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Frontiers in Integrative Neuroscience

Frontiers Media SA

Preprints posted in the last 30 days, ranked by how well they match Frontiers in Integrative Neuroscience's content profile, based on 15 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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The Real-World Impact of Concussions on the Neuropsychological and Menstrual Health of Women

Ravi, P.; Yad-El Ugboji, A.; Osborne, G.; Jokhadze, M.; Oleka, B.; Fatima, F.; Niyomugabo, C.; Snook, M.; Tinney, E. M.; Espana-Irla, G.; Huang, K.-T.; Anto-Ocrah, M.

2026-08-26 neurology 10.64898/2026.08.21.26361020 medRxiv
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Objective: To evaluate long-term neurological, mental, and menstrual health outcomes using a mixed-methods approach among women approximately 2 years after concussion compared with non-head-injured controls. Setting: Participants were recruited from [University X] sites, including the Concussion Clinic, Emergency Departments, Student Health Clinic, and [University X] + Me registry (April 2023 to September 2025). Follow-up occurred October to November 2025. Participants: Eligible participants were assigned female at birth, aged 18 to 45 years, not using hormonal birth control, and, for the concussion group, diagnosed within 7 days of injury. Of 45 concussion patients and 29 controls recruited, 11 concussion patients (mean age 30.4 +/- 8.4 years) and 16 controls (31.3 +/- 7.4 years) completed follow-up. Main Measures: Post-concussion symptoms were assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), depression using the Patient Health Questionnaire-9 (PHQ-9), and anxiety using the Generalized Anxiety Disorder-7 (GAD-7). Menstrual health was assessed using study-specific measures. Qualitative data captured perceived impacts on daily life, with recurring themes summarized using word clouds. Results: At follow-up, concussion patients reported significantly greater symptom burden (RPQ: 31.6 +/- 13.5 vs 9.4 +/- 9.8; p=0.0002; Hedges g=1.90), depression (PHQ-9: 9.5 +/- 6.5 vs 2.3 +/- 2.2; p=0.0005; g=1.60), and anxiety (GAD-7: 9.8 +/- 6.8 vs 2.8 +/- 3.0; p=0.0057; g=1.42). Qualitative findings highlighted persistent headaches, sleep difficulties, reduced interest, and effects on relationships and daily functioning. Conclusions: This study demonstrates significant long-term differences in symptom burden among women with concussions compared to controls. Findings highlight the importance of understanding real-world impacts to improve long-term care.

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Association of the EEG Correlate Of Injury to the Nervous System (COIN) Index with Focal Cerebral Injury in Children Receiving Extracorporeal Membrane Oxygenation

Ghasemzadeh, R.; Finlay, K.; Li, Y.; Numis, A. L.; Jain, R.; Amorim, E.; Benedetti, G. M.; Press, C.; Harrar, D. B.; Thomas, A. X.; Sacks, L. D.; Fox, C. K.; Caffarelli, M.

2026-08-10 neurology 10.64898/2026.08.06.26359920 medRxiv
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BACKGROUND Children receiving extracorporeal membrane oxygenation (ECMO) are at high risk for focal cerebral injury (FCI). There is emerging evidence that electroencephalography (EEG) may aid FCI detection. The EEG Correlate of Injury to the Nervous System (COIN) index quantifies and displays focal background asymmetries. We evaluated whether COIN is associated with FCI in pediatric ECMO. METHODS Retrospective, cross-sectional study of patients age 28 days to 21 years, on venoarterial ECMO at a tertiary children's hospital, who received EEG monitoring and neuroimaging during ECMO. COIN was calculated from all available EEG data. COIN of 0 implies a symmetric EEG and negative COIN values are observed with FCI. Median COIN values near FCI recognition time were compared to median COIN values from randomly selected control EEG batches using logistic regression. A receiver operator characteristic curve was used to identify multilevel FCI test ranges. Likelihood ratios were calculated to estimate the posttest FCI probability for each COIN range. RESULTS During the 8-year study period (2015-2023), 33 of 142 ECMO runs met study criteria for COIN analysis. Twelve patients (36%) had FCI. The COIN cutoff of -13.3 had 92% sensitivity and 67% specificity for FCI. The COIN cutoff of -27.7 had 67% sensitivity and 90% specificity. Likelihood ratios were 0.13 for COIN (0 to -13.3), 1.1 for COIN (-13.3 to -27.7), and 7.0 for COIN (< -27.7). Posttest probability was 0.02, 0.13, 0.49 in each respective range. CONCLUSION FCI on ECMO is associated with COIN-measured EEG asymmetry. COIN may support FCI risk-stratification during ECMO.

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Parent-mediated interventions versus usual care in children with autism: A systematic review with meta-analysis and Trial Sequential Analysis

Conrad, C. E.; Ziegler, S.; Bilenberg, N.; Chistiansen, J.; Davidsen, K. A.; Fagerlund, B.; Faerk, E.; Jakobsen, H.; Jakobsen, R. H.; Jeppesen, P.; Kamp, C.; Kilburn, T. R.; Thomsen, P. H.; Varenne, M.; Vestergaard, M.; Jakobsen, J. C.; Lauritsen, M. B.

