Planet Neuroscience

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Decoding state specific connectivity during speech production and perception

Understanding how dynamic brain networks support language perception and production is central to cognitive neuroscience. A vast network based literature has employed functional connectivity (FC), primarily using resting-state and task-based fMRI. However, methodological limitations have hindered this approach in language processing, particularly during speech production. Here, we address this gap by employing a large cohort of electrocorticographic (ECoG) patients (N=42) to investigate the networks driving speech perception and production. We acquired data while patients were engaged in a controlled battery of speech production tasks focusing on five cognitive states (auditory perception, picture perception, reading perception, speech production, and baseline). Using linear classifiers we were able to robustly decode cognitive states from single-trial FC (i.e. Pearson correlations) of the neural activity patterns, achieving a mean accuracy of 64.4%. These classifiers revealed distinct network signatures underlying auditory and visual perception as well as speech production via stable network connectivity. Importantly, the network signatures included both regions with robust local neural activity and those with minimal or no detectable activation. Such signatures indicate that even low-activity regions contribute critically to differentiating cognitive states. Our findings underscore the significance of functional connectivity analysis as a complementary dimension to investigating local neural activity, and suggest that the functional networks supporting speech extend beyond the most metabolically active regions.

in bioRxiv: Neuroscience on 2025-10-12 00:00:00 UTC.

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Nonlinear hippocampal coding of the pair-bonded partner in prairie voles

Neural representation of specific opposite-sex partners remains largely unexplored. Using monogamous prairie voles, we demonstrated that partner preference required the ventral hippocampus, in which 3-4 Hz oscillations were enhanced following partner interaction. We identified ventral hippocampal neurons responding selectively to the pair-bonded partner and stranger, which encoded identity-related information in a nonlinear manner, shedding light upon how mammalian brains create distinct neural representations of romantic opposite-sex partners.

in bioRxiv: Neuroscience on 2025-10-12 00:00:00 UTC.

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Astrocyte SEMA3C reduction improves Rett Syndrome phenotypes

During typical neurodevelopment, astrocytes secrete proteins that support neuronal connectivity. This process is disrupted in Rett Syndrome (RTT), a regressive neurodevelopmental disorder characterized by motor, sensory, and cognitive impairments. While astrocytes typically promote neuron outgrowth, co-culture of RTT astrocytes with wildtype neurons inhibits their outgrowth, implicating secreted astrocyte factors in RTT pathology. However, the specific factors and their contributions to RTT deficits remain poorly defined. To address this, we focused on the class 3 semaphorin SEMA3C, which shows increased astrocyte secretion in RTT and other neurodevelopmental disorders. Using astrocyte and neuron cell culture, we find that SEMA3C is inhibitory to dendrite outgrowth via PLXND1 and NRP2 receptors in cortical neurons. Genetic reduction of astrocyte SEMA3C in female RTT model mice enhances dendritic arborization and normalizes synaptic activity. Behaviorally, astrocyte SEMA3C reduction normalizes visual acuity and motor behavior, which are established clinical features in RTT. Together, these findings identify astrocyte SEMA3C as a contributor to RTT pathology and highlight the SEMA3C-NRP2-PLXND1 signaling pathway as a potential therapeutic target in disordered neurodevelopment.

in bioRxiv: Neuroscience on 2025-10-12 00:00:00 UTC.

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The neural computations underlying context dependent attribute-based valuation of complex stimuli.

Adaptive decision making requires value computations to be flexible because we often need to value a stimulus differently as the context changes. A stimulus might be highly desirable in one context but completely unappealing in another. However, it is not known how the brain can support such flexible modulation of overall stimulus value. Here we test a model of flexible value construction whereby individual attributes of a stimulus are converted into contextually dependent attribute-specific value representations before being combined into an overall integrated stimulus value. To test this framework, human participants (online n=95, MRI n=35) provided ratings for 75 unique high-dimensional clothing stimuli under three instructed `goal-contexts` designed to elicit differences in overall value judgments for the items. Integrated value ratings for each stimulus were found to be goal-context dependent, while individual stimulus-attributes varied markedly in how they contributed to value ratings across goal contexts. In the fMRI data, representations of the absolute levels of particular attributes were revealed in visual areas. In contrast, encoding of individual attributes in value space, alongside integrated overall stimulus value, was present within distinct regions of prefrontal cortex. More specifically, behaviorally relevant attributes in value space and integrated stimulus value were found in vmPFC and dmPFC respectively. These findings indicate that the construction of value for high-dimensional stimuli is achieved through the computation of goal-context-dependent attributes in value space, providing mechanistic insight into how the brain can flexibly modulate stimulus-values as context changes.

in bioRxiv: Neuroscience on 2025-10-12 00:00:00 UTC.

