Tag: nevin manimala

medRxiv [Preprint]. 2026 Jul 20:2026.07.17.26358090. doi: 10.64898/2026.07.17.26358090.

ABSTRACT

People with Down syndrome have higher age-specific mortality rates compared to the general population as well as peers with other intellectual and developmental disabilities. While a large proportion of mortality is attributable to Alzheimer’s disease, many die prior to Alzheimer’s diagnosis and some live to old ages, dying without Alzheimer’s. Our objectives were to use 11 years of Medicaid and Medicare data to describe characteristics and factors related to death in adults with Down syndrome and use machine learning to identify which conditions most strongly predict death in the full population and stratified by age. We identified death using Center for Medicare and Medicaid Systems reported date of death health conditions using ICD 9 and 10 codes. We used a case-control design with risk set sampling to have that controls to mimic the distribution of times of incident Alzheimer’s disease. We trained gradient boosted trees to identify strongest predictors. Our cohort included 137,293 adults with Down syndrome. Among those, 30,894 (22.5%) died during the study period. Mean age at death among those who died was 55 years (SD=10). Mean age of death in those with Alzheimer’s disease was 59 (SD=7) and those without was 52 (SD=12). The most influential predictors of mortality were any claim for dementia, any claim for pneumonia, re-occurring claim for cardiovascular disease three years before index death, and any claim for heart failure and epilepsy. Our results align with previous clinical work and highlight intervenable areas to reduce mortality in the Down syndrome population.

PMID:42539115 | PMC:PMC13419647 | DOI:10.64898/2026.07.17.26358090

medRxiv [Preprint]. 2026 Jul 24:2026.07.22.26358355. doi: 10.64898/2026.07.22.26358355.

ABSTRACT

Traumatic brain injury (TBI) is a leading cause of death and long-term disability in children, with many experiencing persistent symptoms even after mild TBIs. Exposure to adverse childhood experiences (ACEs) can have physiological effects that may alter how the brain responds to injury, yet the effects of ACEs on white matter injury and recovery processes remain unclear. This study examined whether a history of ACEs is associated with patterns of longitudinal change in white matter microstructure in children with mTBI. Ninety-six concussed adolescents (mean age=14.9 years, range =11.4-17.9, 51% female) from the CARE4Kids consortium completed the Pediatric ACEs and Related Life-Events Screener and underwent diffusion-weighted MRI at baseline (7-35 days after injury) and follow-up (2 months later). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), orientation dispersion index (ODI), and intracellular volume fraction (ICVF) were estimated using tract-based spatial statistics and harmonized across sites. Differences in the magnitude and direction of change in diffusion metrics over time were examined in 15 tracts of interest. Higher ACE exposure was associated with smaller absolute change in AD, MD, ODI, and ICVF across several white matter tracts, including the corpus callosum, internal and external capsules, corona radiata, and posterior thalamic radiation. Groups did not differ in the direction of white matter change for any tract-metric combination. These findings suggest that ACE exposure may blunt white matter reactivity to injury and/or reorganization during recovery processes.

PMID:42539109 | PMC:PMC13419653 | DOI:10.64898/2026.07.22.26358355

medRxiv [Preprint]. 2026 Jul 22:2026.07.20.26358527. doi: 10.64898/2026.07.20.26358527.

ABSTRACT

BACKGROUND: Peripheral artery disease (PAD) is an occlusive arterial disease primarily affecting the lower extremities. It impacts over 230 million people worldwide and is associated with significant morbidity and mortality. The ankle brachial index (ABI) test is a non-invasive method to detect PAD that compares the blood pressure in the ankle and arm to evaluate lower extremity blood flow. An estimated 20-50% of individuals with detectable PAD are asymptomatic and remain undiagnosed; however, ABI screening in high-risk, asymptomatic populations is not currently guideline-recommended. Few studies have evaluated change in ABI over time in asymptomatic populations. Therefore, we aimed to identify distinct trajectories of ABI values from mid-to late-life.