2026-08-10 psychiatry and clinical psychology 10.64898/2026.08.06.26357818 medRxiv
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Objectives To evaluate the positive and adverse effects of parent-mediated interventions (PMIs) versus care as usual for children with autism. Setting Systematic review and meta-analysis and Trial Sequential Analyses (TSA), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods We searched for randomised clinical trials of PMIs for children with autism in the databases CENTRAL, EMBASE, LILACS, PsycINFO, MEDLINE, and SCI-EXPANDED (up to 13 August, 2025), complemented with manual searches. 12,359 articles were screened. Data were synthesised using meta-analyses and Trial Sequential Analyses (TSA), and risks of bias and certainty of the evidence were evaluated. Primary and secondary outcome measures The primary outcome was autism characteristics. Secondary outcomes were adverse effects, child adaptive functioning, child language, child and parent quality of life, and parental stress. Ten exploratory outcomes were included. Results 32 trials (N=1,625) comparing PMIs to usual care, waiting list, or no intervention were included. All trials had a high risk of bias. The multiplicity-adjusted threshold for statistical significance was p = 0.013 due to the number of outcomes. Meta-analyses and TSAs showed it could be rejected that PMIs reduced autism characteristics (MD = -0.88; 95% confidence interval -2.92 to 1.15; p = 0.05, 4 trials, N=353, low certainty), child adaptive functioning (7 trials, N=408), child language (4 trials, N=308), or parental stress (7 trials, N=385). Due to insufficient data, the remaining secondary meta-analyses could not be conducted. Meta-analyses of exploratory outcomes showed beneficial effects concerning child behaviour problems and parent sensitivity/synchronicity. Conclusions This meta-analysis found no benefits of PMIs on child autism characteristics, child adaptive functioning, child language, or parental stress. Benefits were found in reduction of child behaviour problems and improved parent sensitivity/synchronicity. The evidence remains uncertain, and more trials including outcomes of adverse effects and quality of life are needed.

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When are Biomedical Postdocs Ready for the Faculty Job Market? A Mixed-Methods Analysis of Metrics and Resilience Among Faculty Job Seekers

Haage, A.; Cheng, Y.; Smith, C. T.; Kozik, A. J.; Hagan, A. K.; Jadavji, N. M.

2026-08-21 scientific communication and education 10.64898/2026.08.14.744880 medRxiv
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PurposeDiscussions surrounding the biomedical faculty job market often focus on applicant competitiveness and external metrics such as number of publications and funding records. Consequently, there is typically less discussion about applicant readiness, the point at which applicants perceive themselves as prepared to enter the market. Since 2018 our group, the Faculty Job Market Collaboration (FJMC), has conducted annual end-of-cycle surveys of biomedical faculty job applicants, producing the largest longitudinal dataset on this process to date. MethodsWe employed a mixed-methods design examining faculty applicants in biological science fields in North America. Regression analyses were conducted on a longitudinal dataset of 729 respondents across multiple hiring cycles. To determine how applicants evaluated their own preparation, qualitative interviews were conducted with a separate cohort of biomedical postdoctoral applicants during the 2024-2026 job cycles. ResultsOur findings demonstrate that rather than depending on a single quantitative threshold, readiness is a multifaceted construct shaped by actionable and interpersonal drivers. Key factors influencing an applicants perceived readiness include taking agency to submit applications, receiving explicit support from a mentor, incorporating strategic use of artificial intelligence tools into application preparation, and their career stage. ConclusionBy distinguishing individual readiness from systemic assumptions of market competitiveness, this study highlights a blind spot in academic workforce development. Our results suggest that applicants can achieve readiness and successful outcomes through different combinations of support, strategy, and timing rather than a uniform metric profile. By integrating quantitative and qualitative data, our study provides an evidence-based framework for understanding applicant readiness and offers practical guidance to help trainees navigate the increasingly competitive academic job market. Teaser TextOur mixed-model analysis of the biomedical faculty job market is designed to help prospective faculty candidates assess their readiness to enter the job market. By integrating multiple indicators of academic productivity, funding success, and professional experience, our study provides evidence-based benchmarks that can guide applicants in evaluating their competitiveness and identifying areas for further development before pursuing faculty positions.

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The Psychological Footprint of Unruptured Intracranial Aneurysm Discovery

Renedo, D.; Chen, H.; Sheth, K. N.; Gandhi, D.; Malhotra, A.; Matouk, C. C.