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Shared and distinct neural signatures of inhibitory control deficits in attention-deficit/hyperactivity disorder and autism

Background: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share deficits in inhibitory control, yet direct comparisons of their neurobiological underpinnings remain sparse and are often confounded by comorbidity. We examined shared and distinct abnormalities in brain activation and circuit connectivity associated with inhibitory control in non-comorbid ADHD and ASD. Methods: Brain activity and hyperdirect pathway connectivity during inhibitory control were examined in children with non-comorbid ADHD (age: 11.1{+/-}0.24y) and children with non-comorbid ASD (age: 11.1{+/-}0.39y), compared with typically developing (TD) children (age: 10.9{+/-}0.09y), and benchmarked against healthy adults (age: 24.1{+/-}1.26y), using fMRI stop-signal task data. Results: Both ADHD and ASD groups showed reduced activation in salience and frontoparietal network regions alongside increased activation in default mode network (DMN) regions, consistent with triple-network dysfunction. These activation deficits were more pronounced in ASD, whose activation profile also diverged most from adults. At the circuit level, only ASD showed abnormal hyperdirect connectivity, involving insula-STN and preSMA-STN pathways and further reflected in a composite insula/IFG-STN connectivity measure, indicating broader cortical-STN disruption. Importantly, across all children, reduced salience/frontoparietal relative to DMN engagement correlated with greater parent-reported inhibitory control deficits, and in ASD, individual differences in insula/IFG-STN connectivity showed the same association, highlighting the behavioral relevance of both network- and circuit-level abnormalities. Conclusions: ADHD and ASD share network-level but differ in circuit-level abnormalities underlying inhibitory control deficits. Together, these insights advance the neurobiology of inhibitory control in ADHD and ASD and provide potential targets for neuroscience-informed interventions addressing both shared and disorder-specific mechanisms.

in bioRxiv: Neuroscience on 2025-10-12 00:00:00 UTC.

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A role for prefrontal dopamine signaling in control of goal-directed actions

Impairments in behavioral flexibility commonly found across psychiatric disorders have often been attributed to a dysfunction of the medial prefrontal cortex (mPFC), notably in relation with altered dopamine transmission. However, how dopamine transmission shapes neuronal activity in the mPFC to allow adapting to a changing situation remains largely elusive. Here, we show that dopamine dynamics in the mPFC encode the value of instrumental actions, in particular during reversal learning. Such signal shapes the activity of mPFC dopaminoceptive neurons during reversal learning through the recruitment of heteromers formed by dopamine D1 and D2 receptors with NMDA receptors. In accordance, blockade of either D1/NMDA or D2/NMDA heteromers in the mPFC selectively impairs reversal of outcome identities but not learning and expression of initial action-outcome associations. Our findings provide mechanistic evidence for a central role of dopamine in the mPFC to allow updating goal-directed actions.

in bioRxiv: Neuroscience on 2025-10-12 00:00:00 UTC.

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Spatially patterned cytoskeletal organization shapes astrocyte branch complexity

Astrocytes, the most abundant cells in the brain, extend elaborate branches that enable diverse functions, from synapse maintenance to blood-brain-barrier integrity. The cytoskeletal basis of this architecture has remained unclear, since traditional culturing methods produce minimal branching. Using immunopanning and serum-free conditions, we generated primary rodent astrocytes with in-vivo-like morphology and surveyed their cytoskeleton using confocal microscopy and cryogenic electron tomography. We show that astrocyte microtubules are oriented primarily plus-ends-out. Proximally, microtubules appear stabilized by post-translational modifications (PTMs) and microtubule inner proteins (MIPs). Distal regions lack stabilizing microtubule PTMs, and are enriched in intermediate filament (IF) GFAP. Additionally, diverse actin microstructures, including reticular webbing, extend astrocyte boundaries beyond the microtubule--IF framework. Our results uncover fundamental principles of astrocyte cytoskeletal organization that underlie their intricate branching.

in bioRxiv: Neuroscience on 2025-10-12 00:00:00 UTC.

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Thalamus-cortex interactions drive cell type-specific cortical development in human pluripotent stem cell-derived assembloids

The thalamus plays a pivotal role in the development and function of neural circuits in the cerebral cortex. However, how thalamus-cortex interactions influence human cortical development remains unknown primarily because of the inaccessibility of the human embryonic brain. Here, we demonstrate thalamus-dependent gene expression, circuit organization, and neural activity during corticogenesis using human thalamocortical assembloids (hThCAs). Human cortical and thalamic organoids (hCOs and hThOs) derived from induced pluripotent stem cells exhibited region-specific gene expression and spontaneous neuronal activity. Upon the fusion of these organoids, hThCAs reconstructed reciprocal thalamus-cortex axonal projections and synaptic connections. Transcriptomic analysis revealed thalamus-dependent acceleration of cortical maturation, with upregulation of programs linked to axon development, subplate/cortical plate identity, and activity-regulated genes. Histological analysis showed expanded progenitor pools and increased deep-layer neurons within hThCAs. Wide-field Ca2+ imaging demonstrated that wave-like activity originated in the thalamic region and propagated to the cortical region. Furthermore, two-photon Ca2+ imaging of cortical neurons revealed that synchronous activity emerged exclusively in pyramidal tract (PT) and corticothalamic (CT) neurons, whereas intratelencephalic (IT) neurons remain asynchronous, highlighting cell type-specific circuit integration within hThCAs. These synchronized events were absent in isolated hCOs or in cortico-cortical assembloids, underscoring the specificity of thalamic input. Our findings suggest that diffusible thalamic cues broadly enhance progenitor expansion, while long-range thalamic input organizes cell type-specific synchronous activity. This study demonstrates the thalamus-dependent acquisition of mature cortical phenotypes in a cell type-specific manner in hThCAs, establishing developmental mechanisms linking regional interactions and cell type-specific circuit specification. Thus, hThCAs provide a tractable human platform for dissecting human-specific developmental processes and modeling neurodevelopmental disorders with disrupted thalamocortical communication at the molecular, cellular, and circuit levels.

