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Twin Research and Human Genetics

◐ Cambridge University Press (CUP)

Preprints posted in the last 7 days, ranked by how well they match Twin Research and Human Genetics's content profile, based on 11 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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Validation and culture adaptation of the Arabic version of the Rapid Eating Assessment for Participants - Shortened Version (REAP-S): A Confirmatory Factor Analysis and Rasch Analysis Study

Albarrak, T. M.; Al-Qerem, W. N.; AL-Quraan, S. N.; Alharbi, A.; Alkouri, O.

2026-10-16 nursing 10.64898/2026.10.15.26365598 medRxiv
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Abstract Aim: To translate, culturally adapt, and psychometrically validate the Arabic version of the REAP-S among Arabic speaking young adults using Confirmatory Factor Analysis (CFA) and Rasch Measurement Theory (RMT). Design: A cross-sectional methodological psychometric validation study. Methods: The study included 500 undergraduate and postgraduate nursing students recruited from Saudi universities during the 2025-2026 academic year. The REAP-S was translated into Arabic using standardized forward backward translation procedures and cross-cultural adaptation guidelines. Participants completed the Arabic REAP-S through an online self-administered questionnaire. Construct validity was evaluated using CFA with robust estimators, assessing the Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), Root Mean Square Error of Approximation (RMSEA), and Standardized Root Mean Square Residual (SRMR). Rasch Measurement Theory was applied to examine item fit, response category functioning, person item targeting, and person reliability. We assessed internal consistency using Cronbach's alpha and the Rasch Person Separation Index (PSI). Results: Psychometric analyses included 490 participants with a median age of 20 years (IQR = 19-22), of whom 54.1% were female. CFA supported the hypothesized one-factor structure and showed good model fit (CFI = 0.984, TLI = 0.978, RMSEA = 0.076, SRMR = 0.061). Standardized factor loadings ranged from 0.429 to 0.768, and internal consistency was good (Cronbach's = 0.863). Rasch analysis confirmed the scale's unidimensionality, with satisfactory person reliability (Expected A Posteriori [EAP] = 0.872; Weighted Likelihood Estimate [WLE] = 0.848). All items demonstrated acceptable infit and outfit mean square statistics (0.826-1.311 and 0.866-1.283, respectively), with ordered response thresholds and adequate person-item targeting. Overall, the Arabic REAP-S effectively discriminated between different levels of dietary behavior among Arabic-speaking young adults. Conclusion: The Arabic REAP-S demonstrated strong validity and reliability, supporting its unidimensional structure and appropriate psychometric performance. Evidence from both CFA and Rasch analysis confirmed acceptable model fit, good internal consistency, and adequate item functioning. The instrument provides a brief and practical tool for assessing dietary behaviors among Arabic-speaking young adults in clinical and research settings. Implications for the Profession and/or Patient Care: The Arabic REAP-S provides nurses and other healthcare professionals with a brief, standardized tool for rapidly assessing dietary behaviors and identifying individuals at nutritional risk. Its integration into routine clinical and community practice may support early dietary screening, guide nutrition education, and strengthen evidence based preventive care for diet related chronic diseases. Keywords: Arabic REAP-S; Dietary Screening; Confirmatory Factor Analysis; Rasch Measurement Theory; Construct Validity; Young Adults.

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Sex-, age-, and BMI-specific patterns of visual and numerical body-size ideals in Japan: a large cross-sectional web-based survey

Tabata, H.; Sakamoto, S.; Fukumura, K.; Kanda, M.; Adachi, Y.; Yoshizawa, Y.; Tamura, Y.