2026-08-31 neurology 10.64898/2026.08.25.26361377 medRxiv
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Background: Unruptured intracranial aneurysms (UIAs) are increasingly identified incidentally, and management balances rupture risk against treatment risk. UIA diagnosis has been linked to psychological distress, but psychotropic medication initiation after UIA discovery has not been compared across the full UIA management spectrum. Methods: We conducted a retrospective cohort study using IBM MarketScan claims (CCAE, MDCD, and MDCR; 2009-2023) among adults with a UIA diagnosis, continuous enrollment for 365 days before and after the index date, and no SAH/rupture on or before the index date. We compared the prevalence of 6 mental-health diagnoses before versus after UIA discovery and used adjusted logistic regression to examine psychotropic medication initiation within 365 days by management strategy (untreated observation as the reference). Results: Among 54,945 patients (untreated, 78.5%; endovascular, 11.3%; clipping, 3.0%; other/uncertain, 7.2%), prevalence of every mental-health diagnosis was higher after UIA discovery, most for depression (+4.6 percentage points) and anxiety (+4.5 points). Medication initiation was most common for benzodiazepines (8.7%). Endovascular treatment was associated with higher adjusted odds of benzodiazepine (aOR, 1.21), SSRI (aOR, 1.20), and sedative-hypnotic (aOR, 1.25) initiation.Surgical clipping demonstrated the broadest association, with higher odds across 5 of 6 classes, including benzodiazepines (aOR, 1.71) and sedative-hypnotics (aOR, 1.86). Benzodiazepines had the lowest 1-year persistence (10.5%) despite being the most commonly initiated class. Findings were consistent across sensitivity analyses, with the exception of the increase in panic disorder, which was no longer observed after applying a 30-day post-index lag. Conclusions: Mental-health diagnoses and psychotropic medication initiation increased after UIA discovery, and medication initiation was most pronounced among patients treated with surgical clipping. These findings support psychological assessment as part of aneurysm management regardless of strategy.

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Evaluating cranial electrotherapy stimulation for anxiety associated with breathlessness in palliative care: a mixed-methods feasibility study

Bleazard, L.; Copping, S. R.; Booth, S.; Gray, L. J.; Faull, C.; Walker, K.; Griffiths, C.; Wenzel, D.

2026-08-25 palliative medicine 10.64898/2026.08.22.26361094 medRxiv
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Objectives To explore the acceptability and tolerability of cranial electrotherapy stimulation (CES) using Alpha-Stim AID as a potential intervention for anxiety associated with breathlessness in people with advanced chronic respiratory disease. Methods A multicentre, mixed-methods, non-randomised interventional feasibility study with a parallel usual-care control group. Participants were adults with chronic respiratory disease and significant anxiety and breathlessness symptoms (assessed via Integrated Palliative Outcome Scale) receiving care from hospice services. The intervention groups used Alpha-Stim AID for eight weeks either at a fixed or personalised dose, followed by a four-week follow-up period. This feasibility study was not powered to assess clinical efficacy. Results 12.5% of screened patients at the primary site were eligible, and 29 unique participants were recruited. Three participants withdrew from the study (10.3%), none of which were attributable to CES. Most adverse events were mild, with headache reported frequently across control and intervention groups. Outcome measure completion was high, with data missingness below 6.4%. Numerical rating scales of anxiety and breathlessness fluctuated daily and remained broadly static, whereas GAD-7 scores assessing anxiety improved over time across all groups. This feasibility study was not powered to assess clinical efficacy. Conclusion CES using Alpha-Stim AID was deliverable within hospice services and was generally acceptable and tolerable among participants who enrolled. Our findings support further evaluation which should involve a fully-powered randomised controlled trial against a sham device to determine whether CES provides clinically meaningful improvements in anxiety for this patient population.

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Statistical analysis plan for the "Pharyngeal electrical stimulation for acute stroke dysphagia trial" (PhEAST) (ISRCTN98886991)

Woodhouse, L. J.; Mhlanga, I. I.; Roadevin, C.; Benfield, J. K.; Everton, L. F.; Wilkinson, G.; Greatrex, S.; Skinner, C. J.; Squires, G.; Buck, A.; Latulipe, C.; Cadman, K. M.; Sprigg, N.; Krishnan, K.; Appleton, J. P.; Matz, K.; Iversen, H. K.; Mistry, S.; James, M.; England, T. J.; Hamdy, S.; Montgomery, A. A.; Bath, P. M.

2026-08-12 neurology 10.64898/2026.08.11.26360004 medRxiv
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Introduction Post stroke dysphagia is common, associated with poor functional outcome and lacks treatment strategies beyond behaviour therapies delivered by speech & language therapists. Here, we present the statistical analysis plan for the ongoing pharyngeal electrical stimulation for acute stroke dysphagia trial (PhEAST). PES is a candidate treatment for dysphagia present in non-ventilated stroke patients. Methods PhEAST is an investigator-initiated international prospective randomised open-label blinded-endpoint phase-4 superiority trial involving 650 participants with tube-dependent post-stroke dysphagia. Consenting patients are randomised to PES versus no PES given on top of standard care with PES given daily for 6 days. The primary outcome is the dysphagia severity rating scale (DSRS), a measure of swallowing impairment, made at days 14 and 90 and analysed using repeated measures regression. Conclusion We present the statistical analysis plan for the main analyses based on data up to day 90 along with planned secondary analyses including presentation of baseline data, health economics, cognition and extended follow-up to 12 months.

