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40498790
|
Upper Limb Apraxia Is Related to Role Participation Among Patients With Mild to Moderate Stroke.
|
Poststroke, patients often experience decreased role participation, partially because of cognitive impairment. However, the potential relationship between upper limb apraxia (ULA), a cognitive dysfunction, and role participation remains unclear.</AbstractText To evaluate whether ULA is related to role participation among patients with mild to moderate stroke.</AbstractText Cross-sectional study.</AbstractText Randomly selected Spanish public primary care centers.</AbstractText One hundred fifty-three patients with mild to moderate poststroke.</AbstractText Role participation was assessed with the Role Checklist; ULA, with the TULIA Apraxia test and the ADL Observations scale. ULA construct included the components of nonsymbolic imitation, intransitive imitation, transitive imitation, nonsymbolic pantomime, intransitive pantomime, transitive pantomime, and praxis function in daily life activities. Regression analyses were conducted to assess the potential relationship between ULA and role participation.</AbstractText Transitive pantomime explained 20.5% of the variance of the current level of role participation, R2 = .205, F(3, 152) = 12.795, p < .001. Nonsymbolic imitation and transitive imitation explained 15.8% of the variance in changes in role participation after stroke, R2 = .158, F(4, 152) = 6.957, p < .001. Intransitive pantomime accounted for 17.8% of the variance in expectations for future role participation, R2 = .178, F(3, 152) = 10.776, p < .001. Nonsymbolic imitation and intransitive pantomime explained 16.2% of the variance of the assigned value to role participation, R2 = .162, F(4, 152) = 7.170, p < .01.</AbstractText ULA is related to role participation after mild to moderate stroke. These findings serve as the foundation for designing and developing novel clinical interventions in occupational therapy. Plain-Language Summary: After a stroke, patients often experience difficulties participating in roles that provide a sense of purpose in daily activities. This decrease in participation is partly because of cognitive factors. Upper limb apraxia (ULA) is a cognitive sequela of stroke that hinders the ability to perform deliberate and essential movements. ULA can affect daily life by posing challenges in the execution of daily tasks and activities, which can affect a person's independence, participation, and community reintegration. Because ULA is a cognitive dysfunction that affects intentional movements, this study investigated the potential relationship between ULA and role participation. Based on the evaluation of 153 patients with mild to moderate poststroke, the results revealed that ULA is associated with role participation after a stroke. These findings serve as the foundation for occupational therapists to design and develop novel clinical interventions.</AbstractText
|
[
[
"34104033",
"Blue-Light Therapy Strengthens Resting-State Effective Connectivity within Default-Mode Network after Mild TBI.",
"Emerging evidence suggests that post concussive symptoms, including mood changes, may be improved through morning blue-wavelength light therapy (BLT). However, the neurobiological mechanisms underlying these effects remain unknown. We hypothesize that BLT may influence the effective brain connectivity (EC) patterns within the default-mode network (DMN), particularly involving the medial prefrontal cortex (MPFC), which may contribute to improvements in mood.</AbstractText Resting-state functional MRI data were collected from 41 healthy-controls (HCs) and 28 individuals with mild traumatic brain injury (mTBI). Individuals with mTBI also underwent a diffusion-weighted imaging scan and were randomly assigned to complete either 6 weeks of daily morning BLT (N = 14) or amber light therapy (ALT; N = 14). Advanced spectral dynamic causal modeling (sDCM) and diffusion MRI connectometry were used to estimate EC patterns and structural connectivity strength within the DMN, respectively.</AbstractText The sDCM analysis showed dominant connectivity pattern following mTBI (pre-treatment) within the hemisphere contralateral to the one observed for HCs. BLT, but not ALT, resulted in improved directional information flow (ie, EC) from the left lateral parietal cortex (LLPC) to MPFC within the DMN. The improvement in EC from LLPC to MPFC was accompanied by stronger structural connectivity between the 2 areas. For the BLT group, the observed improvements in function and structure were correlated (at a trend level) with changes in self-reported happiness.</AbstractText The current preliminary findings provide empirical evidence that morning short-wavelength light therapy could be used as a novel alternative rehabilitation technique for mTBI.</AbstractText The research protocols were registered in the ClinicalTrials.gov database (CT Identifiers NCT01747811 and NCT01721356).</AbstractText"
],
[
"38688718",
"Structural Neuroplasticity Effects of Singing in Chronic Aphasia.",
"Singing-based treatments of aphasia can improve language outcomes, but the neural benefits of group-based singing in aphasia are unknown. Here, we set out to determine the structural neuroplasticity changes underpinning group-based singing-induced treatment effects in chronic aphasia. Twenty-eight patients with at least mild nonfluent poststroke aphasia were randomized into two groups that received a 4-month multicomponent singing intervention (singing group) or standard care (control group). High-resolution T1 images and multishell diffusion-weighted MRI data were collected in two time points (baseline/5 months). Structural gray matter (GM) and white matter (WM) neuroplasticity changes were assessed using language network region of interest-based voxel-based morphometry (VBM) and quantitative anisotropy-based connectometry, and their associations to improved language outcomes (Western Aphasia Battery Naming and Repetition) were evaluated. Connectometry analyses showed that the singing group enhanced structural WM connectivity in the left arcuate fasciculus (AF) and corpus callosum as well as in the frontal aslant tract (FAT), superior longitudinal fasciculus, and corticostriatal tract bilaterally compared with the control group. Moreover, in VBM, the singing group showed GM volume increase in the left inferior frontal cortex (Brodmann area 44) compared with the control group. The neuroplasticity effects in the left BA44, AF, and FAT correlated with improved naming abilities after the intervention. These findings suggest that in the poststroke aphasia group, singing can bring about structural neuroplasticity changes in left frontal language areas and in bilateral language pathways, which underpin treatment-induced improvement in speech production.</AbstractText"
],
[
"30762012",
"Aphasia rehabilitation based on mirror neuron theory: a randomized-block-design study of neuropsychology and functional magnetic resonance imaging.",
"When watching someone performs an action, mirror neurons are activated in a way that is very similar to the activation that occurs when actually performing that action. Previous single-sample case studies indicate that hand-action observation training may lead to activation and remodeling of mirror neuron systems, which include important language centers, and may improve language function in aphasia patients. In this randomized-block-design experiment, we recruited 24 aphasia patients from, Zhongda Hospital, Southeast University, China. The patients were divided into three groups where they underwent hand-action observation and repetition, dynamic-object observation and repetition, or conventional speech therapy. Training took place 5 days per week, 35 minutes per day, for 2 weeks. We assessed language function via picture naming tests for objects and actions and the Western Aphasia Battery. Among the participants, one patient, his wife and four healthy student volunteers underwent functional magnetic resonance imaging to analyze changes in brain activation during hand-action observation and dynamic-object observation. Results demonstrated that, compared with dynamic-object observation, hand-action observation led to greater performance with respect to the aphasia quotient and affiliated naming sub-tests and a greater Western Aphasia Battery test score. The overall effect was similar to that of conventional aphasia training, yet hand-action observation had advantages compared with conventional training in terms of vocabulary extraction and spontaneous speech. Thus, hand-action observation appears to more strongly activate the mirror neuron system compared with dynamic-object observation. The activated areas included Broca's area, Wernicke's area, and the supramarginal gyrus. These results suggest that hand-action observation combined with repetition might better improve language function in aphasia patients compared with dynamic-object observation combined with repetition. The therapeutic mechanism of this intervention may be associated with activation of additional mirror neuron systems, and may have implications for the possible repair and remodeling of damaged nerve networks. The study protocol was approved by the Ethical Committee of Nanjing Medical University, China (approval number: 2011-SRFA-086) on March 11, 2011. This trial has been registered in the ISRCTN Registry (ISRCTN84827527).</AbstractText"
],
[
"37521287",
"Association between superior longitudinal fasciculus, motor recovery, and motor outcome after stroke: a cohort study.",
"Parieto-frontal interactions are mediated by the superior longitudinal fasciculus (SLF) and are crucial to integrate visuomotor information and mediate fine motor control. In this study, we aimed to characterize the relation of white matter integrity of both parts of the SLF (SLF I and SLF II) to both motor outcome and recovery and its evolution over time in stroke patients with upper limb motor deficits.</AbstractText Fractional anisotropy (FA) values over the SLF I, SLF II, and corticospinal tract (CST) and upper limb motor performance evaluated by both the upper limb Fugl-Meyer Assessment score and maximum grip strength were measured for 16 patients at 3 weeks, 6 weeks, and 12 weeks poststroke. FA changes were assessed over time using repeated-measures Friedman ANOVA, and correlations between motor recovery, motor outcome at 12 weeks, and FA values in the CST, SLF I, and SLF II at 3 weeks were performed using Spearman's rank-order correlation.</AbstractText FA values in the affected hemisphere's SLF I and SLF II at 3 weeks correlated with motor recovery at 12 weeks when assessed by the Fugl-Meyer Assessment for upper limb extremity (rho: 0.502, p: 0.04 and rho: 0.510, p: 0.04, respectively) but not when assessed by grip strength. FA values in the SLF I and SLF II were not correlated with motor outcomes. FA values in the SLF II in the affected hemisphere changed significantly over time (p: 0.016).</AbstractText Both SLF I and SLF II appeared to participate in poststroke motor recovery of complex movements but not in the motor outcome. These results argue that visually/spatially oriented motor tasks as well as more complex motor tasks using parietal associative areas should be used for poststroke rehabilitation strategies.</AbstractText"
],
[
"31257411",
"Neurotechnology-aided interventions for upper limb motor rehabilitation in severe chronic stroke.",
"Upper limb motor deficits in severe stroke survivors often remain unresolved over extended time periods. Novel neurotechnologies have the potential to significantly support upper limb motor restoration in severely impaired stroke individuals. Here, we review recent controlled clinical studies and reviews focusing on the mechanisms of action and effectiveness of single and combined technology-aided interventions for upper limb motor rehabilitation after stroke, including robotics, muscular electrical stimulation, brain stimulation and brain computer/machine interfaces. We aim at identifying possible guidance for the optimal use of these new technologies to enhance upper limb motor recovery especially in severe chronic stroke patients. We found that the current literature does not provide enough evidence to support strict guidelines, because of the variability of the procedures for each intervention and of the heterogeneity of the stroke population. The present results confirm that neurotechnology-aided upper limb rehabilitation is promising for severe chronic stroke patients, but the combination of interventions often lacks understanding of single intervention mechanisms of action, which may not reflect the summation of single intervention's effectiveness. Stroke rehabilitation is a long and complex process, and one single intervention administrated in a short time interval cannot have a large impact for motor recovery, especially in severely impaired patients. To design personalized interventions combining or proposing different interventions in sequence, it is necessary to have an excellent understanding of the mechanisms determining the effectiveness of a single treatment in this heterogeneous population of stroke patients. We encourage the identification of objective biomarkers for stroke recovery for patients' stratification and to tailor treatments. Furthermore, the advantage of longitudinal personalized trial designs compared to classical double-blind placebo-controlled clinical trials as the basis for precise personalized stroke rehabilitation medicine is discussed. Finally, we also promote the necessary conceptual change from 'one-suits-all' treatments within in-patient clinical rehabilitation set-ups towards personalized home-based treatment strategies, by adopting novel technologies merging rehabilitation and motor assistance, including implantable ones.</AbstractText"
]
] |
[
[
"40710562",
"Understanding the Metabolic Effects of Surgically Induced Renal Ischemia in Humans: A Temporal Approach.",
"<b"
],
[
"40480414",
"Flexible beam-based microelectrode arrays integrated with oriented nanofiber scaffolds for electrophysiological monitoring of cardiac tissue.",
"In vitro culture and electrophysiological monitoring of engineered cardiac tissue (ECT) are crucial for the screening and evaluation of cardiotoxic drugs. Microelectrode arrays (MEAs) offer significant advantages in non-invasive, high-throughput detection. However, existing MEAs face challenges in replicating the natural growth environment of cardiomyocytes, which hinders the morphology and functional maturation of cells. In this study, a flexible beam-based microelectrode array (BMEA) integrated with nanofiber scaffolds is presented for the culturing of well-aligned cardiac tissue and the monitoring of electrophysiological signals. Oriented nanofibers are suspended on flexible polydimethylsiloxane beams to create a 3D culture environment for tissue. The BMEA exhibits low impedance (22 ± 7 kΩ@1 kHz for electrode width of 100 μm), stable electrochemical performance, and good biocompatibility. Through a 10-day continuous culture and drug stimulation of human induced pluripotent stem cell-derived cardiomyocytes, the device demonstrates the ability to capture the electrophysiological signals dynamically while promoting the structural and functional maturation of cardiomyocytes, which show better cell orientation, larger cell size, and faster conduction velocity (∼ 21 cm/s). Further drug tests validate the effectiveness of this device. The BMEA provides a perspective tool for screening and evaluation of drug cardiotoxicity to cardiac tissues. STATEMENT OF SIGNIFICANCE: The mechanical mismatch between traditional rigid MEAs and flexible biological tissues has been partially addressed by the development of flexible MEAs based on polymer or hydrogel substrates. However, these 2D adherent culture methods still face several limitations, including lack of biomimetic ECM microstructure, insufficient intercellular interactions, and directional access to nutrients, thereby posing challenges to the growth of cardiac tissue and the maturation of its electrophysiological functions. Herein, a flexible PDMS beam-based microelectrode array (BMEA) integrated with oriented nanofiber scaffolds is proposed for in-situ electrophysiological monitoring of aligned cardiac tissue in a suspended and biomimetic 3D culture environment. The BMEA provides a promising tool for screening and evaluation of drug cardiotoxicity to cardiac tissues.</AbstractText"
],
[
"39883405",
"Psychopathy as a bipolar construct: Testing the risk-promotive status of the four psychopathy checklist-revised/screening version facet scores in six clinical samples.",
"This study tested the possibility that the four facets of the Psychopathy Checklist-Revised/Screening Version (PCL-R/SV) serve as bipolar constructs in predicting future criminal justice outcomes. Organizing scores on the four facets (Interpersonal, Affective, Lifestyle, and Antisocial) into three categories-that is, lowest 25% of cases (best category), highest 25% of cases (worst category), and middle 50% of cases (intermediate category)-we tested bipolarity by crossing the three categories with a dichotomized crime/violence outcome and calculating both promotive (best category vs. worst + intermediate categories) and risk (worst category vs. best + intermediate categories) effects in six samples. Bipolarity was defined as the simultaneous presence of promotive (low scores predicting a good outcome) and risk (high scores predicting a poor outcome) effects for each PCL-R/SV facet in each sample. Odds ratios and the Cochrane-Armitage linear trend test revealed evidence of bipolarity in one of six samples for the Interpersonal facet, three of six samples for the Affective facet, five of six samples for the Lifestyle facet, and all six samples for the Antisocial facet. An item response theory analysis was then conducted, the results of which supported the facet-level findings from the odds ratio and Cochrane-Armitage analyses at the individual item level. These results provide modest (Affective facet) to moderately strong (Lifestyle and Antisocial facets) evidence of bipolarity in three of the four facets of the PCL-R/SV by showing that low scores are just as effective in predicting good criminal justice outcomes as high scores are in predicting poor criminal justice outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).</AbstractText"
],
[
"40439829",
"Misdiagnosis of autoimmune glial fibrillary acidic protein astrocytopathy as infectious meningitis: a case report.",
"Autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A) is a rare autoimmune central nervous system disorder associated with anti-GFAP IgG, presenting with meningoencephalitis or myelitis. Differential diagnosis from infectious causes, such as tuberculous meningitis (TBM), is challenging due to overlapping clinical and radiological features.</AbstractText A 24-year-old Chinese female presented with acute headache, fever, and vomiting. The cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein and decreased glucose level. Brain magnetic resonance imaging (MRI) showed diffuse leptomeningeal enhancement. She was initially diagnosed with infectious meningitis and emperically treated with antibiotics and anti-tuberculosis therapy. However, her symptoms progressed with seizures, urinary retention, and tremor. Subsequent MRI revealed the involvement of the whole spinal cord. CSF analysis identified anti-GFAP IgG (titer 1:32). Bacterial, viral and tuberculous infection were excluded through bacterial culturing, metagenomic next-generation sequencing and Xpert MTB/RIF assay. The patient responded well to intravenous immunoglobulin and corticosteroids, achieving full remission. Finally, the diagnosis of A-GFAP-A was confirmed.</AbstractText A-GFAP-A mimics infectious meningitis such as TBM due to similar CSF abnormalities and neuroimaging findings. This case underscores the importance of GFAP-IgG testing in differential diagnosis of patients with meningitis who have negative microbiological studies and atypical symptoms such as urinary retention and tremor.</AbstractText"
],
[
"39988830",
"Purinergic Receptor P2Y1 Modulates Catecholamine Signaling in Murine Mesenteric Lymph Nodes.",
"Neuroimmune communication is crucial for the body's response to physiological challenges, homeostasis, and immune stress response. Adrenergic and purinergic neurotransmission in the sympathetic nervous system is vital for this communication. This study achieves the first co-detection of adenine-based purines and catecholamines in mesenteric lymph nodes via fast-scan cyclic voltammetry. Additionally, we reveal that manipulating an ATP receptor can impact catecholamine signaling in the lymph node for the first time. The G-protein-coupled receptor P2Y1, which controls intracellular Ca<sup"
]
] |
40509179
|
Towards Cytotoxic Derivatives of Cafestol.