in bioRxiv: Neuroscience on 2025-10-12 00:00:00 UTC.

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Sensorimotor circuits formed by dI3 neurons have distinct connectivity within and across the lumbar and cervical spinal cord

Journal of Neurophysiology, Ahead of Print.

in Journal of Neurophysiology on 2025-10-11 10:24:47 UTC.

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Single‐Cell RNA‐Seq and Machine Learning Reveal Key Feature Genes of Astrocyte in Perioperative Neurocognitive Disorders

Single-cell RNA-seq of the aged mouse hippocampus, integrated with CellChat, pseudotime analysis, hdWGCNA, and machine learning, reveals astrocyte-specific molecular alterations in perioperative neurocognitive disorders. Four key genes linked to neuroinflammation and cognitive decline were identified, offering promising biomarkers and potential therapeutic targets for PND disease.

ABSTRACT

Perioperative neurocognitive disorder (PND) is common in older patients after anesthesia and surgery, significantly increasing morbidity and mortality. However, the role of astrocytes in its pathogenesis remains limitedly understood. Here, we analyzed 9976 and 9484 single-cell transcriptomes from hippocampal cells of aged mice undergoing PND surgery or sham operation, focusing on astrocytes. We identified 13 distinct clusters corresponding to nine cell types, including astrocytes, microglia, neurons, oligodendrocytes, and other relevant cell populations. Specifically, five astrocyte subclusters were identified, with cluster 0 being the most abundant. Its proportion decreased by 5.51% in the PND surgery condition, showing the largest difference between the groups. Functional enrichment analysis revealed that astrocytes are involved in crucial neurodevelopmental processes and pathways associated with nervous system development and synaptic regulation. Pseudotime analysis placed cluster 0 at the early stage of differentiation, suggesting it as a key responsive population. Gene co-expression network further identified modules with peak activity in cluster 0. By intersecting cluster 0 markers with differentially expressed genes (DEGs) and applying machine learning methods, including LASSO, XGBoost, and Random Forest, we pinpointed four feature genes Dbp, PISD, Id4, and Tsc22d3 with differential expression patterns between surgery and control conditions. Transcription factor activity analysis highlighted distinct regulatory networks in astrocytes, providing insights into their functional differences in response to PND surgery. These findings offer a detailed aged hippocampal landscape of astrocyte dynamics and intercellular communication, contributing to our understanding of neuroinflammation and cognitive dysfunction following surgical stress.

in Journal of Neuroscience Research on 2025-10-11 08:56:32 UTC.

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Functional dissection of the CRP-family transcription factor DevH and its interplay with NtcA in a cyanobacterium

Xu et al. uncovered how duplicated transcription factors DevH and NtcA achieve functional specialization in Anabaena. Unlike NtcA, DevH operates at higher cellular levels with broader regulatory capacity. Their work demonstrates how gene duplication diversifies transcriptional networks to optimize cyanobacterial adaptation.

in Cell Reports: Current Issue on 2025-10-11 00:00:00 UTC.

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Molecular mechanisms governing the formation of distinct Upf1-containing complexes in yeast

Iermak et al. show that the conformational state of yeast Upf1 regulates its constitutive association in an endogenous multimeric complex containing the 5′-3′ mRNA exoribonuclease Xrn1. Structural rearrangement of Upf1 facilitates transition to the Upf1-2-3 complex involved in the activation of nonsense-mediated mRNA decay.

in Cell Reports: Current Issue on 2025-10-11 00:00:00 UTC.

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Paternal SARS-CoV-2 infection impacts sperm small noncoding RNAs and increases anxiety in offspring in a sex-dependent manner

Nature Communications, Published online: 11 October 2025; doi:10.1038/s41467-025-64473-0

Whether paternal pre-conceptual SARS-CoV-2 infection impacts sperm RNA content, or effects offspring phenotypes, has not been previously investigated. Here authors report changes in sperm noncoding RNAs in SARS-CoV-2 infected sires and increased anxiety-like behaviors in offspring.

in Nature Communications on 2025-10-11 00:00:00 UTC.

