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Nevin Manimala Statistics

Aortic aneurysm and dissection and its multidimensional impact on cognitive function: The pivotal role of PRDX6 in pathophysiological mechanisms

Atherosclerosis. 2026 May 1;417:120773. doi: 10.1016/j.atherosclerosis.2026.120773. Online ahead of print.

ABSTRACT

AIMS: This study aims to explore the relationship between aortic aneurysm and dissection (AAD) and cognitive impairment, with an emphasis on uncovering the potential biological mechanisms.

METHODS: Utilizing the UK Biobank database, a matched cohort study was performed to assess the association between AAD and the risk of Alzheimer’s disease. Cognitive function was evaluated in a β-aminopropionitrile (BAPN)-induced AAD mouse model through a series of behavioral assays. Drug-target Mendelian randomization analysis was conducted to identify candidate genes implicated in this association. Expression levels of PRDX6 were examined in brain tissues from Alzheimer’s disease patients using datasets from the Gene Expression Omnibus (GEO), as well as in aortic tissues and blood samples obtained from both AAD patients and AAD model mice. Correlative analyses between PRDX6 and pro-inflammatory cytokines (IL-1β and TNF-α) were performed in mouse hippocampal tissues of the mouse model. Additionally, in vitro experiments employing SH-SY5Y cells were carried out to investigate the functional role of PRDX6 in modulating synaptic protein expression and inflammatory responses.

RESULTS: Competing risk regression analysis indicated that AAD is significantly associated with an increased incidence of cognitive impairment. Behavioral testing revealed that AAD model mice exhibited deficits in cognitive performance. Mendelian randomization prioritized PRDX6 was prioritized as a candidate gene of interest. Elevated PRDX6 expression was observed in brain tissues from Alzheimer’s disease patients. Both AAD patients and AAD model mice demonstrated markedly increased PRDX6 levels in aortic tissues and circulating blood; notably, PRDX6 expression was also upregulated in the hippocampus of AAD mice. In the hippocampus, PRDX6 expression positively correlated with levels of IL-1β and TNF-α expression in AAD mice. In SH-SY5Y cells, silencing of PRDX6 resulted in increased expression of synaptic proteins, reduced pro-inflammatory cytokine production, and decreased apoptosis, whereas overexpression of PRDX6 elicited inverse effects.

CONCLUSIONS: The present findings establish a significant association between AAD and heightened risk of cognitive impairment. PRDX6 has been identified as a potential mediator in this relationship, and PRDX6-related neuroinflammation is proposed as a plausible mechanistic pathway linking AAD to cognitive dysfunction.

PMID:42085745 | DOI:10.1016/j.atherosclerosis.2026.120773

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Nevin Manimala Statistics

Beyond the cerebral cortex: cerebellar language-related subregions contributions to fluency in post-stroke aphasia

Neuroimage Clin. 2026 Apr 29;50:103999. doi: 10.1016/j.nicl.2026.103999. Online ahead of print.

ABSTRACT

Although the classical language cortex significantly contributes to post-stroke aphasia (PSA), non-language-specific cortex, such as the cerebellum, is increasingly implicated in language. However, the specific contributions of its subregions to PSA, particularly regarding distinct language dimensions, remain unclear. Given fluency as a core dimension, we investigated the functional and structural integrity of cerebellar language-related subregions to clarify their distinct roles in fluent (FA) versus non-fluent aphasia (nonFA). We enrolled a primary cohort of 81 PSA patients (46 nonFA, 35 FA), and 77 healthy controls (HCs), alongside an independent external validation cohort (Aphasia Recovery Cohort [ARC]; 23 nonFA, 22 FA). Using individualized functional connectivity (FC) and volumetric analyses based on the Multi-Domain Task Battery (MDTB) atlas, we found that nonFA patients exhibited significantly decreased FC between the classical language network (LN) and language-related cerebellar subregions (right MDTB 8 and 9; R_MDTB8/9-LN FC), alongside reduced right Crus II volume. Correlation analysis revealed that these neuroimaging indicators were positively associated with language scores in nonFA, while no such relationships were observed in FA. Furthermore, mediation analysis indicated that right Crus II volume statistically accounted for the observed association between R_MDTB8/9-LN FC and overall Aphasia Quotient (AQ). As the key findings were replicated in the ARC, our results provide compelling evidence that the functional connectivity strength and structural integrity of specific cerebellar subregions contribute to language fluency. Our findings support expanding models of PSA beyond cortical regions and suggest that cerebellar-targeted strategies may improve language rehabilitation outcomes.