2026-10-19 epidemiology 10.64898/2026.10.19.26365487 medRxiv
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Background: Thinness-oriented body ideals are well described among young Japanese women, but variation in visual and numerical ideals by sex, age, and current BMI remains unclear. Methods: We analysed an unweighted web-panel sample of 27,359 Japanese adolescents and adults aged 15-69 years from the Survey of Body Shape and Health Awareness in Japanese People, a cross-sectional web-based survey. Current and ideal BMI were derived from self-reported height and weight, and visual orientation from ideal versus perceived current silhouette. Adult BMI-stratified analyses included participants aged 20-69 years. Findings: Among 27,359 participants (10,094 men and 17,265 women), relative thinness-oriented indicators increased with current BMI in both sexes. Among normal-weight women, 74.7-83.7% selected a smaller ideal silhouette and 79.2-91.2% reported an ideal BMI lower than current BMI. These indicators were also present among underweight women aged 20-29 years (44.9% and 43.4%, respectively), but declined with age. Most underweight men reported weight-gain-oriented ideals. Fine stratification showed that thinness-oriented ideals among women were common in low-normal and mid-normal BMI strata. Interpretation: Body-size ideals differed by sex, age, and current BMI. Thinness-oriented ideals among women extended beyond obesity and young adulthood, whereas underweight men generally preferred a larger body. Longitudinal and behavioural studies are needed. Funding: Cabinet Office of Japan Strategic Innovation Promotion Program (SIP), "Inclusive Community Platform" (grant no. SIPCP23C02).

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Association between Resilience and Financial Toxicity: The Moderating Role of Age, Race and Socioeconomic Factors

Zhan, Y.; Wells, R.; Knobf, T.; Shan, L.; Lustberg, M. B.; Wang, H.-L.

2026-10-21 nursing 10.64898/2026.10.19.26365649 medRxiv
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PURPOSE: Women with metastatic breast cancer (MBC) are at risk of developing financial toxicity due to prolonged treatment. Resilience has been identified as a key protective factor associated with better quality of life among cancer populations. However, it is unknown if resilience is associated with financial toxicity. We sought to examine the relationship between resilience and financial toxicity among women with MBC and explore whether socioeconomic factors moderate this association. PATIENTS AND METHODS: Our sample included 209 women with MBC who completed self-reported questionnaires of the Resilience Scale Specific to Cancer (RS-SC) and the Comprehensive Score for Financial Toxicity (COST). Participants (n=2) with missing data were excluded from analysis. We conducted multiple linear regression to examine the association of resilience with financial toxicity. Interaction terms were used to test moderating effects of age (18-39, 40-64 and > =65 years), race, education, health insurance, household income and employment status. RESULTS: Of the sample, 56.5% were aged 40-64 years, 76.6% were White, and 79.9% had a college or master degree or above. Women reported moderately high resilience with mean RS-SC score of 34.49 (SD = 6.67), and moderate financial toxicity (mean COST score =21.01 [SD = 10.51]). Adjusting for covariates, higher resilience was linked to better financial well-being (b = 0.37, SE= 0.11, 95% CI [0.14, 0.59], P < 0.01). Age, education and health insurance moderated this relationship, with resilience more strongly associated with better financial well-being among those aged 40-64 years, with college/master degree or above and private insurance. Race, household income, and employment status did not moderate the association between resilience and financial toxicity. CONCLUSION: Women with MBC who reported higher resilience are more likely to experience better financial well-being, but the strength of this association varied by socioeconomic factors. Further research is needed to confirm these findings. Our results have important implications for incorporating resilience into financial toxicity interventions and tailoring such interventions based on individual socioeconomic characteristics.

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Professional Identity and Its Influencing Factors Among Nursing Interns: The Mediating Role of Career Adaptability Between Social Support and Professional Identity

Zhao, Y.; Liu, F.; Chen, L.; Li, X.; Wu, B.