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Early menopause is associated with reduced global brain activity

Menopause affects the aging process in women through significant ovarian hormone production decline in midlife. Women who experience early menopause face an accelerated physiological aging rate, along with impaired memory and increased risks of neurodegenerative diseases. However, it remains elusive how the timing of menopause affects brain activity, which could be crucial for understanding menopause-related acceleration of aging and increased risk of dementia. Recent studies have revealed a highly structured infra-slow (< 0.1 Hz) global brain activity across species and linked it to arousal and memory functions, as well as waste clearance in Alzheimer's diseases (AD). In this study, we examined how this global brain activity relates to age of menopause using resting-state fMRI data from the Human Connectome Project-Aging dataset. We found that women who experienced earlier menopause (mean menopausal age 45{+/-}3.5 yr) exhibited weaker global brain activity (p = 5.0x10-4) with reduced coupling to cerebrospinal fluid (CSF) flow (p = 0.017) compared to age-matched later-menopausal women (mean menopausal age 54{+/-}1.2 yr). Differences appeared mainly in higher-order brain regions, where activation levels correlated with memory performance in earlier but not in intermediate or later menopausal women. These findings highlight brain activity changes linked to early menopause, suggesting a potential mechanism underlying memory decline and the increased risk of AD and dementias in early-onset menopausal women.

in bioRxiv: Neuroscience on 2025-10-11 00:00:00 UTC.

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Convergent Control of NREM Sleep and Anesthesia by Prefrontal Layer 5 Extratelencephalic Neurons

The cortical mechanisms governing the transition from consciousness to unconsciousness remain poorly understood. While most cortical neurons are suppressed during NREM sleep and anesthesia, we identify a distinct population of prefrontal cortical (PFC) neurons that are preferentially active in both states. Chemogenetic activation of these excitatory NREM- and Anesthesia-Promoting (NAP) neurons enhances anesthetic potency and deepens NREM sleep, whereas their inhibition blunts anesthetic effects. Anatomical, biophysical, and transcriptomic, biophysical, and anatomical analyses reveal that NAPs are Layer 5 extratelencephalic (L5 ET) neurons that form reciprocal connections with subcortical arousal centers including anterior and reticular thalamic nuclei, hypothalamus, and claustrum. Moreover, L5 ET specific recordings and chemogenetic manipulations reproduced NAP-like activity under anesthesia and its ability to promote NREM sleep. These findings define an excitatory, molecularly and anatomically characterized PFC circuit that contributes to loss of consciousness, consistent with a corticothalamic mechanism of arousal-state transitions in sleep and anesthesia.

in bioRxiv: Neuroscience on 2025-10-11 00:00:00 UTC.

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Brain infiltrating T cells mediate microglial dysregulation and neuronal loss following SAH

The contribution of T cells to neuroinflammation after aneurysmal subarachnoid hemorrhage (SAH) remains poorly understood. Using a murine pre-chiasmatic injection model of SAH we demonstrate that T cell infiltration into the brain modulates microglial activation and promotes neuronal death. Targeted transcriptomic profiling revealed a sustained neuroimmune response at 7 days post injury (dpi) characterized by a major involvement of T cells and microglia activation. Immunohistochemistry confirmed focal CD3+ T cell infiltration, predominantly CD4+, in the brain at the site of blood injection (BI), choroid plexus and meninges in SAH mice at 3- and 7-dpi. This temporal pattern was also observed in the CSF of a human SAH cohort. T cell presence spatially correlated with regions of microglial reactivity and neuronal loss. Notably, CD3-knockout mice exhibited reduced microglial activation and preserved neuronal viability. These findings identify T cells as key amplifiers of post-SAH neuroinflammation and neuronal damage. Targeting T cell-microglia crosstalk may represent a novel therapeutic avenue for SAH.

in bioRxiv: Neuroscience on 2025-10-11 00:00:00 UTC.

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Rethinking Alzheimer's: Harnessing Cannabidiol to Modulate IDO and cGAS Pathways for Neuroinflammation Control