|
This study focuses on the extraction, characterization, and biological evaluation of diterpenes from green coffee beans, specifically, cafestol and kahweol. These compounds, known for their potential health benefits, were isolated via optimized extraction and saponification processes. Separation was achieved using silver nitrate-impregnated silica gel, and structural elucidation was performed through advanced 1D and 2D NMR techniques, including HSQC, HMBC, and (IN)ADEQUATE. Due to kahweol's instability, the research prioritized cafestol for the synthesis of rhodamine B conjugates. Initial ester-linked conjugates proved unstable, prompting the development of more robust derivatives through amide linkage strategies and further functionalization via acetylation and oxidation reactions. Some oxidation methods led to furan ring cleavage, impacting structural integrity. Selected compounds were tested for cytotoxicity using SRB assays on human tumor cell lines (MCF7, A2780) and non-malignant fibroblasts (NIH 3T3). While the parent diterpenes and many derivatives showed minimal activity, several cafestol-rhodamine B conjugates demonstrated notable cytotoxic effects. Compound <b
|
[
[
"27401805",
"Quantitative hemodynamic PET imaging using image-derived arterial input function and a PET/MR hybrid scanner.",
"Positron emission tomography (PET) with <sup"
],
[
"30292731",
"Sleep Disorders.",
"Sleep disorders are frequent and can have serious consequences on patients' health and quality of life. While some sleep disorders are more challenging to treat, most can be easily managed with adequate interventions. We review the main diagnostic features of 6 major sleep disorders (insomnia, circadian rhythm disorders, sleep-disordered breathing, hypersomnia/narcolepsy, parasomnias, and restless legs syndrome/periodic limb movement disorder) to aid medical practitioners in screening and treating sleep disorders as part of clinical practice.</AbstractText"
],
[
"29790649",
"Hyperpolarized NMR Spectroscopy: d-DNP, PHIP, and SABRE Techniques.",
"The intensity of NMR signals can be enhanced by several orders of magnitude by using various techniques for the hyperpolarization of different molecules. Such approaches can overcome the main sensitivity challenges facing modern NMR/magnetic resonance imaging (MRI) techniques, whilst hyperpolarized fluids can also be used in a variety of applications in material science and biomedicine. This Focus Review considers the fundamentals of the preparation of hyperpolarized liquids and gases by using dissolution dynamic nuclear polarization (d-DNP) and parahydrogen-based techniques, such as signal amplification by reversible exchange (SABRE) and parahydrogen-induced polarization (PHIP), in both heterogeneous and homogeneous processes. The various new aspects in the formation and utilization of hyperpolarized fluids, along with the possibility of observing NMR signal enhancement, are described.</AbstractText"
],
[
"25762497",
"Recent applications of UHF-MRI in the study of human brain function and structure: a review.",
"The increased availability of ultra-high-field (UHF) MRI has led to its application in a wide range of neuroimaging studies, which are showing promise in transforming fundamental approaches to human neuroscience. This review presents recent work on structural and functional brain imaging, at 7 T and higher field strengths. After a short outline of the effects of high field strength on MR images, the rapidly expanding literature on UHF applications of blood-oxygenation-level-dependent-based functional MRI is reviewed. Structural imaging is then discussed, divided into sections on imaging weighted by relaxation time, including quantitative relaxation time mapping, phase imaging and quantitative susceptibility mapping, angiography, diffusion-weighted imaging, and finally magnetization-transfer imaging. The final section discusses studies using the high spatial resolution available at UHF to identify explicit links between structure and function. Copyright © 2015 John Wiley & Sons, Ltd.</AbstractText"
],
[
"28480537",
"Accelerated noncontrast-enhanced 4-dimensional intracranial MR angiography using golden-angle stack-of-stars trajectory and compressed sensing with magnitude subtraction.",
"To evaluate the feasibility and performance of compressed sensing (CS) with magnitude subtraction regularization in accelerating non-contrast-enhanced dynamic intracranial MR angiography (NCE-dMRA).</AbstractText A CS algorithm was introduced in NCE-dMRA by exploiting the sparsity of the magnitude difference of the control and label images. The NCE-dMRA data were acquired using golden-angle stack-of-stars trajectory on six healthy volunteers and one patient with arteriovenous fistula. Images were reconstructed using (i) the proposed magnitude-subtraction CS (MS-CS); (ii) complex-subtraction CS; (iii) independent CS; and (iv) view-sharing with k-space weighted image contrast (KWIC). The dMRA image quality was compared across the four reconstruction strategies. The proposed MS-CS method was further compared with KWIC for temporal fidelity of depicting dynamic flow.</AbstractText The proposed MS-CS method was able to reconstruct NCE-dMRA images with detailed vascular structures and clean background. It provided better subjective image quality than the other two CS strategies (P < 0.05). Compared with KWIC, MS-CS showed similar image quality, but reduced temporal blurring in delineating the fine distal arteries.</AbstractText The MS-CS method is a promising CS technique for accelerating NCE-dMRA acquisition without compromising image quality and temporal fidelity. Magn Reson Med 79:867-878, 2018. © 2017 International Society for Magnetic Resonance in Medicine.</AbstractText"
]
] |
[
[
"40647442",
"The Role of ENHO in Pancreatic Adenocarcinoma: A Bioinformatics Approach.",
"Pancreatic adenocarcinoma (PAAD) is an aggressive subtype of pancreatic cancer that is estimated to have a 5-year overall survival rate of only 13%. Most patients present with advanced disease with unpredictable outcomes. The identification of prognostic biomarkers is important to accurately stratify these patients.</AbstractText We investigated the molecular and survival-related role of <i We observed that <i Our results point to a protective role for <i"
],
[
"40384034",
"MR Spectroscopic Imaging of Hyperpolarized 129-Xenon in the Dissolved-Phase to Determine Regional Chemical Shifts of Hyperoxia in Healthy Porcine Lungs.",
"Lung MRI with hyperpolarized xenon (<sup"
],
[
"40746166",
"Sex Differences in White Matter Structure in Attention Deficit Hyperactivity Disorder: MR Diffusion Fixel-Based Analysis.",
"Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder prevalent among adolescents and exhibits notable sex dimorphism. Despite an increasing body of research, the impact of sex on ADHD remains underexplored. This study aimed to examine sex differences in white matter organization in children with ADHD using magnetic resonance (MR) diffusion data analyzed with fixel-based analysis (FBA), a novel technique that enables detailed assessment of both microstructural and macrostructural properties of white matter.</AbstractText Fifty-five children with ADHD and 37 age-matched typically developing controls underwent MR diffusion. FBA was used to assess white matter structure. Group comparisons examined sex differences within and between groups, and correlation analyses were conducted between white matter features and clinical symptoms in the ADHD group.</AbstractText The results demonstrated that no significant sex differences were identified among healthy controls. However, within the ADHD group, the fiber cross-section (FC) metric revealed significant white matter alterations in several tracts, including the arcuate fasciculus, corpus callosum (CC), cingulum (CG), superior longitudinal fascicle, striato-fronto-orbital (ST_FO), and striato-precentral. In addition, the fiber density and cross-section metrics showed comparable abnormalities in the CC, CG, and ST_FO. Females with ADHD showed stronger correlations between FC metrics in bundles of white matter and clinical symptoms.</AbstractText This study is the first to demonstrate sex differences in ADHD white matter bundles using FBA, contributing to a deeper understanding of the pathological mechanisms of ADHD and offering new insights for its diagnosis and treatment.</AbstractText"
],
[
"40631251",
"Subtype-Specific Roles of Nigrostriatal Dopaminergic Neurons in Motor and Associative Learning.",
"Nigrostriatal dopaminergic neurons (DANs) in the <i"
],
[
"40407341",
"Differential Lesion Patterns Associated With Stroke-Induced Apraxia in Women and Men.",
"The motor-cognitive syndrome apraxia is a common stroke sequela and severely affects the outcome after stroke by impairing activities of daily living. Notably, like in many health conditions, there is a massive backlog regarding studies on sex differences in patients with apraxia despite common knowledge that sex influences praxis performance in healthy participants. We investigated putative sex differences in apraxic stroke patients at the behavioral and neural levels.</AbstractText We retrospectively analysed the data of a cohort of 102 left-hemisphere stroke patients in the (sub)acute phase who were apraxic according to the Cologne Apraxia Screening (KAS). We conducted voxel-based lesion-symptom mapping (VLSM) to elucidate the lesion patterns. Further, in an age-matched subsample (tolerance of 5 years) with equal numbers of men and women, behavioral comparisons and a VLSM analysis were conducted to explore differential sex-related lesion patterns.</AbstractText Overall, apraxic deficits were associated with lesions in the parietal, temporal, and frontal regions in the cohort of 102 left-hemisphere stroke patients. The age-matched cohort consisted of 30 women and 30 men and showed no significant differences in demographic and clinical characteristics. There were no performance differences between men and women at the behavioral level regarding praxis functions. In contrast, VLSM revealed differential lesion patterns by sex. Male compared to female apraxic stroke patients significantly more often showed lesions that affected the left inferior frontal gyrus.</AbstractText The data suggest a differential organization of the praxis system in men and women, warranting further exploration.</AbstractText"
]
] |
34519480
|
Antioxidative and Angiogenic Hyaluronic Acid-Based Hydrogel for the Treatment of Peripheral Artery Disease.
|
Peripheral arterial disease (PAD) is a progressive atherosclerotic disorder characterized by blockages of the arteries supplying the lower extremities. Ischemia initiates oxidative damage and mitochondrial dysfunction in the legs of PAD patients, causing injury to the tissues of the leg, significant decline in walking performance, leg pain while walking, and in the most severe cases, nonhealing ulcers and gangrene. Current clinical trials based on cells/stem cells, the trophic factor, or gene therapy systems have shown some promising results for the treatment of PAD. Biomaterial matrices have been explored in animal models of PAD to enhance these therapies. However, current biomaterial approaches have not fully met the essential requirements for minimally invasive intramuscular delivery to the leg. Ideally, a biomaterial should present properties to ameliorate oxidative stress/damage and failure of angiogenesis. Recently, we have created a thermosensitive hyaluronic acid (HA) hydrogel with antioxidant capacity and skeletal muscle-matching stiffness. Here, we further optimized HA hydrogels with the cell adhesion peptide RGD to facilitate the development of vascular-like structures <i
|
[
[
"26282581",
"GABAB receptor-mediated feed-forward circuit dysfunction in the mouse model of fragile X syndrome.",
"Cortico-hippocampal feed-forward circuits formed by the temporoammonic (TA) pathway exhibit a marked increase in excitation/inhibition ratio and abnormal spike modulation functions in Fmr1 knock-out (KO) mice. Inhibitory, but not excitatory, synapse dysfunction underlies cortico-hippocampal feed-forward circuit abnormalities in Fmr1 KO mice. GABA release is reduced in TA-associated inhibitory synapses of Fmr1 KO mice in a GABAB receptor-dependent manner. Inhibitory synapse and feed-forward circuit defects are mediated predominately by presynaptic GABAB receptor signalling in the TA pathway of Fmr1 KO mice. GABAB receptor-mediated inhibitory synapse defects are circuit-specific and are not observed in the Schaffer collateral pathway-associated inhibitory synapses in stratum radiatum.</AbstractText Circuit hyperexcitability has been implicated in neuropathology of fragile X syndrome, the most common inheritable cause of intellectual disability. Yet, how canonical unitary circuits are affected in this disorder remains poorly understood. Here, we examined this question in the context of the canonical feed-forward inhibitory circuit formed by the temporoammonic (TA) branch of the perforant path, the major cortical input to the hippocampus. TA feed-forward circuits exhibited a marked increase in excitation/inhibition ratio and major functional defects in spike modulation tasks in Fmr1 knock-out (KO) mice, a fragile X mouse model. Changes in feed-forward circuits were caused specifically by inhibitory, but not excitatory, synapse defects. TA-associated inhibitory synapses exhibited increase in paired-pulse ratio and in the coefficient of variation of IPSPs, consistent with decreased GABA release probability. TA-associated inhibitory synaptic transmission in Fmr1 KO mice was also more sensitive to inhibition of GABAB receptors, suggesting an increase in presynaptic GABAB receptor (GABAB R) signalling. Indeed, the differences in inhibitory synaptic transmission between Fmr1 KO and wild-type (WT) mice were eliminated by a GABAB R antagonist. Inhibition of GABAB Rs or selective activation of presynaptic GABAB Rs also abolished the differences in the TA feed-forward circuit properties between Fmr1 KO and WT mice. These GABAB R-mediated defects were circuit-specific and were not observed in the Schaffer collateral pathway-associated inhibitory synapses. Our results suggest that the inhibitory synapse dysfunction in the cortico-hippocampal pathway of Fmr1 KO mice causes hyperexcitability and feed-forward circuit defects, which are mediated in part by a presynaptic GABAB R-dependent reduction in GABA release.</AbstractText"
],
[
"35494482",
"Revealing the Neuroimaging Mechanism of Acupuncture for Poststroke Aphasia: A Systematic Review.",
"Aphasia is a common symptom in stroke patients, presenting with the impairment of spontaneous speech, repetition, naming, auditory comprehension, reading, and writing function. Multiple rehabilitation methods have been suggested for the recovery of poststroke aphasia, including medication treatment, behavioral therapy, and stimulation approach. Acupuncture has been proven to have a beneficial effect on improving speech functions in repetition, oral speech, reading, comprehension, and writing ability. Neuroimaging technology provides a visualized way to explore cerebral neural activity, which helps reveal the therapeutic effect of acupuncture therapy. In this systematic review, we aim to reveal and summarize the neuroimaging mechanism of acupuncture therapy on poststroke aphasia to provide the foundation for further study.</AbstractText Seven electronic databases were searched including PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, the Wanfang databases, and the Chinese Scientific Journal Database. After screening the studies according to the inclusion and exclusion criteria, we summarized the neuroimaging mechanism of acupuncture on poststroke aphasia, as well as the utilization of acupuncture therapy and the methodological characteristics.</AbstractText After searching, 885 articles were retrieved. After removing the literature studies, animal studies, and case reports, 16 studies were included in the final analysis. For the acupuncture type, 10 studies used manual acupuncture and 5 studies used electroacupuncture, while body acupuncture (10 studies), scalp acupuncture (7 studies), and tongue acupuncture (8 studies) were applied for poststroke aphasia patients. Based on blood oxygen level-dependent (BOLD) and diffusion tensor imaging (DTI) technologies, 4 neuroimaging analysis methods were used including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), seed-based analysis, and independent component analysis (ICA). Two studies reported the instant acupuncture effect, and 14 studies reported the constant acupuncture's effect on poststroke aphasia patients. 5 studies analyzed the correlation between the neuroimaging outcomes and the clinical language scales.</AbstractText In this systematic review, we found that the mechanism of acupuncture's effect might be associated with the activation and functional connectivity of language-related brain areas, such as brain areas around Broca's area and Wernicke's area in the left inferior temporal gyrus, supramarginal gyrus, middle frontal gyrus, and inferior frontal gyrus. However, these studies were still in the preliminary stage. Multicenter randomized controlled trials (RCT) with large sample sizes were needed to verify current evidence, as well as to explore deeply the neuroimaging mechanisms of acupuncture's effects.</AbstractText"
],
[
"36307487",
"The ex vivo human translaminar autonomous system to study spaceflight associated neuro-ocular syndrome pathogenesis.",
"Spaceflight-Associated Neuro-ocular Syndrome (SANS) is a significant unexplained adverse reaction to long-duration spaceflight. We employ an ex vivo translaminar autonomous system (TAS) to recreate a human ocular ground-based spaceflight analogue model to study SANS pathogenesis. To recapitulate the human SANS conditions, human ocular posterior segments are cultured in the TAS model for 14 days. Translaminar pressure differentials are generated by simulating various flow rates within intracranial pressure (ICP) and intraocular (IOP) chambers to maintain hydrostatic pressures of ICP: IOP (12:16, 15:16, 12:21, 21:16 mmHg). In addition, optic nerves are mechanically kinked by 6- and 10-degree tilt inserts for the ICP: IOP;15:16 mmHg pressure paradigm. The TAS model successfully maintains various pressure differentials for all experimental groups over 14 days. Post culture, we determine inflammatory and extracellular component expression changes within posterior segments. To further characterize the SANS pathogenesis, axonal transport capacity, optic nerve degeneration and retinal functional are measured. Identifiable pathogenic alterations are observed in posterior segments by morphologic, apoptotic, and inflammatory changes including transport and functional deficits under various simulated SANS conditions. Here we report our TAS model provides a unique preclinical application system to mimic SANS pathology and a viable therapeutic testing device for countermeasures.</AbstractText"
],
[
"26391047",
"The NGF Metabolic Pathway in the CNS and its Dysregulation in Down Syndrome and Alzheimer's Disease.",
"It is well established that individuals with Down syndrome develop Alzheimer's disease neuropathology by middle age. Both in Alzheimer's disease and Down syndrome, this is accompanied by the atrophy of NGF-dependent cholinergic neurons of the basal forebrain. An NGF trophic compromise in Alzheimer's disease had been early suspected. This hypothesis was discarded with the finding of unaltered NGF mRNA synthesis and of increased NGF precursor levels (proNGF) in postmortem Alzheimer's disease brains. The possibility of an NGF trophic disconnection has been recently revisited at the light of a newly discovered extracellular NGF metabolic pathway; where proNGF is released in an activity-dependent manner and converted by plasmin to mature NGF in the extracellular space. Mature NGF is ultimately degraded by the metalloprotease MMP-9. This pathway has been shown to be compromised in Alzheimer's disease and Down syndrome brains, thus reviving the trophic factor hypothesis to explain the atrophy of basal forebrain cholinergic neurons in these disorders. This chapter will discuss the physiological role of NGF and its biological significance to cholinergic neurons of the CNS, and present the evidence for a dysregulation of the NGF metabolism in Alzheimer's disease and Down syndrome.</AbstractText"
],
[
"22226359",
"Rejuvenation of regeneration in the aging central nervous system.",
"Remyelination is a regenerative process in the central nervous system (CNS) that produces new myelin sheaths from adult stem cells. The decline in remyelination that occurs with advancing age poses a significant barrier to therapy in the CNS, particularly for long-term demyelinating diseases such as multiple sclerosis (MS). Here we show that remyelination of experimentally induced demyelination is enhanced in old mice exposed to a youthful systemic milieu through heterochronic parabiosis. Restored remyelination in old animals involves recruitment to the repairing lesions of blood-derived monocytes from the young parabiotic partner, and preventing this recruitment partially inhibits rejuvenation of remyelination. These data suggest that enhanced remyelinating activity requires both youthful monocytes and other factors, and that remyelination-enhancing therapies targeting endogenous cells can be effective throughout life.</AbstractText"
]
] |
[
[
"33430634",
"Stroke Imaging Selection Modality and Endovascular Therapy Outcomes in the Early and Extended Time Windows.",
"Advanced imaging has been increasingly used for patient selection in endovascular stroke therapy. The impact of imaging selection modality on endovascular stroke therapy clinical outcomes in extended time window remains to be defined. We aimed to study this relationship and compare it to that noted in early-treated patients.</AbstractText Patients from a prospective multicentric registry (n=2008) with occlusions involving the intracranial internal carotid or the M1- or M2-segments of the middle cerebral arteries, premorbid modified Rankin Scale score 0 to 2 and time to treatment 0 to 24 hours were categorized according to treatment times within the early (0-6 hour) or extended (6-24 hour) window as well as imaging modality with noncontrast computed tomography (NCCT)±CT angiography (CTA) or NCCT±CTA and CT perfusion (CTP). The association between imaging modality and 90-day modified Rankin Scale, analyzed in ordinal (modified Rankin Scale shift) and dichotomized (functional independence, modified Rankin Scale score 0-2) manner, was evaluated and compared within and across the extended and early windows.</AbstractText In the early window, 332 patients were selected with NCCT±CTA alone while 373 also underwent CTP. After adjusting for identifiable confounders, there were no significant differences in terms of 90-day functional disability (ordinal shift: adjusted odd ratio [aOR], 0.936 [95% CI, 0.709-1.238], <i CTP acquisition was not associated with better outcomes in patients treated in the early or extended time windows. While confirmatory data is needed, our data suggests that extended window endovascular stroke therapy may remain beneficial even in the absence of advanced imaging.</AbstractText"
],
[
"34764188",
"NEST Desktop, an Educational Application for Neuroscience.",
"Simulation software for spiking neuronal network models matured in the past decades regarding performance and flexibility. But the entry barrier remains high for students and early career scientists in computational neuroscience since these simulators typically require programming skills and a complex installation. Here, we describe an installation-free Graphical User Interface (GUI) running in the web browser, which is distinct from the simulation engine running anywhere, on the student's laptop or on a supercomputer. This architecture provides robustness against technological changes in the software stack and simplifies deployment for self-education and for teachers. Our new open-source tool, NEST Desktop, comprises graphical elements for creating and configuring network models, running simulations, and visualizing and analyzing the results. NEST Desktop allows students to explore important concepts in computational neuroscience without the need to learn a simulator control language before. Our experiences so far highlight that NEST Desktop helps advancing both quality and intensity of teaching in computational neuroscience in regular university courses. We view the availability of the tool on public resources like the European ICT infrastructure for neuroscience EBRAINS as a contribution to equal opportunities.</AbstractText"
],
[
"34721724",
"Narrative Devices: Neurotechnologies, Information, and Self-Constitution.",
"This article provides a conceptual and normative framework through which we may understand the potentially ethically significant roles that information generated by neurotechnologies about our brains and minds may play in our construction of our identities. Neuroethics debates currently focus disproportionately on the ways that third parties may (ab)use these kinds of information. These debates occlude interests we may have in whether and how we ourselves encounter information about our own brains and minds. This gap is not yet adequately addressed by most allusions in the literature to potential identity impacts. These lack the requisite conceptual or normative foundations to explain why we should be concerned about such effects or how they might be addressed. This article seeks to fill this gap by presenting a normative account of identity as constituted by embodied self-narratives. It proposes that information generated by neurotechnologies can play significant content-supplying and interpretive roles in our construction of our self-narratives. It argues, to the extent that these roles support and detract from the coherence and inhabitability of these narratives, access to information about our brains and minds engages non-trivial identity-related interests. These claims are illustrated using examples drawn from empirical literature reporting reactions to information generated by implantable predictive BCIs and psychiatric neuroimaging. The article concludes by highlighting ways in which information generated by neurotechnologies might be governed so as to protect information subjects' interests in developing and inhabiting their own identities.</AbstractText"
],
[
"34814138",
"Written Discourse Task Helps to Identify Progression from Mild Cognitive Impairment to Dementia.",
"We aimed to investigate: (1) the clinical, diagnostic value of a written discourse task, and (2) the relationship between executive functions and written discourse within the spectrum of individuals with mild cognitive impairment (MCI).</AbstractText To determine whether written discourse performance predicts clinical course among individuals with MCI, we retrospectively classified individuals with MCI as converters (N = 26) who were later diagnosed with dementia or as a stable MCI group (N = 45). We quantified core word measures from written discourse samples obtained from the Cookie Theft picture description task.</AbstractText Written discourse measures differentiated converters from the stable MCI group. Converters produced a fewer number of core words than the stable MCI group. A measure of executive function significantly predicted performance on the production of core words in written discourse for the converters. In a multivariable regression, production of core words remained the only explanatory variable closely associated with the progression to dementia in MCI.</AbstractText Written discourse tasks can predict the likelihood of MCI progressing to dementia, independently of recall and an executive function measure. Correlational results suggest that written discourse performance was associated with executive function as measured by the Trail Making Test. Our findings emphasize the usefulness of including written discourse tasks in language assessment batteries targeting preclinical dementia populations.</AbstractText"
],
[
"33502667",
"Effect of MRI acquisition acceleration via compressed sensing and parallel imaging on brain volumetry.",
"To investigate the effect of compressed SENSE (CS), an acceleration technique combining parallel imaging and compressed sensing, on potential bias and precision of brain volumetry and evaluate it in the context of normative brain volumetry.</AbstractText In total, 171 scans from scan-rescan experiments on three healthy subjects were analyzed. Each subject received 3D-T1-weighted brain MRI scans at increasing degrees of acceleration (CS-factor = 1/4/8/12/16/20/32). Single-scan acquisition times ranged from 00:41 min (CS-factor = 32) to 21:52 min (CS-factor = 1). Brain segmentation and volumetry was performed using two different software tools: md.brain, a proprietary software based on voxel-based morphometry, and FreeSurfer, an open-source software based on surface-based morphometry. Four sub-volumes were analyzed: brain parenchyma (BP), total gray matter, total white matter, and cerebrospinal fluid (CSF). Coefficient of variation (CoV) of the repeated measurements as a measure of intra-subject reliability was calculated. Intraclass correlation coefficient (ICC) with regard to increasing CS-factor was calculated as another measure of reliability. Noise-to-contrast ratio as a measure of image quality was calculated for each dataset to analyze the association between acceleration factor, noise and volumetric brain measurements.</AbstractText For all sub-volumes, there is a systematic bias proportional to the CS-factor which is dependent on the utilized software and subvolume. Measured volumes deviated significantly from the reference standard (CS-factor = 1), e.g. ranging from 1 to 13% for BP. The CS-induced systematic bias is driven by increased image noise. Except for CSF, reliability of brain volumetry remains high, demonstrated by low CoV (< 1% for CS-factor up to 20) and good to excellent ICC for CS-factor up to 12.</AbstractText CS-acceleration has a systematic biasing effect on volumetric brain measurements.</AbstractText"
]
] |
29340183
|
Action observation training to improve motor function recovery: a systematic review.