2026-10-16 occupational and environmental health 10.64898/2026.10.14.26365571 medRxiv
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Purpose: The internship period is a critical stage for nursing students to develop professional values. This study aimed to investigate the current status of professional identity among nursing interns, analyze the effects of social support, perceived stress, psychological resilience, and career adaptability on professional identity, and explore the mediating role of career adaptability between social support and professional identity, so as to provide empirical evidence for enhancing professional identity and optimizing nursing talent training systems. Methods: Using convenience sampling, 407 nursing interns from a tertiary hospital in Quanzhou were selected as participants from May to July 2025. Data were collected using a general information questionnaire, the Social Support Scale, the Perceived Stress Scale, the Psychological Resilience Scale, the Professional Identity Questionnaire for Nursing Students, the Career Adaptability Scale, and the Questionnaire for Nurse Intention to Retention Employed. SPSS 26.0 was used for reliability analysis, descriptive analysis, independent samples t-test, one-way ANOVA, Pearson correlation analysis, and multiple linear regression analysis. The PROCESS macro was employed to test the mediating effect. Results: The total score of professional identity among nursing interns was (61.74{+/-}11.08), with 73.5% showing moderate professional identity. Parents' attitude toward nursing, reasons for choosing the profession, personal attitude toward the major, and employment intention showed statistically significant differences in professional identity scores (p<0.05). Pearson correlation analysis revealed that professional identity was significantly positively correlated with social support (r=0.474), psychological resilience (r=0.389), and career adaptability (r=0.609) (p<0.01), and significantly negatively correlated with perceived stress (r=-0.378) (p<0.01). Multiple linear regression analysis indicated that career adaptability ({beta}=0.309, p<0.001) and social support ({beta}=0.383, p<0.001) were significant positive predictors of professional identity, whereas reasons for choosing the profession ({beta}=-3.603, p=0.001) and employment intention ({beta}=-7.116, p<0.001) were significant negative predictors. The model explained 49.2% of the variance in professional identity. Mediation effect analysis showed that career adaptability played a partial mediating role between social support and professional identity, with a mediation effect value of 0.288 (95% CI: 0.221-0.363), accounting for 40.2% of the total effect. Conclusions: Nursing interns' professional identity is at a moderately high level. Social support and career adaptability are positive influencing factors. Career adaptability plays a partial mediating role between social support and professional identity; social support indirectly enhances professional identity by strengthening career adaptability.

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Development and Validation of a Parsimonious Financial Well-Being Index in the Health and Retirement Study

Habib, M. H.; Mayeda, E. R.; Barry, L.; Arah, O. A.; Nau, C. L.; Zhou, H.; Kezios, K. L.; Nianogo, R. A.

2026-10-20 epidemiology 10.64898/2026.10.18.26365842 medRxiv
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Financial well-being (FWB) encompasses objective and subjective financial status and may influence health. We developed and validated a parsimonious FWB index using data from 23,006 Health and Retirement Study (HRS) participants aged 50 years and older from 2006 to 2022. The FWB-5 Index was derived using correlated two-factor confirmatory factor analysis accounting for household clustering. Indicators included household wealth, household income-to-poverty ratio, monthly financial strain, satisfaction with one's financial situation, and perceived financial mastery. We assessed convergent and discriminant validity using the Consumer Financial Protection Bureau Financial Well-Being (CFPB-FWB) Scale and Satisfaction with Life Scale, respectively. Associations with pre-baseline socioeconomic factors and subsequent depressive symptoms and health conditions were examined to assess construct and predictive validity. Model fit indices supported the two-factor structure (robust comparative fit index = 0.99; robust root mean square error of approximation = 0.05). Correlations were stronger with the CFPB-FWB Scale (Spearman P = 0.80) than with life satisfaction (Spearman P = 0.43). Associations with socioeconomic factors and subsequent health outcomes were in the hypothesized directions. These findings support the FWB-5 Index as a parsimonious measure for examining financial well-being and its associations with health across HRS waves, including those predating the CFPB-FWB Scale.

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Sex-Specific Associations of Added Sugars and Fructose Exposure Across the First 1,000 Days With Body Composition at 24 Months

Fortin-Miller, S. A.; Gajewski, B. J.; Carlson, S. E.; Colombo, J.; Christifano, D. N.; Sullivan, D. K.; Hull, H. R.

