to solve the posed reconstruction problem in both image and k-space domain are presented. These are based on a projection over convex sets and conjugate gradient algorithms. Phantom and in vivo studies demonstrate efficient reconstructions from undersampled Cartesian and spiral trajectories. Reconstructions that include off-resonance correction and nonlinear l(1)-wavelet regularization are also demonstrated.</AbstractText
The effect of age on executive functions in adults is not sex specific. Numerous studies have shown a decrease in executive functions (EF) associated with aging. However, few investigations examined whether this decrease is similar between sexes throughout adulthood. The present study investigated if age-related decline in EF differs between men and women from early to late adulthood.</AbstractText A total of 302 participants (181 women) aged between 18 and 78 years old completed four computer-based cognitive tasks at home: an arrow-based Flanker task, a letter-based Visual search task, the Trail Making Test, and the Corsi task. These tasks measured inhibition, attention, cognitive flexibility, and working memory, respectively. To investigate the potential effects of age, sex, and their interaction on specific EF and a global EF score, we divided the sample population into five age groups (i.e., 18-30, 31-44, 45-54, 55-64, 65-78) and conducted analyses of covariance (MANCOVA and ANCOVA) with education and pointing device as control variables.</AbstractText Sex did not significantly affect EF performance across age groups. However, in every task, participants from the three youngest groups (&lt; 55 y/o) outperformed the ones from the two oldest. Results from the global score also suggest that an EF decrease is distinctly noticeable from 55 years old onward.</AbstractText Our results suggest that age-related decline in EF, including inhibition, attention, cognitive flexibility, and working memory, becomes apparent around the age of 55 and does not differ between sexes at any age. This study provides additional data regarding the effects of age and sex on EF across adulthood, filling a significant gap in the existing literature.</AbstractText
28347679
17349624
28230386
Chronic Traumatic Encephalopathy: The cellular sequela to repetitive brain injury.
Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury.
Does the cerebellum contribute to human navigation by processing sequential information?
This review aims to integrate current literature on the pathogenic mechanisms of Chronic Traumatic Encephalopathy (CTE) to create a multifactorial understanding of the disease. CTE is a progressive neurodegenerative disease, classed as a tauopathy, although it appears the pathogenic mechanisms are more complex than this. It affects those with a history of repetitive mild traumatic brain injury. Currently, there are no treatments for CTE and the disease can only be affirmatively diagnosed in post mortem. Understanding the pathogenesis of the disease will provide an avenue to explore possible treatment and diagnostic modalities. The pathological hallmarks of CTE have been well characterised and have been linked to the pathophysiologic mechanisms in this review. Human studies are limited due to ethical implications of exposing subjects to head trauma. Phosphorylation of tau, microglial activation, TAR DNA-binding protein 43 and diffuse axonal injury have all been implicated in the pathogenesis of CTE. The neuronal loss and axonal dysfunction mediated by these pathognomonic mechanisms lead to the broad psycho-cognitive symptoms seen in CTE.</AbstractText
We assessed the temporal and spatial characteristics of PN-induced oxidative damage and its relationship to calpain-mediated cytoskeletal degradation and neurodegeneration in a severe unilateral controlled cortical impact (CCI) traumatic brain injury (TBI) model. Quantitative temporal time course studies were performed to measure two oxidative damage markers: 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE) at 30 min, 1, 3, 6, 12, 24, 48, 72 h and 7 days after injury in ipsilateral cortex of young adult male CF-1 mice. Secondly, the time course of Ca(++)-activated, calpain-mediated proteolysis was also analyzed using quantitative western-blot measurement of breakdown products of the cytoskeletal protein alpha-spectrin. Finally, the time course of neurodegeneration was examined using de Olmos silver staining. Both oxidative damage markers increased in cortical tissue immediately after injury (30 min) and elevated for the first 3-6 h before returning to baseline. In the immunostaining study, the PN-selective marker, 3NT, and the lipid peroxidation marker, 4HNE, were intense and overlapping in the injured cortical tissue. alpha-Spectrin breakdown products, which were used as biomarker for calpain-mediated cytoskeletal degradation, were also increased after injury, but the time course lagged behind the peak of oxidative damage and did not reach its maximum until 24 h post-injury. In turn, cytoskeletal degradation preceded the peak of neurodegeneration which occurred at 48 h post-injury. These studies have led us to the hypothesis that PN-mediated oxidative damage is an early event that contributes to a compromise of Ca(++) homeostatic mechanisms which causes a massive Ca(++) overload and calpain activation which is a final common pathway that results in post-traumatic neurodegeneration.</AbstractText
Several authors have proposed that the cerebellum has an important role in functions of higher order as a general mode of sequence detection, independently from the nature of the information. The aim of this study was to verify whether the cerebellum mediates the processing of navigational sequential information and to determine whether it is influenced by the modality of the stimuli presentation.</AbstractText We tested 12 cerebellar patients and 12 healthy age-matched participants in 2 comparable navigational tasks (Walking Corsi Test and the Magic Carpet) requiring to memorizing a sequence of spatial locations. The 2 tasks differ each other for the modality of stimuli presentation: in the Walking Corsi Test the sequence is shown by an examiner that walks on the carpet, whereas in the Magic Carpet it is shown by a computer that lights up the tiles in the sequence. We hypothesize that different mental processes are implicated between the Walking Corsi Test and the Magic Carpet. Indeed, whereas watching the examiner, who performs the sequence on the carpet, allows the patient to simulate the action mentally in the Walking Corsi Test, such simulation cannot be triggered in the Magic Carpet.</AbstractText Our results showed that cerebellar patients obtained scores significantly lower than control participants only in the Magic Carpet.</AbstractText We interpreted the patients' performance as a specific deficit in detecting and ordering single independent stimuli as a sequence, when the maintenance of stimulus-response associations is more demanding. (PsycINFO Database Record</AbstractText
Chronic Traumatic Encephalopathy: The cellular sequela to repetitive brain injury. This review aims to integrate current literature on the pathogenic mechanisms of Chronic Traumatic Encephalopathy (CTE) to create a multifactorial understanding of the disease. CTE is a progressive neurodegenerative disease, classed as a tauopathy, although it appears the pathogenic mechanisms are more complex than this. It affects those with a history of repetitive mild traumatic brain injury. Currently, there are no treatments for CTE and the disease can only be affirmatively diagnosed in post mortem. Understanding the pathogenesis of the disease will provide an avenue to explore possible treatment and diagnostic modalities. The pathological hallmarks of CTE have been well characterised and have been linked to the pathophysiologic mechanisms in this review. Human studies are limited due to ethical implications of exposing subjects to head trauma. Phosphorylation of tau, microglial activation, TAR DNA-binding protein 43 and diffuse axonal injury have all been implicated in the pathogenesis of CTE. The neuronal loss and axonal dysfunction mediated by these pathognomonic mechanisms lead to the broad psycho-cognitive symptoms seen in CTE.</AbstractText
Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury. We assessed the temporal and spatial characteristics of PN-induced oxidative damage and its relationship to calpain-mediated cytoskeletal degradation and neurodegeneration in a severe unilateral controlled cortical impact (CCI) traumatic brain injury (TBI) model. Quantitative temporal time course studies were performed to measure two oxidative damage markers: 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE) at 30 min, 1, 3, 6, 12, 24, 48, 72 h and 7 days after injury in ipsilateral cortex of young adult male CF-1 mice. Secondly, the time course of Ca(++)-activated, calpain-mediated proteolysis was also analyzed using quantitative western-blot measurement of breakdown products of the cytoskeletal protein alpha-spectrin. Finally, the time course of neurodegeneration was examined using de Olmos silver staining. Both oxidative damage markers increased in cortical tissue immediately after injury (30 min) and elevated for the first 3-6 h before returning to baseline. In the immunostaining study, the PN-selective marker, 3NT, and the lipid peroxidation marker, 4HNE, were intense and overlapping in the injured cortical tissue. alpha-Spectrin breakdown products, which were used as biomarker for calpain-mediated cytoskeletal degradation, were also increased after injury, but the time course lagged behind the peak of oxidative damage and did not reach its maximum until 24 h post-injury. In turn, cytoskeletal degradation preceded the peak of neurodegeneration which occurred at 48 h post-injury. These studies have led us to the hypothesis that PN-mediated oxidative damage is an early event that contributes to a compromise of Ca(++) homeostatic mechanisms which causes a massive Ca(++) overload and calpain activation which is a final common pathway that results in post-traumatic neurodegeneration.</AbstractText
Does the cerebellum contribute to human navigation by processing sequential information? Several authors have proposed that the cerebellum has an important role in functions of higher order as a general mode of sequence detection, independently from the nature of the information. The aim of this study was to verify whether the cerebellum mediates the processing of navigational sequential information and to determine whether it is influenced by the modality of the stimuli presentation.</AbstractText We tested 12 cerebellar patients and 12 healthy age-matched participants in 2 comparable navigational tasks (Walking Corsi Test and the Magic Carpet) requiring to memorizing a sequence of spatial locations. The 2 tasks differ each other for the modality of stimuli presentation: in the Walking Corsi Test the sequence is shown by an examiner that walks on the carpet, whereas in the Magic Carpet it is shown by a computer that lights up the tiles in the sequence. We hypothesize that different mental processes are implicated between the Walking Corsi Test and the Magic Carpet. Indeed, whereas watching the examiner, who performs the sequence on the carpet, allows the patient to simulate the action mentally in the Walking Corsi Test, such simulation cannot be triggered in the Magic Carpet.</AbstractText Our results showed that cerebellar patients obtained scores significantly lower than control participants only in the Magic Carpet.</AbstractText We interpreted the patients' performance as a specific deficit in detecting and ordering single independent stimuli as a sequence, when the maintenance of stimulus-response associations is more demanding. (PsycINFO Database Record</AbstractText
38116071
25759674
39188554
Frontal lobe epilepsy: an eye tracking study of memory and attention.
Supramodal executive control of attention.
Nurturing the marriages of urinary liquid biopsies and nano-diagnostics for precision urinalysis of prostate cancer.
To explore the characteristics and mechanisms of working memory impairment in patients with frontal lobe epilepsy (FLE) through a memory game paradigm combined with eye tracking technology.</AbstractText We included 44 patients with FLE and 50 healthy controls (HC). All participants completed a series of neuropsychological scale assessments and a short-term memory game on an automated computer-based memory evaluation platform with an eye tracker.</AbstractText Memory scale scores of FLE patients including digit span (U&#x2009;=&#x2009;747.50, <i Patients with FLE exhibited short-term memory impairment probably due to deficits in attentional maintenance, especially during the memory decoding phase. Eye tracking technology provided the possibility to help separate and quantify visual attention from memory processing, contributing to exploring underlying mechanisms of memory impairment in FLE.</AbstractText
The human attentional system can be subdivided into three functional networks of alerting, orienting, and executive control. Although these networks have been extensively studied in the visuospatial modality, whether the same mechanisms are deployed across different sensory modalities remains unclear. In this study we used the attention network test for the visuospatial modality, in addition to two auditory variants with spatial and frequency manipulations to examine cross-modal correlations between network functions. Results showed that among the visual and auditory tasks, the effects of executive control, but not effects of alerting and orienting, were significantly correlated. These findings suggest that while alerting and orienting functions rely more upon modality-specific processes, the executive control of attention coordinates complex behavior via supramodal mechanisms.</AbstractText
Prostate cancer remains the second-most common cancer diagnosed in men, despite the increasingly widespread use of serum prostate-specific antigen (PSA) screening. The controversial clinical implications and cost benefits of PSA screening have been highlighted due to its poor specificity, resulting in a high rate of overdiagnosis and underdiagnosis. Thus, the development of novel biomarkers for prostate cancer detection remains an intriguing challenge. Urine is emerging as a source for prostate cancer biomarker discovery. Currently, new urine biomarkers already outperform serum PSA in clinical diagnosis. Meanwhile, the advances in nanotechnology have provided a suite of diagnostic tools to study prostate cancer in more detail, sparking a new era of biomarker discoveries. In this review, we envision that future prostate cancer diagnosis will probably integrate multiplex nano-diagnostic approaches to detect novel urinary biomarkers. However, challenges remain in differentiating indolent from aggressive cancers to better inform treatment decisions, and clinical translation still needs to be overcome.</AbstractText
Frontal lobe epilepsy: an eye tracking study of memory and attention. To explore the characteristics and mechanisms of working memory impairment in patients with frontal lobe epilepsy (FLE) through a memory game paradigm combined with eye tracking technology.</AbstractText We included 44 patients with FLE and 50 healthy controls (HC). All participants completed a series of neuropsychological scale assessments and a short-term memory game on an automated computer-based memory evaluation platform with an eye tracker.</AbstractText Memory scale scores of FLE patients including digit span (U&#x2009;=&#x2009;747.50, <i Patients with FLE exhibited short-term memory impairment probably due to deficits in attentional maintenance, especially during the memory decoding phase. Eye tracking technology provided the possibility to help separate and quantify visual attention from memory processing, contributing to exploring underlying mechanisms of memory impairment in FLE.</AbstractText
Supramodal executive control of attention. The human attentional system can be subdivided into three functional networks of alerting, orienting, and executive control. Although these networks have been extensively studied in the visuospatial modality, whether the same mechanisms are deployed across different sensory modalities remains unclear. In this study we used the attention network test for the visuospatial modality, in addition to two auditory variants with spatial and frequency manipulations to examine cross-modal correlations between network functions. Results showed that among the visual and auditory tasks, the effects of executive control, but not effects of alerting and orienting, were significantly correlated. These findings suggest that while alerting and orienting functions rely more upon modality-specific processes, the executive control of attention coordinates complex behavior via supramodal mechanisms.</AbstractText
Nurturing the marriages of urinary liquid biopsies and nano-diagnostics for precision urinalysis of prostate cancer. Prostate cancer remains the second-most common cancer diagnosed in men, despite the increasingly widespread use of serum prostate-specific antigen (PSA) screening. The controversial clinical implications and cost benefits of PSA screening have been highlighted due to its poor specificity, resulting in a high rate of overdiagnosis and underdiagnosis. Thus, the development of novel biomarkers for prostate cancer detection remains an intriguing challenge. Urine is emerging as a source for prostate cancer biomarker discovery. Currently, new urine biomarkers already outperform serum PSA in clinical diagnosis. Meanwhile, the advances in nanotechnology have provided a suite of diagnostic tools to study prostate cancer in more detail, sparking a new era of biomarker discoveries. In this review, we envision that future prostate cancer diagnosis will probably integrate multiplex nano-diagnostic approaches to detect novel urinary biomarkers. However, challenges remain in differentiating indolent from aggressive cancers to better inform treatment decisions, and clinical translation still needs to be overcome.</AbstractText
40304297
17761885
40725953
MEA-seqX: High-Resolution Profiling of Large-Scale Electrophysiological and Transcriptional Network Dynamics.
Localization of a stable neural correlate of associative memory.
Combined treatment of a giant duodenal gastrointestinal stromal tumor: A case report.
Concepts of brain function imply congruence and mutual causal influence between molecular events and neuronal activity. Decoding entangled information from concurrent molecular and electrophysiological network events demands innovative methodology bridging scales and modalities. The MEA-seqX platform, integrating high-density microelectrode arrays, spatial transcriptomics, optical imaging, and advanced computational strategies, enables the simultaneous recording and analysis of molecular and electrical network activities at mesoscale spatial resolution. Applied to a mouse hippocampal model of experience-dependent plasticity, MEA-seqX unveils massively enhanced nested dynamics between transcription and function. Graph-theoretic analysis reveals an increase in densely connected bimodal hubs, marking the first observation of coordinated hippocampal circuitry dynamics at molecular and functional levels. This platform also identifies different cell types based on their distinct bimodal profiles. Machine-learning algorithms accurately predict network-wide electrophysiological activity features from spatial gene expression, demonstrating a previously inaccessible convergence across modalities, time, and scales.</AbstractText
Do learning and retrieval of a memory activate the same neurons? Does the number of reactivated neurons correlate with memory strength? We developed a transgenic mouse that enables the long-lasting genetic tagging of c-fos-active neurons. We found neurons in the basolateral amygdala that are activated during Pavlovian fear conditioning and are reactivated during memory retrieval. The number of reactivated neurons correlated positively with the behavioral expression of the fear memory, indicating a stable neural correlate of associative memory. The ability to manipulate these neurons genetically should allow a more precise dissection of the molecular mechanisms of memory encoding within a distributed neuronal network.</AbstractText
Gastrointestinal stromal tumors (GISTs) in the duodenum are usually very rare, accounting for only 3% to 5% of all GISTs. Giant duodenal GISTs with a more than 10&#x2009;cm diameter are even rarer, and there is currently no consensus on their treatment. This article reports a case of successful treatment of a giant duodenal GIST.</AbstractText A 59-year-old woman presented with mid-upper abdominal pain accompanied by nausea and bloating. We underwent contrast-enhanced abdominal computed tomography scans and computed tomography-guided fine needle aspiration biopsy.</AbstractText The final diagnosis was duodenal GIST with a risk stratification of high-risk.</AbstractText After a multidisciplinary team discussion, the patient underwent a combination of targeted-surgical-targeted therapy.</AbstractText The patient ultimately achieved R0 resection at surgery, and no recurrence was noted during the follow-up period.</AbstractText Targeted-surgery-targeted combined therapy is one of the effective means for giant duodenal GIST. At the same time, genetic testing before neoadjuvant therapy is crucial for guiding treatment and is strongly recommended as a basic examination method.</AbstractText
MEA-seqX: High-Resolution Profiling of Large-Scale Electrophysiological and Transcriptional Network Dynamics. Concepts of brain function imply congruence and mutual causal influence between molecular events and neuronal activity. Decoding entangled information from concurrent molecular and electrophysiological network events demands innovative methodology bridging scales and modalities. The MEA-seqX platform, integrating high-density microelectrode arrays, spatial transcriptomics, optical imaging, and advanced computational strategies, enables the simultaneous recording and analysis of molecular and electrical network activities at mesoscale spatial resolution. Applied to a mouse hippocampal model of experience-dependent plasticity, MEA-seqX unveils massively enhanced nested dynamics between transcription and function. Graph-theoretic analysis reveals an increase in densely connected bimodal hubs, marking the first observation of coordinated hippocampal circuitry dynamics at molecular and functional levels. This platform also identifies different cell types based on their distinct bimodal profiles. Machine-learning algorithms accurately predict network-wide electrophysiological activity features from spatial gene expression, demonstrating a previously inaccessible convergence across modalities, time, and scales.</AbstractText
Localization of a stable neural correlate of associative memory. Do learning and retrieval of a memory activate the same neurons? Does the number of reactivated neurons correlate with memory strength? We developed a transgenic mouse that enables the long-lasting genetic tagging of c-fos-active neurons. We found neurons in the basolateral amygdala that are activated during Pavlovian fear conditioning and are reactivated during memory retrieval. The number of reactivated neurons correlated positively with the behavioral expression of the fear memory, indicating a stable neural correlate of associative memory. The ability to manipulate these neurons genetically should allow a more precise dissection of the molecular mechanisms of memory encoding within a distributed neuronal network.</AbstractText
Combined treatment of a giant duodenal gastrointestinal stromal tumor: A case report. Gastrointestinal stromal tumors (GISTs) in the duodenum are usually very rare, accounting for only 3% to 5% of all GISTs. Giant duodenal GISTs with a more than 10&#x2009;cm diameter are even rarer, and there is currently no consensus on their treatment. This article reports a case of successful treatment of a giant duodenal GIST.</AbstractText A 59-year-old woman presented with mid-upper abdominal pain accompanied by nausea and bloating. We underwent contrast-enhanced abdominal computed tomography scans and computed tomography-guided fine needle aspiration biopsy.</AbstractText The final diagnosis was duodenal GIST with a risk stratification of high-risk.</AbstractText After a multidisciplinary team discussion, the patient underwent a combination of targeted-surgical-targeted therapy.</AbstractText The patient ultimately achieved R0 resection at surgery, and no recurrence was noted during the follow-up period.</AbstractText Targeted-surgery-targeted combined therapy is one of the effective means for giant duodenal GIST. At the same time, genetic testing before neoadjuvant therapy is crucial for guiding treatment and is strongly recommended as a basic examination method.</AbstractText
40522077
38992778
40678409
Clinical Characteristics and Outcomes of Acute Ischemic Stroke in Patients With Systemic Lupus Erythematosus. A Nationwide Cohort Study.
Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.
Cost-Effectiveness of Proton Versus Photon Therapy for Medulloblastoma Using Updated Clinical Outcomes.
We aim to study the clinical characteristics and outcomes of acute ischemic stroke (AIS) in patients with and without systemic lupus erythematosus (SLE).</AbstractText We conducted a retrospective cohort study using the National Inpatient Sample (2016-2021) to analyze AIS hospitalizations among patients with and without SLE. Outcomes included in-hospital mortality (primary) and secondary endpoints such as mechanical ventilation, intracerebral hemorrhage, acute kidney injury (AKI), blood transfusion, length of stay, and hospitalization costs. Propensity score matching was performed to adjust for baseline characteristics, and multivariable logistic regression assessed outcome associations, incorporating stroke severity (NIH Stroke Scale).</AbstractText Among 3&#x2009;678&#x2009;244 AIS hospitalizations, 18&#x2009;975 (0.52%) involved SLE patients. SLE patients were younger (mean age 58.1 vs. 69.8&#x2009;years, p&#x2009;&lt;&#x2009;0.001), predominantly female (86.7% vs. 49.4%, p&#x2009;&lt;&#x2009;0.001), and had higher rates of chronic kidney disease and anemia but lower rates of atrial fibrillation and hyperlipidemia. Unadjusted analysis showed lower in-hospital mortality in SLE patients (5.85% vs. 6.67%, p&#x2009;=&#x2009;0.04), which persisted after propensity matching (adjusted OR 0.70, 95% CI 0.60-0.82). However, adjusting for NIHSS attenuated this association (OR 0.96, 95% CI 0.67-1.38), suggesting the mortality benefit was largely driven by less severe strokes in the SLE group.</AbstractText While SLE patients hospitalized for AIS exhibited lower in-hospital mortality, this was primarily attributable to lower stroke severity at presentation. Further research is needed to validate these findings.</AbstractText
Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021.</AbstractText Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed.</AbstractText In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000&#x2009;-&#x2009;16.39/100,000) in 2021, with an EPAC for ASIR&#x2009;&lt;&#x2009;0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03&#x2009;-&#x2009;11.95) and 285.62 (95% UI 209.42&#x2009;-&#x2009;379.65). The burden associated with SAH primarily affected individuals aged between 50&#x2009;-&#x2009;69&#xa0;years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework.</AbstractText The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.</AbstractText
The benefit of proton beam therapy (PBT) is evident in pediatric cancer, as survivors have to face long-term radiation-related side effects and lifetime costs. However, PBT's higher costs cause a challenge especially in middle-income countries. This study analyzed cost-effectiveness of PBT versus photon beam therapy (XRT) for medulloblastoma based on updated clinical outcomes within middle-income country context.</AbstractText Markov and Monte Carlo models were constructed for simulation analysis. We used annual mortality rates based on actual medulloblastoma patients receiving craniospinal irradiation over the first 5 years, combined with general population mortality rates thereafter. Rates and utilities for side effects, including&#xa0;hormone deficiencies, hearing loss, brain tumors, thyroid cancer, and IQ decline, were derived from previous literature, while the cardiac mortality rate was estimated using a linear model. Medical and nonmedical costs, along with other economic parameters and mortality rates during the first 5 years, were derived within the context of a middle-income country, using Thailand as a representative setting where PBT is operational.</AbstractText For the base-case model, the total costs for PBT and XRT were 69 349 USD (2 357 874 THB) and 80 217 USD (2 727 366 THB), respectively, with total utilities of 36.12 and 35.23, respectively. The ICER was&#xa0;-12 211 USD (-415 160 THB)/QALY, and the net monetary benefit for PBT and XRT were 100 627 USD (3 421 326 THB) and 85&#x202f;572 USD (2 909 434 THB), respectively. Including microsimulation and probabilistic sensitivity analysis for side effects rates, mortality rates, inflation, cost reduction, and utility reduction, PBT was still cost-effective. However, XRT was found to be more cost-effective when excluding opportunity loss from IQ decline.</AbstractText Despite its higher cost, PBT was more cost-effective than XRT for treating medulloblastoma in a middle-income country, based on updated clinical outcomes, particularly when incorporating IQ decline into the analysis.</AbstractText
Clinical Characteristics and Outcomes of Acute Ischemic Stroke in Patients With Systemic Lupus Erythematosus. A Nationwide Cohort Study. We aim to study the clinical characteristics and outcomes of acute ischemic stroke (AIS) in patients with and without systemic lupus erythematosus (SLE).</AbstractText We conducted a retrospective cohort study using the National Inpatient Sample (2016-2021) to analyze AIS hospitalizations among patients with and without SLE. Outcomes included in-hospital mortality (primary) and secondary endpoints such as mechanical ventilation, intracerebral hemorrhage, acute kidney injury (AKI), blood transfusion, length of stay, and hospitalization costs. Propensity score matching was performed to adjust for baseline characteristics, and multivariable logistic regression assessed outcome associations, incorporating stroke severity (NIH Stroke Scale).</AbstractText Among 3&#x2009;678&#x2009;244 AIS hospitalizations, 18&#x2009;975 (0.52%) involved SLE patients. SLE patients were younger (mean age 58.1 vs. 69.8&#x2009;years, p&#x2009;&lt;&#x2009;0.001), predominantly female (86.7% vs. 49.4%, p&#x2009;&lt;&#x2009;0.001), and had higher rates of chronic kidney disease and anemia but lower rates of atrial fibrillation and hyperlipidemia. Unadjusted analysis showed lower in-hospital mortality in SLE patients (5.85% vs. 6.67%, p&#x2009;=&#x2009;0.04), which persisted after propensity matching (adjusted OR 0.70, 95% CI 0.60-0.82). However, adjusting for NIHSS attenuated this association (OR 0.96, 95% CI 0.67-1.38), suggesting the mortality benefit was largely driven by less severe strokes in the SLE group.</AbstractText While SLE patients hospitalized for AIS exhibited lower in-hospital mortality, this was primarily attributable to lower stroke severity at presentation. Further research is needed to validate these findings.</AbstractText
Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021. Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021.</AbstractText Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed.</AbstractText In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000&#x2009;-&#x2009;16.39/100,000) in 2021, with an EPAC for ASIR&#x2009;&lt;&#x2009;0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03&#x2009;-&#x2009;11.95) and 285.62 (95% UI 209.42&#x2009;-&#x2009;379.65). The burden associated with SAH primarily affected individuals aged between 50&#x2009;-&#x2009;69&#xa0;years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework.</AbstractText The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.</AbstractText
Cost-Effectiveness of Proton Versus Photon Therapy for Medulloblastoma Using Updated Clinical Outcomes. The benefit of proton beam therapy (PBT) is evident in pediatric cancer, as survivors have to face long-term radiation-related side effects and lifetime costs. However, PBT's higher costs cause a challenge especially in middle-income countries. This study analyzed cost-effectiveness of PBT versus photon beam therapy (XRT) for medulloblastoma based on updated clinical outcomes within middle-income country context.</AbstractText Markov and Monte Carlo models were constructed for simulation analysis. We used annual mortality rates based on actual medulloblastoma patients receiving craniospinal irradiation over the first 5 years, combined with general population mortality rates thereafter. Rates and utilities for side effects, including&#xa0;hormone deficiencies, hearing loss, brain tumors, thyroid cancer, and IQ decline, were derived from previous literature, while the cardiac mortality rate was estimated using a linear model. Medical and nonmedical costs, along with other economic parameters and mortality rates during the first 5 years, were derived within the context of a middle-income country, using Thailand as a representative setting where PBT is operational.</AbstractText For the base-case model, the total costs for PBT and XRT were 69 349 USD (2 357 874 THB) and 80 217 USD (2 727 366 THB), respectively, with total utilities of 36.12 and 35.23, respectively. The ICER was&#xa0;-12 211 USD (-415 160 THB)/QALY, and the net monetary benefit for PBT and XRT were 100 627 USD (3 421 326 THB) and 85&#x202f;572 USD (2 909 434 THB), respectively. Including microsimulation and probabilistic sensitivity analysis for side effects rates, mortality rates, inflation, cost reduction, and utility reduction, PBT was still cost-effective. However, XRT was found to be more cost-effective when excluding opportunity loss from IQ decline.</AbstractText Despite its higher cost, PBT was more cost-effective than XRT for treating medulloblastoma in a middle-income country, based on updated clinical outcomes, particularly when incorporating IQ decline into the analysis.</AbstractText
23749238
23926960
24252535
Acute visual loss in papilloedema: the diagnostic pitfalls.
Long-term visual outcomes in patients with orbitotemporal neurofibromatosis.
Phasic and tonic alerting in mild cognitive impairment: A preliminary study.
Papilloedema is the descriptive term for optic disc swelling caused by proven elevated intracranial pressure (ICP). Commonly, there is preservation of vision, particularly central vision, visual acuity and colour vision, early in the disease process. However, some patients with raised ICP may present with a combination of disc swelling and visual loss. We report on two patients who presented with visual loss and optic disc swelling. They were initially referred to the neuro-ophthalmology clinic with a provisional diagnosis of optic neuritis given the clinical picture of disc swelling with reduced visual acuity. However they were subsequently found to have papilloedema.</AbstractText
The study aimed to review the presentation and long-term visual outcomes of patients with orbitotemporal neurofibromatosis.</AbstractText Retrospective case series.</AbstractText Patients with orbitotemporal neurofibromatosis presenting from 1981 to 2009.</AbstractText Demographic data, examination findings, causes of vision impairment and interventions performed were recorded for each patient from presentation through subsequent follow-up encounters. Visual impairment was defined as an ipsilateral Snellen acuity of &lt;6/12.</AbstractText The proportion of patients with visual impairment or enucleation, the rate of new vision loss during follow up; and causes for vision loss or enucleation.</AbstractText Thirty-seven patients (17 female) were included. Median presenting age was 15 years (range 2-45) with an average follow up of 7.4 years (range 0.5-20.3). Visual impairment occurred in 54% of patients at presentation. Causes were amblyopia (13 of 37), optic atrophy (4 of 37), previous enucleation/evisceration (2 of 37), and optic nerve glioma (1 of 37). At presentation, 76% of patients had ptosis, and 51% had strabismus. Thirty-one patients had surgery, with an average of two procedures per patient. At final follow up, 62% had visual impairment. The rate of visual decline was 2% per patient-years. Causes of visual decline were two patients with optic nerve atrophy, one with exposure keratitis and one whose cause was unknown. Five blind patients had enucleation.</AbstractText The first series of orbitotemporal neurofibromatosis to focus on visual outcomes was presented. Vision loss is common, with a high prevalence of amblyopia. Close monitoring from an early age is needed to prevent visual impairment.</AbstractText
In this preliminary study we assessed the functioning of the different attentional networks in mild cognitive impairment (MCI) patients, taking as theoretical framework the Posner's cognitive neuroscience approach. Two groups of participants were tested in a single short experiment: 20 MCI patients (6 amnestic, 6 non-amnestic and 8 multiple-domain) and 18 healthy matched controls (HC). For attentional assessment we used a version of the Attention Network Test (the ANTI-V) that provided not only a score of the orienting, the executive, and the alerting networks and their interactions, but also an independent measure of vigilance (tonic alerting). The results showed that all subtypes of MCI patients exhibited a selective impairment in the tonic component of alerting, as indexed by a decrease in the d' sensitivity index, and their performance in executive network increased up to the HC group level when phasic alerting was provided by a warning tone. Our findings suggest that a core attentional deficit, especially the endogenous component of alerting, may significantly contribute to the behavioral and cognitive deficits associated with MCI.</AbstractText
Acute visual loss in papilloedema: the diagnostic pitfalls. Papilloedema is the descriptive term for optic disc swelling caused by proven elevated intracranial pressure (ICP). Commonly, there is preservation of vision, particularly central vision, visual acuity and colour vision, early in the disease process. However, some patients with raised ICP may present with a combination of disc swelling and visual loss. We report on two patients who presented with visual loss and optic disc swelling. They were initially referred to the neuro-ophthalmology clinic with a provisional diagnosis of optic neuritis given the clinical picture of disc swelling with reduced visual acuity. However they were subsequently found to have papilloedema.</AbstractText
Long-term visual outcomes in patients with orbitotemporal neurofibromatosis. The study aimed to review the presentation and long-term visual outcomes of patients with orbitotemporal neurofibromatosis.</AbstractText Retrospective case series.</AbstractText Patients with orbitotemporal neurofibromatosis presenting from 1981 to 2009.</AbstractText Demographic data, examination findings, causes of vision impairment and interventions performed were recorded for each patient from presentation through subsequent follow-up encounters. Visual impairment was defined as an ipsilateral Snellen acuity of &lt;6/12.</AbstractText The proportion of patients with visual impairment or enucleation, the rate of new vision loss during follow up; and causes for vision loss or enucleation.</AbstractText Thirty-seven patients (17 female) were included. Median presenting age was 15 years (range 2-45) with an average follow up of 7.4 years (range 0.5-20.3). Visual impairment occurred in 54% of patients at presentation. Causes were amblyopia (13 of 37), optic atrophy (4 of 37), previous enucleation/evisceration (2 of 37), and optic nerve glioma (1 of 37). At presentation, 76% of patients had ptosis, and 51% had strabismus. Thirty-one patients had surgery, with an average of two procedures per patient. At final follow up, 62% had visual impairment. The rate of visual decline was 2% per patient-years. Causes of visual decline were two patients with optic nerve atrophy, one with exposure keratitis and one whose cause was unknown. Five blind patients had enucleation.</AbstractText The first series of orbitotemporal neurofibromatosis to focus on visual outcomes was presented. Vision loss is common, with a high prevalence of amblyopia. Close monitoring from an early age is needed to prevent visual impairment.</AbstractText
Phasic and tonic alerting in mild cognitive impairment: A preliminary study. In this preliminary study we assessed the functioning of the different attentional networks in mild cognitive impairment (MCI) patients, taking as theoretical framework the Posner's cognitive neuroscience approach. Two groups of participants were tested in a single short experiment: 20 MCI patients (6 amnestic, 6 non-amnestic and 8 multiple-domain) and 18 healthy matched controls (HC). For attentional assessment we used a version of the Attention Network Test (the ANTI-V) that provided not only a score of the orienting, the executive, and the alerting networks and their interactions, but also an independent measure of vigilance (tonic alerting). The results showed that all subtypes of MCI patients exhibited a selective impairment in the tonic component of alerting, as indexed by a decrease in the d' sensitivity index, and their performance in executive network increased up to the HC group level when phasic alerting was provided by a warning tone. Our findings suggest that a core attentional deficit, especially the endogenous component of alerting, may significantly contribute to the behavioral and cognitive deficits associated with MCI.</AbstractText
34387168
28137856
35511312
Therapeutic Potential of Adipose-derived Stem Cells in the Treatment of Pulmonary Diseases.
Targeting IRE1 with small molecules counteracts progression of atherosclerosis.
Improving brain B(0) shimming using an easy and accessible multi-coil shim array at ultra-high field.