|
Following the discovery of Mirror Neuron System (MNS), Action Observation Training (AOT) has become an emerging rehabilitation tool to improve motor functions both in neurologic and orthopedic pathologies. The aim of this study is to present the state of the art on the use of AOT in experimental studies to improve motor function recovery in any disease. The research was performed in PubMed, PEDro, Embase, CINAHL and Cochrane Central Register of Controlled Trials (last search July 2015). Randomized controlled trials (RCTs) that analyse efficacy of AOT for recovery of motor functions, regardless of the kind of disease, were retrieved. The validity of the included studies was assessed using the Cochrane Collaboration tool for evaluating risk of bias. Twenty RCTs were eligible. Four studies showed AOT efficacy in improving upper limb functional recovery in participants with chronic stroke, two studies in sub-acute ones and one in acute ones. Six articles suggested its effectiveness on walking performance in chronic stroke individuals, and three of them also suggested an efficacy in improving balance. The use of AOT was also recommended in individuals with Parkinson's disease to improve autonomy in activities of daily living, to improve spontaneous movement rate of self-paced finger movements and to reduce freezing of gait. Other two studies also indicated that AOT improves upper limb motor function in children with cerebral palsy. The last two studies, showed the efficacy of AOT in improving motor recovery in postsurgical orthopedic participants. Overall methodological quality of the considered studies was medium. The majority of analyzed studies suggest the efficacy of AOT, in addition to conventional physiotherapy, to improve motor function recovery in individuals with neurological and orthopedic diseases. However, the application of AOT is very heterogeneous in terms of diseases and outcome measures assessed, which makes it difficult to reach, to date, any conclusion that might influence clinical practice.</AbstractText
|
[
[
"29361441",
"Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review.",
"Electrical stimulation of the auricular branch of the vagus nerve (ABVN) via transcutaneous auricular vagus nerve stimulation (taVNS) may influence afferent vagal networks. There have been 5 prior taVNS/fMRI studies, with inconsistent findings due to variability in stimulation targets and parameters.</AbstractText We developed a taVNS/fMRI system to enable concurrent electrical stimulation and fMRI acquisition to compare the effects of taVNS in relation to control stimulation.</AbstractText We enrolled 17 healthy adults in this single-blind, crossover taVNS/fMRI trial. Based on parameters shown to affect heart rate in healthy volunteers, participants received either left tragus (active) or earlobe (control) stimulation at 500 μs 25 HZ for 60 s (repeated 3 times over 6 min). Whole brain fMRI analysis was performed exploring the effect of: active stimulation, control stimulation, and the comparison. Region of interest analysis of the midbrain and brainstem was also conducted.</AbstractText Active stimulation produced significant increased BOLD signal in the contralateral postcentral gyrus, bilateral insula, frontal cortex, right operculum, and left cerebellum. Control stimulation produced BOLD signal activation in the contralateral postcentral gyrus. In the active vs. control contrast, tragus stimulation produced significantly greater BOLD increases in the right caudate, bilateral anterior cingulate, cerebellum, left prefrontal cortex, and mid-cingulate.</AbstractText Stimulation of the tragus activates the cerebral afferents of the vagal pathway and combined with our review of the literature suggest that taVNS is a promising form of VNS. Future taVNS/fMRI studies should systematically explore various parameters and alternative stimulation targets aimed to optimize this novel form of neuromodulation.</AbstractText"
],
[
"28978697",
"Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence.",
"The role of the frontal cortex in consciousness remains a matter of debate. In this Perspective, we will critically review the clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discuss promising research avenues.<b"
],
[
"26707889",
"Reliability of dissimilarity measures for multi-voxel pattern analysis.",
"Representational similarity analysis of activation patterns has become an increasingly important tool for studying brain representations. The dissimilarity between two patterns is commonly quantified by the correlation distance or the accuracy of a linear classifier. However, there are many different ways to measure pattern dissimilarity and little is known about their relative reliability. Here, we compare the reliability of three classes of dissimilarity measure: classification accuracy, Euclidean/Mahalanobis distance, and Pearson correlation distance. Using simulations and four real functional magnetic resonance imaging (fMRI) datasets, we demonstrate that continuous dissimilarity measures are substantially more reliable than the classification accuracy. The difference in reliability can be explained by two characteristics of classifiers: discretization and susceptibility of the discriminant function to shifts of the pattern ensemble between imaging runs. Reliability can be further improved through multivariate noise normalization for all measures. Finally, unlike conventional distance measures, crossvalidated distances provide unbiased estimates of pattern dissimilarity on a ratio scale, thus providing an interpretable zero point. Overall, our results indicate that the crossvalidated Mahalanobis distance is preferable to both the classification accuracy and the correlation distance for characterizing representational geometries.</AbstractText"
],
[
"26696921",
"The Merit of Synesthesia for Consciousness Research.",
"Synesthesia is a phenomenon in which additional perceptual experiences are elicited by sensory stimuli or cognitive concepts. Synesthetes possess a unique type of phenomenal experiences not directly triggered by sensory stimulation. Therefore, for better understanding of consciousness it is relevant to identify the mental and physiological processes that subserve synesthetic experience. In the present work we suggest several reasons why synesthesia has merit for research on consciousness. We first review the research on the dynamic and rapidly growing field of the studies of synesthesia. We particularly draw attention to the role of semantics in synesthesia, which is important for establishing synesthetic associations in the brain. We then propose that the interplay between semantics and sensory input in synesthesia can be helpful for the study of the neural correlates of consciousness, especially when making use of ambiguous stimuli for inducing synesthesia. Finally, synesthesia-related alterations of brain networks and functional connectivity can be of merit for the study of consciousness.</AbstractText"
],
[
"25636911",
"Unmasking Language Lateralization in Human Brain Intrinsic Activity.",
"Lateralization of function is a fundamental feature of the human brain as exemplified by the left hemisphere dominance of language. Despite the prominence of lateralization in the lesion, split-brain and task-based fMRI literature, surprisingly little asymmetry has been revealed in the increasingly popular functional imaging studies of spontaneous fluctuations in the fMRI BOLD signal (so-called resting-state fMRI). Here, we show the global signal, an often discarded component of the BOLD signal in resting-state studies, reveals a leftward asymmetry that maps onto regions preferential for semantic processing in left frontal and temporal cortex and the right cerebellum and a rightward asymmetry that maps onto putative attention-related regions in right frontal, temporoparietal, and parietal cortex. Hemispheric asymmetries in the global signal resulted from amplitude modulation of the spontaneous fluctuations. To confirm these findings obtained from normal, healthy, right-handed subjects in the resting-state, we had them perform 2 semantic processing tasks: synonym and numerical magnitude judgment and sentence comprehension. In addition to establishing a new technique for studying lateralization through functional imaging of the resting-state, our findings shed new light on the physiology of the global brain signal.</AbstractText"
]
] |
[
[
"26033541",
"Mitochondrial E3 ligase March5 maintains stemness of mouse ES cells via suppression of ERK signalling.",
"Embryonic stem cells (ESCs) possess pluripotency, which is the capacity of cells to differentiate into all lineages of the mature organism. Increasing evidence suggests that the pluripotent state of ESCs is regulated by a combination of extrinsic and intrinsic factors. The underlying mechanisms, however, are not completely understood. Here, we show that March5, an E3 ubiquitin ligase, is involved in maintaining mouse-ESC (mESC) pluripotency. Knockdown of March5 in mESCs led to differentiation from naive pluripotency. Mechanistically, as a transcriptional target of Klf4, March5 catalyses K63-linked polyubiquitination of Prkar1a, a negative regulatory subunit of PKA, to activate PKA, thereby inhibiting the Raf/MEK/ERK pathway. Moreover, March5 is able to replace a MEK/ERK inhibitor to maintain mESC pluripotency under serum-free culture conditions. In addition, March5 can partially replace the use of Klf4 for somatic cell reprogramming. Collectively, our study uncovers a role for the Klf4-March5-PKA-ERK pathway in maintaining the stemness properties of mESCs.</AbstractText"
],
[
"26288755",
"Phase-based metamorphosis of diffusion lesion in relation to perfusion values in acute ischemic stroke.",
"Examining the dynamics of stroke ischemia is limited by the standard use of 2D-volume or voxel-based analysis techniques. Recently developed spatiotemporal models such as the 4D metamorphosis model showed promise for capturing ischemia dynamics. We used a 4D metamorphosis model to evaluate acute ischemic stroke lesion morphology from the acute diffusion-weighted imaging (DWI) to final T2-weighted imaging (T2-w). In 20 representative patients, we metamorphosed the acute lesion to subacute lesion to final infarct. From the DWI lesion deformation maps we identified dynamic lesion areas and examined their association with perfusion values inside and around the lesion edges, blinded to reperfusion status. We then tested the model in ten independent patients from the STroke Imaging Repository (STIR). Perfusion values varied widely between and within patients, and were similar in contracting and expanding DWI areas in many patients in both datasets. In 25% of patients, the perfusion values were higher in DWI-contracting than DWI-expanding areas. A similar wide range of perfusion values and ongoing expansion and contraction of the DWI lesion were seen subacutely. There was more DWI contraction and less expansion in patients who received thrombolysis, although with widely ranging perfusion values that did not differ. 4D metamorphosis modeling shows promise as a method to improve use of multimodal imaging to understand the evolution of acute ischemic tissue towards its fate.</AbstractText"
],
[
"26168047",
"Quantitative Evaluation of Rabbit Brain Injury after Cerebral Hemisphere Radiation Exposure Using Generalized q-Sampling Imaging.",
"Radiation therapy is widely used for the treatment of brain tumors and may result in cellular, vascular and axonal injury and further behavioral deficits. The non-invasive longitudinal imaging assessment of brain injury caused by radiation therapy is important for determining patient prognoses. Several rodent studies have been performed using magnetic resonance imaging (MRI), but further studies in rabbits and large mammals with advanced magnetic resonance (MR) techniques are needed. Previously, we used diffusion tensor imaging (DTI) to evaluate radiation-induced rabbit brain injury. However, DTI is unable to resolve the complicated neural structure changes that are frequently observed during brain injury after radiation exposure. Generalized q-sampling imaging (GQI) is a more accurate and sophisticated diffusion MR approach that can extract additional information about the altered diffusion environments. Therefore, herein, a longitudinal study was performed that used GQI indices, including generalized fractional anisotropy (GFA), quantitative anisotropy (QA), and the isotropic value (ISO) of the orientation distribution function and DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD) over a period of approximately half a year to observe long-term, radiation-induced changes in the different brain compartments of a rabbit model after a hemi-brain single dose (30 Gy) radiation exposure. We revealed that in the external capsule, the GFA right to left (R/L) ratio showed similar trends as the FA R/L ratio, but no clear trends in the remaining three brain compartments. Both the QA and ISO R/L ratios showed similar trends in the all four different compartments during the acute to early delayed post-irradiation phase, which could be explained and reflected the histopathological changes of the complicated dynamic interactions among astrogliosis, demyelination and vasogenic edema. We suggest that GQI is a promising non-invasive technique and as compared with DTI, it has better potential ability in detecting and monitoring the pathophysiological cascades in acute to early delayed radiation-induced brain injury by using clinical MR scanners.</AbstractText"
],
[
"25945544",
"Chronic ciguatoxin treatment induces synaptic scaling through voltage gated sodium channels in cortical neurons.",
"Ciguatoxins are sodium channels activators that cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents with long-term neurological alterations. In central neurons, chronic perturbations in activity induce homeostatic synaptic mechanisms that adjust the strength of excitatory synapses and modulate glutamate receptor expression in order to stabilize the overall activity. Immediate early genes, such as Arc and Egr1, are induced in response to activity changes and underlie the trafficking of glutamate receptors during neuronal homeostasis. To better understand the long lasting neurological consequences of ciguatera, it is important to establish the role that chronic changes in activity produced by ciguatoxins represent to central neurons. Here, the effect of a 30 min exposure of 10-13 days in vitro (DIV) cortical neurons to the synthetic ciguatoxin CTX 3C on Arc and Egr1 expression was evaluated using real-time polymerase chain reaction approaches. Since the toxin increased the mRNA levels of both Arc and Egr1, the effect of CTX 3C in NaV channels, membrane potential, firing activity, miniature excitatory postsynaptic currents (mEPSCs), and glutamate receptors expression in cortical neurons after a 24 h exposure was evaluated using electrophysiological and western blot approaches. The data presented here show that CTX 3C induced an upregulation of Arc and Egr1 that was prevented by previous coincubation of the neurons with the NaV channel blocker tetrodotoxin. In addition, chronic CTX 3C caused a concentration-dependent shift in the activation voltage of NaV channels to more negative potentials and produced membrane potential depolarization. Moreover, 24 h treatment of cortical neurons with 5 nM CTX 3C decreased neuronal firing and induced synaptic scaling mechanisms, as evidenced by a decrease in the amplitude of mEPSCs and downregulation in the protein level of glutamate receptors that was also prevented by tetrodotoxin. These findings identify an unanticipated role for ciguatoxin in the regulation of homeostatic plasticity in central neurons involving NaV channels and raise the possibility that some of the neurological symptoms of ciguatera might be explained by these compensatory mechanisms.</AbstractText"
],
[
"24641323",
"GABA(B) receptors in the bladder and bowel: therapeutic potential for positive allosteric modulators?: Commentary on Kalinichev et al., Br J Pharmacol 171: 995-1006.",
"This article is a Commentary on Kalinichev M, Palea S, Haddouk H, Royer-Urios I, Guilloteau V, Lluel P, Schneider M, Saporito M and Poli S (2014). ADX71441, a novel, potent and selective positive allosteric modulator of the GABAB receptor, shows efficacy in rodent models of overactive bladder. Br J Pharmacol 171: 995-1006. doi: 10.1111/bph.12517.</AbstractText"
]
] |
39560584
|
Mitochondrial related Mendelian randomization identifies causal associations between metabolic disorders and childhood neurodevelopmental disorders.