METHODS: We utilized data from the Atherosclerosis Risk in Communities (ARIC) study; a longitudinal cohort study initiated in 1987 that enrolled 15,792 participants aged 45-64. ABI measurements were collected at five visits over a 30-year period. We used group-based trajectory modeling to identify trajectories of ABI from mid-to late-life. Final model selection was based on visual fit, statistical criteria, group sizes, and substantive knowledge. Lastly, we compared baseline demographics, social determinants of health, and overall cardiovascular (CV) health, assessed using the American Heart Association’s Life’s Essential 8 (LE8) framework, across trajectory groups.

RESULTS: We identified 4,121 participants with ≥3 ABI measurements over the study period in at least one limb. At baseline, participants had an average age of 51.4 ± 4.9 years, were 57.3% female, 22.2% Black, and had an average overall LE8 score of 68.0 ± 13.9 points. Our final model identified three linear trajectories: low-normal, high-normal, and declining. Overall LE8 scores varied significantly across trajectory groups: 67.3 ± 10.7 (high-normal), 61.9 ± 13.3 (low-normal), and 50.1 ± 15.8 points (declining). Women had lower average ABI values, were more likely to experience a declining ABI trajectory, and had a delayed onset of decline compared to men. A greater proportion of Black participants experienced declining ABIs, with earlier, faster, and more severe declines than White participants.

CONCLUSIONS: Poor overall CV health and common CV risk factors are associated with ABI decline. Targeted ABI screening in middle age may help detect PAD in its beginning stages and support early intervention.

PMID:42539097 | PMC:PMC13419634 | DOI:10.64898/2026.07.20.26358527

medRxiv [Preprint]. 2026 Jul 22:2026.03.11.26348169. doi: 10.64898/2026.03.11.26348169.

ABSTRACT

BACKGROUND: CAG repeat expansions in ATXN2 are implicated as risk factors for several neurological diseases, including spinocerebellar ataxia type 2 (SCA2) when >=33 CAG repeats are present, and amyotrophic lateral sclerosis (ALS) when 27-33 CAG repeats are present. However, how haplotypes around the repeats and CAA interruptions within the repeats are associated with disease phenotypes remains poorly understood. Previous studies on haplotypes around ATXN2 were limited to SNPs very close to the repeats (<5kb) or were based on statistical inference only.

METHODS: Here, we used long-read sequencing on the Oxford Nanopore Technologies (ONT) platform to simultaneously infer haplotypes around ATXN2 , the number of CAG repeats, and the number of CAA interruptions, along with NYGC ALS Consortium NGS dataset. We further sequenced 41 individuals (EUR = 39) with neurological diseases with intermediate repeats by ONT.

RESULTS: We found that haplotypes around ATXN2 and the number of interruptions show ethnicity-specific and ALS-specific distribution. Three CAA interruptions are present at low prevalence (∼1%) in control populations in multiple ancestry groups, but high prevalence (∼55%) in ALS individuals with intermediate repeats. Furthermore, we examined 159 individuals with ALS (∼90% European ancestry) with intermediate ATXN2 repeats and found a unique haplotype in ALS individuals with three CAA interruptions, which can be tagged by an SNV, rs148019457. We also validated that the rs148019457-G allele is only present in haplotypes with three CAA interruptions.

CONCLUSIONS: In summary, our study shows that 3 CAA interruptions are rarely seen in healthy controls but are common in those with expanded ATXN2 CAG repeats who have neurological disorders, and that rs148019457 tags a specific haplotype with 3 CAA interruptions within expanded ATXN2 CAG repeats in individuals of European ancestry. These results have implications for the development of precision genomic medicine for neurological disorders, and the tag SNP may help identify those with interruptions from existing population genotyping data.

PMID:42539086 | PMC:PMC13419642 | DOI:10.64898/2026.03.11.26348169

medRxiv [Preprint]. 2026 Jul 21:2026.07.20.26358492. doi: 10.64898/2026.07.20.26358492.

ABSTRACT

IMPORTANCE: Most United States children with neurodevelopmental disorders have not received genetic testing aligned with current guidelines. Integration of genetic counselors into non-genetics departments is a potential strategy to improve uptake, but prevalence and details of integrated care models are unknown.

OBJECTIVE: To characterize availability, utilization, and perceived need for genetic counselors across non-genetics departments caring for patients with neurodevelopmental disorders.