2026-10-19 nutrition 10.64898/2026.10.16.26365755 medRxiv
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Background: Added sugars during early development may influence adiposity, but whether associations vary by developmental timing and child sex is unclear. Objectives: To determine whether child sex modifies associations of added sugars and fructose exposure from pregnancy through 24 months with body composition at 24 months. Methods: This secondary longitudinal analysis included 130 mother-child dyads. Maternal diet was assessed during mid-pregnancy and child diet at 2wk and 6mo (infancy), and 12mo and 24mo (toddlerhood). Multivariable regression tested sex-by-exposure interactions for anthropometric outcomes; 42 children had usable dual-energy X-ray absorptiometry (DXA) data. Results: Prenatal added sugars were more positively associated with percentage body fat and total and regional fat mass in girls than in boys. Prenatal fructose was more positively associated with waist circumference in boys. During infancy, added sugars were more positively associated with percentage body fat and total and regional fat mass in boys, whereas fructose was more positively associated with fat-free mass in girls. Conclusions: Associations of early-life sugars exposure with body composition varied by developmental timing and child sex. Findings from the smaller DXA subset are exploratory and require replication but suggest that susceptibility to early dietary sugars may differ across developmental windows.

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Variation in psychiatric diagnoses and use of psychotropic medication among children, adolescents, and young adults in Denmark

Sonne, H.; Kildegaard, H.; Bech, M.; Wesselhoeft, R.; Hansen, A. S. K.; Ording, A. G.; Pottegaard, A.

2026-10-20 epidemiology 10.64898/2026.10.19.26365872 medRxiv
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Background Psychiatric diagnoses and psychotropic medication use among children, adolescents, and young adults have increased in high-income countries, with concerns about geographic variation. We described national trends and geographic variation in Denmark from 2010 to 2025 and developed an interactive online tool to explore these patterns. Methods We conducted a nationwide, descriptive, repeated cross-sectional register-based study of all Danish residents aged 0-24 years in 2010-2025 (n=2,930,744), using the Danish National Patient Registry and the Danish National Prescription Registry. We estimated annual incidence, prevalence, and, for selected diagnoses, lifetime prevalence, by age and sex, and age- and sex-standardised rates across regions, health councils, and municipalities. We assessed geographic variation using deviations from national means, coefficients of variation, Gini coefficients, and funnel plots. Findings Psychiatric diagnoses and psychotropic medication use increased from 2010 to 2025. The annual prevalence of attention-deficit hyperactivity disorder (ADHD) increased from 0.41 to 2.3 per 100 individuals, autism spectrum disorders from 0.20 to 1.2, and melatonin use from 0.14 to 3.0. ADHD and autism spectrum disorders were more prevalent among boys and anxiety disorders among girls. Sertraline use was also more prevalent among girls. Geographic variation was observed across diagnoses and psychotropic medications at regional, health council, and municipal levels. For example, lifetime prevalence of autism ranged from 1.3 to 5.9 per 100 across municipalities, and in 2025 regional coefficients of variation ranged from 0.11 (sertraline) to 0.41 (atomoxetine). Results can be explored in the interactive online tool (https://bupstat.sdu.dk/?lang=en). Interpretation Psychiatric diagnoses and psychotropic medication use increased among Danish children, adolescents, and young adults, with marked geographic variation. Descriptive data cannot establish the causes of this variation, but the findings identify areas for further review and support continued monitoring. Funding Best for Us project (www.bedstforos.dk), funded by the Novo Nordisk Foundation (NNF24SA0093635) and the Obel Family Foundation (69348).

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Glycemic patterns from continuous glucose monitoring devices among women with regular and irregular menstrual cycles

Wang, Z.; Asokan, G.; Zhang, B.; Werdin, S.; Bojorquez-Ramirez, P.; Suharwardy, S. H.; Onnela, J.-P.; Williams, M. A.; Coull, B. A.; Mahalingaiah, S.