|
Childhood neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder, and Tourette syndrome, are a predominant cause of health-related disabilities in children and adolescents. Nevertheless, disease biomarkers are still limited. The aim of this study was to evaluate the potential, causal relationship between mitochondrial DNA copy number (mtDNA-CN), metabolic disorders, and childhood NDDs using the two-sample Mendelian randomization (MR) method. Genetic associations with mtDNA-CN, disorders of lipoprotein metabolism, and disorders of iron metabolism were selected as exposures, and genome-wide association data from ASD, attention-deficit hyperactivity disorder, and Tourette syndrome were utilized as outcomes. Results of the study suggested that a high degree of disordered lipoprotein metabolism related increases in ASD risk result from a decrease in mtDNA-CN (disordered lipoprotein metabolism-mtDNA: inverse variance weighting β: -0.03, 95% confidence interval: -0.05 to -0.02, P = 2.08 × 10-5; mtDNA-CN-ASD: inverse variance weighting odds ratio: 0.83, 95% confidence interval: 0.69-0.99, P = .034). The research findings implied that mtDNA-CN can mediate disorders of lipoprotein metabolism, potentially influencing the development of ASD. The potential impact of the results of this study for the prevention and treatment of childhood NDDs warrants validation in robust randomized clinical trials.</AbstractText
|
[
[
"36447010",
"Mispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids.",
"Tourette Syndrome (TS) is a neuropsychiatric disorder thought to involve a reduction of basal ganglia (BG) interneurons and malfunctioning of the BG circuitry. However, whether interneurons fail to develop or are lost postnatally remains unknown. To investigate the pathophysiology of early development in TS, induced pluripotent stem cell (iPSC)-derived BG organoids from TS patients and healthy controls were compared on multiple levels of measurement and analysis. BG organoids from TS individuals manifested an impaired medial ganglionic eminence fate and a decreased differentiation of cholinergic and GABAergic interneurons. Transcriptome analyses revealed organoid mispatterning in TS, with a preference for dorsolateral at the expense of ventromedial fates. Our results point to altered expression of GLI transcription factors downstream of the Sonic Hedgehog signaling pathway with cilia disruption at the earliest stages of BG organoid differentiation as a potential mechanism for the BG mispatterning in TS. This study uncovers early neurodevelopmental underpinnings of TS neuropathological deficits using organoids as a model system.</AbstractText"
],
[
"37048598",
"Median Nerve Stimulation for Treatment of Tics: Randomized, Controlled, Crossover Trial.",
"A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained the sensorimotor cortex EEG signal and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested, and stimulation blocks lasted only 1 min. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Preregistration was completed at ClinicalTrials.gov, under number NCT04731714. Thirty-two people with TS, age 15-64, completed two study visits with repeated MNS on and off blocks in random order, one visit for rhythmic and one for arrhythmic MNS. Subjects and staff were blind to order; a video rater was additionally blind to stimulation and to the order of visits and blocks. Rhythmic MNS at 10 Hz improved tics. Both rhythmic and arrhythmic 12 Hz MNS improved tic frequency, intensity, and urges, but the two treatments did not differ significantly. Participant masking was effective, and there was no carryover effect. Several participants described a dramatic benefit. Discomfort was minimal. There was no evidence that the MNS benefit persisted after stimulation ended. These results replicate the tic benefit from MNS but show that the EEG entrainment hypothesis cannot explain that benefit. Another electrophysiological mechanism may explain the benefit; alternatively, these data do not exclude a placebo effect.</AbstractText"
],
[
"36842882",
"Additive and Interactive Effects of Attention-Deficit/Hyperactivity Disorder and Tic Disorder on Brain Connectivity.",
"Attention-deficit/hyperactivity disorder (ADHD) and persistent tic disorder (PTD) are two neurodevelopmental disorders that frequently co-occur. Contributions of each disorder to cognitive and behavioral deficits have been reported. In this paper, we tested 3 models of pathophysiology for the two disorders (additive, interactive, and phenotypic) using resting-state connectivity associated with each disorder separately and together.</AbstractText Participants were 148 children (55 with ADHD only, 33 with ADHD and PTD, 27 with PTD only, and 33 healthy control subjects) at ages 8 to 12 years. Following diagnostic interviews and behavioral assessment, participants underwent a 128-channel electroencephalography recording. Resting-state, cortical source-level effective connectivity was analyzed across the 4 groups using a 2 × 2 factorial design with factors of ADHD (with/without) and PTD (with/without).</AbstractText ADHD diagnosis was the primary driver of cognitive and behavioral deficits, while deficits associated with PTD were primarily with thought problems and internalizing problems when compared with controls. Subadditive effects were observed in co-occurring ADHD+PTD for parent-rated behavioral problems and cognitive functions. Aberrant effective connectivity was primarily associated with ADHD, more specifically with lower posterior and occipital-frontal connectivity, while children with PTD exhibited greater left postcentral to precuneus connectivity. Weaker ADHD-related connectivity was associated with more severe behavioral problems, including internalizing behaviors, thought problems, and working memory deficits.</AbstractText Similar to general behavioral deficits, aberrant resting-state neural connectivity in pediatric ADHD and PTD combines additively in co-occurring cases. The findings of this study support ADHD as a focus of treatment in comorbid cases, given the driving role of ADHD in both behavioral and neurophysiological deficits.</AbstractText"
],
[
"38859549",
"An Online Mindfulness-Based Group Intervention for Tics: A Pilot Randomized Controlled Trial.",
"Current treatments for Tourette syndrome (TS) and persistent tic disorder (PTD) are often insufficiently effective, inaccessible, and frequently associated with adverse events. Thus, we must continue to develop and test effective, accessible, and safe treatment options.</AbstractText We aimed to conduct a pilot randomized controlled trial (RCT) comparing a novel, videoconference-delivered group mindfulness-based intervention for tics (MBIT) to videoconference-delivered group psychoeducation, relaxation, and supportive therapy (PRST) for adults with TS or PTD.</AbstractText Thirty-two adults with TS or PTD were randomly assigned to receive 8 weeks of either MBIT or PRST. Tic severity, tic-related impairment, and global improvement were assessed by a trained, independent evaluator who was masked to treatment condition at baseline (week 0), posttreatment (week 9), 1-month follow-up, and 6-month follow-up. All study procedures were conducted online via secure videoconferencing.</AbstractText Twenty-eight participants began treatment and were included in analyses. MBIT, relative to PRST, was associated with a significantly greater decline in tic severity (d = 0.85) and tic-related impairment (d = 0.99) from baseline to posttreatment. Treatment response was significantly higher in MBIT (69%) than in PRST (13%). Neither treatment resulted in serious adverse effects. The durability of treatment outcomes is also reported and discussed.</AbstractText The results from this pilot RCT suggest that videoconference-delivered group MBIT may be an efficacious, accessible, and safe intervention for adults with tics. Future research is necessary to confirm these preliminary findings. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</AbstractText"
],
[
"38311626",
"The Association of Quality of Life with Psychosocial Factors in Adolescents with Tourette Syndrome.",
"Individuals with Tourette syndrome (TS) have poorer quality of life (QoL) than their peers, yet factors contributing to poor QoL in this population remain unclear. Research to date has predominantly focused on the impact of tics and psychiatric symptoms on QoL in TS samples. The aim of this cross-sectional, multi-informant study was to identify psychosocial variables that may impact adolescent QoL in TS. Thirty-eight adolescents aged 13 to 17 with TS and 28 age-matched controls participated with a caregiver. No group differences were found on QoL, although the TS group reported reduced QoL compared to population normative data. In the TS group, reduced QoL was associated with lower self-esteem, poorer family functioning, higher stress, and greater depression and anxiety; QoL was unrelated to tic severity. In regression analyses, after adjusting for covariates, family functioning was the strongest predictor of QoL. These results emphasize the need to further explore the influence of psychosocial factors, particularly family functioning, on QoL in adolescents with TS.</AbstractText"
]
] |
[
[
"37882378",
"The efficacy of oral corticoids in treating complex regional pain syndrome: A retrospective cohort study.",
"There is growing evidence supporting the role of inflammatory mechanisms in complex regional pain syndrome (CRPS). Corticoids, as most effective anti-inflammatory drugs, are widely used in treating inflammation. The aim of this study was to retrospectively assess the efficacy of oral corticoid treatment in CRPS patients.</AbstractText Patients treated at the center of pain medicine in the Erasmus University Medical Centre between January 2015 and January 2020 were approached to partake in this study. Medical records were screened for age, gender, medical history, duration of CRPS, and CRPS severity score. Also, treatment effect, dose and duration, pain scores (NRS), and side effects were extracted from medical records. In addition, global perceived effect was completed in patients treated with corticoids.</AbstractText Between January 2015 and January 2020, twenty-nine CRPS patients received corticoids and met the inclusion criteria. One extreme outlier was excluded and treatment effect was unknown for one patient. Average daily dose was 28.9 mg (range 10-30 mg) and the mean treatment duration was 10.5 days (7-21 days). Fourteen patients (51.9%) responded positively to treatment and thirteen (48.1%) did not respond. Side effects were reported in five patients (17.9%).</AbstractText Corticoid treatment was effective in more than half of the patients. With only mild side effects reported the treatment also appears to be relatively safe. Further research is needed to investigate the efficacy of corticoids in treating (early) CRPS, preferably in an intervention study.</AbstractText"
],
[
"39243493",
"Aphantasia and autism: An investigation of mental imagery vividness.",
"The present study investigated whether autistic adults report different levels of mental imagery vividness than non-autistic adults, and, moreover, if autism is associated with aphantasia which is defined as a condition of reduced or absent voluntary imagery.</AbstractText Clinically diagnosed and self-identifying autistic participants were compared with non-autistic participants in their mental imagery vividness (vision, sound, smell, taste, touch, bodily sensation and emotional feeling) and autistic traits using an online survey (N = 121).</AbstractText The autistic group scored significantly lower than the non-autistic group on imagery vividness (d = -0.44), in addition to having a higher proportion of participants scoring at cut-off for aphantasia. Moreover, a similar difference was observed for the emotional feel (η<sup The vividness of visual and emotional mental imagery was on average lower for autistic individuals, with a higher proportion presenting at cut-off to be considered an aphantasic.</AbstractText"
],
[
"37364616",
"Erythromelalgia. Part II: Differential diagnoses and management.",
"The management of erythromelalgia is challenging and requires multidisciplinary effort. Patient education is crucial as unsafe self-administered cooling techniques can lead to significant morbidity, including acral necrosis, infection, and amputation. The goal of management is pain control, reduction of flare frequency, and prevention of complications. This text is focused on the management of erythromelalgia and several other incompletely understood and under-recognized neurovascular disorders such as red scrotum syndrome, red ear syndrome, facial flushing, and complex regional pain syndrome.</AbstractText"
],
[
"38608341",
"An automated algorithm for stereoelectroencephalography electrode localization and labelling.",
"Stereoelectroencephalography (sEEG) is increasingly utilized for localization of seizure foci, functional mapping, and neurocognitive research due to its ability to target deep and difficult to reach anatomical locations and to study in vivo brain function with a high signal-to-noise ratio. The research potential of sEEG is constrained by the need for accurate localization of the implanted electrodes in a common template space for group analyses.</AbstractText We present an algorithm to automate the grouping of sEEG electrodes by trajectories, labelled by target and insertion point. This algorithm forms the core of a pipeline that fully automates the entire process of electrode localization in standard space, using raw CT and MRI images to produce atlas labelled MNI coordinates.</AbstractText Across 196 trajectories from 20 patients, the pipeline successfully processed 190 trajectories with localizations within 0.25±0.55 mm of the manual annotation by two reviewers. Six electrode trajectories were not directly identified due to metal artifacts and locations were interpolated based on the first and last contact location and the number of contacts in that electrode as listed in the surgical record.</AbstractText We introduce our algorithm and pipeline for automatically localizing, grouping, and classifying sEEG electrodes from raw CT and MRI. Our algorithm adds to existing pipelines and toolboxes for electrode localization by automating the manual step of marking and grouping electrodes, thereby expedites the analyses of sEEG data, particularly in large datasets.</AbstractText"
],
[
"35962556",
"Subjective Sensitivity to Exteroceptive and Interoceptive processing in Highly Sensitive Person.",
"A highly sensitive person is known to have greater levels of sensory processing sensitivity (SPS) referring to a personality trait to exhibit high stimulation and arousal while processing subtle sensory signals. However, how SPS levels reflect the profile of sensitivity in exteroceptive and interoceptive sensory processing remains inadequately understood. Thus, we collected data using the Highly Sensitive Person Scale (HSPS), the Glasgow Sensory Questionnaire (GSQ), and the Body Perception Questionnaire-Short Form (BPQ-SF) from 600 Japanese adults, and examined their relationships. The results revealed that SPS levels, assessed by the HSPS, were significantly, positively correlated with hypersensitivity scores of the GSQ in several exteroceptive sensory domains. Further, SPS levels were positively correlated with sensitivity in interoceptive awareness assessed by the BPQ-SF; however, it does so scarcely. Our findings suggest that SPS levels reflect a subjective sensitivity to exteroceptive sensory processing regardless of sensory domains and narrowly to the interoceptive sensory processing.</AbstractText"
]
] |
39999454
|
Comorbid Guillain-Barré Syndrome and Tuberculosis: A Case Study and Global Perspective.
|
A 27-year-old man presented with a cough and progressive limb weakness. Initially diagnosed with pulmonary tuberculosis, he showed improvement in his cough after antituberculosis treatment (ATT). However, he subsequently developed worsening weakness and numbness in his lower limbs, leading to mobility loss and difficulty swallowing. A comprehensive diagnostic evaluation, including computed tomography of the lung, cranial magnetic resonance imaging, cerebrospinal fluid analysis, and electromyography, confirmed concurrent diagnoses of tuberculosis (TB) and Guillain-Barré syndrome (GBS). Treatment included immunoglobulin and corticosteroid therapy; however, his symptoms persisted, progressing to respiratory failure that required endotracheal intubation and plasma exchange therapy. After these interventions, his condition gradually improved, and he continued ATT, achieving a favorable recovery. A literature review identified 15 countries reporting cases of GBS associated with TB, with the highest incidence in India. Although most cases showed a positive prognosis, mortality rates were elevated in patients with comorbid TB and GBS compared to those with GBS alone.</AbstractText
|
[
[
"30310069",
"Immune-mediated neuropathies.",
"Since the discovery of an acute monophasic paralysis, later coined Guillain-Barré syndrome, almost 100 years ago, and the discovery of chronic, steroid-responsive polyneuropathy 50 years ago, the spectrum of immune-mediated polyneuropathies has broadened, with various subtypes continuing to be identified, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). In general, these disorders are speculated to be caused by autoimmunity to proteins located at the node of Ranvier or components of myelin of peripheral nerves, although disease-associated autoantibodies have not been identified for all disorders. Owing to the numerous subtypes of the immune-mediated neuropathies, making the right diagnosis in daily clinical practice is complicated. Moreover, treating these disorders, particularly their chronic variants, such as CIDP and MMN, poses a challenge. In general, management of these disorders includes immunotherapies, such as corticosteroids, intravenous immunoglobulin or plasma exchange. Improvements in clinical criteria and the emergence of more disease-specific immunotherapies should broaden the therapeutic options for these disabling diseases.</AbstractText"
],
[
"36212732",
"Development of facial palsy following COVID-19 vaccination: A systematic review.",
"Reports of facial palsy occurring after the receipt of COVID-19 vaccines have raised concerns but are rare. The purpose of this study is to systematically assess the association between COVID-19 vaccination and facial palsy.</AbstractText Our systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist and compiled all the reported cases of facial palsy post-COVID-19 vaccination. We discussed the probable pathophysiology behind facial palsy as a consequence of COVID-19 vaccination and measures to be taken for future reference. Furthermore, we conducted a detailed assessment of characteristics, clinical courses, treatment, and recovery of patients with facial palsy after receiving a COVID-19 vaccine.</AbstractText We included 37 studies providing data on 58 individuals in our review. Over half (51.72%) of the patients complained of facial paralysis following the Oxford-AstraZeneca vaccination. Out of 51 cases, most (88.24%) occurred after the 1st dose. The majority (53.45%) of cases had bilateral facial palsy. Intravenous immunoglobin (IVIg), corticosteroids, and plasmapheresis were the first line of treatment with 75.93% of patients partially recovered, including those undergoing treatment or a lack of follow-up till the end while 22.22% had complete symptomatic recovery.</AbstractText Our review shows that Bell's palsy can be a plausible non-serious adverse effect of COVID-19 vaccination. However, the association observed between COVID-19 vaccination and Bell's palsy is less threatening than the COVID-19 infection. Hence, vaccination should be encouraged because facial palsy, if it occurs, has shown favourable outcomes with treatment.</AbstractText"
],
[
"36669428",
"Prevalence and associated factors with peripheral neuropathies in the general population in the rural area of Adjohoun in Benin.",
"Peripheral neuropathies (PN) are a group of neurological conditions related to damage to the peripheral nervous system. Due to their wide diversity, few studies in sub-Saharan Africa have explored their epidemiology in general population. Our objective was to study the prevalence and associated factors with PN in general population in Adjohoun in Benin.</AbstractText A cross-sectional study has been conducted from February to March 2019 and included people aged ≥ 18 years old living in Adjohoun, Benin. Following a screening phase for PN (using World Health Organization questionnaire for major neurological diseases), a neurologist made a diagnosis after in-depth clinical examinations completed in some cases by electroneuromyography. The EFNS (European Federation of Neurological Societies) 2010 criteria was used for chronic inflammatory demyelinating polyneuropathy diagnosis. Data such as age, occupation, consanguinity, alcohol consumption, diabetes, hypertension were collected. Association between independent variables and PN were investigated using multivariable logistic regression models.</AbstractText In total, 1 655 participants were included, mean age 41.4 ± 16.7 years; 64.8 % are female. The overall prevalence of PN was 6.9 % (95 %CI: 5.7 %-8.2 %). The main types of PN were: polyneuropathies 4.8 % (95 %CI: 3.8 %-5.9 %); polyradiculoneuropathies 1.6 % (95 %CI: 1.0 %-2.2 %). Factors independently associated with PN were age ≥ 40 years (adjusted Odds Ratio aOR = 19.6; 95 %CI: 8.2-46.3), diabetes (aOR = 1.8; 95 %CI: 1.08-2.99) and hypertension (aOR = 1.6; 95 %CI: 1.02-2.5).</AbstractText The prevalence of PN was high in the rural commune of Adjohoun in Benin. Actions on its modifiable associated factors such as diabetes and hypertension could help reduce the proportion of PN and their potential harmful consequences.</AbstractText"
],
[
"39464332",
"Overview of emerging therapies for demyelinating diseases.",
"This paper provides an overview of autoimmune disorders of the central nervous system, specifically those caused by demyelination. We explore new research regarding potential therapeutic interventions, particularly those aimed at inducing remyelination. Remyelination is a detailed process, involving many cell types-oligodendrocyte precursor cells (OPCs), astrocytes, and microglia-and both the innate and adaptive immune systems. Our discussion of this process includes the differentiation potential of neural stem cells, the function of adult OPCs, and the impact of molecular mediators on myelin repair. Emerging therapies are also explored, with mechanisms of action including the induction of OPC differentiation, the transplantation of mesenchymal stem cells, and the use of molecular mediators. Further, we discuss current medical advancements in relation to many myelin-related disorders, including multiple sclerosis, optic neuritis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, transverse myelitis, and acute disseminated encephalomyelitis. Beyond these emerging systemic therapies, we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries. Despite these aforementioned scientific advancements, this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients' quality of life.</AbstractText"
],
[
"39434812",
"Guillain-Barré syndrome in pregnancy: a case report and review of the literature.",