Alzheimer's disease (AD) has traditionally been associated with amyloid-β plaques, but growing evidence underscores the role of neuroinflammation in disease progression. The autoinflammatory hypothesis of AD suggests chronic immune dysfunction contributes to neuronal damage, making immune modulation a promising therapeutic strategy. Cannabidiol (CBD), a phytocannabinoid with anti-inflammatory properties, may offer therapeutic potential. This study investigates how CBD independently influences two key neuroinflammatory regulators in AD: the indoleamine 2,3-dioxygenase (IDO) pathway and the cyclic GMP-AMP synthase (cGAS) pathway. Though mechanistically distinct, both shape CNS immune responses. Targeting these immune-metabolic axes provides a mechanistic alternative to amyloid- or tau-based approaches by addressing upstream drivers of neuroinflammation and immune dysregulation. Using the male 5XFAD transgenic AD mouse model, we administered CBD via inhalation and assessed IDO and cGAS expression using flow cytometry, immunofluorescence (IF), and gene expression analysis. We evaluated cytokine levels and used STRING-based bioinformatics to identify CBD-target interactions. CBD treatment significantly reduced IDO and cGAS expression, correlating with decreased proinflammatory cytokines, including TNF-α, IL-1β, and IFN-. Bioinformatics identified potential interactions between CBD and immune targets such as AKT1, TRPV1, and GPR55. These targets were prioritized based on their roles in neuroinflammatory signaling and high-confidence interactions with CBD. AKT1 regulates inflammatory signaling and cell survival, TRPV1 modulates nociception and neuroinflammation, and GPR55 influences immune cell activation. These findings support CBD as a potential monotherapy or adjunctive treatment for AD by targeting distinct neuroinflammatory pathways, including IDO and cGAS. Further studies are warranted to fully explore its therapeutic potential.

in eNeuro on 2025-10-10 16:30:19 UTC.

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Energy Constraints Determine the Selection of Reaching Movement Trajectories in Macaque Monkeys

Reaching movements, while seemingly simple, involve complex motor control mechanisms that select specific trajectories from infinite possibilities. Despite inherent variability in volitional movements, both humans and monkeys frequently exhibit stereotyped trajectories. The literature has offered numerous explanations for invariant trajectory shapes, including a common planning space in hand space or joint space, as well as factors like kinetic energy (KE) minimization and sensory feedback. However, since most studies have relied on single-session data, crucial insights into the motor principles guiding trajectory selection and their evolution through extended practice remain underexplored. This study fills this gap by investigating how specific trajectories are selected and evolve with practice across multiple sessions, using data from two rhesus monkeys (one male, one female) performing a reaching task in a biomechanically constrained 2D setup. Our behavioral study challenges the idea of a common planning space, revealing instead a significant influence of KE on trajectory shapes. Through a novel biomechanical modeling, we quantified KE for a wide range of trajectory shapes. We discovered that trajectory selection and evolution are not simply about minimizing KE or achieving straight paths. Instead, the monkeys’ motor systems appear to prioritize maintaining a "safe KE range," where slight changes in trajectory shapes have minimal impact on energy expenditure. These findings provide new insights into the adaptive motor control strategies, suggesting that trajectory selection involves balancing energy efficiency and flexibility. Our study enhances the understanding of trajectory selection principles, with implications for rehabilitation strategies, robotics, and broader study of motor control mechanisms.

in eNeuro on 2025-10-10 16:30:19 UTC.

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Single-cell RNA sequencing of cerebrospinal fluid reveals the expansion of innate lymphoid cells with upregulated transposable elements in multiple sclerosis [version 1; peer review: awaiting peer review]

Background Multiple sclerosis (MS) is a chronic and often immune-mediated demyelinating disease with no definitive treatment. Transposable elements (TEs) are receiving increasing attention as potential contributors to neurodegenerative diseases. However, to the best of our knowledge, no studies have examined the possible association of TE expression and its potential role in MS pathogenesis at the single-cell level. Results In this study, we reanalyzed single-cell RNA sequencing data from human cerebrospinal fluid (CSF) samples. Our results revealed that TEs are overexpressed in a cluster of cells annotated as innate lymphoid cells (ILCs). Furthermore, enrichment analysis of the associated transcription factors (TFs) with highly upregulated TEs in ILCs revealed the relevance of these TFs to immune pathways and cis-regulatory regions in DNA. Conclusions We propose that upregulated TEs in ILCs are consistent with the plasticity of these cells, as TEs can insert themselves in coding or regulatory regions of immune-related genes and represent themselves as immune-related TF binding sites. We also hypothesize that ILCs with overexpressed TEs could present TE-derived antigens, potentially reactivating T cell-mediated immunity in the central nervous system (CNS) of MS patients. Therefore, this study indicates a possible mechanism involving TEs in ILC plasticity and their potential role in MS pathogenicity. Additionally, we suggest that repurposing nucleoside reverse transcriptase inhibitors (NRTIs) or developing new high-efficacy NRTIs could be a feasible approach to treating MS.

in F1000Research on 2025-10-10 16:13:14 UTC.