PMID:42085725 | DOI:10.1016/j.nicl.2026.103999

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Nevin Manimala Statistics

Immunization gaps and measles outbreaks in ASEAN (2015-2025): A systematic review and meta-analysis

J Infect Public Health. 2026 Apr 29;19(6):103238. doi: 10.1016/j.jiph.2026.103238. Online ahead of print.

ABSTRACT

BACKGROUND: Despite global elimination goals, measles remains a persistent regional health challenge in the Association of Southeast Asian Nations (ASEAN). This systematic review and meta-analysis characterized the distribution of cases and deaths during ASEAN measles outbreaks (2015-2025) and computed pooled proportions of cases stratified by age, vaccination history, migration status, and indigenous group membership.

METHODS: In this systematic review and meta-analysis (PROSPERO CRD420251149627), we searched Scopus, Medline, Embase, and Google Scholar through January 15, 2026, for studies on measles outbreaks in ASEAN (2015-2025) that stratified cases by age, vaccination history, or marginalized groups. A modified Joanna Briggs Institute/ROBINS-E tool was used to assess the risk of bias. Pooled proportions were calculated using random-effects generalized linear mixed models (GLMM). Heterogeneity and small-study effects were evaluated using I2 statistics and Luis Furuya-Kanamori (LFK) indices, respectively.

FINDINGS: Across 11 studies (15,679 cases), measles disproportionately affected children under five (n = 10,867). Vaccination history reporting was near-complete in children but negligible in adults (0·22%, 95% CI: 0·00-73·41%). Among cases with known history, 73·20% (95% CI: 59·37-83·61%) were unvaccinated. Age-ineligible infants (<9 months) comprised half the unvaccinated burden (49·98%, 95% CI: 24·85-75·13%). Among vaccinated cases, 74·84% (95% CI: 44·48-91·70%) were not fully vaccinated. Significant heterogeneity was observed throughout (I2 ≥ 89·0%). Risk of bias was generally low. Transmission was also documented among migrant and indigenous subpopulations.

INTERPRETATION: ASEAN measles outbreaks are driven by immunity gaps in unvaccinated children, partially vaccinated individuals, and age-ineligible infants. Achieving and sustaining regional measles elimination requires closing coverage gaps and addressing systemic drop-outs between doses. Future strategies must prioritize lifecycle immunity, including enforcement of the 2nd dose of measles containing vaccine (MCV2) and potential adult boosters, digitized vaccine registries, and cross-border collaboration.

PMID:42085724 | DOI:10.1016/j.jiph.2026.103238

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Nevin Manimala Statistics

Saccade dynamics in different spiral tunnels: An investigation of length and radius effects on driver visual load

Traffic Inj Prev. 2026 May 5:1-11. doi: 10.1080/15389588.2026.2653672. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to systematically investigate how key geometric parameters of spiral tunnels, specifically tunnel length and radius and travel direction, influence drivers saccadic eye movements and visual load.

METHODS: A field experiment was conducted using a wearable eye tracker to record saccadic behavior from 30 licensed drivers. Participants drove through 3spiral tunnels with varying lengths and radii under both uphill and downhill traversal conditions. Four saccade metrics (amplitude, duration, frequency, and velocity) were analyzed using descriptive statistics and ANOVA to evaluate visual workload. These metrics have been selected because they collectively reflect distinct aspects of visual scanning behavior: amplitude indicates the breadth of visual search, duration reflects the time required for processing fixated information, frequency represents the rate of gaze shifting, and velocity denotes the efficiency of oculomotor movement.

RESULTS: The findings indicate that tunnel geometry and travel direction significantly affect saccadic dynamics. Longer tunnels and smaller radii resulted in increased saccade amplitude, prolonged duration elevated frequency, and reduced velocity, suggesting heightened visual processing demand. Furthermore uphill traversal consistently produced larger amplitudes, longer durations higher frequencies, and slower velocities than downhill traversal across all tunnels, revealing a directional asymmetry in visual load.

CONCLUSIONS: This study demonstrates that spiral tunnel design, especially extended length and reduced radius, elevates drivers’ visual cognitive load with uphill travel imposing greater demands. The results provide empirical evidence to inform geometry-based design guidelines for optimizing visual ergonomics and improving operational safety in spiral tunnels.