2026-10-21 epidemiology 10.64898/2026.10.16.26365453 medRxiv
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Polyendocrine metabolic ovarian syndrome (PMOS) and early-life irregular cycles (ELIC) carry higher metabolic risks, but real-world glycemic patterns remain inadequately characterized. We analyzed 247,316 continuous glucose monitoring (CGM) days from 716 consented and enrolled participants (11/2019-08/2026) in the Apple Women's Health Study, using cluster-weighted generalized estimating equations to evaluate associations between PMOS, ELIC, and glycemic metrics. Same-day wearable-assessed physical activity, digital dietary logs, and medication health records were assessed as effect modifiers. Compared to participants without PMOS and with regular cycles, those with PMOS had higher mean glucose (6.81 mg/dL; 95% CI: -0.70, 14.72) and %observations above target range (3.77%; 95% CI: 0.04, 8.14). Estimates were smaller-in-magnitude for participants without PMOS but with ELIC, and larger for PMOS with androgen excess. Meeting activity goals, consuming protein-/fiber-rich diets, or using metformin/GLP-1 receptor agonists attenuated these associations. PMOS/ELIC were associated with unfavorable glycemic profiles, suggesting opportunities for risk identification and modification.

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Long Sleep and Insomnia are Associated with Reduced Global Cognitive Function across Diverse Populations

Wyss, A. B.; Zhang, Y.; Brown, M. R.; Bressler, J.; DeCarli, C.; Fornage, M.; Gonzalez, H. M.; Guo, X.; Heckbert, S. R.; Hughes, T. M.; Isasi, C. R.; Kaur, S. S.; Lamar, M.; Liu, P. Y.; Lutsey, P. L.; Morrison, A. C.; Qi, Q.; Ramos, A. R.; Redline, S.; Rotter, J. I.; Sarnowski, C.; Sotres-Alvarez, D.; Tarraf, W.; Taylor, K. D.; Wallace, M. J.; Wood, A. C.; Yu, B.; Sofer, T.

2026-10-20 epidemiology 10.64898/2026.10.19.26365906 medRxiv
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Background: Although sleep disorders are generally associated with cognitive decline, definitions of sleep conditions and cognitive function vary greatly across studies. Therefore, we evaluated associations between consensus definitions of sleep and cognitive outcomes across multiple studies. Methods: Consensus sleep measures were ascertained at baseline visits in three cohort studies (HCHS/SOL, MESA and ARIC, N=11,563): short and long sleep ([&le;]6hours and [&ge;]9hours), insomnia (Women's Health Initiative Insomnia Rating Scale [&ge;]10 or [&ge;]6 for 3 questions), daytime sleepiness (Epworth Sleepiness [&ge;]11) and obstructive sleep apnea (OSA, Apnea-Hypopnea Index [&ge;]15). Cognitive measures were ascertained at baseline and follow-up visits in each study and used to calculate harmonized outcomes: global cognitive function (GCF) at baseline, change in GCF between baseline and follow-up, poor GCF at baseline ([&ge;]1SD below the median), and incident poor GCF at follow-up. Study-specific analyses were adjusted for age, sex, center, education, race/ethnicity, APOE4 and language of cognitive assessments as needed. Results were meta-analyzed across studies. Results: Long sleep was consistently associated with lower baseline GCF ({beta}=-0.19, SE=0.03, p=3.78x10-14, FDR p=7.56x10-13, p-heterogeneity=0.78) and increased odds of poor baseline GCF (OR=1.77, 95% CI=1.49-2.09, p=2.96x10-11, FDR p=2.96x10-10, p-heterogeneity=0.22) across cohorts. Insomnia was also suggestively associated with lower baseline GCF ({beta}=-0.051, SE=0.02, p=0.01, FDR p=0.07, p-heterogeneity=0.005) and increased odds of poor baseline GCF (OR=1.22, 95% CI=1.06-1.41, p=6.76x10-3, FDR p=0.05, p-heterogeneity=0.03). Sleep measures were not associated with change in cognitive function. Discussion: Associations of long sleep and insomnia with harmonized cross-sectional GCF across three large, multiethnic cohorts suggest that cognitive function may be associated with distinct sleep phenotypes.

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Understanding Psychological Health in Adults with Irritable Bowel Syndrome: A Cross-Sectional Study Using the All of Us Research Program

Wu, W.; Li, A.; Chen, J.; You, E.; Liu, P.; Rodriguez, L.; Chen, M.-H.; Cong, X.