"Guillain-Barré syndrome represents a heterogeneous group of immune-mediated peripheral neuropathies that are characterized by various clinical manifestations. Reporting this clinical case emphasizes the rarity of Guillain-Barré syndrome, the diagnostic challenges faced by healthcare providers, and the risk of delayed diagnosis for both the mother and fetus. A 34-year-old pregnant woman at 33 weeks of gestation presented to the inpatient ward complaining of paresthesia in the lower and upper limbs, muscle pain, balance disturbances, moderate headache, nausea and vertigo, general weakness, and pronounced fatigue. The patient had experienced an acute viral respiratory infection 4 weeks before presenting to the hospital. The patient was admitted to the intensive care unit with a preliminary diagnosis of acute viral respiratory infection and nasopharyngitis. The patient's condition worsened dynamically, manifesting bulbar syndrome (swallowing problems), paresthesia of the anterior abdominal wall, reduced perception of fetal movements, numbness of the tongue, and low fever (37.2°C). A diagnosis of acute inflammatory demyelinating polyradiculopathy (Guillain-Barré syndrome) was established. Despite treatment, the neurologic symptoms worsened. The paravertebral radicular type pains were difficult to manage with administered analgesic therapy, and there was a progression of the bulbar syndrome. Treatment with intravenous immunoglobulin was initiated. Consequently, it was recommended by the multidisciplinary council to perform an emergency cesarean delivery, in the interest of the mother and fetus. Guillain-Barré syndrome is a rare condition that occurs during pregnancy and requires thorough evaluation, prompt multidisciplinary assessment, and individualized management of delivery to improve maternal and fetal prognosis.</AbstractText"
]
] |
[
[
"40436348",
"Gene therapy and nanomedicine for meningioma treatment.",
"Meningioma, a prevalent central nervous system (CNS) tumor, exhibits a broad spectrum of clinical behavior, ranging from benign to aggressive. Although surgical resection remains a viable treatment option for most cases, higher-grade meningiomas often require a multifaceted therapeutic approach. Gene therapies have shown potential for use in clinical intervention for the treatment of several types of cancer. Small nucleic acid molecules such as small interfering RNAs (siRNAs) and microRNAs (miRNAs) can restore aberrant gene expression and selectively silence oncogenic drivers. However, their clinical application could be improved by addressing challenges such as molecular instability, off-target toxicity, and limited bioavailability. Despite the rapid progress in nanotechnology that has significantly improved the gene therapy delivery system, its use for meningioma treatment has lagged behind. The lag in research can be attributed to the critical need for a deeper understanding of the molecular landscape of meningioma and its relative resistance to conventional chemotherapy. Therefore, our review article focuses on the complex molecular landscape of meningioma and highlights the challenges in its treatment and management. We also discuss the current gene therapy approaches for meningioma, exploring ongoing clinical trials and elucidating the mechanism of emerging therapies. Furthermore, we investigate the potential of nanomedicine in enhancing gene therapy for meningioma, highlighting the need for innovative delivery techniques. This comprehensive analysis not only outlines the status of the therapy in meningioma but also offers valuable insights into the future research direction and their clinical translation.</AbstractText"
],
[
"40583215",
"Chaperone-Mediated Regulation of Tau Phase Separation, Fibrillation, and Toxicity.",
"Biological condensates are involved in several essential processes but may also be tangled into disease progression in protein misfolding diseases such as Alzheimer's disease and tauopathies. One hallmark of these disorders is the appearance of fibrillar aggregates formed by microtubule-stabilizing Tau protein. Notably, Tau can also assemble into biological condensates and droplets via liquid-liquid phase separation (LLPS). The molecular mechanisms of the conversion of functional Tau toward insoluble fibrils, potentially via LLPS processes, remain largely unknown, and efficient treatment approaches to target toxic pathways and species are still missing. Here, we show that the molecular chaperone-like Bri2 BRICHOS domain efficiently inhibits full-length Tau fibril formation and subsequent neurotoxicity by specifically suppressing secondary nucleation processes. Further, at substoichiometric ratios, Bri2 BRICHOS modulates the potency of Tau to form droplets, incorporates into Tau droplets, and alters the dynamic behavior of Tau. In contrast, at superstoichiometric Bri2 BRICHOS ratios, Tau droplet formation is abolished. Finally, Bri2 BRICHOS reduces Tau fibril toxicity in electrophysiological experiments on hippocampal slice preparations. Taken together, Bri2 BRICHOS targets molecular processes related to protein misfolding, where our study provides molecular insights into how the inhibition of secondary nucleation pathways and modulated droplet formation are eventually linked to attenuated neurotoxicity.</AbstractText"
],
[
"40075518",
"SNUH methylation classifier for CNS tumors.",
"Methylation profiling of central nervous system (CNS) tumors, pioneered by the German Cancer Research Center, has significantly improved diagnostic accuracy. This study aimed to further enhance the performance of methylation classifiers by leveraging publicly available data and innovative machine-learning techniques.</AbstractText Seoul National University Hospital Methylation Classifier (SNUH-MC) addressed data imbalance using the Synthetic Minority Over-sampling Technique (SMOTE) algorithm and incorporated OpenMax within a Multi-Layer Perceptron to prevent labeling errors in low-confidence diagnoses. Compared to two published CNS tumor methylation classification models (DKFZ-MC: Deutsches Krebsforschungszentrum Methylation Classifier v11b4: RandomForest, 767-MC: Multi-Layer Perceptron), our SNUH-MC showed improved performance in F1-score. For 'Filtered Test Data Set 1,' the SNUH-MC achieved higher F1-micro (0.932) and F1-macro (0.919) scores compared to DKFZ-MC v11b4 (F1-micro: 0.907, F1-macro: 0.627). We evaluated the performance of three classifiers; SNUH-MC, DKFZ-MC v11b4, and DKFZ-MC v12.5, using specific criteria. We set established 'Decisions' categories based on histopathology, clinical information, and next-generation sequencing to assess the classification results. When applied to 193 unknown SNUH methylation data samples, SNUH-MC notably improved diagnosis compared to DKFZ-MC v11b4. Specifically, 17 cases were reclassified as 'Match' and 34 cases as 'Likely Match' when transitioning from DKFZ-MC v11b4 to SNUH-MC. Additionally, SNUH-MC demonstrated similar results to DKFZ-MC v12.5 for 23 cases that were unclassified by v11b4.</AbstractText This study presents SNUH-MC, an innovative methylation-based classification tool that significantly advances the field of neuropathology and bioinformatics. Our classifier incorporates cutting-edge techniques such as the SMOTE and OpenMax resulting in improved diagnostic accuracy and robustness, particularly when dealing with unknown or noisy data.</AbstractText"
],
[
"39983830",
"Toxicological mechanisms of carbon polymers in accelerating cognitive decline in Alzheimer's disease.",
"Alzheimer's disease (AD) is the primary cause of dementia and is emerging as a global threat to human health. Increased availability of processed food is identified as a crucial dietary risk factor underlying the prevalence of Alzheimer's disease. Carbon polymers (CPs), as neo-formed substances and ubiquitous in thermally processed foods, the relationship between them and AD onset remains unclear.</AbstractText The effect of CPs on AD onset was examined and the toxicological mechanisms of prolonged exposure to CPs derived from thermal processed foods on AD progression were comprehensively investigated using a scopolamine-induced neuroinflammatory cell models and the transgenic APPswe/PSEN1dE9 (APP/PS1) AD mouse.</AbstractText The CPs were extracted from thermally processed foods and the effects of CPs exposure on oxidative stress in neuroinflammatory cells were evaluated using scopolamine-induced PC12 cells as a neuroinflammation model. Furthermore, APP/PS1 AD mice were used to validate the potential adverse impacts of prolonged exposure to CPs on AD progression through the Morris water maze and open field test. In addition, histopathological examination, including immunofluorescence, immunohistochemistry, Nissl staining, and H&E, of the brain tissue in AD mice after chronic CPs treatment was performed to elucidate the underlying risk of dietary exposure to CPs on AD progression.</AbstractText Exposure to CPs enhanced oxidative damage in neuroinflammatory cells, as demonstrated by impaired mitochondrial function and activated NF-κB/MAPK signaling pathways. Further results from electron spin resonance substantiated the catalytic properties of CPs, which accelerated oxidative damage through promoting free radical generation. Using transgenic AD mice model, our findings also demonstrated that prolonged CPs exposure aggravated AD-associated pathology, as evidenced by increased amyloid-beta deposition and glial cell activation, ultimately accelerating cognitive decline.</AbstractText These findings provide compelling evidence of the potential health risks associated with long-term dietary exposure to CPs and provide insight into the relationship between foodborne risk factors and neurodegenerative diseases.</AbstractText"
],
[
"40540418",
"Analysis of Proton NMR Transverse Magnetization Decay of Mixtures of Compounds and Semicrystalline Polymers: A Least-Squares Fit and the Inverse Laplace Transform.",
"The present study aimed to determine the strategy for analysis of NMR transverse magnetization decay (the <i"
]
] |
30401642
|
Denervated mouse dentate granule cells adjust their excitatory but not inhibitory synapses following in vitro entorhinal cortex lesion.
|
Neurons adjust their synaptic strength in a homeostatic manner following changes in network activity and connectivity. While this form of plasticity has been studied in detail for excitatory synapses, homeostatic plasticity of inhibitory synapses remains not well-understood. In the present study, we employed entorhinal cortex lesion (ECL) of organotypic entorhino-hippocampal tissue cultures to test for homeostatic changes in GABAergic neurotransmission onto partially denervated dentate granule cells. Using single and paired whole-cell patch-clamp recordings, as well as immunostainings for synaptic markers, we find that excitatory synaptic strength is robustly increased 3 days post lesion (dpl), whereas GABAergic neurotransmission is not changed after denervation. Even under conditions of pharmacological inhibition of glutamatergic neurotransmission, which prevents neurons to compensate for the loss of input via excitatory synaptic scaling, down-scaling of GABAergic synapses does not emerge 3 days after denervation. We conclude that granule cells maintain structural and functional properties of GABAergic synapses even in the face of substantial changes in network connectivity. Hence, alterations in inhibitory neurotransmission, as seen in pathological brain states, may not simply reflect a homeostatic response to disconnection.</AbstractText
|
[
[
"11031127",
"The genomic action potential.",
"Neurons compute in part by integrating, on a time scale of milliseconds, many synaptic inputs and generating a digital output-the \"action potential\" of classic electrophysiology. Recent discoveries indicate that neurons also perform a second, much slower, integration operating on a time scale of minutes or even hours. The output of this slower integration involves a pulse of gene expression which may be likened to the electrophysiological action potential. Its function, however, is not directed toward immediate transmission of a synaptic signal but rather toward the experience-dependent modification of the underlying synaptic circuitry. Commonly termed the \"immediate early gene\" (IEG) response, this phenomenon is often assumed to be a necessary component of a linear, deterministic cascade of memory consolidation. Critical review of the large literature describing the phenomenon, however, leads to an alternative model of IEG function in the brain. In this alternative, IEG activation is not directed at the consolidation of memories of a specific inducing event; instead, it sets the overall gain or efficiency of memory formation and directs it to circuits engaged by behaviorally significant contexts. The net result is a sharpening of the selectivity of memory formation, a recruitment of temporally correlated associations, and an ultimate enhancement of long-term memory retrieval.</AbstractText"
],
[
"26109571",
"Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade.",
"Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up.</AbstractText"
],
[
"29861281",
"Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia.",
"We employed multi-electrode array recording to evaluate the influence of NMDA receptors (NMDAR) on spike-timing dynamics in prefrontal networks of monkeys as they performed a cognitive control task measuring specific deficits in schizophrenia. Systemic, periodic administration of an NMDAR antagonist (phencyclidine) reduced the prevalence and strength of synchronous (0-lag) spike correlation in simultaneously recorded neuron pairs. We employed transfer entropy analysis to measure effective connectivity between prefrontal neurons at lags consistent with monosynaptic interactions and found that effective connectivity was persistently reduced following exposure to the NMDAR antagonist. These results suggest that a disruption of spike timing and effective connectivity might be interrelated factors in pathogenesis, supporting an activity-dependent disconnection theory of schizophrenia. In this theory, disruption of NMDAR synaptic function leads to dysregulated timing of action potentials in prefrontal networks, accelerating synaptic disconnection through a spike-timing-dependent mechanism.</AbstractText"
],
[
"27241695",
"Mechanisms of homeostatic plasticity in the excitatory synapse.",
"Brain development, sensory information processing, and learning and memory processes depend on Hebbian forms of synaptic plasticity, and on the remodeling and pruning of synaptic connections. Neurons in networks implicated in these processes carry out their functions while facing constant perturbation; homeostatic responses are therefore required to maintain neuronal activity within functional ranges for proper brain function. Here, we will review in vitro and in vivo studies demonstrating that several mechanisms underlie homeostatic plasticity of excitatory synapses, and identifying participant molecular players. Emerging evidence suggests a link between disrupted homeostatic synaptic plasticity and neuropsychiatric and neurologic disorders. Hebbian forms of synaptic plasticity, such as long-term potentiation (LTP), induce long-lasting changes in synaptic strength, which can be destabilizing and drive activity to saturation. Conversely, homeostatic plasticity operates to compensate for prolonged activity changes, stabilizing neuronal firing within a dynamic physiological range. We review mechanisms underlying homeostatic plasticity, and address how neurons integrate distinct forms of plasticity for proper brain function. This article is part of a mini review series: \"Synaptic Function and Dysfunction in Brain Diseases\".</AbstractText"
],
[
"29107520",
"Deprivation-Induced Homeostatic Spine Scaling In Vivo Is Localized to Dendritic Branches that Have Undergone Recent Spine Loss.",
"Synaptic scaling is a key homeostatic plasticity mechanism and is thought to be involved in the regulation of cortical activity levels. Here we investigated the spatial scale of homeostatic changes in spine size following sensory deprivation in a subset of inhibitory (layer 2/3 GAD65-positive) and excitatory (layer 5 Thy1-positive) neurons in mouse visual cortex. Using repeated in vivo two-photon imaging, we find that increases in spine size are tumor necrosis factor alpha (TNF-α) dependent and thus are likely associated with synaptic scaling. Rather than occurring at all spines, the observed increases in spine size are spatially localized to a subset of dendritic branches and are correlated with the degree of recent local spine loss within that branch. Using simulations, we show that such a compartmentalized form of synaptic scaling has computational benefits over cell-wide scaling for information processing within the cell.</AbstractText"
]
] |
[
[
"30312809",
"Depth-dependent intracortical myelin organization in the living human brain determined by in vivo ultra-high field magnetic resonance imaging.",
"Intracortical myelin is a key determinant of neuronal synchrony and plasticity that underpin optimal brain function. Magnetic resonance imaging (MRI) facilitates the examination of intracortical myelin but presents with methodological challenges. Here we describe a whole-brain approach for the in vivo investigation of intracortical myelin in the human brain using ultra-high field MRI.</AbstractText Twenty-five healthy adults were imaged in a 7 Tesla MRI scanner using diffusion-weighted imaging and a T<sub Intracortical T<sub We demonstrate the usefulness of an automatic, whole-brain method to perform depth-dependent examination of intracortical myelin organization. The extracted metrics, T<sub"
],
[
"31474812",
"Perspectives About Time Frames in Stem Cell Research for Multiple Sclerosis: \"Time Is Brain\".",
"Stem cell research has been a focus of inquiry in the field of neurology for nearly 3 decades and has led to much hope for people with multiple sclerosis (MS). Previous studies, however, demonstrate that information about the pace of developments in the stem cell arena is less accessible than are representations of potential benefits.</AbstractText To explore the understanding and perspectives of adult patients with MS and MS clinicians about the time frames associated with stem cell research, we conducted semistructured interviews with 20 patients with MS across Canada and 15 clinicians who specialize in MS. Patients who participated did not have any previous stem cell interventions. Interviews were analyzed for recurring themes and individual variations using the constant comparative approach.</AbstractText We found that patients with MS have a limited understanding about the time that it takes for stem cell research to reach the clinic. In parallel, they express a desire to know more than they do about the translational process. Clinicians offer strategies to address patients' questions about the pace of stem cell research and to promote informed hope about experimental interventions.</AbstractText These results underscore opportunities to promote transparency in clinical discourse about the pace of stem cell research for MS and other progressive neurologic diseases.</AbstractText"
],
[
"30562166",
"MR image corrections for PET-induced gradient distortions.",
"The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) by using PET inserts in existing MRI scanners is an attractive approach. When designing the PET insert, mutual influences of both imaging modalities need to be minimized. The gradient magnetic fields induce eddy currents in all conductive components of the PET insert. Eddy currents produce superimposing magnetic fields distorting the gradient magnetic field. However, the gradient magnetic fields determine how the MRI data is acquired in the k-space. A distorted gradient shape produces a distorted k-space trajectory which then results in a distorted image. The dynamic performance of the gradient system can be characterized by measuring its gradient impulse response function (GIRF). Knowledge of the GIRF enables to correct the k-space trajectory and thereby enables to reduce image distortions. We characterized the influence of a preclinical PET insert, i.e. the Hyperion II<sup"
],
[
"31278681",
"Semantic Integration and Enrichment of Heterogeneous Biological Databases.",
"Biological databases are growing at an exponential rate, currently being among the major producers of Big Data, almost on par with commercial generators, such as YouTube or Twitter. While traditionally biological databases evolved as independent silos, each purposely built by a different research group in order to answer specific research questions; more recently significant efforts have been made toward integrating these heterogeneous sources into unified data access systems or interoperable systems using the FAIR principles of data sharing. Semantic Web technologies have been key enablers in this process, opening the path for new insights into the unified data, which were not visible at the level of each independent database. In this chapter, we first provide an introduction into two of the most used database models for biological data: relational databases and RDF stores. Next, we discuss ontology-based data integration, which serves to unify and enrich heterogeneous data sources. We present an extensive timeline of milestones in data integration based on Semantic Web technologies in the field of life sciences. Finally, we discuss some of the remaining challenges in making ontology-based data access (OBDA) systems easily accessible to a larger audience. In particular, we introduce natural language search interfaces, which alleviate the need for database users to be familiar with technical query languages. We illustrate the main theoretical concepts of data integration through concrete examples, using two well-known biological databases: a gene expression database, Bgee, and an orthology database, OMA.</AbstractText"
],
[
"30947159",
"MRI artifact simulation for clinically relevant MRI sequences for guidance of prostate HDR brachytherapy.",
"For the purpose of magnetic resonance imaging (MRI) guidance of prostate high-dose-rate (HDR) brachytherapy, this paper presents a study on the potential of clinically relevant MRI sequences to facilitate tracking or localization of brachytherapy devices (HDR source/titanium needle), and which could simultaneously be used to visualize the anatomy. The tracking or localization involves simulation of the MRI artifact in combination with a template matching algorithm. Simulations of the MRI artifacts induced by an HDR brachytherapy source and a titanium needle were implemented for four types of sequences: spoiled gradient echo, spin echo, balanced steady-state free precession (bSSFP) and bSSFP with spectral attenuated inversion recovery (SPAIR) fat suppression. A phantom study was conducted in which mentioned sequences (in 2D) as well as the volumetric MRI sequences of the current clinical scan protocol were applied to obtain the induced MRI artifacts for an HDR source and a titanium needle. Localization of the objects was performed by a phase correlation based template matching algorithm. The simulated images demonstrated high correspondences with the acquired MR images, and allowed localization of the objects. A comparison between the object positions obtained for all applied MRI sequences showed deviations (from the average position) of 0.2-0.3 mm, proving that all MRI sequences were suitable for localization of the objects, irrespective of their 2D or volumetric nature. This study demonstrated that the MRI artifact induced by an HDR source or a titanium needle could be simulated for the four investigated types of MRI sequences (spoiled gradient echo, spin echo, bSSFP and bSSFP-SPAIR), valuable for real-time object localization in clinical practice. This leads to more flexibility in the choice of MRI sequences for guidance of HDR brachytherapy, as they are suitable for both object localization and anatomy visualization.</AbstractText"
]
] |
37257216
|
Prednisolone 20 mg vs 40 mg in complex regional pain syndrome type I: A randomized controlled trial.