PMID:42085709 | DOI:10.1080/15389588.2026.2653672

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Nevin Manimala Statistics

“Optimizing Learning in Integrated Curriculum”-Comparative Effectiveness of Online and Face-to-Face Formative Assessments: Mixed Methods Study

JMIR Med Educ. 2026 May 5;12:e84935. doi: 10.2196/84935.

ABSTRACT

BACKGROUND: Assessment is a critical component of teaching and learning and serves as the foundation for how learners demonstrate success in achieving learning objectives. Formative assessments (FAs) and timely feedback play a crucial role in integrated curricula, whereas basic and clinical sciences are taught in a coordinated manner. Feedback-based FA supports student learning, and teachers can determine learning gaps to monitor progress in learning. Based on existing evidence, limited literature compared the effect of online versus onsite FA on summative performance in a fully integrated curriculum.

OBJECTIVE: This study aimed to examine the effectiveness of online versus on-site FAs and feedback on summative assessment in the integrated medical curriculum.

METHODS: This study used an exploratory mixed methods approach to delving into students’ experiences with face-to-face versus online FA and feedback, and its effect on their summative performance in the integrated Bachelor of Medicine, Bachelor of Surgery program. This study was conducted at Fakeeh College for Medical Sciences in Jeddah, Saudi Arabia. A total of 143 consenting students were recruited into the study. The students in the study were distributed voluntarily into 2 groups regardless of age, sex, or academic performance. Group 1 (n=92) was assigned to receive online FAs and immediate online feedback throughout the module using the Speedwell system. However, Group 2 (n=51) was assigned to receive onsite FAs and face-to-face feedback throughout the module in the examination hall in the college. The quantitative part of the study involved analyzing student scores of summative assessments in 2 groups exposed to online and onsite FA and feedback. The qualitative part aimed to explore students’ perceptions of FA and feedback.

RESULTS: The passing rate in summative examinations (quiz, midmodule, and final) was higher in the onsite group (61.2%, 51%, and 62.7%, respectively) compared with the online group (53.3%, 48.3%, and 45.7%, respectively). However, the difference was statistically significant only in the quiz examination. Four key themes were identified from the qualitative analyses regarding participants’ different experiences of FA and feedback: the accessibility of the examination format facilitates flexibility in learning; FA is a means of recognizing learning opportunities; FAs help shift student attitudes toward learning; and the last theme is opportunities for discussion and personalized feedback.

CONCLUSIONS: This research sheds light on the intricate interplay between assessment modalities and student learning outcomes by demonstrating that onsite FA followed by onsite feedback is more effective than online FA and feedback in fostering student engagement and promoting deep understanding and improving students’ performance in summative examinations. Thereafter, this study contributes to the ongoing discourse surrounding effective assessment practices in contemporary educational settings.

PMID:42085703 | DOI:10.2196/84935

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Nevin Manimala Statistics

Closing the Gap to Interventions for Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND): Protocol for a Longitudinal Study of TAND Severity, Predictors, and Caregiver Well-Being (TANDem-2)

JMIR Res Protoc. 2026 May 5;15:e91726. doi: 10.2196/91726.

ABSTRACT

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by pathogenic variants in the TSC1 or TSC2 genes. Apart from multisystem physical manifestations, most individuals with TSC experience TSC-associated neuropsychiatric disorders (TAND). Little is known about how TAND severity changes over time and what factors may predict these changes. Preliminary data suggest the presence of differential TAND severity trajectories. Caregiver well-being may act as a mediator of TAND severity, and a well-being intervention designed for caregivers of children with developmental disabilities may improve caregiver well-being.

OBJECTIVE: The study aims are to (1) examine longitudinal trajectories of TAND severity in a large sample of individuals with TSC and to examine potential predictors of differential trajectories, (2) evaluate the association between caregiver well-being characteristics, TAND severity, and severity trajectories, and (3) adapt and evaluate the feasibility, acceptability, and potential efficacy of a brief, online group-based well-being intervention for family caregivers.

METHODS: For the first 2 aims, 500 individuals with TSC or their caregivers will be recruited in an accelerated longitudinal design to document TAND severity at 5 time points over 12 months via a web-based app. At each time point, participants will complete demographic, TSC characteristics, intervention, and well-being questionnaires. Data will be analyzed using latent class mixed and multinomial regression modeling (aim 1) and structural equation and mediation modeling (aim 2). Participatory methods will be used to adapt an existing caregiver well-being intervention for the TSC community (aim 3). Thirty caregivers will be invited to participate in the adapted group-based online well-being intervention.