Stem cells derived from adipose tissues (ADSCs) have emerged as an ideal candidate for various models of respiratory diseases, including asthma, Chronic Obstructive Pulmonary Disease (COPD), and acute respiratory distress syndrome. ADSCs have qualities that may make them better suited for treating inflammatory lung diseases than other MSCs. ADSCs show a lower senescence ratio, higher proliferative capacity and stability in terms of their genetic and morphology during long-term culture over Bone Marrow-derived Mesenchymal Stem Cells (BMMSCs). With enhanced research methodologies, the beneficial benefits of ADSCs appear to be restricted to their capacity to engraft, differentiate, and be connected to trophic factor secretion. These trophic factors influence treatment and regenerative results in a variety of lung inflammatory disorders. Taken together, these particular qualities of ADSCs make them significantly relevant for clinical applications. This article discusses a recent advance of ADSCs biology and their translational application, emphasizing their anti-inflammatory, immunomodulatory and regenerative properties, particularly on lung inflammatory diseases. Besides, the relevant advancements made in the field, the regulatory aspects, and other challenges and obstacles will be highlighted.</AbstractText
Metaflammation, an atypical, metabolically induced, chronic low-grade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ER-resident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions. Using RNA sequencing in macrophages, we discovered that IRE1 regulates the expression of many proatherogenic genes, including several important cytokines and chemokines. We show that IRE1 inhibitors uncouple lipid-induced ER stress from inflammasome activation in both mouse and human macrophages. In vivo, these IRE1 inhibitors led to a significant decrease in hyperlipidemia-induced IL-1&#x3b2; and IL-18 production, lowered T-helper type-1 immune responses, and reduced atherosclerotic plaque size without altering the plasma lipid profiles in apolipoprotein E-deficient mice. These results show that pharmacologic modulation of IRE1 counteracts metaflammation and alleviates atherosclerosis.</AbstractText
Improve shimming capabilities of ultra-high field systems, with addition of an accessible low-complexity B<sub An eight channel B<sub The eight-channel shim array provided 12% improvement in whole brain static shimming and provided 33% improvement when using slice-based shimming. With this, the eight-channel array performed similar to third-order dynamic shimming (without the need for higher order eddy current compensation). More complex shim arrays with 32 and 48 channels performed better, but require a dedicated RF coil.</AbstractText The designed eight-channel shim array provides a low-complexity and low-cost approach for improving B<sub
Therapeutic Potential of Adipose-derived Stem Cells in the Treatment of Pulmonary Diseases. Stem cells derived from adipose tissues (ADSCs) have emerged as an ideal candidate for various models of respiratory diseases, including asthma, Chronic Obstructive Pulmonary Disease (COPD), and acute respiratory distress syndrome. ADSCs have qualities that may make them better suited for treating inflammatory lung diseases than other MSCs. ADSCs show a lower senescence ratio, higher proliferative capacity and stability in terms of their genetic and morphology during long-term culture over Bone Marrow-derived Mesenchymal Stem Cells (BMMSCs). With enhanced research methodologies, the beneficial benefits of ADSCs appear to be restricted to their capacity to engraft, differentiate, and be connected to trophic factor secretion. These trophic factors influence treatment and regenerative results in a variety of lung inflammatory disorders. Taken together, these particular qualities of ADSCs make them significantly relevant for clinical applications. This article discusses a recent advance of ADSCs biology and their translational application, emphasizing their anti-inflammatory, immunomodulatory and regenerative properties, particularly on lung inflammatory diseases. Besides, the relevant advancements made in the field, the regulatory aspects, and other challenges and obstacles will be highlighted.</AbstractText
Targeting IRE1 with small molecules counteracts progression of atherosclerosis. Metaflammation, an atypical, metabolically induced, chronic low-grade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ER-resident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions. Using RNA sequencing in macrophages, we discovered that IRE1 regulates the expression of many proatherogenic genes, including several important cytokines and chemokines. We show that IRE1 inhibitors uncouple lipid-induced ER stress from inflammasome activation in both mouse and human macrophages. In vivo, these IRE1 inhibitors led to a significant decrease in hyperlipidemia-induced IL-1&#x3b2; and IL-18 production, lowered T-helper type-1 immune responses, and reduced atherosclerotic plaque size without altering the plasma lipid profiles in apolipoprotein E-deficient mice. These results show that pharmacologic modulation of IRE1 counteracts metaflammation and alleviates atherosclerosis.</AbstractText
Improving brain B(0) shimming using an easy and accessible multi-coil shim array at ultra-high field. Improve shimming capabilities of ultra-high field systems, with addition of an accessible low-complexity B<sub An eight channel B<sub The eight-channel shim array provided 12% improvement in whole brain static shimming and provided 33% improvement when using slice-based shimming. With this, the eight-channel array performed similar to third-order dynamic shimming (without the need for higher order eddy current compensation). More complex shim arrays with 32 and 48 channels performed better, but require a dedicated RF coil.</AbstractText The designed eight-channel shim array provides a low-complexity and low-cost approach for improving B<sub
25713527
23576128
26216769
Emotional discrimination during viewing unpleasant pictures: timing in human anterior ventrolateral prefrontal cortex and amygdala.
The salience network causally influences default mode network activity during moral reasoning.
MR Imaging of Wrist Ligaments.
The ventrolateral prefrontal cortex (VLPFC) and amygdala have critical roles in the generation and regulation of unpleasant emotions, and in this study the dynamic neural basis of unpleasant emotion processing was elucidated by using paired-samples permutation t-tests to identify the timing of emotional discrimination in various brain regions. We recorded the temporal dynamics of blood-oxygen-level-dependent (BOLD) signals in those brain regions during the viewing of unpleasant pictures by using functional magnetic resonance imaging (fMRI) with high temporal resolution, and we compared the time course of the signal within the volume of interest (VOI) across emotional conditions. Results show that emotional discrimination in the right amygdala precedes that in the left amygdala and that emotional discrimination in both those regions precedes that in the right anterior VLPFC. They support the hypotheses that the right amygdala is part of a rapid emotional stimulus detection system and the left amygdala is specialized for sustained stimulus evaluation and that the right anterior VLPFC is implicated in the integration of viscerosensory information with affective signals between the bilateral anterior VLPFCs and the bilateral amygdalae.</AbstractText
Large-scale brain networks are integral to the coordination of human behaviour, and their anatomy provides insights into the clinical presentation and progression of neurodegenerative illnesses such as Alzheimer's disease, which targets the default mode network, and behavioural variant frontotemporal dementia, which targets a more anterior salience network. Although the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, patients with Alzheimer's disease give normal responses to these dilemmas whereas patients with behavioural variant frontotemporal dementia give abnormal responses to these dilemmas. We hypothesized that this apparent discrepancy between activation- and patient-based studies of moral reasoning might reflect a modulatory role for the salience network in regulating default mode network activation. Using functional magnetic resonance imaging to characterize network activity of patients with behavioural variant frontotemporal dementia and healthy control subjects, we present four converging lines of evidence supporting a causal influence from the salience network to the default mode network during moral reasoning. First, as previously reported, the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, but patients with behavioural variant frontotemporal dementia producing atrophy in the salience network give abnormally utilitarian responses to these dilemmas. Second, patients with behavioural variant frontotemporal dementia have reduced recruitment of the default mode network compared with healthy control subjects when deliberating about these dilemmas. Third, a Granger causality analysis of functional neuroimaging data from healthy control subjects demonstrates directed functional connectivity from nodes of the salience network to nodes of the default mode network during moral reasoning. Fourth, this Granger causal influence is diminished in patients with behavioural variant frontotemporal dementia. These findings are consistent with a broader model in which the salience network modulates the activity of other large-scale networks, and suggest a revision to a previously proposed 'dual-process' account of moral reasoning. These findings also characterize network interactions underlying abnormal moral reasoning in frontotemporal dementia, which may serve as a model for the aberrant judgement and interpersonal behaviour observed in this disease and in other disorders of social function. More broadly, these findings link recent work on the dynamic interrelationships between large-scale brain networks to observable impairments in dementia syndromes, which may shed light on how diseases that target one network also alter the function of interrelated networks.</AbstractText
This article discusses the normal anatomy and pathologic appearances of the intrinsic and extrinsic wrist ligaments using MR Imaging. Technological advances in surface coil design and higher magnetic field strengths have improved radiologists' ability to consistently visualize these small ligaments in their entirety. Wrist ligament anatomy, in the context of proper physiologic function, is emphasized, including common normal variants, and their appearances on MR imaging. The spectrum of disorders, incorporating overlapping appearances of senescent degenerative changes, and destabilizing ligament tears, is outlined. The diagnostic performance of MR imaging to date for various ligament abnormalities is discussed, along with significant limitations.</AbstractText
Emotional discrimination during viewing unpleasant pictures: timing in human anterior ventrolateral prefrontal cortex and amygdala. The ventrolateral prefrontal cortex (VLPFC) and amygdala have critical roles in the generation and regulation of unpleasant emotions, and in this study the dynamic neural basis of unpleasant emotion processing was elucidated by using paired-samples permutation t-tests to identify the timing of emotional discrimination in various brain regions. We recorded the temporal dynamics of blood-oxygen-level-dependent (BOLD) signals in those brain regions during the viewing of unpleasant pictures by using functional magnetic resonance imaging (fMRI) with high temporal resolution, and we compared the time course of the signal within the volume of interest (VOI) across emotional conditions. Results show that emotional discrimination in the right amygdala precedes that in the left amygdala and that emotional discrimination in both those regions precedes that in the right anterior VLPFC. They support the hypotheses that the right amygdala is part of a rapid emotional stimulus detection system and the left amygdala is specialized for sustained stimulus evaluation and that the right anterior VLPFC is implicated in the integration of viscerosensory information with affective signals between the bilateral anterior VLPFCs and the bilateral amygdalae.</AbstractText
The salience network causally influences default mode network activity during moral reasoning. Large-scale brain networks are integral to the coordination of human behaviour, and their anatomy provides insights into the clinical presentation and progression of neurodegenerative illnesses such as Alzheimer's disease, which targets the default mode network, and behavioural variant frontotemporal dementia, which targets a more anterior salience network. Although the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, patients with Alzheimer's disease give normal responses to these dilemmas whereas patients with behavioural variant frontotemporal dementia give abnormal responses to these dilemmas. We hypothesized that this apparent discrepancy between activation- and patient-based studies of moral reasoning might reflect a modulatory role for the salience network in regulating default mode network activation. Using functional magnetic resonance imaging to characterize network activity of patients with behavioural variant frontotemporal dementia and healthy control subjects, we present four converging lines of evidence supporting a causal influence from the salience network to the default mode network during moral reasoning. First, as previously reported, the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, but patients with behavioural variant frontotemporal dementia producing atrophy in the salience network give abnormally utilitarian responses to these dilemmas. Second, patients with behavioural variant frontotemporal dementia have reduced recruitment of the default mode network compared with healthy control subjects when deliberating about these dilemmas. Third, a Granger causality analysis of functional neuroimaging data from healthy control subjects demonstrates directed functional connectivity from nodes of the salience network to nodes of the default mode network during moral reasoning. Fourth, this Granger causal influence is diminished in patients with behavioural variant frontotemporal dementia. These findings are consistent with a broader model in which the salience network modulates the activity of other large-scale networks, and suggest a revision to a previously proposed 'dual-process' account of moral reasoning. These findings also characterize network interactions underlying abnormal moral reasoning in frontotemporal dementia, which may serve as a model for the aberrant judgement and interpersonal behaviour observed in this disease and in other disorders of social function. More broadly, these findings link recent work on the dynamic interrelationships between large-scale brain networks to observable impairments in dementia syndromes, which may shed light on how diseases that target one network also alter the function of interrelated networks.</AbstractText
MR Imaging of Wrist Ligaments. This article discusses the normal anatomy and pathologic appearances of the intrinsic and extrinsic wrist ligaments using MR Imaging. Technological advances in surface coil design and higher magnetic field strengths have improved radiologists' ability to consistently visualize these small ligaments in their entirety. Wrist ligament anatomy, in the context of proper physiologic function, is emphasized, including common normal variants, and their appearances on MR imaging. The spectrum of disorders, incorporating overlapping appearances of senescent degenerative changes, and destabilizing ligament tears, is outlined. The diagnostic performance of MR imaging to date for various ligament abnormalities is discussed, along with significant limitations.</AbstractText
40161910
37560913
40365323
To compare the efficacy of three techniques in reducing etomidate-induced myoclonus - A randomised controlled trial.
Pharmacological interventions for reducing the incidence of myoclonus in patients receiving etomidate for induction of general anesthesia: an umbrella review.
Successful Pregnancy Management of a Woman With Severe Methylmalonic Acidemia.
Etomidate is the preferred induction agent in haemodynamically unstable patients. Preventing etomidate-induced myoclonus (EIM) is important. The objective of this study was to compare the efficacy of three techniques of etomidate administration in preventing EIM.</AbstractText This randomised, controlled study included 296 patients. General anaesthesia (GA) was induced with etomidate as per the randomly allocated groups: control (C), priming (P), slow (S), and priming with slow injection (T). The incidence, time of onset, and grade of myoclonus were noted. The grade of pain on injection and the effect on various haemodynamic parameters were noted. The Kruskal-Wallis, Fisher's exact, and Chi-square tests were used for statistical analysis. <i The study shows that the incidence of myoclonus was highest amongst Group C (73.0%), followed by Group P (52.7%), Group S (48.6%), and Group T (37.8%) (<i We observed that the priming and slow injection techniques were similar in reducing the incidence of EIM. However, the combination of priming and slow technique was the most effective.</AbstractText
The objective of this umbrella review was to examine various pharmacologic interventions for their potential to reduce etomidate-induced myoclonus. A secondary objective was to compare the relative effectiveness of those medications in reducing the incidence of myoclonus when etomidate is utilized for the induction of general anesthesia.</AbstractText Etomidate is the drug of choice when inducing general anesthesia in hemodynamically unstable patients. However, its use is limited among the general surgical population due to its ability to cause adrenal suppression, vomiting, and myoclonus. Myoclonus can lead to damage of muscle fibers, myalgias, and patient discomfort, and can also be detrimental in patients with low cardiac reserve. Several systematic reviews have reported on the effectiveness of various intravenous medications in reducing mild, moderate, and severe myoclonus; however, a more thorough examination of their influence was lacking.</AbstractText This review included systematic reviews and meta-analyses of randomized controlled trials involving the use of pharmacologic interventions to reduce etomidate-induced myoclonus. Reviews in English and conducted after 1965 were considered for inclusion.</AbstractText A comprehensive search of 11 databases was conducted to identify published and unpublished reviews up to March 2022. Critical appraisal was conducted by 2 independent reviewers using the standardized JBI appraisal tool. Quantitative findings were summarized according to the dose, timing of administration, and relative risk using a data matrix, and were synthesized in tabular format with supporting narrative text. Results were organized by severity of myoclonus (overall, mild, moderate, and severe) and by type of intervention.</AbstractText Eight systematic reviews were included in this umbrella review, which included 48 relevant studies, after removal of duplicates (3909 participants included in the primary studies). Five of the systematic reviews examined the effectiveness of various types of opioids in the prevention of myoclonus, and 3 systematic reviews examined the effectiveness of non-opioid interventions, such as lidocaine, midazolam, and dexmedetomidine. Seven reviews searched at least 4 databases for pertinent studies and specifically indicated that blinded reviewers appraised the articles. All reviews used a published and validated appraisal instrument. The overall quality of all included reviews was judged to be moderate to high. The absolute risk reduction indicating the effectiveness of the prophylactic medications ranged from 47% to 81% for mild, 52% to 92% for moderate, and 61% to 96% for severe myoclonus. Opioids demonstrated the most consistent and substantial effect on the reduction in myoclonus.</AbstractText All pharmacologic interventions identified in this review demonstrated a statistically significant reduction in the incidence of myoclonus. Future studies and reviews should focus on elucidating the particular dose range and timing that is most effective. Anesthesia providers should consider a pre-treatment dose of one of the medications described in this umbrella review as a means to reduce myoclonus and the untoward effects of that condition.</AbstractText
Isolated methylmalonic acidemia (MMA) is a rare, genetically heterogeneous group of metabolic disorders resulting from a deficiency of the enzyme methylmalonyl-CoA mutase (MMUT), defects in the metabolism of its cofactor, adenosylcobalamin, or deficiency of the enzyme methylmalonyl-CoA epimerase. With improved awareness, earlier diagnosis, and advances in care, women with MMA are increasingly reaching childbearing age, and successful pregnancies have been documented in patients with milder forms of the disease. This report details, for the first time, the management and outcomes of pregnancy in a woman with severe mut<sup
To compare the efficacy of three techniques in reducing etomidate-induced myoclonus - A randomised controlled trial. Etomidate is the preferred induction agent in haemodynamically unstable patients. Preventing etomidate-induced myoclonus (EIM) is important. The objective of this study was to compare the efficacy of three techniques of etomidate administration in preventing EIM.</AbstractText This randomised, controlled study included 296 patients. General anaesthesia (GA) was induced with etomidate as per the randomly allocated groups: control (C), priming (P), slow (S), and priming with slow injection (T). The incidence, time of onset, and grade of myoclonus were noted. The grade of pain on injection and the effect on various haemodynamic parameters were noted. The Kruskal-Wallis, Fisher's exact, and Chi-square tests were used for statistical analysis. <i The study shows that the incidence of myoclonus was highest amongst Group C (73.0%), followed by Group P (52.7%), Group S (48.6%), and Group T (37.8%) (<i We observed that the priming and slow injection techniques were similar in reducing the incidence of EIM. However, the combination of priming and slow technique was the most effective.</AbstractText
Pharmacological interventions for reducing the incidence of myoclonus in patients receiving etomidate for induction of general anesthesia: an umbrella review. The objective of this umbrella review was to examine various pharmacologic interventions for their potential to reduce etomidate-induced myoclonus. A secondary objective was to compare the relative effectiveness of those medications in reducing the incidence of myoclonus when etomidate is utilized for the induction of general anesthesia.</AbstractText Etomidate is the drug of choice when inducing general anesthesia in hemodynamically unstable patients. However, its use is limited among the general surgical population due to its ability to cause adrenal suppression, vomiting, and myoclonus. Myoclonus can lead to damage of muscle fibers, myalgias, and patient discomfort, and can also be detrimental in patients with low cardiac reserve. Several systematic reviews have reported on the effectiveness of various intravenous medications in reducing mild, moderate, and severe myoclonus; however, a more thorough examination of their influence was lacking.</AbstractText This review included systematic reviews and meta-analyses of randomized controlled trials involving the use of pharmacologic interventions to reduce etomidate-induced myoclonus. Reviews in English and conducted after 1965 were considered for inclusion.</AbstractText A comprehensive search of 11 databases was conducted to identify published and unpublished reviews up to March 2022. Critical appraisal was conducted by 2 independent reviewers using the standardized JBI appraisal tool. Quantitative findings were summarized according to the dose, timing of administration, and relative risk using a data matrix, and were synthesized in tabular format with supporting narrative text. Results were organized by severity of myoclonus (overall, mild, moderate, and severe) and by type of intervention.</AbstractText Eight systematic reviews were included in this umbrella review, which included 48 relevant studies, after removal of duplicates (3909 participants included in the primary studies). Five of the systematic reviews examined the effectiveness of various types of opioids in the prevention of myoclonus, and 3 systematic reviews examined the effectiveness of non-opioid interventions, such as lidocaine, midazolam, and dexmedetomidine. Seven reviews searched at least 4 databases for pertinent studies and specifically indicated that blinded reviewers appraised the articles. All reviews used a published and validated appraisal instrument. The overall quality of all included reviews was judged to be moderate to high. The absolute risk reduction indicating the effectiveness of the prophylactic medications ranged from 47% to 81% for mild, 52% to 92% for moderate, and 61% to 96% for severe myoclonus. Opioids demonstrated the most consistent and substantial effect on the reduction in myoclonus.</AbstractText All pharmacologic interventions identified in this review demonstrated a statistically significant reduction in the incidence of myoclonus. Future studies and reviews should focus on elucidating the particular dose range and timing that is most effective. Anesthesia providers should consider a pre-treatment dose of one of the medications described in this umbrella review as a means to reduce myoclonus and the untoward effects of that condition.</AbstractText
Successful Pregnancy Management of a Woman With Severe Methylmalonic Acidemia. Isolated methylmalonic acidemia (MMA) is a rare, genetically heterogeneous group of metabolic disorders resulting from a deficiency of the enzyme methylmalonyl-CoA mutase (MMUT), defects in the metabolism of its cofactor, adenosylcobalamin, or deficiency of the enzyme methylmalonyl-CoA epimerase. With improved awareness, earlier diagnosis, and advances in care, women with MMA are increasingly reaching childbearing age, and successful pregnancies have been documented in patients with milder forms of the disease. This report details, for the first time, the management and outcomes of pregnancy in a woman with severe mut<sup
21549885
17699422
20934191
[Kidney and iodinated and gadolinium-based contrast agents].
Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure--role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate.
MRI of the eye muscles in a case of ophthalmoplegia caused by common carotid artery occlusion suggests ischemic myopathy.
In patients with renal failure, iodinated contrast agents may cause acute deterioration of the renal function and gadolinium-based contrast agents (GBCAs) may cause nephrogenic systemic fibrosis (NSF). The administration of a contrast agent must thus be reviewed for each patient and evaluation of renal function is paramount even though its estimation using formulas derived from the creatinine level may fluctuate. For iodinated contrast agents, contrast induced nephropathy is reduced by hydratation, preferably intravenous, when the GFR is less than 60 ml/min. The risk for intravenous injections is less than the risk for arterial injections, and the GFR threshold may be reduced to 45 ml/min. For gadolinium-based contrast agents, patients at risk for NSF are those with end-stage renal disease and patients undergoing dialysis. In such cases, the injection of a gadolinium-based contrast agent is only considered after a risk-benefit analysis has been completed, an alternate linear or macrocyclic agent issued and the dose limited to 0,1 mmol Gd/kg. Recently, recommendations from US and European agencies have converged.</AbstractText to be familiar with the risk factors of CIN with iodinated contrast agents; to be familiar with hydration procedures for patients at risk of CIN; to be familiar with the diagnostic criteria of NSF; to be familiar with the classification of GBCA with regards to the risk of NSF; to be familiar with the contraindications of the different groups of GBCA.</AbstractText
Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NSF) is an emerging scleromyxedema-like cutaneous disorder of unknown cause that is seen in patients with renal failure, and the number of reported cases has grown significantly since its first recognition. Recent case reports associated the use of gadolinium (Gd3+)-based contrast agents with the development of NSF. Herein is reported an additional patient who had NSF and had multiple previous exposures to Gd3+-based magnetic resonance imaging studies and had marked improvement in pain and skin changes after a trial of intravenous sodium thiosulfate. Discussed are the possible association of Gd3+-based contrast media with the development of NSF and potential for the use of sodium thiosulfate in the treatment of NSF.</AbstractText
Ocular muscle palsies following carotid artery disease is thought to be caused by ischemia of the cranial oculomotor nerves but it may also be due to ischemia of the extraocular muscles (EOM). We studied a patient with common carotid artery occlusion syndrome (CCAOS) to elucidate the two competing hypotheses. MRI and sonography of the orbita showed oedematous swelling of all left EOM. MRI short-tau inversion recovery (STIR) sequences showed hyperintensities and a prolonged T2-relaxation time in EOM indicating muscle oedema. It decreased within two weeks as ophthalmoplegia improved. For several reasons ischemic EOM myopathy rather than ischemic neuropathy seems to be the morphological correlate of ophthalmoplegia after ipsilateral CCAOS in this patient.</AbstractText
[Kidney and iodinated and gadolinium-based contrast agents]. In patients with renal failure, iodinated contrast agents may cause acute deterioration of the renal function and gadolinium-based contrast agents (GBCAs) may cause nephrogenic systemic fibrosis (NSF). The administration of a contrast agent must thus be reviewed for each patient and evaluation of renal function is paramount even though its estimation using formulas derived from the creatinine level may fluctuate. For iodinated contrast agents, contrast induced nephropathy is reduced by hydratation, preferably intravenous, when the GFR is less than 60 ml/min. The risk for intravenous injections is less than the risk for arterial injections, and the GFR threshold may be reduced to 45 ml/min. For gadolinium-based contrast agents, patients at risk for NSF are those with end-stage renal disease and patients undergoing dialysis. In such cases, the injection of a gadolinium-based contrast agent is only considered after a risk-benefit analysis has been completed, an alternate linear or macrocyclic agent issued and the dose limited to 0,1 mmol Gd/kg. Recently, recommendations from US and European agencies have converged.</AbstractText to be familiar with the risk factors of CIN with iodinated contrast agents; to be familiar with hydration procedures for patients at risk of CIN; to be familiar with the diagnostic criteria of NSF; to be familiar with the classification of GBCA with regards to the risk of NSF; to be familiar with the contraindications of the different groups of GBCA.</AbstractText
Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure--role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate. Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NSF) is an emerging scleromyxedema-like cutaneous disorder of unknown cause that is seen in patients with renal failure, and the number of reported cases has grown significantly since its first recognition. Recent case reports associated the use of gadolinium (Gd3+)-based contrast agents with the development of NSF. Herein is reported an additional patient who had NSF and had multiple previous exposures to Gd3+-based magnetic resonance imaging studies and had marked improvement in pain and skin changes after a trial of intravenous sodium thiosulfate. Discussed are the possible association of Gd3+-based contrast media with the development of NSF and potential for the use of sodium thiosulfate in the treatment of NSF.</AbstractText
MRI of the eye muscles in a case of ophthalmoplegia caused by common carotid artery occlusion suggests ischemic myopathy. Ocular muscle palsies following carotid artery disease is thought to be caused by ischemia of the cranial oculomotor nerves but it may also be due to ischemia of the extraocular muscles (EOM). We studied a patient with common carotid artery occlusion syndrome (CCAOS) to elucidate the two competing hypotheses. MRI and sonography of the orbita showed oedematous swelling of all left EOM. MRI short-tau inversion recovery (STIR) sequences showed hyperintensities and a prolonged T2-relaxation time in EOM indicating muscle oedema. It decreased within two weeks as ophthalmoplegia improved. For several reasons ischemic EOM myopathy rather than ischemic neuropathy seems to be the morphological correlate of ophthalmoplegia after ipsilateral CCAOS in this patient.</AbstractText
32738198
27089287
32824808
Post-traumatic Confusional State: A Case Definition and Diagnostic Criteria.
Effectiveness of Sensory Stimulation to Improve Arousal and Alertness of People in a Coma or Persistent Vegetative State After Traumatic Brain Injury: A Systematic Review.
Cache-Based Privacy Preserving Solution for Location and Content Protection in Location-Based Services.
In response to the need to better define the natural history of emerging consciousness after traumatic brain injury and to better describe the characteristics of the condition commonly labeled posttraumatic amnesia, a case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed. This project was completed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group. The case definition was informed by an exhaustive literature review and expert opinion of workgroup members from multiple disciplines. The workgroup reviewed 2466 abstracts and extracted evidence from 44 articles. Consensus was reached through teleconferences, face-to-face meetings, and 3 rounds of modified Delphi voting. The case definition provides detailed description of PTCS (1) core neurobehavioral features, (2) associated neurobehavioral features, (3) functional implications, (4) exclusion criteria, (5) lower boundary, and (6) criteria for emergence. Core neurobehavioral features include disturbances of attention, orientation, and memory as well as excessive fluctuation. Associated neurobehavioral features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while upper boundary is marked by significant improvement in the 4 core and 5 associated features. Key research goals are establishment of cutoffs on assessment instruments and determination of levels of behavioral function that distinguish persons in PTCS from those who have emerged to the period of continued recovery.</AbstractText
This systematic review evaluates the effectiveness of sensory stimulation to improve arousal and alertness of people in a coma or persistent vegetative state after traumatic brain injury (TBI).</AbstractText Databases searched included Medline, PsycINFO, CINAHL, OTseeker, and the Cochrane Database of Systematic Reviews. The search was limited to outcomes studies published in English in peer-reviewed journals between 2008 and 2013.</AbstractText Included studies provide strong evidence that multimodal sensory stimulation improves arousal and enhances clinical outcomes for people in a coma or persistent vegetative state after TBI. Moderate evidence was also provided for auditory stimulation, limited evidence was provided for complex stimuli, and insufficient evidence was provided for median nerve stimulation.</AbstractText Interventions should be tailored to client tolerance and premorbid preferences. Bimodal or multimodal stimulation should begin early, be frequent, and be sustained until more complex activity is possible.</AbstractText
Location-Based Services (LBSs) are playing an increasingly important role in people's daily activities nowadays. While enjoying the convenience provided by LBSs, users may lose privacy since they report their personal information to the untrusted LBS server. Although many approaches have been proposed to preserve users' privacy, most of them just focus on the user's location privacy, but do not consider the query privacy. Moreover, many existing approaches rely heavily on a trusted third-party (TTP) server, which may suffer from a single point of failure. To solve the problems above, in this paper we propose a Cache-Based Privacy-Preserving (CBPP) solution for users in LBSs. Different from the previous approaches, the proposed CBPP solution protects location privacy and query privacy simultaneously, while avoiding the problem of TTP server by having users collaborating with each other in a mobile peer-to-peer (P2P) environment. In the CBPP solution, each user keeps a buffer in his mobile device (e.g., smartphone) to record service data and acts as a micro TTP server. When a user needs LBSs, he sends a query to his neighbors first to seek for an answer. The user only contacts the LBS server when he cannot obtain the required service data from his neighbors. In this way, the user reduces the number of queries sent to the LBS server. We argue that the fewer queries are submitted to the LBS server, the less the user's privacy is exposed. To users who have to send live queries to the LBS server, we employ the l-diversity, a powerful privacy protection definition that can guarantee the user's privacy against attackers using background knowledge, to further protect their privacy. Evaluation results show that the proposed CBPP solution can effectively protect users' location and query privacy with a lower communication cost and better quality of service.</AbstractText
Post-traumatic Confusional State: A Case Definition and Diagnostic Criteria. In response to the need to better define the natural history of emerging consciousness after traumatic brain injury and to better describe the characteristics of the condition commonly labeled posttraumatic amnesia, a case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed. This project was completed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group. The case definition was informed by an exhaustive literature review and expert opinion of workgroup members from multiple disciplines. The workgroup reviewed 2466 abstracts and extracted evidence from 44 articles. Consensus was reached through teleconferences, face-to-face meetings, and 3 rounds of modified Delphi voting. The case definition provides detailed description of PTCS (1) core neurobehavioral features, (2) associated neurobehavioral features, (3) functional implications, (4) exclusion criteria, (5) lower boundary, and (6) criteria for emergence. Core neurobehavioral features include disturbances of attention, orientation, and memory as well as excessive fluctuation. Associated neurobehavioral features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while upper boundary is marked by significant improvement in the 4 core and 5 associated features. Key research goals are establishment of cutoffs on assessment instruments and determination of levels of behavioral function that distinguish persons in PTCS from those who have emerged to the period of continued recovery.</AbstractText
Effectiveness of Sensory Stimulation to Improve Arousal and Alertness of People in a Coma or Persistent Vegetative State After Traumatic Brain Injury: A Systematic Review. This systematic review evaluates the effectiveness of sensory stimulation to improve arousal and alertness of people in a coma or persistent vegetative state after traumatic brain injury (TBI).</AbstractText Databases searched included Medline, PsycINFO, CINAHL, OTseeker, and the Cochrane Database of Systematic Reviews. The search was limited to outcomes studies published in English in peer-reviewed journals between 2008 and 2013.</AbstractText Included studies provide strong evidence that multimodal sensory stimulation improves arousal and enhances clinical outcomes for people in a coma or persistent vegetative state after TBI. Moderate evidence was also provided for auditory stimulation, limited evidence was provided for complex stimuli, and insufficient evidence was provided for median nerve stimulation.</AbstractText Interventions should be tailored to client tolerance and premorbid preferences. Bimodal or multimodal stimulation should begin early, be frequent, and be sustained until more complex activity is possible.</AbstractText
Cache-Based Privacy Preserving Solution for Location and Content Protection in Location-Based Services. Location-Based Services (LBSs) are playing an increasingly important role in people's daily activities nowadays. While enjoying the convenience provided by LBSs, users may lose privacy since they report their personal information to the untrusted LBS server. Although many approaches have been proposed to preserve users' privacy, most of them just focus on the user's location privacy, but do not consider the query privacy. Moreover, many existing approaches rely heavily on a trusted third-party (TTP) server, which may suffer from a single point of failure. To solve the problems above, in this paper we propose a Cache-Based Privacy-Preserving (CBPP) solution for users in LBSs. Different from the previous approaches, the proposed CBPP solution protects location privacy and query privacy simultaneously, while avoiding the problem of TTP server by having users collaborating with each other in a mobile peer-to-peer (P2P) environment. In the CBPP solution, each user keeps a buffer in his mobile device (e.g., smartphone) to record service data and acts as a micro TTP server. When a user needs LBSs, he sends a query to his neighbors first to seek for an answer. The user only contacts the LBS server when he cannot obtain the required service data from his neighbors. In this way, the user reduces the number of queries sent to the LBS server. We argue that the fewer queries are submitted to the LBS server, the less the user's privacy is exposed. To users who have to send live queries to the LBS server, we employ the l-diversity, a powerful privacy protection definition that can guarantee the user's privacy against attackers using background knowledge, to further protect their privacy. Evaluation results show that the proposed CBPP solution can effectively protect users' location and query privacy with a lower communication cost and better quality of service.</AbstractText
32184015
26912590
32705146
Lemairamin, isolated from the Zanthoxylum plants, alleviates pain hypersensitivity via spinal α7 nicotinic acetylcholine receptors.
Desensitization-resistant and -sensitive GPCR-mediated inhibition of GABA release occurs by Ca2+-dependent and -independent mechanisms at a hypothalamic synapse.
Structural white matter connectometry of word production in aphasia: an observational study.