|
High dose of corticosteroid has been found beneficial in complex regional pain syndrome type I (CRPS-I). We report the efficacy and safety of prednisolone 20 mg versus 40 mg in CRPS-I in an open label randomized controlled trial.</AbstractText The patients with CRPS-I of the shoulder joint with a CRPS score of ≥8 were included. Their demographic details, comorbidities, and underlying etiology were noted. The severity of CRPS was assessed using a 0-14 CRPS scale, the pain using a 0-10 Visual Analogue Scale (VAS), and sleep quality using a 0-10. Daily Sleep Interference Scale (DSIS). Patients were randomized to prednisolone 40 mg/day (group I) or 20 mg/day (group II) for 14 days, then tapered to 10 mg in group I and to 5 mg in group II by 1 month. Thereafter both groups received prednisolone 5 mg/day for 2 months. The primary outcome was a >50% reduction in VAS score, and secondary outcomes were a reduction in CRPS score, DSIS score, and adverse events.</AbstractText Fifty patients were included, and their baseline characteristics were comparable. At one month, all the patients had >50% reduction in the VAS score. The effect size was 0.38 (95% CI 0.93-0.20; p = 0.20). On the Kaplan-Mayer analysis, the improvement in the VAS score (Hazard ratio-1.43, 95 % CI-0.80-2.56, p = 0.22) and the CRPS score (HR-0.79,95 % CI-0.45-1.39; p = 0.41) was insignificant between the two groups. The DSIS score improved in group II (HR-1.85,95 % Cl-1.04-3.31,p = 0.04). Group I patients needed frequent adjustment of antidiabetic drugs (14 vs 6; p = 0.04).</AbstractText The efficacy of prednisolone 20 mg is not inferior to 40 mg in CRPS-I, and is safe in diabetic patients.</AbstractText This is an open label randomized controlled trial with small sample size without a placebo arm.</AbstractText
|
[
[
"40149508",
"Cannabinoids in Chronic Pain Management: A Review of the History, Efficacy, Applications, and Risks.",
"<b"
],
[
"40280127",
"The gut microbiota promotes pain in fibromyalgia.",
"Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.</AbstractText"
],
[
"33494023",
"Ignoring space around a painful limb? No evidence for a body-related visuospatial attention bias in complex regional pain syndrome.",
"Complex Regional Pain Syndrome (CRPS) is a disorder of severe chronic pain in one or more limb(s). People with CRPS report unusual perceptions of the painful limb suggesting altered body representations, as well as difficulty attending to their affected limb (i.e., a 'neglect-like' attention bias). Altered body representations and attention in CRPS might be related, however, existing evidence is unclear. We hypothesized that if there were a body-related visuospatial attention bias in CRPS, then any attention bias away from the affected side should be larger for or limited to circumstances when the (impaired) body representation is involved in the task versus when this is not the case.</AbstractText We included 40 people with CRPS, 40 with other limb pain conditions, and 40 pain-free controls. In half of the people with pain, their upper limb was affected, in the other half their lower limb. We administered computerized tasks of spatial attention, including free viewing of images, shape cancellation, temporal order judgement, and dot-probe. The degree to which different versions of each task involved body representation was manipulated by one or more of the following: (1) presenting stimuli nearer versus further away from the body, (2) using body related versus neutral stimuli, and (3) inducing mental rotation of body parts versus no mental rotation. In addition to perceptual judgements, eye movements were recorded as a sensitive index of spatial attention. Bayesian repeated measures analyses were performed.</AbstractText We found no evidence for a (body-related) visuospatial attention bias in upper limb CRPS. Secondary analyses suggested the presence of a body-related visuospatial attention bias away from the affected side in some participants with lower limb CRPS.</AbstractText Our results add to growing evidence that there might be no general visuospatial attention bias away from the affected side in CRPS.</AbstractText"
],
[
"40106017",
"Gray matter structural and functional brain abnormalities in Parkinson's disease: a meta-analysis of VBM and ALFF data.",
"Previous studies based on resting-state functional imaging and voxel-based morphometry (VBM) have revealed structural and functional alterations in several brain regions in patients with Parkinson's disease (PD), but their results have been inconsistent. Furthermore, no studies have investigated specific and common functional and structural alterations in PD.</AbstractText The whole-brain voxel-wise meta-analyses on the VBM and amplitude of low-frequency fluctuation (ALFF) studies were conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software, respectively, with multimodal overlapping to comprehensively identify the gray matter volume (GMV) and spontaneous functional activity changes in patients with PD.</AbstractText A total of 30 independent studies for ALFF (1413 PD and 1424 HCs) and 27 independent studies for VBM (1236 PD and 1185 HCs) were included. Compared with HCs, patients with PD displayed significantly decreased spontaneous functional activity in the left striatum. For the VBM meta-analysis, patients with PD showed significantly decreased GMV in the right temporal pole: superior temporal gyrus (extending to the right hippocampus, parahippocampal gyrus, and amygdala), the left superior temporal gyrus (extending to the left insula, and temporal pole: superior temporal gyrus), and the left striatum. Furthermore, after overlapping functional and structural differences, patients with PD displayed a conjoint decrease of spontaneous functional activity and GMV in the left striatum.</AbstractText The multimodal meta-analysis revealed that PD showed similar pattern of aberrant brain functional activity and structure in the striatum. In addition, some brain regions within the within the temporal lobe and limbic system displayed only structural deficits. These findings provide useful insights for understanding the underlying pathophysiology of PD.</AbstractText"
],
[
"38702506",
"Functional connectivity associated with attention networks differs among subgroups of fibromyalgia patients: an observational case-control study.",
"Fibromyalgia is a heterogenous chronic pain disorder diagnosed by symptom-based criteria. The aim of this study was to clarify different pathophysiological characteristics between subgroups of patients with fibromyalgia. We identified subgroups with distinct pain thresholds: those with a low pressure pain threshold (PL; 16 patients) and those with a normal pressure pain threshold (PN; 15 patients). Both groups experienced severe pain. We performed resting-state functional MRI analysis and detected 11 functional connectivity pairs among all 164 ROIs with distinct difference between the two groups (p < 0.001). The most distinctive one was that the PN group had significantly higher functional connectivity between the secondary somatosensory area and the dorsal attention network (p < 0.0001). Then, we investigated the transmission pathway of pain stimuli. Functional connectivity of the thalamus to the insular cortex was significantly higher in the PL group (p < 0.01 - 0.05). These results suggest that endogenous pain driven by top-down signals via the dorsal attention network may contribute to pain sensation in a subgroup of fibromyalgia patients with a normal pain threshold. Besides, external pain driven by bottom-up signals via the spinothalamic tract may contribute to pain sensations in another group of patients with a low pain threshold. Trial registration: UMIN000037712.</AbstractText"
]
] |
[
[
"36347341",
"The neural mechanism of non-phase-locked EEG activity in task switching.",
"Flexible switching between different tasks is an important cognitive ability for humans and it is often studied using the task-switching paradigm. Although the neural mechanisms of task switching have been extensively explored in previous studies using event-related potentials techniques, the activity and process mechanisms of non-phase-locked electroencephalography (EEG) have rarely been revealed. For this reason, this paper discusses the processing of non-phase-locked EEG oscillations in task switching based on frequency-band delineation. First, the roles of each frequency band in local brain regions were summarized. In particular, during the proactive control process (the cue-stimulus interval), delta, theta, and alpha oscillations played more roles in the switch condition while beta played more roles in repeat task. In the reactive control process (post-target), delta, alpha, and beta are all related to sensorimotor function. Then, utilizing the functional connectivity (FC) method, delta connections in the frontotemporal regions and theta connections located in the parietal-to-occipital sites are involved in the preparatory period before task switching, while alpha connections located in the sensorimotor areas and beta connections located in the frontal-parietal cortex are involved in response inhibition. Finally, cross-frequency coupling (CFC) play an important role in working memory among different band oscillation. The present study shows that in addition to the processing mechanisms specific to each frequency band, there are some shared and interactive neural mechanism in task switching by using different analysis techniques.</AbstractText"
],
[
"37145250",
"COMPASS: a formal framework and aggregate dataset for generalized surgical procedure modeling.",
"We propose a formal framework for the modeling and segmentation of minimally invasive surgical tasks using a unified set of motion primitives (MPs) to enable more objective labeling and the aggregation of different datasets.</AbstractText We model dry-lab surgical tasks as finite state machines, representing how the execution of MPs as the basic surgical actions results in the change of surgical context, which characterizes the physical interactions among tools and objects in the surgical environment. We develop methods for labeling surgical context based on video data and for automatic translation of context to MP labels. We then use our framework to create the COntext and Motion Primitive Aggregate Surgical Set (COMPASS), including six dry-lab surgical tasks from three publicly available datasets (JIGSAWS, DESK, and ROSMA), with kinematic and video data and context and MP labels.</AbstractText Our context labeling method achieves near-perfect agreement between consensus labels from crowd-sourcing and expert surgeons. Segmentation of tasks to MPs results in the creation of the COMPASS dataset that nearly triples the amount of data for modeling and analysis and enables the generation of separate transcripts for the left and right tools.</AbstractText The proposed framework results in high quality labeling of surgical data based on context and fine-grained MPs. Modeling surgical tasks with MPs enables the aggregation of different datasets and the separate analysis of left and right hands for bimanual coordination assessment. Our formal framework and aggregate dataset can support the development of explainable and multi-granularity models for improved surgical process analysis, skill assessment, error detection, and autonomy.</AbstractText"
],
[
"36993887",
"Neural correlates of the attention training technique as used in metacognitive therapy - A randomized sham-controlled fMRI study in healthy volunteers.",
"The Attention Training Technique (ATT) developed as part of metacognitive therapy is a psychotherapeutic treatment method used to enhance top-down attentional flexibility and control. This study investigated potential neurocognitive changes due to ATT and its underlying neural mechanisms using pre-to-post functional magnetic resonance imaging (fMRI).</AbstractText Fifty-four healthy participants were subjected to a randomized, sham-controlled attention training and evaluated using a neurocognitive test battery that partly took place in an fMRI environment. Participants received two doses ATT or sham ATT daily for 1 week. On day eight, all subjects completed the neurocognitive test battery again.</AbstractText After the training, the ATT group showed a significant improvement in reaction times regarding attentional disengagement compared to the sham ATT group. fMRI data showed decreased levels of activation in the anterior cingulate cortex (ACC) when comparing the ATT group to the sham ATT group during attentional disengagement post intervention. No ATT > sham ATT effects were found regarding selective auditory attention, working memory performance and inhibitory control.</AbstractText These findings putatively indicate that ATT facilitates faster attention allocation and increased attentional flexibility in healthy subjects. The fMRI results suggest this ATT-dependent improvement is accompanied by reduced ACC activity, indicating a more flexible attentional state.</AbstractText"
],
[
"37732305",
"Research hotspots and trends of brain-computer interface technology in stroke: a bibliometric study and visualization analysis.",
"The incidence and mortality rates of stroke are escalating due to the growing aging population, which presents a significant hazard to human health. In the realm of stroke, brain-computer interface (BCI) technology has gained considerable attention as a means to enhance treatment efficacy and improve quality of life. Consequently, a bibliometric visualization analysis was performed to investigate the research hotspots and trends of BCI technology in stroke, with the objective of furnishing reference and guidance for future research.</AbstractText This study utilized the Science Citation Index Expanded (SCI-Expanded) within the Web of Science Core Collection (WoSCC) database as the data source, selecting relevant literature published between 2013 and 2022 as research sample. Through the application of VOSviewer 1.6.19 and CiteSpace 6.2.R2 visualization analysis software, as well as the bibliometric online analysis platform, the scientific knowledge maps were constructed and subjected to visualization display, and statistical analysis.</AbstractText This study encompasses a total of 693 relevant literature, which were published by 2,556 scholars from 975 institutions across 53 countries/regions and have been collected by 185 journals. In the past decade, BCI technology in stroke research has exhibited an upward trend in both annual publications and citations. China and the United States are high productivity countries, while the University of Tubingen stands out as the most contributing institution. Birbaumer N and Pfurtscheller G are the authors with the highest publication and citation frequency in this field, respectively. <i This study comprehensively and visually presents the extensive and in-depth literature resources of BCI technology in stroke research in the form of knowledge maps, which facilitates scholars to gain a more convenient understanding of the development and prospects in this field, thereby promoting further research work.</AbstractText"
],
[
"36547366",
"Optimizing Ramadan fasting: A randomised controlled trial for people with type 2 diabetes during Ramadan applying the principles of the ADA/EASD consensus.",
"Fasting during the holy month of Ramadan is one of the five pillars of Islam. Fasting is not meant to create excessive hardship on the Muslim individual according to religious tenets. It is important that health professionals are aware of potential risks associated with fasting during the month of Ramadan (mainly hypoglycemia and hyperglycemia).</AbstractText To explore the impact of applying the principles of our 2020 recommendations for the management of type 2 diabetes (T2D) during the month of Ramadan.</AbstractText A multinational randomized controlled trial (RCT) was conducted in five Muslim majority countries. Six hundred and sixty participants were deemed eligible for the study; however, 23% declined to participate later for various reasons. In total, 506 participants were enroled and were equally randomized to the intervention or the control group. At the end of the study, data from 231 participants in the intervention group and 221 participants from the control group were collected after 12.6% and 8.7% were, respectively, lost to follow-up. Participants were randomized to receive a Ramadan-focussed education with treatment for diabetes adjusted as per our 2020 recommendation update compared with the local usual care (control group). Results are presented using mean, standard deviation, odds ratio (OR), and percentages.</AbstractText At the end of the study, the number of hypoglycemic episodes in the intervention group was less than in participants who received usual care. The intervention group had significantly lower severe hypoglycemia compared to the control group with an OR of 0.2 [0.1-0.8]. Compared to baseline, both groups had a significant reduction in glycated haemoglobin (HbA1c), but the improvements were significantly greater in the intervention group. Whilst body weight reduced and high-density lipoprotein cholesterol increased with the intervention, these changes were not significantly different from usual care.</AbstractText A pre-Ramadan assessment of people with T2D coupled with pre-Ramadan education and an adjustment of glucose-lowering treatment as per our updated 2020 recommendations can prevent acute complications and allow a safer fast for people with T2D. We have shown that such an approach reduces the risk of developing severe hypoglycemia and improves the metabolic outcomes in people with T2D.</AbstractText"
]
] |
40748959
|
Orexin effect on physiological pulsations of the human brain.
|
Sleep promotes cerebrospinal fluid (CSF) to interstitial fluid (ISF) exchange in the brain facilitated by brain pulsations. Especially brain vasomotion and arterial pulsations modulated by noradrenaline drive the intracranial fluid dynamics. Narcolepsy type 1 (NT1) entails lessened orexinergic output to wake-promoting systems including the noradrenergic locus coeruleus. As arousal state and noradrenergic signaling affect CSF-ISF clearance, we chose patients with NT1 as a human orexin-targeted model of sleep-related pathology bridging the gap between healthy awake and sleep with respect to CSF flow pulsations. We also investigated the sensitivity of magnetic resonance encephalography to detect flow with a phantom model and sought to replicate earlier pulsation findings in sleep. In this case-control study, we used fast functional MRI to map brain pulsations in groups of healthy sleeping controls (n = 13), healthy awake controls (n = 79), and awake NT1 (n = 21) patients. We measured the very low frequency (0.008 to 0.1) and cardiorespiratory frequencies and calculated in each frequency band the coefficient of variation, spectral power, and full band spectral entropy to obtain brain pulsation maps. We uncovered a brain pulsation profile from healthy waking to sleep to a sleep-related pathology NT1 prominently affected in the vascular-related vasomotor and brain arterial pulsations. Our results established how drivers of brain hydrodynamics are affected by a specific loss of key neurotransmitter governing arousal compared to healthy sleep. We also showed with a phantom model that MREG is sensitive to flow-related signal changes and solidified evidence of brain pulsations in the healthy states of sleep and wakefulness.</AbstractText
|
[
[
"40111737",
"Narcolepsy: Beyond the Classic Pentad.",
"Narcolepsy is a rare, disabling, chronic neurologic disorder that requires lifelong management of symptoms with pharmacologic and nonpharmacologic methods. The pentad symptoms of narcolepsy include excessive daytime sleepiness, cataplexy, disrupted nighttime sleep, sleep paralysis, and hypnagogic/hypnopompic hallucinations. However, people with narcolepsy often experience additional symptoms and disability related to nonpentad symptoms and comorbidities, such as cognitive, psychiatric, metabolic, and sleep disturbances. Current treatment strategies have focused primarily on addressing two of the pentad symptoms, excessive daytime sleepiness, and cataplexy, mainly owing to medication options being approved by the US Food and Drug Administration for these specific indications, neglecting the full 24-h impact and spectrum of symptoms. Meanwhile, the burden of disease extends far beyond these symptoms, and optimal management should reflect a comprehensive, patient-specific approach that not only addresses the entire pentad, but also goes beyond it to include the complete clinical presentation and manifestations of the disease. Individualized treatment must consider the patient's age and stage of life, most debilitating symptoms, support system and structure, comorbid conditions, treatment goals, and overall health. This review discusses care considerations for people living with narcolepsy in the context of their clinical characteristics beyond the hallmark features of narcolepsy.</AbstractText"
],
[
"38337347",
"Characterization of the Increase in Narcolepsy following the 2009 H1N1 Pandemic in Sweden.",
"(1) Background: In the context of the H1N1 pandemic and the Pandemrix vaccination campaign, an increased number of narcolepsy cases were noted in several countries. In Sweden, this phenomenon was attributed to the effect of the Pandemrix vaccination in the first place. Studies from China indicated that narcolepsy could occur as a consequence of the H1N1 infection itself. We performed an analysis of the increase, with a specific interest in age and sex distribution. We also aimed to validate the origin of the excess cases, post hoc. (2) Methods: Data for narcolepsy patients (ICD code G 47.4, both type 1 and type 2) distributed by sex and age at 5-year intervals, annually between 2005 and 2017, were retrieved from the National Patient Register. Information on the total population was collected from the Swedish Population Register. (3) Results: The number of narcolepsy cases increased markedly from 2009 to 2014 compared to the period before 2009. A particular increase in 2011 among children and teenagers was observed. The sex ratio did not change significantly during the study period. (4) Conclusions: Our results support an association between the increased prevalence of narcolepsy cases and Pandemrix vaccination, but the effect of the virus itself cannot be ruled out as a contributing factor.</AbstractText"
],
[
"39484812",
"The Lehigh Valley Health Network Narcolepsy Cohort: clinical and polysomnographic analysis of 304 cases.",
"We aimed to characterize clinical features, comorbidities, and polysomnographic characteristics of a large cohort of patients with narcolepsy.</AbstractText We undertook a retrospective chart and polysomnographic review of all patients with a diagnosis of narcolepsy type 1 (NT1) or narcolepsy type 2 (NT2) seen within the Lehigh Valley Health Network between 2000 and 2022.</AbstractText We found 304 cases with a diagnosis of narcolepsy (52 NT1, 252 NT2), based on <i This is one of the largest monocentric studies to date of patients with narcolepsy and confirms the frequent comorbidities of narcolepsy. Specific clinical characteristics and comorbidities may help differentiate NT1 from NT2.</AbstractText Jiang RY, Rochart R, Chu I, Duka S, Vendrame M. The Lehigh Valley Health Network Narcolepsy Cohort: clinical and polysomnographic analysis of 304 cases. <i Methylphenidate is FDA-approved for the treatment of ADHD in adults and children 6 years and older. Additionally, methylphenidate serves as a second-line therapy for narcolepsy in adults. Off-label uses include cancer-related fatigue, refractory depression in older adults, apathy in patients with Alzheimer disease, and cognitive enhancement (eg, memory improvement); the efficacy of methylphenidate for these conditions is moderate at best.</AbstractText"
],
[
"39092633",
"Orexin increases the neuronal excitability of several brain areas associated with maintaining of arousal.",
"Orexin is exclusively produced in neurons localized within the lateral hypothalamic area (LHA) and perifornical area (PFA). Orexin has been identified as a key promotor of arousal. The selective loss of orexinergic neurons results in narcolepsy. It is known that the intrinsic electrophysiological properties are critical for neurons to perform their functions in corresponding brain regions. In addition to hypothalamic orexin, other brain nuclei are involved in the regulation of sleep and wakefulness. Quite a lot of studies focus on elucidating orexin-induced regulation of sleep-wake states and modulation of neuronal electrophysiological properties in several brain regions. Here, we summarize that the orexinergic neurons exhibit spontaneous firing activity which is associated with the states of sleep-wake cycle. Orexin mainly exerts postsynaptic excitatory effects on multiple brain nuclei associated with the process of sleep and wakefulness. This review may provide a background to guide future research about the cellular mechanisms of orexin-induced maintaining of arousal.</AbstractText"
],
[
"38783152",
"Navigating narcolepsy: exploring coping strategies and their association with quality of life in patients with narcolepsy type 1.",
"Narcolepsy type 1 (NT1) is a chronic neurological disorder characterized by symptoms such as excessive daytime sleepiness, sudden sleep episodes, disrupted nocturnal sleep, cataplexy, sleep paralysis, and hypnagogic hallucinations, which significantly impact the overall well-being and quality of life of individuals. While psychological factors have gained attention, there is limited research on the coping strategies employed by patients with NT1 and their association with quality of life. This study aimed to compare coping strategies in patients with NT1 and controls, as well as assess the relationship between coping strategies and quality of life in patients with NT1. A total of 122 individuals diagnosed with NT1 and 138 controls were enrolled in this cross-sectional study. Participants completed questionnaires assessing coping strategies and health-related quality of life. A Mann-Whitney U test was conducted to compare the use of different coping strategies by patients with NT1 and controls. Spearman's rho correlation was performed to examine the association between coping strategies and quality of life in the NT1 group. Results showed that patients with NT1 exhibited differences in the use of coping strategies compared to controls. They reported lower use of active coping, planning, instrumental, and emotional social support, and higher use of behavioral and mental disengagement. Denial and behavioral disengagement were significantly and negatively associated with quality of life. Identifying coping strategies and their association with quality of life may aid in the development of tailored interventions aimed at improving the adoption of effective coping strategies and reducing the use of maladaptive coping strategies.</AbstractText"