RESULTS: This study was funded from July 2024 (HT94252410790 and HT94252410791), and ethics approvals were obtained from the University of Cape Town (July 2024), Vrije Universiteit Brussel (November 2024), and the Department of Defense Office of Human Research Oversight (December 2024). The TAND Toolkit app was adapted for longitudinal data collection (aims 1 and 2). Recruitment started in December 2025 and will continue until 500 participants are enrolled (anticipated December 2026). Primary outputs are expected by July 2028. For aim 3, experiential and adaptation workshops were completed in June 2025, the pilot intervention was delivered in November 2025, and data collection will continue till May 2026. Outputs are expected by December 2026.

CONCLUSIONS: Identification of differential longitudinal TAND trajectories and their correlates will stimulate research in TSC and generate evidence for the self-report quantified TAND checklist as a clinical outcome measure. Understanding the association between caregiver well-being and TAND severity will provide support for targeted well-being interventions. A successful pilot trial will provide preliminary data for larger-scale clinical trials, with the potential to support caregivers and improve TAND outcomes. Together, the findings from the study will help close the gap in interventions for TAND.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06879665; https://clinicaltrials.gov/study/NCT06879665.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/91726.

PMID:42085697 | DOI:10.2196/91726

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Nevin Manimala Statistics

The Associations Between Sensitivity and Specificity With Prevalence in Data Matching

J Public Health Manag Pract. 2026 May 5. doi: 10.1097/PHH.0000000000002355. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the associations between sensitivity and specificity with prevalence in data matching.

METHODS: Using publicly available data, a synthetic dataset of names (“source population”; 8 million records) was created with records randomly assigned as positive or negative for a health outcome, as well as sex and birth date. All positives were included in file 1 (“disease registry”), and a random sample of positives and negatives were selected and merged to create file 2 (“study population”). The prevalence in the source population was defined as the proportion of individuals in the synthetic dataset who were randomly assigned as positive, and the prevalence in the study population as the proportion of individuals in the study population who were positive. Multiple disease registry and study population file pairs were created and matched with various prevalence in the source and study populations. Link Plus 3.0, a probabilistic record linkage program, was used for the data matching.

RESULTS: As the prevalence in the source population increases from 0.1% to 10%, the sensitivity increases from 80.0% to 94.6% and the specificity decreases slightly; as the prevalence in the study population increases from 10% to 99%, the sensitivity remains stable around 95.0% and the specificity stays at about 100.0%.

CONCLUSIONS: In data matching, the sensitivity is positively and the specificity is negatively associated with the prevalence in the source population, but not associated with the prevalence in the study population.

PMID:42085690 | DOI:10.1097/PHH.0000000000002355

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Nevin Manimala Statistics

Correcting for Complexity: Incorporating Trait-Numbers Enhances the Performance of EMMLi in Investigating Modularity

Evolution. 2026 May 5:qpag080. doi: 10.1093/evolut/qpag080. Online ahead of print.

ABSTRACT

Adams and Collyer (2019) evaluated the statistical performance of several approaches for quantifying morphological modularity and found that EMMLi had inflated type I error rates and a bias towards more complex models compared to the Covariance Ratio (CR) approach. They suggested that this may have been at least partly driven by the fact that AICc values from EMMLi do not incorporate trait numbers, but this was not verified. Here I present a performance analysis of a trait-number corrected EMMLi approach (“EMMLip”), showing that this ameliorates rates of false discovery and produces conservative results that favor less complex models. The corrected EMMLi approach was effective at differentiating models of modularity with varying between- and within-module covariation especially when effect size or dataset size were sufficiently large. While CR tests remained more effective at specifically detecting overall modularity, I found that CR tests are sensitive to varying within/between module covariation, and in some cases had inflated model misspecification between 2- and 3-module hypotheses. With this minor correction (albeit incomplete), the combination of EMMLip and CR tests becomes the best available toolkit for detecting and contrasting modularity hypotheses. This toolkit is however still imperfect, and I discuss future avenues for improvements.

PMID:42085682 | DOI:10.1093/evolut/qpag080

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Nevin Manimala Statistics

Remote Monitoring of Bioelectrical Impedance in Patients With Breast Cancer-Related Lymphedema: 1-Year Pilot Longitudinal Study

JMIR Biomed Eng. 2026 May 5;11:e86624. doi: 10.2196/86624.