Lemairamin (also known as wgx-50), is isolated from the pericarps of the Zanthoxylum plants. As an agonist of &#x3b1;7 nicotinic acetylcholine receptors (&#x3b1;7nAChRs), it can reduce neuroinflammation in Alzheimer's disease. This study evaluated its antinociceptive effects in pain hypersensitivity and explored the underlying mechanisms. The data showed that subcutaneous lemairamin injection dose-dependently inhibited formalin-induced tonic pain but not acute nociception in mice and rats, while intrathecal lemairamin injection also dose-dependently produced mechanical antiallodynia in the ipsilateral hindpaws of neuropathic and bone cancer pain rats without affecting mechanical thresholds in the contralateral hindpaws. Multiple bi-daily lemairamin injections for 7 days did not induce mechanical antiallodynic tolerance in neuropathic rats. Moreover, the antinociceptive effects of lemairamin in formalin-induced tonic pain and mechanical antiallodynia in neuropathic pain were suppressed by the &#x3b1;7nAChR antagonist methyllycaconitine. In an &#x3b1;7nAChR antagonist-reversible manner, intrathecal lemairamin also stimulated spinal expression of IL-10 and &#x3b2;-endorphin, while lemairamin treatment induced IL-10 and &#x3b2;-endorphin expression in primary spinal microglial cells. In addition, intrathecal injection of a microglial activation inhibitor minocycline, anti-IL-10 antibody, anti-&#x3b2;-endorphin antiserum or &#x3bc;-opioid receptor-preferred antagonist naloxone was all able to block lemairamin-induced mechanical antiallodynia in neuropathic pain. These data demonstrated that lemairamin could produce antinociception in pain hypersensitivity through the spinal IL-10/&#x3b2;-endorphin pathway following &#x3b1;7nAChR activation.</AbstractText
Whereas the activation of G&#x3b1;i/o-coupled receptors commonly results in postsynaptic responses that show acute desensitization, the presynaptic inhibition of transmitter release caused by many G&#x3b1;i/o-coupled receptors is maintained during agonist exposure. However, an exception has been noted where GABAB receptor (GABABR)-mediated inhibition of inhibitory postsynaptic currents (IPSCs) recorded in mouse proopiomelanocortin (POMC) neurons exhibit acute desensitization in &#x223c;25% of experiments. To determine whether differential effector coupling confers sensitivity to desensitization, voltage-clamp recordings were made from POMC neurons to compare the mechanism by which &#x3bc;-opioid receptors (MORs) and GABABRs inhibit transmitter release. Neither MOR- nor GABABR-mediated inhibition of release relied on the activation of presynaptic K(+) channels. Both receptors maintained the ability to inhibit release in the absence of external Ca(2+) or in the presence of ionomycin-induced Ca(2+) influx, indicating that inhibition of release can occur through a Ca(2+)-independent mechanism. Replacing Ca(2+) with Sr(2+) to disrupt G-protein-mediated inhibition of release occurring directly at the release machinery did not alter MOR- or GABAB -mediated inhibition of IPSCs, suggesting that reductions in evoked release can occur through the inhibition of Ca(2+) channels. Additionally, both receptors inhibited evoked IPSCs in the presence of selective blockers of N- or P/Q-type Ca(2+) channels. Altogether, the results show that MORs and GABABRs can inhibit transmitter release through the inhibition of calcium influx and by direct actions at the release machinery. Furthermore, since both the desensitizing and nondesensitizing presynaptic receptors are similarly coupled, differential effector coupling is unlikely responsible for differential desensitization of the inhibition of release.</AbstractText
While current dual-steam neurocognitive models of language function have coalesced around the view that distinct neuroanatomical networks subserve semantic and phonological processing, respectively, the specific white matter components of these networks remain a matter of debate. To inform this debate, we investigated relationships between structural white matter connectivity and word production in a cross-sectional study of 42 participants with aphasia due to unilateral left hemisphere stroke. Specifically, we reconstructed a local connectome matrix for each participant from diffusion spectrum imaging data and regressed these matrices on indices of semantic and phonological ability derived from their responses to a picture-naming test and a computational model of word production. These connectometry analyses indicated that both dorsally located (arcuate fasciculus) and ventrally located (inferior frontal-occipital, uncinate, and middle longitudinal fasciculi) tracts were associated with semantic ability, while associations with phonological ability were more dorsally situated, including the arcuate and middle longitudinal fasciculi. Associations with limbic pathways including the posterior cingulum bundle and the fornix were also found. All analyses controlled for total lesion volume and all results showing positive associations obtained false discovery rates &lt; 0.05. These results challenge dual-stream accounts that deny a role for the arcuate fasciculus in semantic processing, and for ventral-stream pathways in language production. They also illuminate limbic contributions to both semantic and phonological processing for word production.</AbstractText
Lemairamin, isolated from the Zanthoxylum plants, alleviates pain hypersensitivity via spinal α7 nicotinic acetylcholine receptors. Lemairamin (also known as wgx-50), is isolated from the pericarps of the Zanthoxylum plants. As an agonist of &#x3b1;7 nicotinic acetylcholine receptors (&#x3b1;7nAChRs), it can reduce neuroinflammation in Alzheimer's disease. This study evaluated its antinociceptive effects in pain hypersensitivity and explored the underlying mechanisms. The data showed that subcutaneous lemairamin injection dose-dependently inhibited formalin-induced tonic pain but not acute nociception in mice and rats, while intrathecal lemairamin injection also dose-dependently produced mechanical antiallodynia in the ipsilateral hindpaws of neuropathic and bone cancer pain rats without affecting mechanical thresholds in the contralateral hindpaws. Multiple bi-daily lemairamin injections for 7 days did not induce mechanical antiallodynic tolerance in neuropathic rats. Moreover, the antinociceptive effects of lemairamin in formalin-induced tonic pain and mechanical antiallodynia in neuropathic pain were suppressed by the &#x3b1;7nAChR antagonist methyllycaconitine. In an &#x3b1;7nAChR antagonist-reversible manner, intrathecal lemairamin also stimulated spinal expression of IL-10 and &#x3b2;-endorphin, while lemairamin treatment induced IL-10 and &#x3b2;-endorphin expression in primary spinal microglial cells. In addition, intrathecal injection of a microglial activation inhibitor minocycline, anti-IL-10 antibody, anti-&#x3b2;-endorphin antiserum or &#x3bc;-opioid receptor-preferred antagonist naloxone was all able to block lemairamin-induced mechanical antiallodynia in neuropathic pain. These data demonstrated that lemairamin could produce antinociception in pain hypersensitivity through the spinal IL-10/&#x3b2;-endorphin pathway following &#x3b1;7nAChR activation.</AbstractText
Desensitization-resistant and -sensitive GPCR-mediated inhibition of GABA release occurs by Ca2+-dependent and -independent mechanisms at a hypothalamic synapse. Whereas the activation of G&#x3b1;i/o-coupled receptors commonly results in postsynaptic responses that show acute desensitization, the presynaptic inhibition of transmitter release caused by many G&#x3b1;i/o-coupled receptors is maintained during agonist exposure. However, an exception has been noted where GABAB receptor (GABABR)-mediated inhibition of inhibitory postsynaptic currents (IPSCs) recorded in mouse proopiomelanocortin (POMC) neurons exhibit acute desensitization in &#x223c;25% of experiments. To determine whether differential effector coupling confers sensitivity to desensitization, voltage-clamp recordings were made from POMC neurons to compare the mechanism by which &#x3bc;-opioid receptors (MORs) and GABABRs inhibit transmitter release. Neither MOR- nor GABABR-mediated inhibition of release relied on the activation of presynaptic K(+) channels. Both receptors maintained the ability to inhibit release in the absence of external Ca(2+) or in the presence of ionomycin-induced Ca(2+) influx, indicating that inhibition of release can occur through a Ca(2+)-independent mechanism. Replacing Ca(2+) with Sr(2+) to disrupt G-protein-mediated inhibition of release occurring directly at the release machinery did not alter MOR- or GABAB -mediated inhibition of IPSCs, suggesting that reductions in evoked release can occur through the inhibition of Ca(2+) channels. Additionally, both receptors inhibited evoked IPSCs in the presence of selective blockers of N- or P/Q-type Ca(2+) channels. Altogether, the results show that MORs and GABABRs can inhibit transmitter release through the inhibition of calcium influx and by direct actions at the release machinery. Furthermore, since both the desensitizing and nondesensitizing presynaptic receptors are similarly coupled, differential effector coupling is unlikely responsible for differential desensitization of the inhibition of release.</AbstractText
Structural white matter connectometry of word production in aphasia: an observational study. While current dual-steam neurocognitive models of language function have coalesced around the view that distinct neuroanatomical networks subserve semantic and phonological processing, respectively, the specific white matter components of these networks remain a matter of debate. To inform this debate, we investigated relationships between structural white matter connectivity and word production in a cross-sectional study of 42 participants with aphasia due to unilateral left hemisphere stroke. Specifically, we reconstructed a local connectome matrix for each participant from diffusion spectrum imaging data and regressed these matrices on indices of semantic and phonological ability derived from their responses to a picture-naming test and a computational model of word production. These connectometry analyses indicated that both dorsally located (arcuate fasciculus) and ventrally located (inferior frontal-occipital, uncinate, and middle longitudinal fasciculi) tracts were associated with semantic ability, while associations with phonological ability were more dorsally situated, including the arcuate and middle longitudinal fasciculi. Associations with limbic pathways including the posterior cingulum bundle and the fornix were also found. All analyses controlled for total lesion volume and all results showing positive associations obtained false discovery rates &lt; 0.05. These results challenge dual-stream accounts that deny a role for the arcuate fasciculus in semantic processing, and for ventral-stream pathways in language production. They also illuminate limbic contributions to both semantic and phonological processing for word production.</AbstractText
40251179
36965035
40773395
AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain.
Acetylated α-tubulin alleviates injury to the dendritic spines after ischemic stroke in mice.
Distribution-Aware Knowledge Aligning and Prototyping for Non-Exemplar Lifelong Person Re-Identification.
Adeno-associated viral (AAV) vector-based gene therapy is gaining foothold as treatment for genetic neurological diseases with encouraging clinical results. Nonetheless, dose-dependent adverse events have emerged in recent clinical trials through mechanisms that remain unclear. We have modelled here the impact of AAV transduction in cell models of the human central nervous system (CNS), taking advantage of induced pluripotent stem cells. Our work uncovers vector-induced innate immune mechanisms that contribute to cell death. While empty AAV capsids were well tolerated, the AAV genome triggered p53-dependent DNA damage responses across CNS cell types followed by the induction of inflammatory responses. In addition, transgene expression led to MAVS-dependent activation of type I interferon responses. Formation of DNA damage foci in neurons and gliosis were confirmed in murine striatum upon intraparenchymal AAV injection. Transduction-induced cell death and gliosis could be prevented by inhibiting p53 or by acting downstream on STING- or IL-1R-mediated responses. Together, our work identifies innate immune mechanisms of vector sensing in the CNS that can potentially contribute to AAV-associated neurotoxicity.</AbstractText
Functional recovery is associated with the preservation of dendritic spines in the penumbra area after stroke. Previous studies found that polymerized microtubules (MTs) serve a crucial role in regulating dendritic spine formation and plasticity. However, the mechanisms that are involved are poorly understood. This study is designed to understand whether the upregulation of acetylated &#x3b1;-tubulin (&#x3b1;-Ac-Tub, a marker for stable, and polymerized MTs) could alleviate injury to the dendritic spines in the penumbra area and motor dysfunction after ischemic stroke.</AbstractText Ischemic stroke was mimicked both in an in vivo and in vitro setup using middle cerebral artery occlusion and oxygen-glucose deprivation models. Thy1-YFP mice were utilized to observe the morphology of the dendritic spines in the penumbra area. MEC17 is the specific acetyltransferase of &#x3b1;-tubulin. Thy1 Cre<sup &#x3b1;-Ac-Tub was colocalized with postsynaptic density 95. Although knockout of MEC17 in the pyramidal neurons did not affect the density of the dendritic spines, it significantly aggravated the injury to them in the penumbra area and motor dysfunction after stroke. However, MEC17 upregulation in the pyramidal neurons and TBA treatment could maintain mature dendritic spine density and alleviate motor dysfunction after stroke.</AbstractText Our study demonstrated that &#x3b1;-Ac-Tub plays a crucial role in the maintenance of the structure and functions of mature dendritic spines. Moreover, &#x3b1;-Ac-Tub protected the dendritic spines in the penumbra area and alleviated motor dysfunction after stroke.</AbstractText
Lifelong person re-identification&#xa0;(LReID) suffers from the catastrophic forgetting problem when learning from non-stationary data streams. Existing exemplar-based and knowledge distillation-based LReID methods encounter data privacy and limited acquisition capacity, respectively. In this paper, we introduce the prototype, which is under-investigated in LReID, to better balance knowledge retention and acquisition. Previous prototype-based works primarily focused on the classification task, where prototypes were modeled as discrete points or statistical distributions. However, they either discarded the distribution information or omitted instance-level diversity, which are crucial fine-grained clues for LReID. Furthermore, the domain shifts between data sources result in a feature gap between the new and old data, which restricts the utilization of the fine-grained information in prototypes. To address these challenges, we propose Distribution-aware Knowledge Aligning and Prototyping&#xa0;(DKP++), a novel framework for modeling and leveraging prototypes in LReID. First, an Instance-level Distribution Modeling network is introduced to capture the local diversity of each instance. Next, a Distribution-oriented Prototype Generation algorithm transforms the instance-level diversity into identity-level distributions which are stored as prototypes. Then, a Prototype-based Knowledge Transfer module distills the knowledge within the prototypes to the new model. To mitigate the impact of domain shifts during knowledge transfer, we introduce a privacy-friendly Distribution Aligning module that transforms new input data to fit the historical distribution, which is incorporated with feature-level alignment constraints to enhance the coherence between new and old knowledge, effectively improving historical prototype utilization. Extensive experiments demonstrate that our method achieves a superior balance between plasticity and stability, outperforming state-of-the-art LReID methods by a large margin.</AbstractText
AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain. Adeno-associated viral (AAV) vector-based gene therapy is gaining foothold as treatment for genetic neurological diseases with encouraging clinical results. Nonetheless, dose-dependent adverse events have emerged in recent clinical trials through mechanisms that remain unclear. We have modelled here the impact of AAV transduction in cell models of the human central nervous system (CNS), taking advantage of induced pluripotent stem cells. Our work uncovers vector-induced innate immune mechanisms that contribute to cell death. While empty AAV capsids were well tolerated, the AAV genome triggered p53-dependent DNA damage responses across CNS cell types followed by the induction of inflammatory responses. In addition, transgene expression led to MAVS-dependent activation of type I interferon responses. Formation of DNA damage foci in neurons and gliosis were confirmed in murine striatum upon intraparenchymal AAV injection. Transduction-induced cell death and gliosis could be prevented by inhibiting p53 or by acting downstream on STING- or IL-1R-mediated responses. Together, our work identifies innate immune mechanisms of vector sensing in the CNS that can potentially contribute to AAV-associated neurotoxicity.</AbstractText
Acetylated α-tubulin alleviates injury to the dendritic spines after ischemic stroke in mice. Functional recovery is associated with the preservation of dendritic spines in the penumbra area after stroke. Previous studies found that polymerized microtubules (MTs) serve a crucial role in regulating dendritic spine formation and plasticity. However, the mechanisms that are involved are poorly understood. This study is designed to understand whether the upregulation of acetylated &#x3b1;-tubulin (&#x3b1;-Ac-Tub, a marker for stable, and polymerized MTs) could alleviate injury to the dendritic spines in the penumbra area and motor dysfunction after ischemic stroke.</AbstractText Ischemic stroke was mimicked both in an in vivo and in vitro setup using middle cerebral artery occlusion and oxygen-glucose deprivation models. Thy1-YFP mice were utilized to observe the morphology of the dendritic spines in the penumbra area. MEC17 is the specific acetyltransferase of &#x3b1;-tubulin. Thy1 Cre<sup &#x3b1;-Ac-Tub was colocalized with postsynaptic density 95. Although knockout of MEC17 in the pyramidal neurons did not affect the density of the dendritic spines, it significantly aggravated the injury to them in the penumbra area and motor dysfunction after stroke. However, MEC17 upregulation in the pyramidal neurons and TBA treatment could maintain mature dendritic spine density and alleviate motor dysfunction after stroke.</AbstractText Our study demonstrated that &#x3b1;-Ac-Tub plays a crucial role in the maintenance of the structure and functions of mature dendritic spines. Moreover, &#x3b1;-Ac-Tub protected the dendritic spines in the penumbra area and alleviated motor dysfunction after stroke.</AbstractText
Distribution-Aware Knowledge Aligning and Prototyping for Non-Exemplar Lifelong Person Re-Identification. Lifelong person re-identification&#xa0;(LReID) suffers from the catastrophic forgetting problem when learning from non-stationary data streams. Existing exemplar-based and knowledge distillation-based LReID methods encounter data privacy and limited acquisition capacity, respectively. In this paper, we introduce the prototype, which is under-investigated in LReID, to better balance knowledge retention and acquisition. Previous prototype-based works primarily focused on the classification task, where prototypes were modeled as discrete points or statistical distributions. However, they either discarded the distribution information or omitted instance-level diversity, which are crucial fine-grained clues for LReID. Furthermore, the domain shifts between data sources result in a feature gap between the new and old data, which restricts the utilization of the fine-grained information in prototypes. To address these challenges, we propose Distribution-aware Knowledge Aligning and Prototyping&#xa0;(DKP++), a novel framework for modeling and leveraging prototypes in LReID. First, an Instance-level Distribution Modeling network is introduced to capture the local diversity of each instance. Next, a Distribution-oriented Prototype Generation algorithm transforms the instance-level diversity into identity-level distributions which are stored as prototypes. Then, a Prototype-based Knowledge Transfer module distills the knowledge within the prototypes to the new model. To mitigate the impact of domain shifts during knowledge transfer, we introduce a privacy-friendly Distribution Aligning module that transforms new input data to fit the historical distribution, which is incorporated with feature-level alignment constraints to enhance the coherence between new and old knowledge, effectively improving historical prototype utilization. Extensive experiments demonstrate that our method achieves a superior balance between plasticity and stability, outperforming state-of-the-art LReID methods by a large margin.</AbstractText
40486729
38237588
40574519
Brain organoid model systems of neurodegenerative diseases: recent progress and future prospects.
Selective vulnerability of layer 5a corticostriatal neurons in Huntington's disease.
Contemporary clinical conversations about stuttering: Telling parents why their child began to stutter.