2026-10-21 gastroenterology 10.64898/2026.10.20.26365988 medRxiv
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Background: Psychological health is an important aspect of health and well-being among adults with irritable bowel syndrome, yet the interrelationships among individual vulnerabilities, social experiences, perceived stress, and psychological health outcomes remain poorly understood. Objective: To characterize psychological health and examine direct and indirect associations of childhood adversity and adult attention-deficit/hyperactivity disorder-related symptoms within an adapted Stress Process Model. Design: Cross-sectional secondary analysis. Setting: The United States All of Us Research Program. Participants: 2,417 adults with electronic health record-documented irritable bowel syndrome and complete data on the primary analysis variables and covariates. Methods: Separate structural equation models examined childhood adversity and adult attention-deficit/hyperactivity disorder-related symptoms in relation to perceived stress, anxiety and depressive symptoms, and positive psychological well-being, with loneliness and perceived social support as psychosocial pathways. Models adjusted for sociodemographic and social-context factors. Results: The median age was 54.39 years; 80.7% were female and 84.4% were White. Moderate-to-high perceived stress was reported by 56.2%, at least moderate anxiety symptoms by 21.0%, and at least moderate depressive symptoms by 24.3%. Higher ACE-8 scores were associated with greater perceived stress, anxiety symptoms, and depressive symptoms and lower psychological well-being ({beta} = 0.063, 0.089, 0.116, and -0.100, respectively); corresponding associations for higher ASRS-6 scores were {beta} = 0.299, 0.355, 0.390, and -0.260. Loneliness-specific indirect associations were positive for perceived stress, anxiety, and depressive symptoms (ACE-8: {beta} = 0.023-0.034; ASRS-6: {beta} = 0.043-0.075) and negative for psychological well-being (ACE-8: {beta} = -0.039; ASRS-6: {beta} = -0.089; all p < .001). Social support-specific indirect associations were not significant in the ACE-8 model and were small and significant only for anxiety and depression in the ASRS-6 model ({beta} = 0.003-0.004). Conclusions: Psychological health among adults with irritable bowel syndrome was associated with interconnected individual and social factors within an adapted Stress Process Model. Childhood adversity and adult attention-deficit/hyperactivity disorder-related symptoms showed direct and indirect associations with psychological health, with loneliness emerging as the most consistent social factor. These findings support prospective investigation of individual vulnerabilities and social experiences in psychological health. The cross-sectional design does not establish temporal ordering or causal mediation.

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Sex-stratified and interaction multi-omics analysis of DNA methylation and gene expression in asthma

Dessie, E. Y.; Gautam, Y.; Rosen, B. H.; Mendy, A.; Kang, M.; Mersha, T. B.

2026-10-21 respiratory medicine 10.64898/2026.10.19.26365928 medRxiv
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Background: Sex differences in asthma are well recognized, but sex-associated airway DNA methylation (DNAm) patterns and their relationships with gene expression remain incompletely characterized. We therefore conducted cis- and trans-expression quantitative trait methylation (eQTM) analyses using sex-stratified and CpG-by-sex interaction models. Methods: We analyzed nasal airway epithelial DNAm and transcriptomic data from 298 participants in the CAAPA discovery cohort. Asthma-associated differentially methylated CpGs (DMCs) were identified using sex-combined and sex-stratified models. Cis- and trans-eQTM analyses were then performed in participants with asthma using sex-combined, sex-stratified, and CpG-by-sex interaction models. To prioritize asthma-associated regulatory relationships, eQTMs that were also significant in non-asthmatic controls were excluded from downstream analyses. Replication in an independent bronchial epithelial cohort was defined by concordant effect direction and P < 0.05. Replicated targets underwent pathway and network analyses. Findings: Asthma-associated DMCs were predominantly hypomethylated in females and hypermethylated in males. Among trans-eQTMs, 379 associations were shared across all four models, whereas the majority were model-specific, indicating extensive sex-dependent regulatory architecture. We replicated 3, 1, 9, and 2 cis-eQTMs and 96, 84, 216, and 41 trans-eQTMs in the sex-combined, female-stratified, male-stratified, and interaction models, respectively. Sex-combined targets implicated innate immune and inflammatory signaling (TNF, IRF8); female-stratified targets implicated cytoskeletal remodeling, focal adhesion, and PI3K-Akt signaling (ITGA10); male-stratified targets implicated transcriptional regulation and post-translational modification (MOV10, HDAC7, CSF1, KAT2A); and interaction targets implicated lipid-mediator metabolism and inflammatory signaling and resolution (CYP2C9, LTB4R, CCL19). Our sex-dependent analyses showed that the majority of eQTMs resided within the trans-regulatory architecture, suggesting that sex-dependent gene expression differences are associated predominantly with trans rather than cis regulatory mechanisms. Pathway analyses revealed enrichment of innate immunity in the sex-combined model, structural remodeling in females, transcriptional control in males, and inflammatory resolution in the sex-interaction model. Interpretation: Sex-specific and sex-dependent airway methylation-expression associations were largely undetected by sex-combined analysis. Sex-aware analytical models may help resolve epigenetic mechanisms underlying sex differences in asthma biology.