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Evaluating artificial intelligence for accurate detection of hand and wrist fractures: a systematic review and meta-analysis [version 1; peer review: awaiting peer review]

Background and Objectives Hand and wrist fractures are among the most frequently encountered injuries in emergency departments and are often misdiagnosed, particularly when interpreted by non-specialist clinicians. These diagnostic errors can lead to treatment delays and long-term complications. Artificial intelligence (AI), particularly deep learning algorithms, is emerging as a promising adjunct to improve diagnostic accuracy in radiographic fracture detection. This study aims to evaluate the effectiveness of Artificial Intelligence (AI) in detecting hand and wrist fractures compared to manual radiographic interpretation by clinicians. Materials and Methods A systematic review and meta-analysis were conducted to assess the diagnostic performance of AI models in detecting hand and wrist fractures compared to conventional radiographic interpretation by clinicians. A comprehensive search of PubMed, Google Scholar, Science Direct, and Wiley Online Library was performed. Eligible studies included those utilizing AI for fracture detection with sensitivity and specificity data. Pooled estimates were calculated using fixed- and random-effects models. Heterogeneity was assessed via I2 statistics, and publication bias was examined using funnel plots and Egger’s test. Results Eighteen studies met inclusion criteria. The pooled sensitivity and specificity under the random-effects model were 0.910 and 0.912, respectively, indicating high diagnostic accuracy of AI models. However, substantial heterogeneity (I2 = 99.09% for sensitivity; 96.43% for specificity) and publication bias were observed, likely due to variations in AI algorithms, sample sizes, and study designs. Conclusions Most AI models demonstrated good diagnostic accuracy, with high sensitivity and specificity scores (≥90%). However, some models fell short in sensitivity and specificity (≤90%), indicating performance variations across different AI models or algorithms. From a clinical perspective, AI models with lower sensitivity scores may fail to detect hand and wrist fractures, potentially delaying treatment, while those with lower specificity scores could lead to unnecessary interventions—treating hands and wrists that are not fractured.

in F1000Research on 2025-10-10 16:11:04 UTC.

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Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. (Euphorbiaceae) 'Sweet stick' leaves in Rattus rattus var. albinus [version 3; peer review: 2 approved, 1 not approved]

Introduction Diabetes mellitus (DM) is a chronic metabolic disease representing a global public health concern and is associated with severe complications such as cardiovascular and renal diseases. Although several species of the genus Acalypha have demonstrated biological activity, no prior studies have evaluated the hypoglycemic effect of Acalypha argomuelleri Briq., making this study relevant. Method The hypoglycemic effect of the aqueous leaf extract of A. argomuelleri Briq. (AAAE) was evaluated in an experimental model using Rattus rattus var. albinus (males). A randomized, prospective design was employed, consisting of a control group and three treatment groups receiving doses of 100, 150, and 300 mg/kg of the extract, respectively. Hyperglycemia was induced via oral glucose administration. Results The qualitative phytochemical analysis of AAAE revealed the presence of flavonoids, phenols, cardiotonic glycosides, and diterpenes, with no reducing sugars. The 300 mg/kg dose produced a significant and sustained reduction in blood glucose levels, reaching near-normal values at 90 minutes, demonstrating a dose- and time-dependent hypoglycemic effect. Discussion The study confirmed that AAAE has a dose-dependent hypoglycemic effect, with optimal efficacy at 300 mg/kg. This dose showed a faster and more sustained reduction in glucose levels compared to 100 and 150 mg/kg, suggesting higher efficacy at elevated concentrations. The identified flavonoids and phenols, associated with glucose metabolism modulation and pancreatic β-cell protection, likely explain the observed effect. The absence of reducing sugars indicates the hypoglycemic effect is linked to secondary metabolites. Conclusions The AAAE exhibited a significant dose- and time-dependent hypoglycemic effect, with optimal efficacy at 300 mg/kg after 90 minutes. These findings support the potential of A. argomuelleri Briq. as a natural alternative for blood glucose control, though further studies are needed to assess its safety and efficacy in clinical models.

in F1000Research on 2025-10-10 16:09:26 UTC.

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Project-based learning in mathematics and science: a review of contributions, prevalence, and challenges [version 1; peer review: awaiting peer review]

The integration of project-based learning (PjBL) in Mathematics and Science has received much attention because of its potential to engage students and expose them in real-world problem-solving. However, research examining the contributions, prevalence, and challenges of Project-Based Learning in mathematics and science remains limited. This review employed a systematic review approach, with articles systematically retrieved from multiple academic databases to investigate the contributions, prevalence, and challenges of PjBL in Mathematics and science education. Thus, 202 articles downloaded from Google Scholar, Academia, Search 4 Life, Scopus, and Web of Science databases. Through the filtering process, 20 articles fell into the study’s scope and were considered and used for analysis. The results from the reviewed studies showed that project-based learning contributes to enhancing students’ engagement, creativity, communication, and conceptual understanding in Mathematics and Sciences. Also, the reviewed literature showed that PjBL dominates in Mathematics and Physics with the highest prevalence of 35% each in applying PjBL pedagogy. Integrated Science shows 10% of prevalence, while Chemistry records the least with only 5%. Nevertheless, challenges such as limited resources, rigid curriculum, and inadequate teacher training on monitoring students’ projects and providing adequate assessment were also identified. This study recommends a need for teacher training and resources mobilization in schools support educators to effectively embrace Project-based learning pedagocy in mathematics and science subjects.

in F1000Research on 2025-10-10 16:08:13 UTC.