Neurological diseases are a leading cause of disability, morbidity, and mortality, affecting 43% of the world's population. The detailed study of neurological diseases, testing of drugs, and repair of site-specific defects require physiologically relevant models that recapitulate key events and dynamic neurodevelopmental processes in a highly organized fashion. As an evolving technology, self-organizing and self-assembling brain organoids offer the advantage of modeling different stages of brain development in a 3D microenvironment. Herein, we review the utility, advantages, and limitations of the latest breakthroughs in brain organoid endeavors in the context of modeling three of the most prevalent neurodegenerative diseases-Alzheimer's, Parkinson's, and Huntington's disease. We conclude the review with a perspective on the future prospects of brain organoid models with their myriad possible applications in translational medicine.</AbstractText
The properties of the cell types that are selectively vulnerable in Huntington's disease (HD) cortex, the nature of somatic CAG expansions of mHTT in these cells, and their importance in CNS circuitry have not been delineated. Here, we employed serial fluorescence-activated nuclear sorting (sFANS), deep molecular profiling, and single-nucleus RNA sequencing (snRNA-seq) of motor-cortex samples from thirteen predominantly early stage, clinically diagnosed HD donors and selected samples from cingulate, visual, insular, and prefrontal cortices to demonstrate loss of layer 5a pyramidal neurons in HD. Extensive mHTT CAG expansions occur in vulnerable layer 5a pyramidal cells, and in Betz cells, layers 6a and 6b neurons that are resilient in HD. Retrograde tracing experiments in macaque brains identify layer 5a neurons as corticostriatal pyramidal cells. We propose that enhanced somatic mHTT CAG expansion and altered synaptic function act together to cause corticostriatal disconnection and selective neuronal vulnerability in HD cerebral cortex.</AbstractText
Parents of children who have begun to stutter need an explanation why this has occurred. For that explanation, clinicians have many research findings available to them from many disciplines. It may be challenging for junior clinicians and students of speech-language pathology to integrate and synthesise that knowledge for parents. The purpose of this clinical conversation is to provide guidance in that matter. The issue was discussed by speech-language pathologists and researchers. Written conversational turns in an exchange were limited to 100 words each. There was general agreement about core material to be conveyed to parents: An explanation of stuttering onset needs to be multifactorial, incorporating a physical mechanism driving causality. We recommend this explanation needs to include current empirical research and theoretical perspectives about stuttering. To do that, clinicians need to keep up to date with current research and thinking about the condition. An explanation to parents must not overwhelm or alarm them, but be supportive and provide groundwork for intervention. Finally, it is essential to explore parent views about why a child began to stutter. Supplementary materials are provided (Appendix A): Participants present their model of how they would tell parents why their child began to stutter and a reading list is provided.</AbstractText
Brain organoid model systems of neurodegenerative diseases: recent progress and future prospects. Neurological diseases are a leading cause of disability, morbidity, and mortality, affecting 43% of the world's population. The detailed study of neurological diseases, testing of drugs, and repair of site-specific defects require physiologically relevant models that recapitulate key events and dynamic neurodevelopmental processes in a highly organized fashion. As an evolving technology, self-organizing and self-assembling brain organoids offer the advantage of modeling different stages of brain development in a 3D microenvironment. Herein, we review the utility, advantages, and limitations of the latest breakthroughs in brain organoid endeavors in the context of modeling three of the most prevalent neurodegenerative diseases-Alzheimer's, Parkinson's, and Huntington's disease. We conclude the review with a perspective on the future prospects of brain organoid models with their myriad possible applications in translational medicine.</AbstractText
Selective vulnerability of layer 5a corticostriatal neurons in Huntington's disease. The properties of the cell types that are selectively vulnerable in Huntington's disease (HD) cortex, the nature of somatic CAG expansions of mHTT in these cells, and their importance in CNS circuitry have not been delineated. Here, we employed serial fluorescence-activated nuclear sorting (sFANS), deep molecular profiling, and single-nucleus RNA sequencing (snRNA-seq) of motor-cortex samples from thirteen predominantly early stage, clinically diagnosed HD donors and selected samples from cingulate, visual, insular, and prefrontal cortices to demonstrate loss of layer 5a pyramidal neurons in HD. Extensive mHTT CAG expansions occur in vulnerable layer 5a pyramidal cells, and in Betz cells, layers 6a and 6b neurons that are resilient in HD. Retrograde tracing experiments in macaque brains identify layer 5a neurons as corticostriatal pyramidal cells. We propose that enhanced somatic mHTT CAG expansion and altered synaptic function act together to cause corticostriatal disconnection and selective neuronal vulnerability in HD cerebral cortex.</AbstractText
Contemporary clinical conversations about stuttering: Telling parents why their child began to stutter. Parents of children who have begun to stutter need an explanation why this has occurred. For that explanation, clinicians have many research findings available to them from many disciplines. It may be challenging for junior clinicians and students of speech-language pathology to integrate and synthesise that knowledge for parents. The purpose of this clinical conversation is to provide guidance in that matter. The issue was discussed by speech-language pathologists and researchers. Written conversational turns in an exchange were limited to 100 words each. There was general agreement about core material to be conveyed to parents: An explanation of stuttering onset needs to be multifactorial, incorporating a physical mechanism driving causality. We recommend this explanation needs to include current empirical research and theoretical perspectives about stuttering. To do that, clinicians need to keep up to date with current research and thinking about the condition. An explanation to parents must not overwhelm or alarm them, but be supportive and provide groundwork for intervention. Finally, it is essential to explore parent views about why a child began to stutter. Supplementary materials are provided (Appendix A): Participants present their model of how they would tell parents why their child began to stutter and a reading list is provided.</AbstractText
40774957
33273503
40705372
SuperSalt: equivariant neural network force fields for multicomponent molten salts system.
Identifications and classifications of human locomotion using Rayleigh-enhanced distributed fiber acoustic sensors with deep neural networks.
Diagnosing Osteoporosis for the Spine Practitioner.
Molten salts are crucial for clean energy applications, yet exploring their thermophysical properties across diverse chemical space remains challenging. We present the development of a machine learning interatomic potential (MLIP) called SuperSalt, which targets 11-cation chloride melts and captures the essential physics of molten salts with near-DFT accuracy. Using an efficient workflow that integrates systems of one, two, and 11 components, the SuperSalt potential can accurately predict thermophysical properties such as density, bulk modulus, thermal expansion, and heat capacity. Our model is validated across a broad chemical space, demonstrating excellent transferability. We further illustrate how Bayesian optimization combined with SuperSalt can accelerate the discovery of optimal salt compositions with desired properties. This work provides a foundation for future studies that allows easy extensions to more complex systems, such as those containing additional elements.</AbstractText
This paper reports on the use of machine learning to delineate data harnessed by fiber-optic distributed acoustic sensors (DAS) using fiber with enhanced Rayleigh backscattering to recognize vibration events induced by human locomotion. The DAS used in this work is based on homodyne phase-sensitive optical time-domain reflectometry (&#x3c6;-OTDR). The signal-to-noise ratio (SNR) of the DAS was enhanced using femtosecond laser-induced artificial Rayleigh scattering centers in single-mode fiber cores. Both supervised and unsupervised machine-learning algorithms were explored to identify people and specific events that produce acoustic signals. Using convolutional deep neural networks, the supervised machine learning scheme achieved over 76.25% accuracy in recognizing human identities. Conversely, the unsupervised machine learning scheme achieved over 77.65% accuracy in recognizing events and human identities through acoustic signals. Through integrated efforts on both sensor device innovation and machine learning data analytics, this paper shows that the DAS technique can be an effective security technology to detect and to identify highly similar acoustic events with high spatial resolution and high accuracies.</AbstractText
Literature review.</AbstractText Review updated criteria that categorizes patient's bone health for operative and non-operative patients.</AbstractText Osteoporosis is common in spine patients including those with fragility fractures and in the elective surgery population. Untreated osteoporosis is associated with secondary spine fractures and increased likelihood of osteoporotic bone related complications after elective surgery. Recently, the definition of osteoporosis is expanded beyond use of bone mineral density (BMD) to also include fracture history and fracture risk. Most spine practitioners are not aware of this definition.</AbstractText Recent clinical guidelines and recommendations for the diagnosis of osteoporosis are reviewed. Included are the use of dual x-ray absorptiometry (DXA), adjuncts such as trabecular bone score and vertebral fracture assessment, and other factors such as comorbidities, fracture history, and opportunistic use of other imaging studies.</AbstractText The use of the clinical diagnosis based on BMD, fracture history, and fracture risk increases the diagnosis of osteoporosis in spine patients. BMD is measured using DXA, which is sensitive and precise, although errors in analysis and interpretation are common. Fracture history is a strong predictor of secondary fracture and poor surgical outcomes. Reducing fracture risk is the goal of medical treatment but is rarely performed by spine practitioners. Fracture risk can be stratified into low, high, and very high-risk groups. High and very high-risk patients are candidates for medical management. Other clues to the presence of osteoporosis that should prompt further bone health assessment are based on history, height loss, risk factors, and opportunistic use plain radiographs, CT, and MRI.</AbstractText Spine practitioners should be aware of newer concepts in the diagnosis of osteoporosis. Utilizing the clinical diagnosis of osteoporosis based on BMD thresholds, fracture history, and fracture risk will identify patients who should be considered for further health assessment and treatment.</AbstractText
SuperSalt: equivariant neural network force fields for multicomponent molten salts system. Molten salts are crucial for clean energy applications, yet exploring their thermophysical properties across diverse chemical space remains challenging. We present the development of a machine learning interatomic potential (MLIP) called SuperSalt, which targets 11-cation chloride melts and captures the essential physics of molten salts with near-DFT accuracy. Using an efficient workflow that integrates systems of one, two, and 11 components, the SuperSalt potential can accurately predict thermophysical properties such as density, bulk modulus, thermal expansion, and heat capacity. Our model is validated across a broad chemical space, demonstrating excellent transferability. We further illustrate how Bayesian optimization combined with SuperSalt can accelerate the discovery of optimal salt compositions with desired properties. This work provides a foundation for future studies that allows easy extensions to more complex systems, such as those containing additional elements.</AbstractText
Identifications and classifications of human locomotion using Rayleigh-enhanced distributed fiber acoustic sensors with deep neural networks. This paper reports on the use of machine learning to delineate data harnessed by fiber-optic distributed acoustic sensors (DAS) using fiber with enhanced Rayleigh backscattering to recognize vibration events induced by human locomotion. The DAS used in this work is based on homodyne phase-sensitive optical time-domain reflectometry (&#x3c6;-OTDR). The signal-to-noise ratio (SNR) of the DAS was enhanced using femtosecond laser-induced artificial Rayleigh scattering centers in single-mode fiber cores. Both supervised and unsupervised machine-learning algorithms were explored to identify people and specific events that produce acoustic signals. Using convolutional deep neural networks, the supervised machine learning scheme achieved over 76.25% accuracy in recognizing human identities. Conversely, the unsupervised machine learning scheme achieved over 77.65% accuracy in recognizing events and human identities through acoustic signals. Through integrated efforts on both sensor device innovation and machine learning data analytics, this paper shows that the DAS technique can be an effective security technology to detect and to identify highly similar acoustic events with high spatial resolution and high accuracies.</AbstractText
Diagnosing Osteoporosis for the Spine Practitioner. Literature review.</AbstractText Review updated criteria that categorizes patient's bone health for operative and non-operative patients.</AbstractText Osteoporosis is common in spine patients including those with fragility fractures and in the elective surgery population. Untreated osteoporosis is associated with secondary spine fractures and increased likelihood of osteoporotic bone related complications after elective surgery. Recently, the definition of osteoporosis is expanded beyond use of bone mineral density (BMD) to also include fracture history and fracture risk. Most spine practitioners are not aware of this definition.</AbstractText Recent clinical guidelines and recommendations for the diagnosis of osteoporosis are reviewed. Included are the use of dual x-ray absorptiometry (DXA), adjuncts such as trabecular bone score and vertebral fracture assessment, and other factors such as comorbidities, fracture history, and opportunistic use of other imaging studies.</AbstractText The use of the clinical diagnosis based on BMD, fracture history, and fracture risk increases the diagnosis of osteoporosis in spine patients. BMD is measured using DXA, which is sensitive and precise, although errors in analysis and interpretation are common. Fracture history is a strong predictor of secondary fracture and poor surgical outcomes. Reducing fracture risk is the goal of medical treatment but is rarely performed by spine practitioners. Fracture risk can be stratified into low, high, and very high-risk groups. High and very high-risk patients are candidates for medical management. Other clues to the presence of osteoporosis that should prompt further bone health assessment are based on history, height loss, risk factors, and opportunistic use plain radiographs, CT, and MRI.</AbstractText Spine practitioners should be aware of newer concepts in the diagnosis of osteoporosis. Utilizing the clinical diagnosis of osteoporosis based on BMD thresholds, fracture history, and fracture risk will identify patients who should be considered for further health assessment and treatment.</AbstractText
37342875
28441580
36571622
Serotonin 5-HT(7) receptor slows down the G(s) protein: a single molecule perspective.
The computer-aided discovery of novel family of the 5-HT(6) serotonin receptor ligands among derivatives of 4-benzyl-1,3,5-triazine.
Revisiting the use of Hoffmann reflex in motor control research on humans.
The 5-hydroxytryptamine (serotonin) receptor type 7 (5-HT<sub
The work describes a discovery of new chemical family of potent ligands for the 5-HT<sub
Research in movement science aims at unravelling mechanisms and designing methods for restoring and maximizing human functional capacity, and many techniques provide access to neural adjustments (acute changes) or long-term adaptations (chronic changes) underlying changes in movement capabilities. First described by Paul Hoffmann over a century ago, when an electrical stimulus is applied to a peripheral nerve, this causes action potentials in afferent axons, primarily the Ia afferents of the muscle spindles, which recruit homonymous motor neurons, thereby causing an electromyographic response known as the Hoffmann (H) reflex. This technique is a valuable tool in the study of the neuromuscular function in humans and has provided relevant information in the neural control of movement. The large use of the H reflex in motor control research on humans relies in part to its relative simplicity. However, such simplicity masks subtleties that require rigorous experimental protocols and careful data interpretation. After highlighting basic properties and methodological aspects that should be considered for the correct use of the H-reflex technique, this brief narrative review discusses the purpose of the H reflex and emphasizes its use as a tool to assess the effectiveness of Ia afferents in discharging motor neurones. The review also aims to reconsider the link between H-reflex modulation and Ia presynaptic inhibition, the use of the H-reflex technique in motor control studies, and the effects of ageing. These aspects are summarized as recommendations for the use of the H reflex in motor control research on humans.</AbstractText
Serotonin 5-HT(7) receptor slows down the G(s) protein: a single molecule perspective. The 5-hydroxytryptamine (serotonin) receptor type 7 (5-HT<sub
The computer-aided discovery of novel family of the 5-HT(6) serotonin receptor ligands among derivatives of 4-benzyl-1,3,5-triazine. The work describes a discovery of new chemical family of potent ligands for the 5-HT<sub
Revisiting the use of Hoffmann reflex in motor control research on humans. Research in movement science aims at unravelling mechanisms and designing methods for restoring and maximizing human functional capacity, and many techniques provide access to neural adjustments (acute changes) or long-term adaptations (chronic changes) underlying changes in movement capabilities. First described by Paul Hoffmann over a century ago, when an electrical stimulus is applied to a peripheral nerve, this causes action potentials in afferent axons, primarily the Ia afferents of the muscle spindles, which recruit homonymous motor neurons, thereby causing an electromyographic response known as the Hoffmann (H) reflex. This technique is a valuable tool in the study of the neuromuscular function in humans and has provided relevant information in the neural control of movement. The large use of the H reflex in motor control research on humans relies in part to its relative simplicity. However, such simplicity masks subtleties that require rigorous experimental protocols and careful data interpretation. After highlighting basic properties and methodological aspects that should be considered for the correct use of the H-reflex technique, this brief narrative review discusses the purpose of the H reflex and emphasizes its use as a tool to assess the effectiveness of Ia afferents in discharging motor neurones. The review also aims to reconsider the link between H-reflex modulation and Ia presynaptic inhibition, the use of the H-reflex technique in motor control studies, and the effects of ageing. These aspects are summarized as recommendations for the use of the H reflex in motor control research on humans.</AbstractText
38365452
38705943
39517924
Invasive versus non-invasive paediatric home mechanical ventilation: review of the international evolution over the past 24 years.
Long-Term Comparative Efficacy and Safety of Risdiplam and Nusinersen in Children with Type 1 Spinal Muscular Atrophy.
A Federated Reinforcement Learning Framework via a Committee Mechanism for Resource Management in 5G Networks.