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Pickleball injuries, search interest, and participation in the United States, 2014-2023: an ecological time series study

Kim, D. S.; Lobelo, F.; Durieux, J. C.; Colovos, C.

2026-10-16 epidemiology 10.64898/2026.10.14.26365555 medRxiv
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OBJECTIVE: To describe (1) US emergency department-treated pickleball injury burden and the injury-to-participation measure among total players, with burden among adults aged 60 to 79 years as a descriptive subgroup, and (2) determine whether general internet search interest for 'pickleball' is also associated with total pickleball-related injuries. DESIGN: Ecological time series study, United States, 2014 to 2023. DATA SOURCES: National Electronic Injury Surveillance System (NEISS) emergency department microdata yielded 1,738 adjudicated pickleball cases, 921 of them orthopedic, weighted to an estimated 101,450 injuries nationally. Google Trends, English Wikipedia pageviews, and GDELT news volume served as general pickleball attention signals, with the Trends index for 'sourdough' as a negative control. Sports and Fitness Industry Association (SFIA) participation estimates supplied a total player denominator. MAIN OUTCOME MEASURES: Annual national injury estimates with design-based 95 percent confidence intervals; injury-to-participation measures; and correlations between total pickleball-related injuries and general pickleball attention signals before and after removing trend and seasonality. RESULTS: Estimated emergency department-treated pickleball injuries rose 17.5-fold, from 1,391 in 2014 (highly unstable) to 24,294 in 2023. 70 percent of adjudicated cases involved adults aged 60 to 79. During 2017-2023, injury estimates rose 4.0-fold and participation rose about 4.4-fold. No temporal trend was detected in the injury-to-participation measure (P=0.59). Search interest looked like an excellent proxy: in annual levels it correlated with total pickleball-related injuries at R=0.96, and Pickleball Wikipedia pageviews at R=0.98. However, so did searches for "sourdough", at R=0.76. Removing trend and seasonality left little (monthly residual R=0.084; year-on-year R=0.28 over 96 months, 2015-2023), and the seasons ran opposite, with injuries peaking in February and searches in July, such that, on 12-month mean profiles, the sourdough negative control fitted the injury season (R=0.96) while pickleball ran against it (R=-0.40). General pickleball search interest and pickleball news coverage remained correlated in year-on-year changes in 2017-2023 (R=0.64), whereas their corresponding correlations with total pickleball-related injuries in 2017-2023 were 0.25 and 0.20. CONCLUSIONS: The absolute burden of emergency department-treated pickleball injury has grown substantially, but the available surveillance data cannot resolve whether the sport has become more hazardous per participant. The observed rise is consistent with growth in exposure alone. The strong correlation between search interest and injury counts was not specific, the association was substantially attenuated after detrending, and the seasonal patterns were opposed. These descriptive results do not establish that search interest can substitute for injury surveillance, and series that rise together should not be assumed to be related.