ABSTRACT

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a chronic complication that impairs quality of life through persistent fluid accumulation. While clinical guidelines recommend longitudinal surveillance, implementation is often limited by the logistical challenges of frequent in-clinic visits. Bioelectrical impedance analysis (BIA), specifically the segmental extracellular water-to-total body water (ECW/TBW) ratio, offers a noninvasive method for tracking fluid status. However, the technical agreement between in-clinic and patient-led home-based BIA systems, as well as the feasibility of long-term self-monitoring in real-world settings, remains to be fully established.

OBJECTIVE: Our primary objective was to evaluate the agreement between in-clinic and home-based BIA systems for key body composition and fluid-related parameters. Our secondary objective was to characterize longitudinal fluid patterns and diurnal variations in ECW/TBW ratios to assess the feasibility of home-based monitoring.

METHODS: This prospective, patient-driven, 12-month observational study enrolled breast cancer survivors at risk for lymphedema. Agreement between the in-clinic BIA system (InBody 770) and the home-based device (BWA ON) was assessed using Bland-Altman analysis, intraclass correlation coefficients (ICCs), and the Lin concordance correlation coefficient (CCC). Longitudinal home-based ECW/TBW measurements were analyzed using linear mixed-effects models to evaluate diurnal differences (before-noon vs after-noon) across groups defined by limb dominance and BCRL status (International Society of Lymphology [ISL] stage 0 vs stage 1).

RESULTS: Over 12 months, ECW/TBW ratios measured by the home-based device demonstrated strong agreement with in-clinic measurements, showing minimal bias and high ICC/CCC values. Longitudinal analysis revealed that ECW/TBW changes did not follow uniform patterns within ISL stage categories, showing substantial physiological heterogeneity even among clinically stable groups. Diurnal analysis identified a small but statistically significant decrease in ECW/TBW ratios in the afternoon (P<.001). The magnitude of this decrease differed by limb dominance and BCRL status, with the most pronounced reduction observed in participants whose dominant arm was affected and who had a history of stage 1 lymphedema. ECW/TBW variability was driven more by within-individual factors (eg, measurement timing) than by between-individual differences.

CONCLUSIONS: Home-based segmental bioimpedance provides reliable longitudinal data and reveals granular fluid patterns not captured by conventional ISL staging alone. The significant impact of diurnal variation, particularly in relation to limb dominance, underscores the need for standardizing measurement protocols. Standardizing home-based measurements to a fixed monitoring time can minimize physiological noise and enhance the interpretability of long-term self-monitoring strategies for breast cancer survivors.

PMID:42085680 | DOI:10.2196/86624

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Nevin Manimala Statistics

Epidemiological Distribution Characteristics of Tuberculosis Among Older Adults in Chongqing (2020-2024): Spatial-Temporal Analysis

JMIR Public Health Surveill. 2026 May 5;12:e89671. doi: 10.2196/89671.

ABSTRACT

BACKGROUND: With global aging, the burden of tuberculosis (TB) among older adults escalates, yet spatial studies on this group are scarce. In Chongqing, where 18.87% of the population are aged 65 years and older and TB burden is high, controlling older adult TB remains a major challenge.

OBJECTIVE: This study analyzed the spatiotemporal patterns of TB among adults aged 65 years and older in Chongqing, China, to inform local prevention and control strategies.

METHODS: The study data were obtained from the Tuberculosis Information Management System of China. Global and local spatial autocorrelation analyses were conducted using ArcGIS (version 10.7) to identify high-risk spatial clusters and visualize their distribution. Spatiotemporal scan statistics were performed using SaTScan (version 10.3.2) to detect clusters of TB cases among the older adult population. Statistical significance was set at P<.05.

RESULTS: The average annual incidence of TB among older adults in Chongqing was 69.59 per 100,000 population, with peaks occurring in spring and summer. The global Moran I ranged from 0.618 to 0.756 (P<.001 in all cases), indicating significant clustering. Persistent high-risk areas were identified in the northeastern and southeastern parts of Chongqing. Spatiotemporal scan statistics detected 1 most likely cluster (relative risk=3.52, 95% CI 3.37-3.68; log-likelihood ratio=1017.43; P<.001) and 3 secondary clusters.

CONCLUSIONS: Significant seasonal patterns of TB among older adults were observed in Chongqing. High-risk areas were predominantly concentrated in the northeastern and southeastern parts of the municipality. More targeted public health interventions are imperative.

PMID:42085675 | DOI:10.2196/89671