Home mechanical ventilation (HMV) is the treatment for chronic hypercapnic alveolar hypoventilation. The proportion and evolution of paediatric invasive (IMV) and non-invasive (NIV) HMV across the world is unknown, as well as the disorders and age of children using HMV.</AbstractText Search of Medline/PubMed for publications of paediatric surveys on HMV from 2000 to 2023.</AbstractText Data from 32 international reports, representing 8815 children (59% boys) using HMV, were analysed. A substantial number of children had neuromuscular disorders (NMD; 37%), followed by cardiorespiratory (Cardio-Resp; 16%), central nervous system (CNS; 16%), upper airway (UA; 13%), other disorders (Others; 10%), central hypoventilation (4%), thoracic (3%) and genetic/congenital disorders (Gen/Cong; 1%). Mean age&#xb1;SD (range) at HMV initiation was 6.7&#xb1;3.7 (0.5-14.7) years. Age distribution was bimodal, with two peaks around 1-2 and 14-15 years. The number and proportion of children using NIV was significantly greater than that of children using IMV (n=6362 vs 2453, p=0.03; 72% vs 28%, p=0.048), with wide variations among countries, studies and disorders. NIV was used preferentially in the preponderance of children affected by UA, Gen/Cong, Thoracic, NMD and Cardio-Resp disorders. Children with NMD still receiving primary invasive HMV were mainly type I spinal muscular atrophy (SMA). Mean age&#xb1;SD at initiation of IMV and NIV was 3.3&#xb1;3.3&#x2009;and 8.2&#xb1;4.4 years (p&lt;0.01), respectively. The rate of children receiving additional daytime HMV was higher with IMV as compared with NIV (69% vs 10%, p&lt;0.001). The evolution of paediatric HMV over the last two decades consists of a growing number of children using HMV, in parallel to an increasing use of NIV in recent years (2020-2023). There is no clear trend in the profile of children over time (age at HMV). However, an increasing number of patients requiring HMV were observed in the Gen/Cong, CNS and Others groups. Finally, the estimated prevalence of paediatric HMV was calculated at 7.4/100 000 children.</AbstractText Patients with NMD represent the largest group of children using HMV. NIV is increasingly favoured in recent years, but IMV is still a prevalent intervention in young children, particularly in countries indicating less experience with NIV.</AbstractText
Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disease characterized by a loss of motor neurons and progressive muscle weakness. Children with untreated type&#xa0;1 SMA never sit independently and require increasing levels of ventilatory support as the disease progresses. Without intervention, and lacking ventilatory support, death typically occurs before the age of 2&#xa0;years. There are currently no head-to-head trials comparing available treatments in SMA. Indirect treatment comparisons are therefore needed to provide information on the relative efficacy and safety of SMA treatments for healthcare decision-making.</AbstractText The long-term efficacy and safety of risdiplam versus nusinersen in children with type&#xa0;1 SMA was evaluated using indirect treatment comparison methodology to adjust for differences between population baseline characteristics, to reduce any potential bias in the comparative analysis. An unanchored matching-adjusted indirect comparison was conducted using risdiplam data from 58 children in FIREFISH (NCT02913482) and published aggregate nusinersen data from 81 children obtained from the ENDEAR (NCT02193074) and SHINE (NCT02594124) clinical trials with at least 36&#xa0;months of follow-up.</AbstractText Children with type&#xa0;1 SMA treated with risdiplam had a 78% reduction in the rate of death, an 81% reduction in the rate of death or permanent ventilation, and a 57% reduction in the rate of serious adverse events compared with children treated with nusinersen. Children treated with risdiplam also had a 45% higher rate of achieving a Hammersmith Infant Neurological Examination, Module&#xa0;2 motor milestone response and a 186% higher rate of achieving a &#x2265;&#x2009;4-point improvement in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders compared with children treated with nusinersen.</AbstractText Long-term data supported risdiplam as a superior alternative to nusinersen in children with type&#xa0;1 SMA. Video abstract available for this article. Video abstract (MP4 184542 KB).</AbstractText Risdiplam and nusinersen are two approved treatments for patients with type&#xa0;1 spinal muscular atrophy (SMA). There are currently no head-to-head trials that compare the outcomes of these treatments in patients. This study conducted a statistical comparison of the efficacy and safety of risdiplam and nusinersen in children with type&#xa0;1 SMA who received treatment for at least 36&#xa0;months. Risdiplam data were collected from 58 children who participated in the FIREFISH trial (NCT02913482). Published combined data were collected from 81 children treated with nusinersen who participated in the ENDEAR (NCT02193074) and SHINE (NCT02594124) trials. Outcomes from the two studies were compared using matching-adjusted indirect comparison (MAIC) methodology. MAIC adjusts for differences in baseline characteristics between patients in two trials to make the populations more similar and reduce bias in the comparison. Results suggested that children with type&#xa0;1 SMA treated with risdiplam had a 78% reduction in the rate of death and an 81% reduction in the rate of death or permanent ventilation compared with children treated with nusinersen. With risdiplam, children also had a higher rate of achieving motor function responses, and a longer time to the first serious adverse event compared with children treated with nusinersen. These results support risdiplam as a superior alternative to nusinersen in children with type&#xa0;1 SMA over 36&#xa0;months of follow-up. Access to long-term data beyond 36&#xa0;months would allow for additional indirect comparisons between SMA treatments. These comparisons are key to guiding treatment decision-making in the absence of head-to-head trials.</AbstractText
This paper proposes a novel decentralized federated reinforcement learning (DFRL) framework that integrates deep reinforcement learning (DRL) with decentralized federated learning (DFL). The DFRL framework boosts efficient virtual instance scaling in Mobile Edge Computing (MEC) environments for 5G core network automation. It enables multiple MECs to collaboratively optimize resource allocation without centralized data sharing. In this framework, DRL agents in each MEC make local scaling decisions and exchange model parameters with other MECs, rather than sharing raw data. To enhance robustness against malicious server attacks, we employ a committee mechanism that monitors the DFL process and ensures reliable aggregation of local gradients. Extensive simulations were conducted to evaluate the proposed framework, demonstrating its ability to maintain cost-effective resource usage while significantly reducing blocking rates across diverse traffic conditions. Furthermore, the framework demonstrated strong resilience against adversarial MEC nodes, ensuring reliable operation and efficient resource management. These results validate the framework's effectiveness in adaptive and efficient resource management, particularly in dynamic and varied network scenarios.</AbstractText
Invasive versus non-invasive paediatric home mechanical ventilation: review of the international evolution over the past 24 years. Home mechanical ventilation (HMV) is the treatment for chronic hypercapnic alveolar hypoventilation. The proportion and evolution of paediatric invasive (IMV) and non-invasive (NIV) HMV across the world is unknown, as well as the disorders and age of children using HMV.</AbstractText Search of Medline/PubMed for publications of paediatric surveys on HMV from 2000 to 2023.</AbstractText Data from 32 international reports, representing 8815 children (59% boys) using HMV, were analysed. A substantial number of children had neuromuscular disorders (NMD; 37%), followed by cardiorespiratory (Cardio-Resp; 16%), central nervous system (CNS; 16%), upper airway (UA; 13%), other disorders (Others; 10%), central hypoventilation (4%), thoracic (3%) and genetic/congenital disorders (Gen/Cong; 1%). Mean age&#xb1;SD (range) at HMV initiation was 6.7&#xb1;3.7 (0.5-14.7) years. Age distribution was bimodal, with two peaks around 1-2 and 14-15 years. The number and proportion of children using NIV was significantly greater than that of children using IMV (n=6362 vs 2453, p=0.03; 72% vs 28%, p=0.048), with wide variations among countries, studies and disorders. NIV was used preferentially in the preponderance of children affected by UA, Gen/Cong, Thoracic, NMD and Cardio-Resp disorders. Children with NMD still receiving primary invasive HMV were mainly type I spinal muscular atrophy (SMA). Mean age&#xb1;SD at initiation of IMV and NIV was 3.3&#xb1;3.3&#x2009;and 8.2&#xb1;4.4 years (p&lt;0.01), respectively. The rate of children receiving additional daytime HMV was higher with IMV as compared with NIV (69% vs 10%, p&lt;0.001). The evolution of paediatric HMV over the last two decades consists of a growing number of children using HMV, in parallel to an increasing use of NIV in recent years (2020-2023). There is no clear trend in the profile of children over time (age at HMV). However, an increasing number of patients requiring HMV were observed in the Gen/Cong, CNS and Others groups. Finally, the estimated prevalence of paediatric HMV was calculated at 7.4/100 000 children.</AbstractText Patients with NMD represent the largest group of children using HMV. NIV is increasingly favoured in recent years, but IMV is still a prevalent intervention in young children, particularly in countries indicating less experience with NIV.</AbstractText
Long-Term Comparative Efficacy and Safety of Risdiplam and Nusinersen in Children with Type 1 Spinal Muscular Atrophy. Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disease characterized by a loss of motor neurons and progressive muscle weakness. Children with untreated type&#xa0;1 SMA never sit independently and require increasing levels of ventilatory support as the disease progresses. Without intervention, and lacking ventilatory support, death typically occurs before the age of 2&#xa0;years. There are currently no head-to-head trials comparing available treatments in SMA. Indirect treatment comparisons are therefore needed to provide information on the relative efficacy and safety of SMA treatments for healthcare decision-making.</AbstractText The long-term efficacy and safety of risdiplam versus nusinersen in children with type&#xa0;1 SMA was evaluated using indirect treatment comparison methodology to adjust for differences between population baseline characteristics, to reduce any potential bias in the comparative analysis. An unanchored matching-adjusted indirect comparison was conducted using risdiplam data from 58 children in FIREFISH (NCT02913482) and published aggregate nusinersen data from 81 children obtained from the ENDEAR (NCT02193074) and SHINE (NCT02594124) clinical trials with at least 36&#xa0;months of follow-up.</AbstractText Children with type&#xa0;1 SMA treated with risdiplam had a 78% reduction in the rate of death, an 81% reduction in the rate of death or permanent ventilation, and a 57% reduction in the rate of serious adverse events compared with children treated with nusinersen. Children treated with risdiplam also had a 45% higher rate of achieving a Hammersmith Infant Neurological Examination, Module&#xa0;2 motor milestone response and a 186% higher rate of achieving a &#x2265;&#x2009;4-point improvement in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders compared with children treated with nusinersen.</AbstractText Long-term data supported risdiplam as a superior alternative to nusinersen in children with type&#xa0;1 SMA. Video abstract available for this article. Video abstract (MP4 184542 KB).</AbstractText Risdiplam and nusinersen are two approved treatments for patients with type&#xa0;1 spinal muscular atrophy (SMA). There are currently no head-to-head trials that compare the outcomes of these treatments in patients. This study conducted a statistical comparison of the efficacy and safety of risdiplam and nusinersen in children with type&#xa0;1 SMA who received treatment for at least 36&#xa0;months. Risdiplam data were collected from 58 children who participated in the FIREFISH trial (NCT02913482). Published combined data were collected from 81 children treated with nusinersen who participated in the ENDEAR (NCT02193074) and SHINE (NCT02594124) trials. Outcomes from the two studies were compared using matching-adjusted indirect comparison (MAIC) methodology. MAIC adjusts for differences in baseline characteristics between patients in two trials to make the populations more similar and reduce bias in the comparison. Results suggested that children with type&#xa0;1 SMA treated with risdiplam had a 78% reduction in the rate of death and an 81% reduction in the rate of death or permanent ventilation compared with children treated with nusinersen. With risdiplam, children also had a higher rate of achieving motor function responses, and a longer time to the first serious adverse event compared with children treated with nusinersen. These results support risdiplam as a superior alternative to nusinersen in children with type&#xa0;1 SMA over 36&#xa0;months of follow-up. Access to long-term data beyond 36&#xa0;months would allow for additional indirect comparisons between SMA treatments. These comparisons are key to guiding treatment decision-making in the absence of head-to-head trials.</AbstractText
A Federated Reinforcement Learning Framework via a Committee Mechanism for Resource Management in 5G Networks. This paper proposes a novel decentralized federated reinforcement learning (DFRL) framework that integrates deep reinforcement learning (DRL) with decentralized federated learning (DFL). The DFRL framework boosts efficient virtual instance scaling in Mobile Edge Computing (MEC) environments for 5G core network automation. It enables multiple MECs to collaboratively optimize resource allocation without centralized data sharing. In this framework, DRL agents in each MEC make local scaling decisions and exchange model parameters with other MECs, rather than sharing raw data. To enhance robustness against malicious server attacks, we employ a committee mechanism that monitors the DFL process and ensures reliable aggregation of local gradients. Extensive simulations were conducted to evaluate the proposed framework, demonstrating its ability to maintain cost-effective resource usage while significantly reducing blocking rates across diverse traffic conditions. Furthermore, the framework demonstrated strong resilience against adversarial MEC nodes, ensuring reliable operation and efficient resource management. These results validate the framework's effectiveness in adaptive and efficient resource management, particularly in dynamic and varied network scenarios.</AbstractText
37698244
31299496
36976650
My child and I: self- and child-reference effects among parents with self-worth contingent on children's performance.
Numbers in action during cognitive flexibility - A neurophysiological approach on numerical operations underlying task switching.
Redistribution of the chromatin remodeler Brg1 directs smooth muscle-derived adventitial progenitor-to-myofibroblast differentiation and vascular fibrosis.
Research shows that parents' self-worth may be contingent on their children's performance, with implications for their interactions with children. This study examined whether such child-based worth is manifested in parents' recognition memory. Parents of school-age children in China (<i
Cognitive flexibility is a major competence to cope with daily life requirements and is usually investigated using task switching paradigms. Often, numerical stimuli are used to examine switching between task rules. Based upon functional neuroanatomical considerations we hypothesize that the ability to efficiently perform task switching varies depending on the cognitive operations performed with these numerical stimuli during task switching (magnitude vs&#xa0;parity judgments). We use a system-neurophysiological approach combining EEG and event-related potential (ERP) recordings with temporal data decomposition and source localization methods. We show that task switching processes are more demanding during parity judgments, compared to magnitude judgments. This, however, was only the case when task switching processes were triggered by external sensory stimuli, but not when memory-based processes had to be used during task switching. After accounting for intra-individual variability in the EEG data, the neurophysiological data showed that these effects were due to very specific subprocesses reflecting processes to update task sets and stimulus-response mappings during task switching. Source reconstructions show that left inferior and superior parietal areas (BA40 and BA7) were associated with these processes. The data show how different numerical operations differentially affect cognitive flexibility processes. Especially parity judgments exacerbate processes to update and reconfigure task sets during task switching in parietal areas. These findings are a valuable contribution to further reflections on the theories developed to date in task switching.</AbstractText
Vascular smooth muscle-derived Sca1+ adventitial progenitor (AdvSca1-SM) cells are tissue-resident, multipotent stem cells that contribute to progression of vascular remodeling and fibrosis. Upon acute vascular injury, AdvSca1-SM cells differentiate into myofibroblasts and are embedded in perivascular collagen and the extracellular matrix. While the phenotypic properties of AdvSca1-SM-derived myofibroblasts have been defined, the underlying epigenetic regulators driving the AdvSca1-SM-to-myofibroblast transition are unclear. We show that the chromatin remodeler Smarca4/Brg1 facilitates AdvSca1-SM myofibroblast differentiation. Brg1 mRNA and protein were upregulated in AdvSca1-SM cells after acute vascular injury, and pharmacological inhibition of Brg1 by the small molecule PFI-3 attenuated perivascular fibrosis and adventitial expansion. TGF-&#x3b2;1 stimulation of AdvSca1-SM cells in vitro reduced expression of stemness genes while inducing expression of myofibroblast genes that was associated with enhanced contractility; PFI blocked TGF-&#x3b2;1-induced phenotypic transition. Similarly, genetic knockdown of Brg1 in vivo reduced adventitial remodeling and fibrosis and reversed AdvSca1-SM-to-myofibroblast transition in vitro. Mechanistically, TGF-&#x3b2;1 promoted redistribution of Brg1 from distal intergenic sites of stemness genes and recruitment to promoter regions of myofibroblast-related genes, which was blocked by PFI-3. These data provide insight into epigenetic regulation of resident vascular progenitor cell differentiation and support that manipulating the AdvSca1-SM phenotype will provide antifibrotic clinical benefits.</AbstractText
My child and I: self- and child-reference effects among parents with self-worth contingent on children's performance. Research shows that parents' self-worth may be contingent on their children's performance, with implications for their interactions with children. This study examined whether such child-based worth is manifested in parents' recognition memory. Parents of school-age children in China (<i
Numbers in action during cognitive flexibility - A neurophysiological approach on numerical operations underlying task switching. Cognitive flexibility is a major competence to cope with daily life requirements and is usually investigated using task switching paradigms. Often, numerical stimuli are used to examine switching between task rules. Based upon functional neuroanatomical considerations we hypothesize that the ability to efficiently perform task switching varies depending on the cognitive operations performed with these numerical stimuli during task switching (magnitude vs&#xa0;parity judgments). We use a system-neurophysiological approach combining EEG and event-related potential (ERP) recordings with temporal data decomposition and source localization methods. We show that task switching processes are more demanding during parity judgments, compared to magnitude judgments. This, however, was only the case when task switching processes were triggered by external sensory stimuli, but not when memory-based processes had to be used during task switching. After accounting for intra-individual variability in the EEG data, the neurophysiological data showed that these effects were due to very specific subprocesses reflecting processes to update task sets and stimulus-response mappings during task switching. Source reconstructions show that left inferior and superior parietal areas (BA40 and BA7) were associated with these processes. The data show how different numerical operations differentially affect cognitive flexibility processes. Especially parity judgments exacerbate processes to update and reconfigure task sets during task switching in parietal areas. These findings are a valuable contribution to further reflections on the theories developed to date in task switching.</AbstractText
Redistribution of the chromatin remodeler Brg1 directs smooth muscle-derived adventitial progenitor-to-myofibroblast differentiation and vascular fibrosis. Vascular smooth muscle-derived Sca1+ adventitial progenitor (AdvSca1-SM) cells are tissue-resident, multipotent stem cells that contribute to progression of vascular remodeling and fibrosis. Upon acute vascular injury, AdvSca1-SM cells differentiate into myofibroblasts and are embedded in perivascular collagen and the extracellular matrix. While the phenotypic properties of AdvSca1-SM-derived myofibroblasts have been defined, the underlying epigenetic regulators driving the AdvSca1-SM-to-myofibroblast transition are unclear. We show that the chromatin remodeler Smarca4/Brg1 facilitates AdvSca1-SM myofibroblast differentiation. Brg1 mRNA and protein were upregulated in AdvSca1-SM cells after acute vascular injury, and pharmacological inhibition of Brg1 by the small molecule PFI-3 attenuated perivascular fibrosis and adventitial expansion. TGF-&#x3b2;1 stimulation of AdvSca1-SM cells in vitro reduced expression of stemness genes while inducing expression of myofibroblast genes that was associated with enhanced contractility; PFI blocked TGF-&#x3b2;1-induced phenotypic transition. Similarly, genetic knockdown of Brg1 in vivo reduced adventitial remodeling and fibrosis and reversed AdvSca1-SM-to-myofibroblast transition in vitro. Mechanistically, TGF-&#x3b2;1 promoted redistribution of Brg1 from distal intergenic sites of stemness genes and recruitment to promoter regions of myofibroblast-related genes, which was blocked by PFI-3. These data provide insight into epigenetic regulation of resident vascular progenitor cell differentiation and support that manipulating the AdvSca1-SM phenotype will provide antifibrotic clinical benefits.</AbstractText
40694062
19170790
40236570
Lumateperone monotherapy for major depressive episodes associated with bipolar disorder: efficacy and safety in a randomized placebo-controlled trial.
Persistent delirium predicts greater mortality.
Catalytic activity study of a laccase-like copper-gallic acid MOF and its applications in the colorimetric determination of norepinephrine and degradation of environmental pollutants.
This Phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of lumateperone to treat bipolar depression. Patients (18-75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode were randomized 1:1:1 to 6-week lumateperone 28&#x2005;mg (n&#x2005;=&#x2005;183), lumateperone 42&#x2005;mg (n&#x2005;=&#x2005;185), or placebo (n&#x2005;=&#x2005;186). Primary and key secondary endpoints were change from baseline to Day 43 in the Montgomery-&#xc5;sberg Depression Rating Scale (MADRS) Total score and time to first sustained response (&#x2265;50% reduction from baseline in MADRS Total score), respectively. Safety assessments included adverse events, extrapyramidal symptoms (EPS), laboratory evaluations, and vital signs. Neither dose of lumateperone achieved significant improvement vs. placebo (P &gt; 0.05) in the primary endpoint (MADRS Total score, least squares mean difference vs. placebo: 28&#x2005;mg, 0.9; 42&#x2005;mg, -1.0) or in the key secondary endpoint (MADRS Total time to first sustained response hazard ratio vs. placebo: 28&#x2005;mg, 1.00; 42&#x2005;mg, 0.93), likely due to a high placebo response. Both lumateperone doses were well tolerated, with low EPS risk and minimal changes in weight, prolactin, and cardiometabolic or endocrine parameters. While study efficacy objectives were not met, both doses of lumateperone were generally safe and well tolerated in patients with bipolar depression.</AbstractText
To examine the association between persistent delirium and 1-year mortality in newly admitted postacute care (PAC) facility patients with delirium who were followed regardless of residence.</AbstractText Observational cohort study.</AbstractText Eight greater-Boston skilled nursing facilities specializing in PAC.</AbstractText Four hundred twelve PAC patients with delirium at admission after an acute hospitalization.</AbstractText Assessments were done at baseline and four follow-up times: 2, 4, 12, and 26 weeks. Delirium, defined using the Confusion Assessment Method, was assessed, as were factors used as covariates in analyses: age, sex, comorbidity, functional status, and dementia. The outcome was 1-year mortality determined according to the National Death Index and corroborated using medical record and proxy telephone interview.</AbstractText Nearly one-third of subjects remained delirious at 6 months. Cumulative 1-year mortality was 39%. Independent of age, sex, comorbidity, functional status, and dementia, subjects with persistent delirium were 2.9 (95% confidence interval 51.9-4.4) times as likely to die during the 1-year follow-up as subjects whose delirium resolved. This association remained strong and significant in groups with and without dementia. Additionally, when delirium resolved, the risk of death diminished thereafter.</AbstractText In patients who were delirious at the time of PAC admission, persistent delirium was a significant independent predictor of 1-year mortality.</AbstractText
Laccases enzymes have garnered significant research interest owing to their extensive applications in pollutant degradation, the food industry, and biosensing technologies. These green biocatalysts are distinguished by the presence of four copper active sites which are integral to their enzymatic functions. Recent advancements have led to the development of copper-based organic-inorganic nanocomposites as laccase mimetics. Hence, this study focused on the synthesis and study of the catalytic properties of a copper-gallic acid metal-organic framework (Cu-GA MOF) heterostructure as a laccase mimic. Using <i
Lumateperone monotherapy for major depressive episodes associated with bipolar disorder: efficacy and safety in a randomized placebo-controlled trial. This Phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of lumateperone to treat bipolar depression. Patients (18-75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode were randomized 1:1:1 to 6-week lumateperone 28&#x2005;mg (n&#x2005;=&#x2005;183), lumateperone 42&#x2005;mg (n&#x2005;=&#x2005;185), or placebo (n&#x2005;=&#x2005;186). Primary and key secondary endpoints were change from baseline to Day 43 in the Montgomery-&#xc5;sberg Depression Rating Scale (MADRS) Total score and time to first sustained response (&#x2265;50% reduction from baseline in MADRS Total score), respectively. Safety assessments included adverse events, extrapyramidal symptoms (EPS), laboratory evaluations, and vital signs. Neither dose of lumateperone achieved significant improvement vs. placebo (P &gt; 0.05) in the primary endpoint (MADRS Total score, least squares mean difference vs. placebo: 28&#x2005;mg, 0.9; 42&#x2005;mg, -1.0) or in the key secondary endpoint (MADRS Total time to first sustained response hazard ratio vs. placebo: 28&#x2005;mg, 1.00; 42&#x2005;mg, 0.93), likely due to a high placebo response. Both lumateperone doses were well tolerated, with low EPS risk and minimal changes in weight, prolactin, and cardiometabolic or endocrine parameters. While study efficacy objectives were not met, both doses of lumateperone were generally safe and well tolerated in patients with bipolar depression.</AbstractText
Persistent delirium predicts greater mortality. To examine the association between persistent delirium and 1-year mortality in newly admitted postacute care (PAC) facility patients with delirium who were followed regardless of residence.</AbstractText Observational cohort study.</AbstractText Eight greater-Boston skilled nursing facilities specializing in PAC.</AbstractText Four hundred twelve PAC patients with delirium at admission after an acute hospitalization.</AbstractText Assessments were done at baseline and four follow-up times: 2, 4, 12, and 26 weeks. Delirium, defined using the Confusion Assessment Method, was assessed, as were factors used as covariates in analyses: age, sex, comorbidity, functional status, and dementia. The outcome was 1-year mortality determined according to the National Death Index and corroborated using medical record and proxy telephone interview.</AbstractText Nearly one-third of subjects remained delirious at 6 months. Cumulative 1-year mortality was 39%. Independent of age, sex, comorbidity, functional status, and dementia, subjects with persistent delirium were 2.9 (95% confidence interval 51.9-4.4) times as likely to die during the 1-year follow-up as subjects whose delirium resolved. This association remained strong and significant in groups with and without dementia. Additionally, when delirium resolved, the risk of death diminished thereafter.</AbstractText In patients who were delirious at the time of PAC admission, persistent delirium was a significant independent predictor of 1-year mortality.</AbstractText
Catalytic activity study of a laccase-like copper-gallic acid MOF and its applications in the colorimetric determination of norepinephrine and degradation of environmental pollutants. Laccases enzymes have garnered significant research interest owing to their extensive applications in pollutant degradation, the food industry, and biosensing technologies. These green biocatalysts are distinguished by the presence of four copper active sites which are integral to their enzymatic functions. Recent advancements have led to the development of copper-based organic-inorganic nanocomposites as laccase mimetics. Hence, this study focused on the synthesis and study of the catalytic properties of a copper-gallic acid metal-organic framework (Cu-GA MOF) heterostructure as a laccase mimic. Using <i
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Benefits and limits of anticholinergic use in schizophrenia: focusing on its effect on cognitive function.
Genome-wide association mapping of loci for antipsychotic-induced extrapyramidal symptoms in mice.
Refining the continuous tracking paradigm to investigate implicit motor learning.
All currently available antipsychotic drugs are the dopamine D2 receptor antagonists and are capable of producing extrapyramidal side-effects (EPS). Anticholinergic drugs are primarily used to treat EPS or prevent EPS induced by antipsychotics in the treatment of psychosis and schizophrenia. However, they can cause a variety of distressing peripheral side-effects (e.g. dry mouth, urinary disturbances, and constipation) and central adverse effects (e.g. cognitive impairment, worsening of tardive dyskinesia, and delirium). Disturbances in cognitive abilities are cardinal features of schizophrenia from its earliest phases and account for much of the functional disability associated with the illness. It is likely that long-term concomitant administration of anticholinergics exacerbates the underlying cognitive impairment in patients with schizophrenia and subsequently affects patients' quality of life. Thus, current treatment guidelines for schizophrenia generally do not recommend the prophylactic and long-term use of anticholinergics. However, the high use of long-term anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in several countries. To assess the benefits and limits of anticholinergic use in psychosis and schizophrenia, this article will provide a brief review of the pharmacology and clinical profiles of anticholinergic drugs and will focus on their effects on cognitive function in schizophrenia, particularly during the course of the early phase of the illness. In addition, we will address the effects of discontinuation of anticholinergics on cognitive function in patients with schizophrenia and provide a strategy for adjunctive anticholinergic use in patients treated with long-acting injectable antipsychotics.</AbstractText
Tardive dyskinesia (TD) is a debilitating, unpredictable, and often irreversible side effect resulting from chronic treatment with typical antipsychotic agents such as haloperidol. TD is characterized by repetitive, involuntary, purposeless movements primarily of the orofacial region. In order to investigate genetic susceptibility to TD, we used a validated mouse model for a systems genetics analysis geared toward detecting genetic predictors of TD in human patients. Phenotypic data from 27 inbred strains chronically treated with haloperidol and phenotyped for vacuous chewing movements were subject to a comprehensive genomic analysis involving 426,493 SNPs, 4,047 CNVs, brain gene expression, along with gene network and bioinformatic analysis. Our results identified ~50 genes that we expect to have high prior probabilities for association with haloperidol-induced TD, most of which have never been tested for association with human TD. Among our top candidates were genes regulating the development of brain motor control regions (Zic4 and Nkx6-1), glutamate receptors (Grin1 and Grin2a), and an indirect target of haloperidol (Drd1a) that has not been studied as well as the direct target, Drd2.</AbstractText
In two experiments we investigated factors that undermine conclusions about implicit motor learning in the continuous tracking paradigm. In Experiment 1, we constructed a practice phase in which all three segments of the waveform pattern were random, in order to examine whether tracking performance decreased as a consequence of time spent on task. Tracking error was lower in the first segment than in the middle segment and lower in the middle segment than in the final segment, indicating that tracking performance decreased as a function of increasing time-on-task. In Experiment 2, the waveform pattern presented in the middle segment was identical in each trial of practice. In a retention test, tracking performance on the repeated segment was superior to tracking performance on the random segments of the waveform. Furthermore, substitution of the repeated pattern with a random pattern (in a transfer test) resulted in a significantly increased tracking error. These findings imply that characteristics of the repeated pattern were learned. Crucially, tests of pattern recognition implied that participants were not explicitly aware of the presence of a recurring segment of waveform. Recommendations for refining the continuous tracking paradigm for implicit learning research are proposed.</AbstractText
Benefits and limits of anticholinergic use in schizophrenia: focusing on its effect on cognitive function. All currently available antipsychotic drugs are the dopamine D2 receptor antagonists and are capable of producing extrapyramidal side-effects (EPS). Anticholinergic drugs are primarily used to treat EPS or prevent EPS induced by antipsychotics in the treatment of psychosis and schizophrenia. However, they can cause a variety of distressing peripheral side-effects (e.g. dry mouth, urinary disturbances, and constipation) and central adverse effects (e.g. cognitive impairment, worsening of tardive dyskinesia, and delirium). Disturbances in cognitive abilities are cardinal features of schizophrenia from its earliest phases and account for much of the functional disability associated with the illness. It is likely that long-term concomitant administration of anticholinergics exacerbates the underlying cognitive impairment in patients with schizophrenia and subsequently affects patients' quality of life. Thus, current treatment guidelines for schizophrenia generally do not recommend the prophylactic and long-term use of anticholinergics. However, the high use of long-term anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in several countries. To assess the benefits and limits of anticholinergic use in psychosis and schizophrenia, this article will provide a brief review of the pharmacology and clinical profiles of anticholinergic drugs and will focus on their effects on cognitive function in schizophrenia, particularly during the course of the early phase of the illness. In addition, we will address the effects of discontinuation of anticholinergics on cognitive function in patients with schizophrenia and provide a strategy for adjunctive anticholinergic use in patients treated with long-acting injectable antipsychotics.</AbstractText
Genome-wide association mapping of loci for antipsychotic-induced extrapyramidal symptoms in mice. Tardive dyskinesia (TD) is a debilitating, unpredictable, and often irreversible side effect resulting from chronic treatment with typical antipsychotic agents such as haloperidol. TD is characterized by repetitive, involuntary, purposeless movements primarily of the orofacial region. In order to investigate genetic susceptibility to TD, we used a validated mouse model for a systems genetics analysis geared toward detecting genetic predictors of TD in human patients. Phenotypic data from 27 inbred strains chronically treated with haloperidol and phenotyped for vacuous chewing movements were subject to a comprehensive genomic analysis involving 426,493 SNPs, 4,047 CNVs, brain gene expression, along with gene network and bioinformatic analysis. Our results identified ~50 genes that we expect to have high prior probabilities for association with haloperidol-induced TD, most of which have never been tested for association with human TD. Among our top candidates were genes regulating the development of brain motor control regions (Zic4 and Nkx6-1), glutamate receptors (Grin1 and Grin2a), and an indirect target of haloperidol (Drd1a) that has not been studied as well as the direct target, Drd2.</AbstractText
Refining the continuous tracking paradigm to investigate implicit motor learning. In two experiments we investigated factors that undermine conclusions about implicit motor learning in the continuous tracking paradigm. In Experiment 1, we constructed a practice phase in which all three segments of the waveform pattern were random, in order to examine whether tracking performance decreased as a consequence of time spent on task. Tracking error was lower in the first segment than in the middle segment and lower in the middle segment than in the final segment, indicating that tracking performance decreased as a function of increasing time-on-task. In Experiment 2, the waveform pattern presented in the middle segment was identical in each trial of practice. In a retention test, tracking performance on the repeated segment was superior to tracking performance on the random segments of the waveform. Furthermore, substitution of the repeated pattern with a random pattern (in a transfer test) resulted in a significantly increased tracking error. These findings imply that characteristics of the repeated pattern were learned. Crucially, tests of pattern recognition implied that participants were not explicitly aware of the presence of a recurring segment of waveform. Recommendations for refining the continuous tracking paradigm for implicit learning research are proposed.</AbstractText
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Machine learning segmentation of core and penumbra from acute stroke CT perfusion data.
Differentiating the histologic grades of gliomas preoperatively using amide proton transfer-weighted (APTW) and intravoxel incoherent motion MRI.
The effects of augmenting traditional rehabilitation with audio biofeedback in people with persistent imbalance following mild traumatic brain injury.
Computed tomography perfusion (CTP) imaging is widely used in cases of suspected acute ischemic stroke to positively identify ischemia and assess suitability for treatment through identification of reversible and irreversible tissue injury. Traditionally, this has been done <i We used machine learning (ML) models based on four different algorithms, combining four CTP measures (cerebral blood flow, cerebral blood volume, mean transit time and delay time) plus 3D-neighborhood (patch) analysis to predict the acute ischemic core and perfusion lesion volumes. The model was developed using 86 patient images, and then tested further on 22 images.</AbstractText XGBoost was the highest-performing algorithm. With standard threshold-based core and penumbra measures as the reference, the model demonstrated moderate agreement in segmenting core and penumbra on test images. Dice similarity coefficients for core and penumbra were 0.38 &#xb1; 0.26 and 0.50 &#xb1; 0.21, respectively, demonstrating moderate agreement. Skull-related image artefacts contributed to lower accuracy.</AbstractText Further development may enable us to move beyond the current overly simplistic core and penumbra definitions using single thresholds where a single error or artefact may lead to substantial error.</AbstractText
The purpose of this work was to investigate the diagnostic performance of amide proton transfer-weighted (APTW) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the preoperative grading of gliomas. Fifty-one patients with suspected gliomas were recruited and underwent a preoperative MRI examination that included APTW and IVIM sequences. All cases were confirmed by postsurgical histopathology. APTW signal intensity, true diffusion coefficient (D), perfusion fraction (f) and pseudo-diffusion coefficient (D*) were applied to assess the solid tumor component and contralateral normal-appearing white matter. The relative APTW signal intensity (rAPTW) was also used. Independent-sample and paired-sample t-tests were used to compare differences in MRI parameters between low-grade glioma (LGG) and high-grade glioma (HGG) groups. The diagnostic performance was assessed with the receiver operating characteristic curve. Twenty-six patients were pathologically diagnosed with LGG and 25 were diagnosed with HGG. APTW, rAPTW and f values were significantly higher (all p&#xa0;&lt;&#xa0;0.001), whereas D values were significantly lower (p&#xa0;&lt;&#xa0;0.001) in the HGG group than in the LGG group. There was no significant difference between D* values for the two groups. rAPTW had an area under the curve (AUC) of 0.957, with a sensitivity of 100% and a specificity of 84.6%, followed by APTW, f, D and D*. The combined use of APTW and IVIM showed the best diagnostic performance, with an AUC of 0.986. In conclusion, APTW and IVIM, as two promising supplementary sequences for routine MRI, could be valuable in differentiating LGGs from HGGs.</AbstractText
Complaints of non-resolving imbalance are common in individuals with chronic mild traumatic brain injury (mTBI). Vestibular rehabilitation therapy may be beneficial for this population. Additionally, wearable sensors can enable biofeedback, specifically audio biofeedback (ABF), and aid in retraining balance control mechanisms in people with balance impairments. In this study, we described the effectiveness of vestibular rehabilitation therapy with and without ABF to improve balance in people with chronic mTBI. Participants (<i
Machine learning segmentation of core and penumbra from acute stroke CT perfusion data. Computed tomography perfusion (CTP) imaging is widely used in cases of suspected acute ischemic stroke to positively identify ischemia and assess suitability for treatment through identification of reversible and irreversible tissue injury. Traditionally, this has been done <i We used machine learning (ML) models based on four different algorithms, combining four CTP measures (cerebral blood flow, cerebral blood volume, mean transit time and delay time) plus 3D-neighborhood (patch) analysis to predict the acute ischemic core and perfusion lesion volumes. The model was developed using 86 patient images, and then tested further on 22 images.</AbstractText XGBoost was the highest-performing algorithm. With standard threshold-based core and penumbra measures as the reference, the model demonstrated moderate agreement in segmenting core and penumbra on test images. Dice similarity coefficients for core and penumbra were 0.38 &#xb1; 0.26 and 0.50 &#xb1; 0.21, respectively, demonstrating moderate agreement. Skull-related image artefacts contributed to lower accuracy.</AbstractText Further development may enable us to move beyond the current overly simplistic core and penumbra definitions using single thresholds where a single error or artefact may lead to substantial error.</AbstractText
Differentiating the histologic grades of gliomas preoperatively using amide proton transfer-weighted (APTW) and intravoxel incoherent motion MRI. The purpose of this work was to investigate the diagnostic performance of amide proton transfer-weighted (APTW) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the preoperative grading of gliomas. Fifty-one patients with suspected gliomas were recruited and underwent a preoperative MRI examination that included APTW and IVIM sequences. All cases were confirmed by postsurgical histopathology. APTW signal intensity, true diffusion coefficient (D), perfusion fraction (f) and pseudo-diffusion coefficient (D*) were applied to assess the solid tumor component and contralateral normal-appearing white matter. The relative APTW signal intensity (rAPTW) was also used. Independent-sample and paired-sample t-tests were used to compare differences in MRI parameters between low-grade glioma (LGG) and high-grade glioma (HGG) groups. The diagnostic performance was assessed with the receiver operating characteristic curve. Twenty-six patients were pathologically diagnosed with LGG and 25 were diagnosed with HGG. APTW, rAPTW and f values were significantly higher (all p&#xa0;&lt;&#xa0;0.001), whereas D values were significantly lower (p&#xa0;&lt;&#xa0;0.001) in the HGG group than in the LGG group. There was no significant difference between D* values for the two groups. rAPTW had an area under the curve (AUC) of 0.957, with a sensitivity of 100% and a specificity of 84.6%, followed by APTW, f, D and D*. The combined use of APTW and IVIM showed the best diagnostic performance, with an AUC of 0.986. In conclusion, APTW and IVIM, as two promising supplementary sequences for routine MRI, could be valuable in differentiating LGGs from HGGs.</AbstractText
The effects of augmenting traditional rehabilitation with audio biofeedback in people with persistent imbalance following mild traumatic brain injury. Complaints of non-resolving imbalance are common in individuals with chronic mild traumatic brain injury (mTBI). Vestibular rehabilitation therapy may be beneficial for this population. Additionally, wearable sensors can enable biofeedback, specifically audio biofeedback (ABF), and aid in retraining balance control mechanisms in people with balance impairments. In this study, we described the effectiveness of vestibular rehabilitation therapy with and without ABF to improve balance in people with chronic mTBI. Participants (<i