DESIGN: Cross-sectional observational department-level survey.

SETTING: Child neurology, adult neurology, developmental pediatrics, child psychiatry, and adult psychiatry departments at Intellectual and Developmental Disabilities Research Centers.

PARTICIPANTS: The survey was distributed to 67 departments across 15 institutions. The departmental response rate was 52% (35/67), with at least one response from 87% (13/15) of institutions.

EXPOSURE: Presence/absence of dedicated genetic counselor(s), where “dedicated” was defined as hired by the department.

MAIN OUTCOMES AND MEASURES: This was a descriptive study only, with no comparative statistical analyses due to the exploratory nature.

RESULTS: One third of departments (34%; 12/35) reported having dedicated clinical genetic counselors. Prevalence was highest in child neurology (67%; 8/12), followed by adult neurology (40%; 2/5) and developmental pediatrics (22%; 2/9), with none in child psychiatry (0/7) or adult psychiatry (0/2). In almost all departments with genetic counselors (92%; 11/12), they directly billed for their services, which universally included pre-test counseling/consent and post-test counseling. In departments without genetic counselors, only 39% (9/23) reported providers ordered their own genetic testing. Among all departments, over half (57%) were interested in adding/increasing genetic counseling support, while 26% were unsure and 17% uninterested. Insufficient funding was the most cited barrier; only one department reported insufficient need.

CONCLUSIONS AND RELEVANCE: Though currently implemented in only one third of departments, our findings suggest those with dedicated genetic counselors directly pursue genetic testing (without referring to genetics) more than those without genetic counselors. Interest in increasing or adding genetic counseling support was high, and though funding was a reported barrier, feasible funding models were described. In the context of limited medical geneticists and expanding precision therapies, alternate delivery models for neurodevelopmental genetic testing including genetic counselor integration in non-genetics departments may help to scale and sustain uptake.

KEY POINTS: QUESTION: What is the availability, utilization, and perceived need for genetic counselors in non-genetics departments caring for individuals with neurodevelopmental disorders?FINDINGS: In this cross-sectional study of 35 neurology, psychiatry, and developmental pediatrics departments, one third reported having dedicated genetic counselors for clinical care. Most were interested in increasing or adding genetic counselor support; insufficient funding was the most reported barrier and only one department reported insufficient need.MEANING: Many non-genetics departments caring for individuals with neurodevelopmental disorders continue to rely on the traditional referral model to genetics departments for testing/counseling despite substantial interest and support for integrating genetic counselors.

PMID:42539083 | PMC:PMC13419643 | DOI:10.64898/2026.07.20.26358492

Res Sq [Preprint]. 2026 Jul 25:rs.3.rs-10093990. doi: 10.21203/rs.3.rs-10093990/v1.

ABSTRACT

Background Human papillomavirus (HPV)-based screening is increasingly being adopted as the primary strategy for cervical cancer prevention due to its superior sensitivity compared with cytology. However, effective triage of women who test positive for high-risk HPV (hrHPV), particularly those infected with non-HPV16/18 genotypes, remains a significant challenge in low-resource settings. Cytology-based triage requires substantial laboratory infrastructure and technical expertise, which may limit its scalability. Risk-stratified triage approaches incorporating readily available clinical and demographic factors may offer a practical alternative for identifying women at highest risk of cervical precancer while reducing unnecessary referrals. Aim The ” STRAT-CIN Trial ” aims to determine whether a risk-stratified triage algorithm is non-inferior to standard cytology-based triage for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) among women positive for non-HPV16/18 high-risk HPV types. Methods This protocol describes a two-arm, parallel, open-label, non-inferiority randomized controlled trial involving sexually active women aged 30-65 years who test positive for non-HPV16/18 high-risk HPV types during routine cervical cancer screening at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, between June 2026 and January 2027. A total of 148 eligible women will be randomized in a 1:1 ratio to either a risk-stratified triage arm or a cytology-based triage arm. Participants in the intervention arm will be triaged using a composite algorithm incorporating age, HIV status, cigarette smoking, long-term oral contraceptive use, and multiple hrHPV genotype infections, while participants in the control arm will undergo reflex cytology according to the Bethesda 2014 classification. The primary outcome is the proportion of histologically confirmed CIN2 + lesions detected in each study arm. Secondary outcomes include diagnostic performance metrics, referral rates for colposcopy, colposcopic yield, and predictors of CIN2+. Analyses will follow the intention-to-treat principle. Differences in CIN2 + detection rates will be assessed using risk differences and corresponding 95% confidence intervals. Non-inferiority will be concluded if the lower bound of the confidence interval exceeds the pre-specified non-inferiority margin of – 10%. Logistic regression analyses will be used to identify independent predictors of CIN2+, and statistical significance will be set at P < 0.05. Discussion The ” STRAT-CIN Trial ” will evaluate whether a simplified risk-stratified triage approach can achieve diagnostic performance comparable to conventional cytology-based triage among women with non-HPV16/18 high-risk HPV infections. By integrating easily obtainable clinical and demographic risk factors into triage decision-making, this study has the potential to reduce unnecessary colposcopy referrals, improve screening efficiency, and support the implementation of context-appropriate cervical cancer prevention strategies in resource-constrained settings. The findings will contribute important evidence toward optimizing HPV-based cervical cancer screening programs in Nigeria and other low- and middle-income countries. Registration : PACTR202606895128487 (2nd June 2026).