]
] |
[
[
"40455869",
"Modelling fragile X-associated neuropsychiatric disorders in young inducible 90CGG premutation mice.",
"Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a preCGG repeat expansion in the FMR1 gene. Individuals with the FMR1 premutation often exhibit neuropsychiatric symptoms before FXTAS onset, leading to the identification of fragile X-associated neuropsychiatric disorders (FXAND). Rodent models of FXTAS show motor impairments, pathological intranuclear inclusions, and heightened anxiety. However, the early onset of neuropsychiatric features and underlying mechanisms remain poorly understood. To address the above issues, we used the doxycycline (dox)-inducible 90CGG mouse model, with transgene activation at two developmental stages: adolescence and young adulthood. Mice were evaluated in a behavioural battery to assess anxiety-like behaviour, exploration, and motor coordination and learning. Next, we conducted a combination of ex vivo extracellular local field potential recordings to measure synaptic physiology and oscillatory activity in the limbic system, particularly in the basolateral amygdala (BLA) and ventral hippocampus (vH) regions. Parvalbumin interneurons and intranuclear inclusions in the amygdala and hippocampus were investigated by immunofluorescence, while mass spectrometry and gene set enrichment were used to identify differentially expressed proteins molecular pathways. Adolescent 90CGG mice displayed early-onset hyperactivity, transitioning to heightened anxiety in young adulthood, coinciding with the accumulation of intranuclear inclusions in the BLA and vH. Electrophysiological analysis revealed augmented gamma oscillations in the vH, emerging during adolescence and persisting in young adulthood. These changes correlated with a reduction in parvalbumin interneurons in these regions, and together likely contribute to enhanced BLA excitability and impaired vH plasticity. Finally, proteomic analysis of the vH revealed altered proteins linked to attention deficit hyperactivity disorder in adolescence and anxiety/depression in adulthood, aligning well with behavioural findings. Importantly, these behavioural, electrophysiological, and cellular alterations were reversible upon transgene inactivation. This study reveals a temporal progression of CGG premutation effects on behaviour, from hyperactivity to heightened anxiety to late onset motor dysfunction. Moreover, these findings provide altered network activity in the limbic system as a putative mechanism in neuropsychiatric features of premutation carriers.</AbstractText"
],
[
"40475568",
"Selectivity filter mutation in Na (V) 1.5 promotes ventricular tachycardia.",
"Loss-of-Function (LoF) mutations in the <i Na <sub"
],
[
"40346697",
"Functional analysis of JPH2-knockout cardiomyocytes identifies ECCD as a novel indicator in a human cardiac modelJPH2.",
"Junctophilin-2 (JPH2) is a vital protein in cardiomyocytes, anchoring T-tubule and sarcoplasmic reticulum membranes to facilitate excitation-contraction coupling, a process essential for cardiac contractile function. Dysfunction of JPH2 is associated with cardiac disorders such as heart failure; however, prior studies using mouse models or primary human cardiomyocytes are limited by interspecies differences or poor cell viability, respectively. This study aimed to investigate JPH2's role in human cardiac function and disease using a novel stem cell-derived model, while introducing a new indicator to evaluate related cardiac impairments.</AbstractText We generated a JPH2-knockout model using human embryonic stem cell-derived cardiomyocytes (hESC-CMs) with CRISPR/Cas9. Cellular morphology, contractile function, calcium dynamics, and electrophysiological properties were assessed via transmission electron microscopy, the CardioExcyte96 system, calcium imaging with Fluo-4 AM, and multi-electrode array recordings, respectively. Wild-type JPH2 was overexpressed through lentiviral transfection to evaluate rescue effects, and two JPH2 variants-one benign (G505S) and one pathogenic (E85K)-were introduced to study mutation-specific effects.</AbstractText JPH2 knockout disrupted excitation-contraction coupling in hESC-CMs by impairing junctional membrane complex structure, leading to heart failure-like phenotypes with reduced contractility, altered calcium dynamics, and electrophysiological irregularities. Overexpression of wild-type JPH2 restored these functions, affirming its critical role in cardiac physiology. We identified excitation-contraction coupling delay (ECCD) as a novel indicator that precisely quantified coupling impairment severity, with its applicability validated across distinct JPH2 variants (G505S and E85K).</AbstractText This study demonstrates JPH2's essential role in sustaining excitation-contraction coupling by stabilizing the junctional membrane complex, with its deficiency driving heart failure-like cardiac dysfunction. ECCD is established as a sensitive, comprehensive indicator for assessing JPH2-related impairment severity. These findings advance our understanding of JPH2 in cardiac pathology and position ECCD as a valuable tool for research and potential clinical evaluation, with JPH2 and calcium regulation emerging as promising therapeutic targets.</AbstractText"
],
[
"40582948",
"Effects of Negative Emotions and Personality Traits on Laryngeal and Speech Motor Control.",
"The purpose of this study was to identify the effects of negative affective stimuli on oral and laryngeal motor control. It was also aimed to examine the role of personality traits in emotion-motor interaction.</AbstractText Thirty-five female volunteers (age range: 18-25) were included in the study. Affective stimuli were selected from within the Nencki Affective Picture System (70 pictures with neutral affective valence and 70 with negative affective valence). Participants' personality traits were assessed using the five-factor personality inventory (FFPI). Skin conductance response and heart rate variability assessments were made simultaneously with the presentation of affective pictures. Oral and laryngeal motor skills were assessed via seven vocal tasks: one task was based on electroglottographic analysis (fundamental frequency-F<sub The abductor L-DDK rate, adductor L-DDK rate, syllabic rate, and EGG-CQ values obtained in the presence of negative affective stimuli were statistically significantly higher than those obtained in the presence of neutral affective stimuli (P < 0.05). There was no statistically significant difference between the two stimulus types in terms of their F2rate and O-DDK rate values (P > 0.05). Moreover, neuroticism and extraversion as personality traits were significantly correlated with the F<sub Negative affective stimuli led to an increase in oral and laryngeal motor movement speed by likely activating the sympathetic nervous system. There was also an increase in the CQ of the vocal folds. Furthermore, participants who scored higher on the FFPI personality trait of \"extraversion\" had lower EGG-CQ scores, while those who scored higher on the personality trait of \"neuroticism\" had higher EGG average jitter and F<sub"
],
[
"40763289",
"The genomic configurations driving antimicrobial resistance and virulence in colistin resistant Pseudomonas aeruginosa from an Egyptian Tertiary Oncology Hospital.",
"Pseudomonas aeruginosa, recognized by the World Health Organization as a critical priority pathogen, exhibits significant genomic plasticity and a high potential for developing resistance to multiple antimicrobials. This study provides comprehensive genomic insights into colistin-resistant P. aeruginosa isolates obtained from cancer patients. Phenotypic assays were conducted to evaluate antibiotic susceptibility, biofilm formation, efflux pump activity, swarming motility, and pigment production. Whole genome sequencing of the collected isolates was performed using Oxford-Nanopore technology to examine sequence types, resistome profiles, virulence-associated genes, and mobile genetic elements. Our findings reveled that out of 52 isolates, 10 (19.2%) were resistant to colistin. Ceftolozane/tazobactam demonstrated full efficacy against 60% of colistin resistant P. aeruginosa isolates. Within this colistin resistant subset, high-risk clones ST308 and ST773 emerged as dominant, both harboring blaNDM-1 and exhibiting extensive resistance profiles, including resistance to colistin and, in some cases, ceftolozane/tazobactam. The first detection of ST1143 and ST1693 in Egypt carrying blaOXA-1028 and blaOXA-904, respectively was documented, neither of which had been previously reported in the country. The accessory genome, accounting for up to 34.6% of the total genome, highlights the remarkable genomic plasticity of P. aeruginosa, and its capacity for horizontal acquisition of resistance and virulence genes via mobile genetic elements, such as integrative and conjugative elements (ICEs). Virulome analysis revealed the presence of the exoU gene in high-risk clones, a marker closely linked to hypervirulence in infection models, whereas other sequence types were associated with less virulent factors, such as exoS. Despite phenotypic variability in biofilm formation, pigment production, and motility, the underlying genetic determinants of these traits were highly conserved. Mutational analysis revealed mutations in the regulatory system PhoPQ as the primary mechanism of colistin resistance, with no mcr genes detected. In conclusion, the substantial genomic plasticity of P. aeruginosa, reflected by an extensive accessory genome facilitates horizontal gene transfer (HGT), and significantly influences antimicrobial resistance and virulence. Colistin resistance was predominantly mediated by chromosomal mutations. Virulome and resistome analyses underscores the high pathogenicity and resistance potential of high-risk clones ST773 and ST308. The detection of horizontally acquired elements, such as integrative and conjugative elements (ICEs) carrying resistance genes such as blaNDM-1, underscores their role in disseminating resistance determinants. These findings emphasize the need urgent for targeted antimicrobial stewardship and surveillance strategies within Egyptian healthcare settings.</AbstractText"
]
] |
40653907
|
Integrin β4-Enriched Small Extracellular Vesicle as Drug Delivery Vehicle for Targeting Pulmonary Metastasis of Hepatocellular Carcinoma.
|
Small extracellular vesicles (sEVs) hold significant promise for targeted drug delivery, owing to their unique ability to target and accumulate in specific tissues. The organotropism of sEVs is primarily determined by the presence of integrins on their surface. In this study, sEV with enriched integrin β4, designated as XP-ITGβ4-sEV, are engineered to enhance lung-targeting capabilities. The therapeutic efficacy of doxorubicin-loaded XP-ITGβ4-sEV (XP-ITGβ4-sEV/Dox) is evaluated in targeting pulmonary metastasis of advanced hepatocellular carcinoma (HCC) using a murine lung metastasis model. Remarkably, treatment with XP-ITGβ4-sEV/Dox effectively suppresses tumor cell colonization in the lungs compared to an equivalent dose of free doxorubicin. Histological analyses reveal a reduction in lung metastatic foci, inhibition of proliferation, and an increase in apoptosis of HCC cells. Notably, XP-ITGβ4-sEV/Dox exhibits a superior therapeutic efficacy with an improved safety profile compared to a higher dose of free doxorubicin that demonstrates similar efficacy. These findings collectively underscore the potential of integrin β4-enriched sEVs as a targeted drug delivery system for addressing pulmonary metastasis of HCC.</AbstractText
|
[
[
"32772213",
"Splice variants of RAS-translational significance.",
"One of the mechanisms potentially explaining the discrepancy between the number of human genes and the functional complexity of organisms is generating alternative splice variants, an attribute of the vast majority of multi-exon genes. Members of the RAS family, such as NRAS, KRAS and HRAS, all of which are of significant importance in cancer biology, are no exception. The structural and functional differences of these splice variants, particularly if they contain the canonical (and therefore routinely targeted for diagnostic purposes) hot spot mutations, pose a significant challenge for targeted therapies. We must therefore consider whether these alternative splice variants constitute a minor component as originally thought and how therapies targeting the canonical isoforms affect these alternative splice variants and their overall functions.</AbstractText"
],
[
"27716417",
"Importance of rare gene copy number alterations for personalized tumor characterization and survival analysis.",
"It has proven exceedingly difficult to ascertain rare copy number alterations (CNAs) that may have strong effects in individual tumors. We show that a regulatory network inferred from gene expression and gene copy number data of 768 human cancer cell lines can be used to quantify the impact of patient-specific CNAs on survival signature genes. A focused analysis of tumors from six tissues reveals that rare patient-specific gene CNAs often have stronger effects on signature genes than frequent gene CNAs. Further comparison to a related network-based approach shows that the integration of indirectly acting gene CNAs significantly improves the survival analysis.</AbstractText"
],
[
"33789737",
"Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis.",
"Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties.</AbstractText ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson's trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice.</AbstractText The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs.</AbstractText This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.</AbstractText"
],
[
"23430739",
"Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes.",
"Emerging evidence indicates that exosomes play a key role in tumor-host cross-talk and that exosome secretion, composition, and functional capacity are altered as tumors progress to an aggressive phenotype. However, little is known regarding the mechanisms that regulate these changes. Heparanase is an enzyme whose expression is up-regulated as tumors become more aggressive and is associated with enhanced tumor growth, angiogenesis, and metastasis. We have discovered that in human cancer cells (myeloma, lymphoblastoid, and breast cancer), when expression of heparanase is enhanced or when tumor cells are exposed to exogenous heparanase, exosome secretion is dramatically increased. Heparanase enzyme activity is required for robust enhancement of exosome secretion because enzymatically inactive forms of heparanase, even when present in high amounts, do not dramatically increase exosome secretion. Heparanase also impacts exosome protein cargo as reflected by higher levels of syndecan-1, VEGF, and hepatocyte growth factor in exosomes secreted by heparanase-high expressing cells as compared with heparanase-low expressing cells. In functional assays, exosomes from heparanase-high cells stimulated spreading of tumor cells on fibronectin and invasion of endothelial cells through extracellular matrix better than did exosomes secreted by heparanase-low cells. These studies reveal that heparanase helps drive exosome secretion, alters exosome composition, and facilitates production of exosomes that impact both tumor and host cell behavior, thereby promoting tumor progression.</AbstractText"
],
[
"30726905",
"Multiple functions of the ER-resident VAP and its extracellular role in neural development and disease.",
"VAP (VAMP-associated protein) is a type II integral membrane protein of the endoplasmic reticulum (ER), and its N-terminal major sperm protein (MSP) domain faces the cytoplasmic side. VAP functions as a tethering molecule at the membrane contact sites between the ER and intracellular organelles and regulates a wide variety of cellular functions, including lipid transport, membrane trafficking, microtubule reorganization and unfolded protein response. VAP-point mutations in human vapb are strongly associated with amyotrophic lateral sclerosis. Importantly, the MSP domain of VAP is cleaved, secreted and interacts with the axon growth cone guidance receptors (Eph, Robo, Lar), suggesting that VAP could function as a circulating hormone similar to the Caenorhabditis elegans MSP protein. In this review, we discuss not only the intracellular functions of VAP but also the recently discovered extracellular functions and their implications for neurodegenerative disease.</AbstractText"
]
] |
[
[
"40796324",
"Exploring the Diagnostic Potential of Core Targets of 6PPD and Its Metabolite 6PPD-Q in Cardiovascular Diseases: An Integrated Analysis Based on Network Toxicology, Molecular Docking, and In Vitro Validation.",
"6PPD (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine) and its oxidized form, 6PPD-Q (2-((4-methylpentan-2-yl)amino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione), are commonly used in rubber-based materials and have been increasingly found in the environment. Recent studies suggest that these compounds may be toxic to the cardiovascular system, but the exact molecular mechanisms are not well understood. This study used a combination of network toxicology, molecular docking, and bioinformatics to investigate how 6PPD and 6PPD-Q affect the heart, particularly in relation to atherosclerosis, acute myocardial infarction, and heart failure. By screening multiple databases and analyzing Gene Expression Omnibus (GEO) transcriptome data, we identified key targets that are involved in these diseases. We built PPI networks and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore the related pathways. Additionally, we validated four core targets-nuclear receptor subfamily 4 group A member 3 (NR4A3), sphingosine-1-phosphate receptor 3 (S1PR3), nicotinamide phosphoribosyltransferase (NAMPT), and formyl peptide receptor 1 (FPR1)-that showed high diagnostic value in all three diseases using receiver operating characteristic (ROC) analysis. Molecular docking revealed that both 6PPD and 6PPD-Q strongly bind to these targets. Further in vitro experiments revealed that 6PPD and 6PPD-Q induce damage in H9c2 cells. The mechanism may be associated with these four targets. This study sheds light on how these environmental pollutants harm the cardiovascular system and demonstrates the value of combining network toxicology with omics and structural biology in risk assessment and therapeutic development.</AbstractText"
],
[
"39956966",
"Structural covariance network patterns linked to neuropsychiatric symptoms in biologically defined Alzheimer's disease: Insights from the mild behavioral impairment checklist.",
"The frequent presentation of Alzheimer's disease (AD) with neuropsychiatric symptoms (NPS) in the context of normal or minimally-impaired cognitive function led to the concept of Mild Behavioral Impairment (MBI). While MBI's impact on subsequent cognitive decline is recognized, its association with brain network changes in biologically-defined AD remains unexplored.</AbstractText To investigate the correlation of structural covariance networks with MBI-C checklist sub-scores in biologically-defined AD patients.</AbstractText We analyzed 33 biologically-defined AD patients, ranging from mild cognitive impairment to early dementia, all characterized as amyloid-positive through cerebrospinal fluid analysis or amyloid positron emission tomography scans. Regional network properties were assessed through graph theory.</AbstractText Affective dysregulation correlated with decreased segregation and integration in the right inferior frontal gyrus (IFG). Impulse dyscontrol and social inappropriateness correlated positively with centrality and efficiency in the right posterior cingulate cortex (PCC). Global network properties showed a preserved small-world organization.</AbstractText This study reveals associations between MBI subdomains and structural brain network alterations in biologically-confirmed AD. The IFG's involvement is crucial for mood dysregulation, while the PCC could be involved in compensatory mechanisms for social cognition and impulse control. These findings underscore the significance of biomarker-based neuroimaging for the characterization of NPS across the AD spectrum.</AbstractText Altered mental status is one of the most common presenting complaints in older adult patients and is often related to \"3 Ds\": delirium, dementia, and depression. Out of the 3 Ds, delirium and dementia are more commonly encountered in clinical practice. The 2 terms are frequently used interchangeably and, therefore, unrecognized during the initial assessment. Understanding that delirium and dementia are distinct syndromes with different prognoses and management is essential, though distinguishing between both diagnoses in the clinical setting can be difficult, even for experienced clinicians. While an acute confusional state that fluctuates and develops over days to weeks is likely to be delirium, a more persistent and chronic progression is more suggestive of dementia; however, these clinical features may not be as evident in patients with underlying dementia who develop acute delirium. Additionally, this distinction is blurred in cases of persistent delirium and reversible dementia etiologies. Cognition is assessed in 6 domains: memory and learning, language, executive functioning, complex attention, perceptual-motor, and social cognition.  Delirium is characterized by an altered awareness mainly affecting attention, whereas dementia is defined as cognitive decline, which interferes with 1 or more domains. Delirium is an abrupt onset of reduced orientation or awareness of the environment in contrast to dementia, a gradual process leading to disturbance in the core features, with attention being affected much later in the disease course.  Typically, dementia is a neurodegenerative disorder seen in older age and is of various subtypes, with the age of onset depending on the subtype. On the other hand, delirium is an age-independent process that occurs more commonly in older adult patients and can happen under variable circumstances. Delirium typically occurs from hours to days, whereas dementia is a slow progressive course over months to years. Delirium and dementia commonly coexist, with preexisting dementia being a leading risk factor for delirium. Sometimes, when dementia is rapidly progressive, it can be challenging to differentiate between the conditions in patients without a prior history of dementia. Therefore, distinguishing between these conditions or identifying superimposed delirium in a preexisting dementia patient is essential, as misdiagnosis may lead to a prolonged hospital stay, accelerated cognitive and functional decline, increased healthcare costs, and even death.</AbstractText"
],
[
"40700061",
"The Co-Occurrence of Autism Spectrum Disorder and Aarskog-Scott Syndrome in an Accomplished Young Man.",
"<b"
],
[
"40730985",
"The effect of emotion regulation difficulties and loneliness on anxiety, depression, and stress levels in remote workers.",
"While remote work brings flexibility to work life, it can also bring loneliness, emotion regulation difficulties, and some mental health symptoms. This study examined the relationship between loneliness and emotion regulation difficulties and levels of depression, anxiety, and stress in remote workers and the role of some sociodemographic variables in these relationships.</AbstractText An analytical cross-sectional observational study was conducted. One hundred twenty-one participants (53.7% female, 46.3% male), aged 23-56 and working remotely for at least six months, were reached through snowball sampling and evaluated using online survey forms. Data were collected using a sociodemographic information form, the UCLA Loneliness Scale, the Depression Anxiety Stress Scale, and the Difficulties in Emotion Regulation Scale. In addition to correlation analyses and group comparisons, mediation analyses were conducted using the bootstrap method.</AbstractText Emotion regulation difficulties and loneliness were significantly positively associated with depression, anxiety, and stress. An increase in the number of days working remotely per week increased anxiety levels, and emotion regulation difficulties mediated this effect. Loneliness had a mediating role in the relationship between emotion regulation difficulties and depression.</AbstractText Emotion regulation difficulties and loneliness have a significant impact on symptoms of depression, anxiety, and stress in individuals working remotely. These findings support the need to strengthen emotion regulation skills and develop policies that increase social interaction to support the mental health of remote workers.</AbstractText"
],
[
"40371238",
"Development and validation of Restless Legs Syndrome Diary for the assessment of severity and course of symptoms - A cross-sectional study.",
"The clinical course and severity of restless legs syndrome (RLS) are variable. Existing questionnaires measure the severity of RLS based on recall. One possible solution could be the daily charting of symptoms in a diary.</AbstractText Development and validation of a diary for the longitudinal assessment of symptoms and the impact of RLS.</AbstractText This study was conducted in two phases. In phase 1, an RLS diary was developed. During phase 2, it was given to patients presenting with RLS. They were explained how to fill in the information in the diary. It collected information related to symptoms as well as sleep. Adverse effects of the symptoms on mood and daytime function were also assessed. Three scores were calculated from the data-the burden of RLS, the burden of severe RLS symptoms, and the overall burden of RLS. The convergent validity of the diary was calculated by comparing it with the international RLS severity rating scale (IRLS).</AbstractText During phase 1, RLS Diary attained a score of one during content validation by universal agreement. Of 34 participants, 63.6% were females with an average age of 46.6 ± 14 years. Cronbach's alpha of the diary was 0.92. RLS diary showed the temporal change in time of onset of RLS, change in severity, and topography. The composite score from the RLS diary for week four had weak to moderate positive correlations with IRLS (week four).</AbstractText RLS Diary is a valid and psychometrically optimal tool for detailed assessment of the severity of RLS symptoms and the burden of RLS. However, there was a poor to the moderate correlation with recall-based measures of the severity of RLS.</AbstractText"
]
] |
38447117
|
Disparities in Genetic Testing for Neurologic Disorders.