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Exploring the relationship between student-content interaction, student-student interaction, self-efficacy, and learning achievements in a student-centered classroom [version 2; peer review: 1 approved, 1 approved with reservations]

Background With the growing mismatch between traditional academic training and the demands of the modern workforce, student-centered education has emerged as a key reform in higher education. This study examines the relationships among student-content interaction, student-student interaction, self-efficacy, and learning achievement in student-centered classrooms at Chinese application-oriented universities. Methods Data were collected from 524 undergraduate students via online questionnaires and analyzed using Confirmatory Factor Analysis (CFA) and Structural Equation Modeling (SEM). Results The results indicate that both student-content and student-student interactions significantly enhance learning achievement, with self-efficacy playing a critical mediating role. Higher levels of self-efficacy were also directly associated with improved academic achievement, underscoring its central importance in student success. Conclusions These findings highlight the value of fostering interactive learning environments and promoting the development of self-efficacy to improve educational outcomes. Educators are encouraged to implement instructional strategies that facilitate meaningful engagement, thereby supporting both the cognitive and motivational dimensions of learning. This study provides empirical evidence to inform the design of effective student-centered teaching practices in higher education.

in F1000Research on 2025-10-10 16:07:03 UTC.

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Exploring the Potential of Peptides Derived from the Coelomic Fluid of Echinometra lucunter Targeting Inflammatory Cytokines in Placental Syndromes: In Silico Study [version 1; peer review: awaiting peer review]

Background Placental syndromes—encompassing pregnancy loss, preterm birth, gestational diabetes mellitus, and preeclampsia—have been strongly linked to dysregulated inflammatory responses at the maternal–fetal interface. This study aims to explore the potential of peptides derived from the coelomic fluid of Echinometra lucunter targeting the inflammatory cytokines involved in placental syndromes using in silico approaches. Methods The 3D molecular structure of peptides was modeled using the UCSF Chimera application. The absorption, distribution, metabolism, and excretion (ADMET) properties were analysed using SwissADME and the ProTox web server. The PerMM web server was used to estimate membrane permeability. Crystal structures of target proteins—including c-Met, Interleukin-1β (IL-1β), Interleukin-10 (IL-10), Macrophage Migration Inhibitory Factor (MIF), Platelet-Derived Growth Factor (PDGF), and TNF-Related Apoptosis-Inducing Ligand (TRAIL)—were obtained from the Protein Data Bank Japan (PDBj). Molecular docking and structural visualization were conducted using Molecular Operating Environment (MOE) software, while molecular dynamics simulations were subsequently performed using the YASARA Dynamics software to assess the stability and conformational behavior of the ligand-receptor complexes. Results Peptide A was selected based on favorable ADMET properties. Molecular docking results revealed that Peptide A exhibits low binding affinities toward pro-inflammatory mediators, including TRAIL (–10.02 kcal/mol), MIF (–9.32 kcal/mol), IL-1β (–8.29 kcal/mol), and PDGF (–10.44 kcal/mol). Furthermore, Peptide A showed potential agonistic interactions with IL-10 (–10.26 kcal/mol) and c-Met (–9.27 kcal/mol), indicating a possible role in restoring anti-inflammatory and angiogenic signaling. Molecular dynamics simulations supported the stability of the peptide–receptor complexes. Conclusions Peptide A holds promise as a dual-function therapeutic agent in placental syndromes. However, experimental validation is necessary to confirm its biological efficacy and safety.

in F1000Research on 2025-10-10 16:04:04 UTC.

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Differential equation modeling of cell population dynamics in skeletal muscle regeneration from single-cell transcriptomic data

by Renad Al-Ghazawi, Hassan Lezzeik, Xiaojian Shao, Theodore J. Perkins

Skeletal muscle regeneration is a complex process orchestrated by diverse cell populations within a dynamic niche. In response to muscle damage and intercellular signaling, these cells undergo cell fate and migration decisions including quiescence, activation, proliferation, differentiation, infiltration, apoptosis, and exfiltration. The emergence of single-cell RNA sequencing (scRNA-seq) studies of muscle regeneration offers a significant opportunity to refine models of regeneration and enhance our understanding of cellular interactions. To better understand how crosstalk between cell types governs cell fate decisions and cell population dynamics, we developed a novel non-linear ordinary differential equation model guided by scRNA-seq data. Our model consists of 9 variables and 17 parameters, capturing the dynamics of key myogenic lineage and immune cell types. We calibrated time-series scRNA-seq data to units of cells per cubic millimeter of tissue and fit our model’s parameters to capture the observed dynamics, validating on an independent time series. The model successfully captures key features of regeneration dynamics, particularly after incorporating a novel regulatory interaction between M2 macrophages and satellite cells that has been hypothesized in the literature. Our model lays a foundation for future computational explorations of muscle regeneration, modeling of disease conditions, and in silico testing of therapeutic strategies.

in PLoS Computational Biology on 2025-10-10 14:00:00 UTC.