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A wireless modular platform for neuro-behavioral recording and closed-loop manipulation in small animals

Zhao, Z.; Chang, H.; Paudel, P.; Park, J.; Liu, C.; Aurelio, M. Q.; Oliva, A.; Fernandez-Ruiz, A.

2026-08-30 neuroscience 10.64898/2026.08.25.747153 medRxiv
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Investigating the neural mechanisms of social group interactions and other naturalistic behaviors in small animals remains limited by current technology. Tethered neural recording systems are incompatible with many of these behaviors, while existing wireless devices for small animals are constrained by weight, bandwidth, recording duration, and the lack of closed-loop modulation capabilities. To overcome these limitations, we developed a Wireless, Interactive, Lightweight Datalogger (WILD) with integrated flexible neural probes, optogenetics, an inertial measurement unit, an ultrasonic microphone, and a head-mounted camera. This platform enables simultaneous, long-term recording of neural activity, locomotor variables, vocalizations, and eye movements from groups of freely moving mice in both laboratory and outdoor settings. Model-based real-time signal processing detects specific neural events and behavioral motifs to trigger closed-loop neural interventions. By combining multimodal recordings with advanced onboard signal-processing capabilities in a compact device, WILD enables the investigation of neural mechanisms underlying a broad range of natural behaviors in small animals.

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The impact of hormonal changes on Functional Neurological Disorder: An International Online Survey

von der Weid, L.; Concetti, C.; Di Vico, I. A.; Balint, B.; Barbey, A.; Bertaina, I.; Coebergh, J.; Corral, C.; da Costa, L.; D Andrea, L.; Efthymiou, E.; Gandolfi, M.; Gharib, A.; Gilmour, G. S.; Kern, D.; Kanaan, R. A.; Lehn, A.; L'Erario, Z. P.; Palmer, D. D. G.; Schwingenschuh, P.; Stancu, C.; Tinazzi, M.; Weissbach, A.; Hoeritzauer, I.; Aybek, S.

2026-08-18 neurology 10.64898/2026.08.17.26360584 medRxiv
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Introduction: Functional Neurological Disorder (FND) affects women approximately three times more often than men. This disparity has largely been attributed to higher trauma prevalence and diagnostic bias, while the potential contribution of hormonal influences has received little attention. Methods: An online questionnaire was distributed through FND clinics in thirteen countries, assessing self-reported symptom change across five hormonal events: hormonal contraception, pregnancy, the menstrual cycle, menopause, and gender-affirming hormone therapy. Eligible participants were cisgender women with a diagnosis of FND, or gender minority individuals (transgender or non-binary). Perceived symptom change was rated on a five-point scale ranging from large improvement to large worsening. Results: Among 262 respondents (96% female; mean age 39 years), several hormonal contexts were associated with self-reported symptom changes. Overall, hormonal contraception and pregnancy were frequently associated with worsening of motor and cognitive symptoms, and menopause with worsening across all symptom domains. Menstrual cycle analysis revealed a phase-dependent pattern: worsening was most frequently reported during menstruation and the luteal phase, whereas improvement was most frequent during the follicular phase. Reported changes were not uniform, with a substantial proportion of participants describing no change or improvement. Conclusion: Self-reported FND symptom severity appears to vary with hormonal context, with motor and cognitive symptoms most consistently affected. Given the retrospective, self-report design, these findings are hypothesis-generating and support prospective research into the role of hormonal transitions in FND.

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Elucidating the Role of Cerebellar Nuclei Parvalbumin Activity on Adolescent Reversal Learning

Lyle, T.; Berkley, A.; Verpeut, J.

2026-08-25 neuroscience 10.64898/2026.08.20.746009 medRxiv
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The cerebellar nuclei (CN) has demonstrated its influence on cognitive behavior via the cerebello-cortico circuit, yet the role of CN critical period mechanisms and how they may influence cognitive behavior, such as parvalbumin (PV) expressing interneurons enwrapped by perineuronal nets (PNNs), is still unclear. Therefore, we investigated the role of the lateral CN (LCN) PV cell calcium activity while animals performed a visual discrimination touchscreen cognitive task. All animals received the PV cell calcium indicator GCaMP6f at postnatal day 21 (P21). We targeted the LCN critical period by manipulating neural activity in male mice using the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) from postnatal day 21 to 35 or by injecting an Hapln1-AAV vector to selectively target LCN PNN development. After animals completed the visual discrimination task, cerebellar tissue was collected for viral recovery and antibody staining for PNN components, Hapln1 and aggrecan. Results revealed DREADD animals showed improved reversal learning, an increase in calcium response to learning-related activity and altered PNN expression (Hapln1 and aggrecan). Hapln1 treated animals displayed a decrease in final day acquisition performance, lower reversal performance compared to DREADD groups, a decrease in reversal calcium learning-related activity, and an increase in PNN expression (Hapln1). Together, these data provide further evidence of LCN mechanisms associated with learning as well as the importance of understanding region-specific critical periods of plasticity.