|
Genetic testing is now the standard of care for many neurologic conditions. Health care disparities are unfortunately widespread in the US health care system, but disparities in the utilization of genetic testing for neurologic conditions have not been studied. We tested the hypothesis that access to and results of genetic testing vary according to race, ethnicity, sex, socioeconomic status, and insurance status for adults with neurologic conditions.</AbstractText We analyzed retrospective data from patients who underwent genetic evaluation and testing through our institution's neurogenetics program. We tested for differences between demographic groups in 3 steps of a genetic evaluation pathway: (1) attending a neurogenetic evaluation, (2) completing genetic testing, and (3) receiving a diagnostic result. We compared patients on this genetic evaluation pathway with the population of all neurology outpatients at our institution, using univariate and multivariable logistic regression analyses.</AbstractText Between 2015 and 2022, a total of 128,440 patients were seen in our outpatient neurology clinics and 2,540 patients underwent genetic evaluation. Black patients were less than half as likely as White patients to be evaluated (odds ratio [OR] 0.49, <i We observed unequal utilization of our clinical neurogenetics program for patients from marginalized and minoritized demographic groups, especially Black patients. Among patients who do undergo evaluation, all groups benefit similarly from genetic testing when it is indicated. Understanding and removing barriers to accessing genetic testing will be essential to health care equity and optimal care for all patients with neurologic disorders.</AbstractText
|
[
[
"36685225",
"A functional network of highly pure enteric neurons in a dish.",
"The enteric nervous system (ENS) is the intrinsic nervous system that innervates the entire digestive tract and regulates major digestive functions. Recent evidence has shown that functions of the ENS critically rely on enteric neuronal connectivity; however, experimental models to decipher the underlying mechanisms are limited. Compared to the central nervous system, for which pure neuronal cultures have been developed for decades and are recognized as a reference in the field of neuroscience, an equivalent model for enteric neurons is lacking. In this study, we developed a novel model of highly pure rat embryonic enteric neurons with dense and functional synaptic networks. The methodology is simple and relatively fast. We characterized enteric neurons using immunohistochemical, morphological, and electrophysiological approaches. In particular, we demonstrated the applicability of this culture model to multi-electrode array technology as a new approach for monitoring enteric neuronal network activity. This <i"
],
[
"37350014",
"Attentional modulation of neural sound tracking in children with and without dyslexia.",
"Auditory selective attention forms an important foundation of children's learning by enabling the prioritisation and encoding of relevant stimuli. It may also influence reading development, which relies on metalinguistic skills including the awareness of the sound structure of spoken language. Reports of attentional impairments and speech perception difficulties in noisy environments in dyslexic readers are also suggestive of the putative contribution of auditory attention to reading development. To date, it is unclear whether non-speech selective attention and its underlying neural mechanisms are impaired in children with dyslexia and to which extent these deficits relate to individual reading and speech perception abilities in suboptimal listening conditions. In this EEG study, we assessed non-speech sustained auditory selective attention in 106 7-to-12-year-old children with and without dyslexia. Children attended to one of two tone streams, detecting occasional sequence repeats in the attended stream, and performed a speech-in-speech perception task. Results show that when children directed their attention to one stream, inter-trial-phase-coherence at the attended rate increased in fronto-central sites; this, in turn, was associated with better target detection. Behavioural and neural indices of attention did not systematically differ as a function of dyslexia diagnosis. However, behavioural indices of attention did explain individual differences in reading fluency and speech-in-speech perception abilities: both these skills were impaired in dyslexic readers. Taken together, our results show that children with dyslexia do not show group-level auditory attention deficits but these deficits may represent a risk for developing reading impairments and problems with speech perception in complex acoustic environments. RESEARCH HIGHLIGHTS: Non-speech sustained auditory selective attention modulates EEG phase coherence in children with/without dyslexia Children with dyslexia show difficulties in speech-in-speech perception Attention relates to dyslexic readers' speech-in-speech perception and reading skills Dyslexia diagnosis is not linked to behavioural/EEG indices of auditory attention.</AbstractText"
],
[
"39169183",
"Thermal infrared directs host-seeking behaviour in Aedes aegypti mosquitoes.",
"Mosquito-borne diseases affect hundreds of millions of people annually and disproportionately impact the developing world<sup"
],
[
"38832639",
"Extended haplotype with rs41524547-G defines the ancestral origin of SCA10.",
"Spinocerebellar ataxia type 10 (SCA10) is a rare autosomal dominant ataxia caused by a large expansion of the (ATTCT)n repeat in ATXN10. SCA10 was described in Native American and Asian individuals which prompted a search for an expanded haplotype to confirm a common ancestral origin for the expansion event. All patients with SCA10 expansions in our cohort share a single haplotype defined at the 5'-end by the minor allele of rs41524547, located ~35 kb upstream of the SCA10 expansion. Intriguingly, rs41524547 is located within the miRNA gene, MIR4762, within its DROSHA cleavage site and just outside the seed sequence for mir4792-5p. The world-wide frequency of rs41524547-G is less than 5% and found almost exclusively in the Americas and East Asia-a geographic distribution that mirrors reported SCA10 cases. We identified rs41524547-G(+) DNA from the 1000 Genomes/International Genome Sample Resource and our own general population samples and identified SCA10 repeat expansions in up to 25% of these samples. The reduced penetrance of these SCA10 expansions may be explained by a young (pre-onset) age at sample collection, a small repeat size, purity of repeat units, or the disruption of miR4762-5p function. We conclude that rs41524547-G is the most robust at-risk SNP allele for SCA10, is useful for screening of SCA10 expansions in population genetics studies and provides the most compelling evidence to date for a single, prehistoric origin of SCA10 expansions sometime prior to or during the migration of individuals across the Bering Land Bridge into the Americas.</AbstractText"
],
[
"36905813",
"The evolution of comprehensive genetic analysis in neurology: Implications for precision medicine.",
"Technological advancements have facilitated the availability of reliable and thorough genetic analysis in many medical fields, including neurology. In this review, we focus on the importance of selecting the appropriate genetic test to aid in the accurate identification of disease utilizing currently employed technologies for analyzing monogenic neurological disorders. Moreover, the applicability of comprehensive analysis via NGS for various genetically heterogeneous neurological disorders is reviewed, revealing its efficiency in clarifying a frequently cloudy diagnostic picture and delivering a conclusive and solid diagnosis that is essential for the proper management of the patient. The feasibility and effectiveness of medical genetics in neurology require interdisciplinary cooperation among several medical specialties and geneticists, to select and perform the most relevant test according to each patient's medical history, using the most appropriate technological tools. The prerequisites for a comprehensive genetic analysis are discussed, highlighting the utility of appropriate gene selection, variant annotation, and classification. Moreover, genetic counseling and interdisciplinary collaboration could improve diagnostic yield further. Additionally, a sub-analysis is conducted on the 1,502,769 variation records with submitted interpretations in the Clinical Variation (ClinVar) database, with a focus on neurology-related genes, to clarify the value of suitable variant categorization. Finally, we review the current applications of genetic analysis in the diagnosis and personalized management of neurological patients and the advances in the research and scientific knowledge of hereditary neurological disorders that are evolving the utility of genetic analysis towards the individualization of the treatment strategy.</AbstractText"
]
] |
[
[
"39556800",
"Middle fossa approach for a petrous apex bony spur causing trigeminal neuralgia: illustrative case.",
"Trigeminal neuralgia (TN) can arise from trigeminal nerve compression at the root entry zone due to neurovascular conflict, which most often presents in the 6th decade of life. The authors report the case of a young patient with TN with a petrous apex bony spur near the entrance of Meckel's cave, causing compression of the proximal trigeminal nerve.</AbstractText A 21-year-old woman presented with a 5-year history of progressive right-sided TN. Axial T2 sampling perfection with application optimized contrast using different flip angle evolution magnetic resonance imaging (MRI) did not reveal vascular compression of the trigeminal nerve. However, sagittal reformats demonstrated a prominent bony ridge along the petrous apex, causing compression of the right trigeminal nerve at the porus trigeminus. Removal of the bony spur via a middle fossa approach completely resolved the patient's symptoms.</AbstractText Although TN is most frequently caused by neurovascular compression, it is vital to examine the entire course of the trigeminal nerve on MRI to identify alternative causes of nerve compression in the absence of neurovascular conflict. Bony compression is a rare cause of TN that should be considered, particularly in younger patients. The presence of prominent osseous structures along the course of the trigeminal nerve can be evaluated reliably on sagittal MRI. https://thejns.org/doi/10.3171/CASE24321.</AbstractText"
],
[
"38104774",
"Cognitive inflexibility and heightened error monitoring are related to lower sexual functioning.",
"Sexual functioning is an important predictor of well-being and relationship satisfaction. Previous research indicates that several aspects of cognitive function are related to sex-related behaviors and functioning among individuals with sex-related disorders, neurological disorders, and in older adults; however, this has been relatively underexamined in younger populations. To examine this, the present study assessed whether behavioral and/or neurophysiological measures of cognitive function are associated with sexual functioning in a community sample of young 489 adults (64 % female) ages 18-30. Cognitive flexibility (n = 460) and inhibition (n = 466) were measured using neuropsychological assessment (D-KEFS), and conflict monitoring and error monitoring were measured by event-related potentials (conflict N2: n = 394; error-related negativity: n = 389). After separately testing relations between the different measures of cognitive function and sexual functioning, we assessed whether results (1) remained after covarying for externalizing and internalizing dimensions (PID-5; n = 489) or (2) varied by gender. Finally, we tested whether any aspects of cognitive function were unique predictors of sexual functioning. Cognitive flexibility and error monitoring (i.e., error-related negativity) were both significantly related to sexual functioning among males and females, such that poorer cognitive flexibility and heightened error monitoring were related to lower sexual functioning. No significant effects emerged for inhibition or conflict monitoring. In a multiple regression model, cognitive flexibility and error monitoring each accounted for a unique portion of variance in sexual functioning beyond other aspects of cognitive function and psychopathology-related traits. Results suggest that cognitive function is a meaningful correlate of sexual functioning in young adulthood, which should be considered further in future research.</AbstractText"
],
[
"38095981",
"Can speech perception deficits cause phonological impairments? Evidence from short-term memory for ambiguous speech.",
"Poor performance on phonological tasks is characteristic of neurodevelopmental language disorders (dyslexia and/or developmental language disorder). Perceptual deficit accounts attribute phonological dysfunction to lower-level deficits in speech-sound processing. However, a causal pathway from speech perception to phonological performance has not been established. We assessed this relationship in typical adults by experimentally disrupting speech-sound discrimination in a phonological short-term memory (pSTM) task. We used an automated audio-morphing method (Rogers & Davis, 2017) to create ambiguous intermediate syllables between 16 letter name-letter name (\"B\"-\"P\") and letter name-word (\"B\"-\"we\") pairs. High- and low-ambiguity syllables were used in a pSTM task in which participants (<i"
],
[
"38184375",
"Evaluation of 2D ion chamber arrays for patient specific quality assurance using a static phantom at a 0.35 T MR-Linac.",
"Patient specific quality assurance (QA) in MR-Linacs can be performed with MR-compatible ion chamber arrays. However, the presence of a static magnetic field can alter the angular response of such arrays substantially. This works investigates the suitability of two ion chamber arrays, an air-filled and a liquid-filled array, for patient specific QA at a 0.35 T MR-Linac using a static phantom.</AbstractText In order to study the angular response, the two arrays were placed in a static, solid phantom and irradiated with 9.96 × 9.96 cm<sup The air-filled array showed asymmetric angular response changes of central chamber dose of up to 18% and down to local 3 mm / 3% gamma rates of 20%, while only minor differences within 3% (excluding parallel irradiation and beams through the couch edges) were found for the liquid-filled ion chamber array without rotating the phantom. Patient plan QA using the liquid-filled array yielded a median local 3 mm / 3% 3D gamma passing rate of 99.8% (range 96.9%-100%).</AbstractText A liquid-filled ionization chamber array in combination with a static phantom can be used for efficient patient specific plan QA in a single measurement set-up in a 0.35 T MR-Linac, while the air-filled ion chamber array phantom shows large angular response changes and has its limitations regarding patient specific QA measurements.</AbstractText"
],
[
"38844198",
"Electrophysiological markers of vestibular-mediated self-motion perception - A pilot study.",
"Peripheral vestibular activation results in multi-level responses, from brainstem-mediated reflexes (e.g. vestibular ocular reflex - VOR) to perception of self-motion. While VOR responses indicate preserved vestibular peripheral and brainstem functioning, there are no automated measures of vestibular perception of self-motion - important since some patients with brain disconnection syndromes manifest a vestibular agnosia (intact VOR but impaired self-motion perception). Electroencephalography ('EEG') - may provide a surrogate marker of vestibular perception of self-motion. A related objective is obtaining an EEG marker of vestibular sensory signal processing, distinct from vestibular-motion perception. We performed a pilot study comparing EEG responses in the dark when healthy participants sat in a vibrationless computer-controlled motorised rotating chair moving at near threshold of self-motion perception, versus a second situation in which subjects sat in the chair at rest in the dark who could be induced (or not) into falsely perceiving self-motion. In both conditions subjects could perceive self-motion perception, but in the second there was no bottom-up reflex-brainstem activation. Time-frequency analyses showed: (i) alpha frequency band activity is linked to vestibular sensory-signal activation; and (ii) theta band activity is a marker of vestibular-mediated self-motion perception. Consistent with emerging animal data, our findings support the role of theta activity in the processing of self-motion perception.</AbstractText"
]
] |
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Jerjes/neuro-specter2-triplets-multi-pool
This dataset contains anchor papers with their top-K most similar (positive) and most dissimilar (negative) papers based on SPECTER2 embeddings.
Dataset Structure
Each row contains:
anchor_id: Unique identifier for the anchor paperanchor_title: Title of the anchor paperanchor_abstract: Abstract of the anchor paperpositive_pool: List of 5 most similar papers, each as [id, title, abstract]negative_pool: List of 5 most dissimilar papers, each as [id, title, abstract]
Dataset Statistics
- Total anchors: 100,000
- Positives per anchor: 5
- Negatives per anchor: 5
- Embedding model: allenai/specter2_base
Usage
from datasets import load_dataset
dataset = load_dataset("Jerjes/neuro-specter2-triplets-multi-pool")
# Access a sample
sample = dataset["train"][0]
print(f"Anchor: {sample['anchor_title']}")
print(f"Top positive: {sample['positive_pool'][0][1]}") # title of most similar paper
print(f"Top negative: {sample['negative_pool'][0][1]}") # title of most dissimilar paper
Citation
If you use this dataset, please cite the original SPECTER2 paper:
@inproceedings{specter2,
title={SPECTER2: Better Scientific Paper Representations Through Augmented Word Embeddings},
author={Pradeep Dasigi and Kyle Lo and Iz Beltagy and Arman Cohan and Noah A. Smith and Matt Gardner},
booktitle={Proceedings of the 2021 Conference on Empirical Methods in Natural Language Processing},
year={2021}
}
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