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Learning spatial hearing via innate mechanisms

by Yang Chu, Wayne Luk, Dan F. M. Goodman

The acoustic cues used by humans and other animals to localise sounds are subtle, and change throughout our lifetime. This means that we need to constantly relearn or recalibrate our sound localisation circuit. This is often thought of as a “supervised” learning process where a “teacher” (for example, a parent, or your visual system) tells you whether or not you guessed the location correctly, and you use this information to update your localiser. However, there is not always an obvious teacher (for example in babies or blind people). Using computational models, we showed that approximate feedback from a simple innate circuit, such as that can distinguish left from right (e.g. the auditory orienting response), is sufficient to learn an accurate full-range sound localiser. Moreover, using this mechanism in addition to supervised learning can more robustly maintain the adaptive neural representation. We find several possible neural mechanisms that could underlie this type of learning, and hypothesise that multiple mechanisms may be present and provide examples in which these mechanisms can interact with each other. We conclude that when studying spatial hearing, we should not assume that the only source of learning is from the visual system or other supervisory signals. Further study of the proposed mechanisms could allow us to design better rehabilitation programmes to accelerate relearning/recalibration of spatial hearing.

in PLoS Computational Biology on 2025-10-10 14:00:00 UTC.

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Epstein–Barr Virus, Lower Vitamin D, Low Sun Exposure, and HLA‐DRB1*1501 Risk Variant Share Common Epigenetic Pathways Leading to Multiple Sclerosis Onset

Objectives

Multiple sclerosis (MS) onset risk factors include Epstein–Barr virus (EBV) indices (including host response), lower serum 25-vitamin D (25(OH)D) levels, low sun exposure, and HLA-DRB1*1501. The underlying molecular mechanisms are unclear. Here, we examined mediation through differential DNA methylation (DNAm) to better understand possible epigenetic programming.

Methods

Two case-control studies (Ausimmune Study, Australia = 206 cases + 348 controls; and Epidemiologic Investigations of MS [EIMS], Sweden = 140 cases + 139 controls). DNAm was measured using Illumina arrays. Dimension-reduction methods generated MS-associated DNAm modules. Pathway enrichment analyses were used to describe DNAm modules’ system-level biological characteristics. Individual and joint associations with MS risk were assessed using logistic regression. DNAm module mediation of risk factor-outcome associations were assessed using mediation analysis. A range of temporality analyses were used.

Results

EBV indices (infectious mononucleosis history and anti-EBNA IgG titer), lower 25(OH)D, low sun exposure, and HLA-DRB1*1501 risk variant were individually and jointly associated with MS risk. In each study, 2 DNAm modules were found which mediated multiple exposure-MS associations. Proportions mediated ranged from 21 to 47% in Ausimmune and 25 to 53% in EIMS. Results were robust to sensitivity analyses. Top-ranked genomewide association study (GWAS) MS risk-associated genes were over-represented in both Ausimmune DNAm modules, A1 3.5-fold (p = 0.004) and A2 3-fold (p = 0.015). Reactome pathways enriched for DNAm had cross-study overlap – 45% of pathways enriched in Ausimmune DNAm modules were also enriched in EIMS (4.82-fold, p < 0.001).

Interpretation

EBV, lower vitamin D, low sun exposure, and HLA-DRB1*1501 risk variant act in concert and through common epigenetic pathways to impact MS onset risk. ANN NEUROL 2025

in Annals of Neurology on 2025-10-10 11:21:01 UTC.

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Letter on the Role of Electroencephalography in Predicting Post‐Stroke Seizures and an Updated Prognostic Model (SeLECT‐EEG)

in Annals of Neurology on 2025-10-10 10:16:25 UTC.

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Reply to “The Role of EEG in Predicting Post‐Stroke Seizures and an Updated Prognostic Model (SeLECT‐EEG)”

in Annals of Neurology on 2025-10-10 10:15:47 UTC.

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Inter- and intrahemispheric sources of vestibular signals to V1

Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025.
SignificanceInformation about head motion is fundamental to the visual interpretation of our environment. Indeed, head motion signals originating from the vestibular system robustly modulate activity in the visual cortex (VC). Despite this profound ...

in PNAS on 2025-10-10 07:00:00 UTC.

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A midbrain-to-ventral-striatum dopaminergic pathway orchestrates odor-guided insect predation in mice

Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025.
SignificanceUnderstanding how predators identify and select nutritious prey is fundamental to deciphering interspecies interactions and energy flow within ecosystems. This study reveals that both laboratory and wild rodents preferentially feed on ...

in PNAS on 2025-10-10 07:00:00 UTC.

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Activity-dependent citrate dynamics in neurons

Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025.
SignificanceDifficulty in quantifying the small-molecule modulators of glycolysis dynamically and in specific compartments of live cells limits our understanding of metabolic regulation. We engineered a quantitative fluorescent biosensor to study the ...

in PNAS on 2025-10-10 07:00:00 UTC.

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