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Prevalence of the photic sneeze reflex: A systematic review and meta-analysis

Trinkl, J.; Munkwitz, S.; Bickerstaff, L.; Eto, T.; Spitschan, M.

2026-08-12 neurology 10.64898/2026.08.10.26359569 medRxiv
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The photic sneeze reflex (PSR), in which exposure to bright light triggers sneezing, is widely recognised but inconsistently defined and measured. We conducted the first systematic review and meta-analysis of PSR prevalence to synthesise the epidemiological evidence, assess methodological quality, and identify priorities for future research. We included 18 articles comprising 31 study groups and extracted prevalence estimates, study characteristics, ascertainment methods, and epidemiological information. Fifteen eligible study groups classified as healthy were included in the primary meta-analysis. The pooled prevalence was 22% (95% CI, 15%-29%), with extreme between-study heterogeneity (I2 = 99.3%). Reported prevalence estimates and associations with participant characteristics varied widely, and nearly all studies were judged to be at high risk of bias. The pooled estimate should therefore be interpreted as a descriptive summary of the available evidence rather than a precise estimate of population prevalence. Future studies require a standardised operational definition, representative sampling, transparent reporting, and reproducible methods for assessing light-triggered sneezing.

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Domain-Specific Effects of GABA-Modulating Pharmacotherapies in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Palakodeti, S.; Hinduja, K. K.; Misra, G.; R, S.; Pabbaraju, A.; Balaji, B. S.; Parmar, T.

2026-08-23 neurology 10.64898/2026.08.23.26361086 medRxiv
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Background: Altered gamma-aminobutyric acid (GABA) neurotransmission is a proposed mechanism underlying autism spectrum disorder (ASD), prompting evaluation of several GABA-modulating pharmacotherapies. However, it remains unclear whether these interventions improve ASD broadly or preferentially affect specific symptom domains. Methods: We conducted a systematic review and random-effects meta-analysis of randomized controlled trials evaluating GABA-modulating pharmacotherapies in individuals with ASD. PubMed/MEDLINE, Embase, Scopus, and CENTRAL were searched from inception to April 1, 2026. Outcomes were prespecified as global autism severity, social communication, functional communication, restricted and repetitive behaviours (RRBs), adaptive behaviour, and irritability. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using GRADE. Results: Thirteen randomized controlled trials evaluating three GABA-modulating interventions (bumetanide, arbaclofen, and valproate) were included. GABA-modulating therapies were associated with statistically significant improvements in global autism severity (Hedges' g = -0.25, 95% CI -0.46 to -0.03; p = 0.028) and adaptive behaviour (Hedges' g = -0.09, 95% CI -0.15 to -0.02; p = 0.023). No significant pooled effects were observed for social communication (Hedges' g = -0.26, p = 0.077), functional communication (Hedges' g = -0.01, p = 0.869), RRBs (Hedges' g = -0.21, p = 0.126), or irritability (Hedges' g = -0.07, p = 0.543). After Holm-Bonferroni step down procedure, neither global autism severity nor adaptive behaviour remained statistically significant (Holm-adjusted p = .140 and .138, respectively). Adverse events were predominantly gastrointestinal, neurological, metabolic, and appetite-related. Overall risk of bias was variable, and the certainty of evidence ranged from very low to moderate. Conclusions: GABA-modulating pharmacotherapies did not demonstrate a robust, multiplicity-corrected benefit in any of the six prespecified ASD symptom domains. Nominal, unadjusted improvements in global autism severity and adaptive behaviour did not withstand correction for multiple comparisons and should be regarded as hypothesis-generating rather than confirmatory. Larger, adequately powered randomized trials using standardized domain-specific outcome measures are needed to determine whether individual GABA-modulating agents provide clinically meaningful benefit.

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Testing Claimed Associations of Prenatal Acetaminophen with Neurodevelopmental Disorders: Re-analysis Using Bias-Correction Methods

Grover, A.; Reis-Pardal, J.; Ellis, R. J.; Ioannidis, J.; Patel, C. J.