PMID:42539082 | PMC:PMC13419630 | DOI:10.21203/rs.3.rs-10093990/v1

medRxiv [Preprint]. 2026 Jul 24:2026.04.04.19007310. doi: 10.64898/2026.04.04.19007310.

ABSTRACT

BACKGROUND: Madariaga virus (MADV), has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien province.

METHODS: We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. Additionally, by applying a catalytic, force-of-infection statistical model to two serosurveys from Darien province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically.

FINDINGS: In 2017, MADV and VEEV IgM seroprevalence was 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%; VEEV: 16.8%; Una virus (UNAV): 16.0%; and Mayaro virus (MAYV): 1.1%. Active viral circulation was not detected. Evidence of MADV and UNAV infection was found near households raising questions about its vectors and enzootic transmission cycles. Insomnia was associated with MADV and VEEV infection, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in some regions.

INTERPRETATION: The lack of additional neurological cases suggests that severe MADV and VEEV infections occur only rarely. Our results indicate that, over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially.

PMID:42539076 | PMC:PMC13419557 | DOI:10.64898/2026.04.04.19007310

Res Sq [Preprint]. 2026 Jul 20:rs.3.rs-10008196. doi: 10.21203/rs.3.rs-10008196/v1.

ABSTRACT

Background : Prolonged grief reactions in children and adolescents are linked to marked emotional distress, social withdrawal, academic disruption, and impaired daily functioning. These difficulties may be intensified in contexts of chronic threat and instability, such as the ongoing war in Ukraine, where bereavement is widespread and support systems are disrupted. Valid, culturally adapted assessment tools are essential for identifying youth experiencing clinically significant grief responses. This study aimed to adapt and validate the Ukrainian version of the Prolonged Grief Assessment for Children (PGA‑C) in a sample of bereaved young people living under wartime conditions. Methods : A total of 129 bereaved children and adolescents (63.6% female; M age = 12.1, SD = 3.14) completed structured interviews. Analyses included descriptive statistics, internal consistency (Cronbach’s α), test-retest reliability over 4-5 weeks (ICC), exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity testing, and regression analyses. Convergent/divergent validity was examined through associations with PTSD symptoms (CRIES‑8), anxiety and depression (RCADS‑25), and health‑related quality of life (KIDSCREEN‑27). Results : Internal consistency was excellent for the total PGA‑C scale (α = 0.92) and strong for both identified factors (α = 0.89 and 0.88). Test-retest reliability was high (ICC = 0.88, 95% CI [0.82-0.91], p < 0.001). PGA‑C scores showed strong negative associations with quality of life (r = -0.622, 95% CI [-0.729, -0.488]) and positive associations with depression (r = 0.480, 95% CI [0.330-0.620]) and PTSD symptoms (r = 0.438, 95% CI [0.273-0.585]). Correlations of PTSD (r = -0.333, 95% CI [-0.483, -0.162]) and depression (r = -0.350, 95% CI [-0.500, -0.190]) with components of quality of life were clearly weaker than those of PGA-C. No significant differences in PGA-C scores were found for sex, age, relationship to the deceased, or cause of death. EFA of the PGA-C supported a two-factor structure – Detachment/Avoidance and Yearning/Disbelief, yet CFA of the PGA-C showed limited fit of the data to this model (CFI < 0.90, RMSEA > 0.10). Strong internal consistency of the total scale and its concurrent/divergent validity support the use of the PGA-C total score. Conclusions : The Ukrainian PGA‑C demonstrates excellent internal consistency, strong test-retest reliability, and robust convergent and divergent validity. Findings support its use as a reliable tool for assessing prolonged grief among bereaved children and adolescents living in high‑adversity wartime contexts.