2026-09-04 epidemiology 10.64898/2026.08.28.26361666 medRxiv
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Background: A 2025 systematic review concluded there was "strong evidence of a likely relationship" between prenatal acetaminophen exposure and neurodevelopmental disorders, informing a federal health advisory, based on qualitative synthesis without quantitative pooling or bias correction. We reanalysed the same studies to test whether this association withstands standard meta-analytic and bias-correction methods. Methods: We used 24 of 46 studies from a 2025 Navigation Guide systematic review (PubMed search through 25 February 2025) that reported a ratio measure (hazard ratio, odds ratio, relative risk, or incidence rate ratio). Estimates were collapsed to one per study, outcome group, and design, yielding 30 study-level estimates (sample sizes, 307-2,480,797) for attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and other neurodevelopmental disorders. We applied random-effects meta-analysis, eight publication-bias-correction methods, a credibility-ceiling sensitivity analysis, and five quality-filtered subsets, then repeated all analyses after harmonising odds and hazard ratios onto a common risk-ratio scale. Results: The ASD association attenuated from 1.14 (95% CI, 1.01-1.28) to 1.08 (95% CI, 0.97-1.19; P=.17) once each study was weighted once rather than by its number of sub-analyses, before any bias correction. The ADHD association remained positive under most bias-correction methods (range, 1.02-1.31), but its 95% CI crossed 1.00 under a 15% credibility ceiling. The other-NDD association reversed direction under one method (ratio, 0.98; 95% CI, 0.65-1.19) and showed no right-skew on p-curve testing (P=.71). Conclusions: The claim of "strong evidence" for an acetaminophen-neurodevelopmental-disorder association was not supported by this reanalysis. A modest ADHD association persisted, while ASD and other-NDD estimates moved toward the null.

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Metabolomic and Lipidomic Signatures of Depressive Symptoms in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

Dagli, C.; Armstrong, N. D.; Patel, P. G.; Boakye, E. A.; Ament, Z.; Demopoulos, A.; Tiwari, H.; Howard, V. J.; Kimberly, W. T.; Irvin, M. R.

2026-08-12 genetic and genomic medicine 10.64898/2026.08.10.26360141 medRxiv
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Background Depression is a highly prevalent condition with a substantial health burden and known links to metabolic dysfunction. We investigated plasma metabolites and lipids associated with depressive symptoms at baseline, including sex- and race-specific differences, and subsequently examined longitudinal associations of baseline metabolites and lipids with depressive symptoms over follow-up. Methods Baseline plasma samples were profiled for 162 metabolites and 195 lipid species using targeted mass spectrometry in the REasons for Geographic And Racial Differences in Stroke (REGARDS) stroke case-cohort. Depressive symptoms were assessed using the 4-item Center for Epidemiologic Studies Depression Scale (CES-D-4) at baseline and during follow-up. Cross-sectional associations were evaluated using weighted logistic regression, and longitudinal associations were assessed using weighted generalized estimating equations. Effect modification by sex and race was examined. Model 1 was adjusted for age, race, and sex (and time in longitudinal analyses). Model 2 was further adjusted for body mass index, smoking status, alcohol use, physical activity, perceived stress, and incident stroke. False discovery rate (FDR) correction was applied to account for multiple testing. Results Of 1,938 participants, 205 had depressive symptoms at baseline. At baseline, several metabolites (e.g., glycine, cyclic AMP) and lipid species were nominally associated with depressive symptoms, though none remained significant after FDR correction. In longitudinal analyses, stronger and more consistent associations emerged. Higher levels of anserine (OR=1.27, 95% CI: 1.16-1.39) and glucose (OR=1.36, 95% CI: 1.10-1.68) were associated with increased odds of depressive symptoms, with anserine remaining significant after FDR correction. Multiple lipid species, particularly phosphatidylethanolamines (PEs) and triglycerides (TGs), were significantly associated with depressive symptoms after FDR correction in longitudinal models. Significant sex interactions were observed for several lipid species, with stronger positive associations in females and attenuated or inverse associations in males. Conclusions In this stroke-enriched case-cohort, PEs and TGs were associated with depressive symptoms over time. Sex-specific lipid differences highlight biological heterogeneity. These results identify amino acid, phospholipid, and triacylglycerol pathways in depressive symptoms, supporting further mechanistic and biomarker investigations.

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Decompression Alone Versus Decompression With Fusion for Symptomatic Lumbar Synovial Facet Cysts: A Systematic Review and Meta-analysis

Fahim, F.; Mohammad Moradi, F.; Mojtahedzadeh, A.; Shahinzadeh, A.; Khorram, A.; Amini, P.; Farhadian, D.; Sangtarashha, P.; Faramin Lashkarian, M.; Khazaei, F.; Zali, A.

2026-08-21 neurology 10.64898/2026.08.17.26360613 medRxiv
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Background: Pain relief is the principal patient-centered goal of surgery for symptomatic lumbar synovial facet cysts, yet comparative reviews have often emphasized cyst recurrence. Whether adding fusion improves postoperative pain or reduces later surgery remains uncertain. Objective: To compare decompression alone with decompression plus fusion, with postoperative back- and leg-pain outcomes as the primary domain. Methods: PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to 2 June 2026. Comparative cohorts and case series with at least five patients were eligible. Twenty-two studies were re-extracted for VAS/NRS scores, change scores, and persistent or recurrent pain. Random-effects restricted maximum likelihood models with Hartung-Knapp inference were used; clinically distinct pain outcomes were analyzed separately. Results: Twenty-two studies (16 cohorts, 6 case series; 51,899 participants) were included. Two studies provided compatible final VAS data. Fusion did not improve postoperative back pain (MD -0.04, 95% CI -0.17 to 0.10; I2=0%) or leg pain (MD -0.03, 95% CI -0.28 to 0.21; I2=0%). Postoperative back pain (RR 0.58, 95% CI 0.14-2.30) and leg/radicular symptoms (RR 0.75, 95% CI 0.42-1.32) were also not significantly reduced. Fusion decreased confirmed cyst recurrence (RR 0.29, 95% CI 0.15-0.57) but not reoperation or subsequent lumbar surgery (RR 0.80, 95% CI 0.42-1.50). Conclusion: Current comparative evidence does not demonstrate superior postoperative pain control with routine fusion. Fusion reduces cyst recurrence without clearly reducing reoperation, supporting selective use when instability is present or anticipated.

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How Mentoring Networks Shape Early-Career Grant Success: Evidence from NIH K-awardees

Setiono, F. J.; Ho, E.; Lambert, W. M.

2026-08-13 scientific communication and education 10.64898/2026.08.11.743320 medRxiv
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Effective mentorship is essential for strengthening the STEMM (Science, Technology, Engineering, Mathematics, and Medicine) workforce, yet empirical evidence on how mentorship networks are structured and linked to career success remains limited. Here, we analyze mentorship networks among recipients of NIH career development (K) awards to characterize network size, mentor roles, and their associations with mentee-reported outcomes, including potential variation by sociodemographic characteristics. We found that K-awardees rely on mentors beyond their primary advisor, who play varying roles beyond being a Research mentor. Different mentor roles led to different types of mentoring outcomes; while Research mentors were associated with research-related outcomes such as Publications and Grants, career- and psychosocial-related mentoring outcomes were more likely to come from other types of mentors, such as Coaches, Connectors, and Sponsors. Larger networks, as well as having Peer and Identity mentors are additively beneficial for researchers who identify as underrepresented in science more than their counterparts. This study provides large-scale evidence on how mentorship network configurations relate to early-career grant success.

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A single-session randomised crossover fNIRS study comparing three upper-limb mirror therapy task paradigms in healthy adults: a study protocol

Yang, T.; Wei, S.; Wang, Y.; Bai, D.

2026-09-02 rehabilitation medicine and physical therapy 10.64898/2026.08.28.26361691 medRxiv
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Background Mirror therapy (MT)-specifically paradigms using mirror visual feedback (MVF)-is widely used in neurorehabilitation; however, mechanistic implementations vary substantially in movement content, rhythmicity and attentional demands. This protocol describes an acute mechanistic, within-participant fNIRS screening study designed to compare three prespecified upper-limb mirror-therapy task paradigms and to quantify associated subjective experience after each condition in healthy adults during a single visit. Methods and analysis This is a single-centre, within-participant, randomised crossover study conducted at Wuhan Wuchang Hospital (Wuhan, China). Healthy adults aged 18-35 years will complete three task conditions once each in a counterbalanced order using a 3*3 Latin-square scheme: UMT1 (task-oriented rhythmic functional movement), UMT2 (open-ended free movement with auditory control), and UMT3 (non-functional rhythmic movement). fNIRS will be acquired using the NirSmart-6000A system during a standardised block design. The primary outcome is ROI-level HbO activation quantified as GLM-derived {beta} estimates within the prespecified primary ROIs (bilateral SM1/M1 and bilateral PMC). Secondary outcomes include ROI-level windowed {Delta}HbO (5-20 s post-onset relative to the immediately preceding rest; descriptive only), ROI-level {Delta}HbR, and post-condition subjective ratings (illusion, immersion, confusion and fatigue; 1-7 Likert). Condition effects will be analysed using linear mixed-effects models with fixed effects for condition and period and prespecified multiplicity-adjusted pairwise contrasts. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Wuchang Hospital Affiliated to Wuhan University of Science and Technology (Approval No.: 2025-112-01; approved on 2025-08-21). The study is expected to be minimal risk. Findings will be disseminated through publication of this protocol manuscript and subsequent results manuscripts and conference presentations. Trial registration number Chinese Clinical Trial Registry (ChiCTR2600116634). This study is conducted as a prespecified mechanistic sub-study under the overarching registered project.

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Comparative analyses of tailbeat frequency and stride length reveal how regionally endothermic fishes cruise fast

Tokunaga, S.; Payne, N. L.; Kawabe, R.; Nakamura, I.; Furukawa, S.; Chiang, W.-C.; Semmens, J. M.; Meyer, C. G.; Watanabe, Y. Y.