PMID:42539067 | PMC:PMC13419585 | DOI:10.21203/rs.3.rs-10008196/v1

ArXiv [Preprint]. 2026 Jul 21:arXiv:2607.19316v1.

ABSTRACT

In the primate visual system, center-preferring cortical populations have higher spatial resolution and overlap face- and word-selective regions while periphery-preferring populations have lower spatial resolution and overlap scene-selective regions. This “eccentricity bias” may reflect differential task-relevance: central vision may better support fine-grained tasks like face recognition and reading, while peripheral vision may better support scene understanding. To test whether eccentricity-dependent coding can emerge from natural experience, we used egocentric video and eye-tracking data from the Visual Experience Dataset (VEDB). We trained ResNet-18 models using contrastive learning (SimCLR) on frames modified to isolate different eccentricities (gaze-contingent fovea-only crops, periphery-only crops, and periphery-only crops with a NeuroFovea transform applied). We evaluated downstream task performance and model alignment with human fMRI data (Natural Scenes Dataset; encoding models). In-domain VEDB frame classification showed systematic differences between fovea- and periphery-only models across categories, indicating differential informativeness across tasks. On downstream classification, VEDB-pretrained models generalized better to scene categorization (Places365) than face recognition (VGGFace2), with fovea-only models stronger on both. Across visual cortex, VEDB-pretrained models matched neural predictivity of models trained on mid-sized non-egocentric datasets (ImageNet-100), suggesting egocentric data supports emergence of cortically-aligned representations. In scene-selective cortex (PPA, RSC), periphery-only models held a small but consistent advantage in explained variance over fovea-only models, suggesting these regions are aligned with peripheral statistics. Together, these results suggest egocentric experience may adaptively constrain cortical information processing.

PMID:42539066 | PMC:PMC13419636

medRxiv [Preprint]. 2026 Jul 21:2026.07.15.26358129. doi: 10.64898/2026.07.15.26358129.

ABSTRACT

SUMMARY: It has become standard practice to visualize regional signals from genome-wide association studies (GWAS) using LocusZoom plots. Similarly, GWAS signals are compared to regionally matched quantitative trait loci (QTLs), i.e. variant-to-gene regulation data, using LocusCompare plots to aid assessment of candidate trait-related genes. Despite broad usage, these tools annotate variants by linkage disequilibrium (LD) to a single lead or index variant. This single-index representation has limitations for visualizing complex loci that contain multiple independent signals. We present LocusBlend, an interactive web application for multi-index LD-blended visualization of genomic loci. LocusBlend supports one or two genomic association summary-statistic datasets and one to three index variants, multi-index LocusZoom color-blended plots, and matching LocusCompare visualizations. Applications to Alzheimer’s disease GWAS and QTL signals illustrate LocusBlend enables visualization and separation of independent signals despite shared LD and high genomic complexity. Overall, LocusBlend is aimed at supporting researchers handle the continuously expanding complexity of human genomics findings.

AVAILABILITY AND IMPLEMENTATION: LocusBlend is freely available at https://locusblend.wustl.edu . Publication ready plots are generated in <1min. Source code, documentation, example datasets, input templates, and reproducibility instructions are available at https://github.com/Belloy-Lab/LocusBlend . LocusBlend is implemented in Python using Streamlit, Plotly, and PLINK.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:42539024 | PMC:PMC13419561 | DOI:10.64898/2026.07.15.26358129