2026-08-19 animal behavior and cognition 10.64898/2026.08.14.744074 medRxiv
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Cruising speed is a key factor affecting prey-search efficiency and migration range in continuously swimming animals. Tunas and lamnid sharks (e.g., white sharks) have convergently evolved traits for high-speed cruising, including the ability to maintain slow-twitch, aerobic red muscle (RM) warmer than ambient water, known as RM endothermy. Despite their well-known high cruising speeds, kinematic features underlying their elevated speeds remain unclear. Swim speed is the product of tailbeat frequency (TBF; Hz) and stride length (SL, the absolute distance traveled per tailbeat; m). RM endothermy is expected to elevate TBF by enhancing muscle contraction performance. Furthermore, within RM-endothermic fishes, tunas and lamnid sharks may exhibit distinct kinematic features because of differences in caudal fin morphology and tailbeat amplitude. Here, we compiled kinematic parameters from 20 fish species, including five RM-endothermic species, measured in the wild using animal-borne sensors. Comparative analyses showed that, for a given body mass and water temperature, RM-endothermic fishes exhibited 1.9 times higher cruising speed and TBF than ectothermic fishes, while SL remained similar. Within RM-endothermic fishes, tunas exhibited 2.3 times higher TBF than similar-sized lamnid sharks, whereas lamnid sharks showed 1.7 times longer SL than similar-sized tunas. These results indicate that RM endothermy is generally associated with higher TBF, while significant kinematic differences remain between tunas and lamnid sharks. This divergence may be partly explained by the greater caudal fin area and tailbeat amplitude in lamnid sharks. It may also reflect contrasting skeletal types of teleosts and elasmobranchs, which potentially influence body stiffness and swimming kinematics.

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Efficacy of Psychological self-monitoring and goal-setting Intervention in Anterior Cruciate Ligament Reconstruction Rehabilitation mid-phase: A Randomized Controlled Trial

Sorrentino, M.; Cantu, P.; Landenna, A.; Botturi, F.; Castenetto, M.

2026-08-10 psychiatry and clinical psychology 10.64898/2026.08.07.26359958 medRxiv
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Background: Despite achieving clinical stability, many athletes fail to reach their pre-injury level of activity following anterior cruciate ligament reconstruction due to unresolved psychological barriers. Factors such as kinesiophobia, low self-efficacy, and a lack of psychological readiness often persist even when physical milestones are met, creating a psychological gap in traditional rehabilitation. Current evidence suggests that addressing these modifiable deficits through targeted interventions is essential for a successful return to sport. Objective: This randomized controlled trial evaluated the impact of a structured psychological self-monitoring and goal-setting intervention on kinesiophobia, psychological readiness, and adherence during the mid-phase of ACLR rehabilitation. Methods: Twelve patients (N=12) in the mid-phase of ACLR recovery were randomized to receive either a 4-week integrated psychological intervention or standard-of-care physical therapy. The experimental protocol focused on goal setting, positive self-talk, and imagery skills previously shown to correlate with higher adherence to home-based exercise. Results: The analysis of the baseline demographics confirms that both groups were well-matched. The primary behavioral outcome was measured using the Rehabilitation Compliance Questionnaire, a 20-item scale assessing attendance, instruction following, intensity of effort, and communication. For the Intervention Group, the improvement did not reach statistical significance (p = 0.144). The Control Group showed a trend toward significance (p = 0.063). Conclusion: Implementing psychological self-monitoring and goal-setting during the mid-phase of ACLR rehabilitation addresses the biopsychosocial complexities of recovery. This approach potentially enhances the alignment between physical function and mental readiness, providing a more comprehensive pathway for athletes returning to pivoting sports

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The influence of sleep on emotional and social recognition memory and gist abstraction in children

Meyer-Jajkov, P. T.; Kurz, E.-M.; Höpfner, F. M.; Tuncel, Z.; Hebborn, L.; Paetow, J.; Kölle, K.; Ngo-Dehning, H.-V. V.; Conzelmann, A.; Prehn-Kristensen, A.

2026-08-19 psychiatry and clinical psychology 10.64898/2026.08.18.26360653 medRxiv
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Sleep is proposed to have a beneficial effect on the consolidation of memories and gist abstraction in adults. For children, gist abstraction is of special relevance to transform new information from social and emotional contexts into stable representations. This study investigated the effect of sleep on emotional and social recognition and gist abstraction on N=34 typically developing children assessed in a sleep and a wake condition. In an emotional memory task, reward-associated stimuli were presented, while a social memory task used face-stimuli to implement social acceptance or rejection from peers. Both paradigms relied on a hidden rule to be abstracted. In general, children were able to remember emotional and social stimuli and to abstract gist information. With respect to sleep, we found a beneficial effect of sleep on the recognition of emotional stimuli but no sleep-dependent enhancement for either social recognition or emotional or social gist abstraction. Overall, our results indicate, that sleep-dependent recognition might depend on the type of memory task. Furthermore, nighttime sleep as compared to daytime wakefulness has no differential influence on gist abstraction in children as assessed in our paradigms, contrasting previous results found in adults.