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Biological aging markers in South African women with HIV and variable exposure to childhood maltreatment

Maloka, K. M. S.; Spies, G.; du Plessis, S.; Hemmings, S. M. J.; Letendre, S.; Seedat, S.; Womersley, J. S.

2026-10-16 hiv aids 10.64898/2026.10.15.26365601 medRxiv
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Introduction: HIV and childhood maltreatment (CM) are both chronic stressors that disproportionately affect women, with each contributing to accelerated biological aging. Whether biological aging markers are convergent and associate with HIV and CM is unclear. Methods: We studied 238 women (122 with HIV), characterised for CM severity, and assessed biological aging using absolute telomere length (aTL), mitochondrial DNA copy number (mtDNAcn), magnetic resonance imaging-based brain-predicted age difference (MRI-BPAD), and DNA methylation age (DNAmAge) clocks. CM was measured with the Childhood Trauma Questionnaire-Short Form total score. We examined intercorrelations among biological aging markers to assess convergence and conducted linear regression models to test moderation by HIV status and CM severity. Results: PWH had shorter aTL, lower MRI-BPAD, and higher Horvath age acceleration (HorvathAA), HannumAA, PhenoAA, and extrinsic epigenetic age acceleration (EEAA). CM had limited associations with biological aging markers. Absolute TL correlated weakly with mtDNAcn (p = 0.36), PhenoAA (p = -0.18), and EEAA (p = -0.18), while MRI-BPAD correlated weakly with PhenoAA (r = 0.20). DNAmAge clocks were moderately to strongly intercorrelated (r = 0.35 - 0.93). No robust two- or three-way moderation effects were observed after false discovery rate correction. Conclusion: Our findings support a multidimensional pattern of biological aging, with substantial convergence among epigenetic aging measures but limited relationships across different markers, largely independent of HIV status and CM severity. Longitudinal approaches are needed to clarify how distinct biological aging markers relate to one another and to health outcomes over time in vulnerable populations.

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When Prescribing Diverges From Published Lactation Compatibility Guidance: A National Claims Analysis

Krutsch, K.; Appiah, D.

2026-10-21 epidemiology 10.64898/2026.10.19.26365940 medRxiv
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Purpose Prescribing to lactating women is constrained by limited evidence. Published compatibility classifications provide clinical guidance and a discrete research comparator. How often prescribing diverges from that guidance, and what characteristics are associated with divergence, is unknown at national scale. Methods Retrospective analysis of prescriptions filled during lactation, identified in the 2012-2014 MarketScan Commercial Claims Database. Prescriptions were classified as concordant (Hale's lactation risk category L1-L3) or discordant (L4-L5). Multivariable logistic regression identified factors associated with concordance. Results Of 96,484 new prescriptions, 95,710 (99.2%) were concordant and 774 (0.8%) were discordant. Discordant prescriptions were filled later after delivery (median 59 vs 33 days) and had a day supply three times longer (30 vs 10 days). In multivariable analysis (N=28,732), concordant prescriptions were associated with maternal age under 35 (adjusted odds ratio (aOR)=1.34, 95% confidence interval (CI): 1.02-1.75) and chronic-condition medications (aOR=10.94, 95% CI: 6.47-18.50), and were less likely within 14 days of delivery (aOR=0.53, 95% CI: 0.38-0.73) and with each additional day of supply (aOR=0.96, 95% CI: 0.96-0.96). Compared with family practice, concordance did not differ for obstetric, internal medicine, or emergency medicine prescriptions, but prescriptions from other provider types had lower odds of concordance (aOR=0.57, 95% CI: 0.41-0.79). Conclusions Prescribing during lactation was overwhelmingly concordant with published compatibility guidance; the rare divergence was patterned by prescription and prescriber characteristics. Because the categories are an expert classification rather than consensus guidance, divergence should not be read as inappropriate prescribing.

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Validation of the Qualisex Questionnaire for Psychometric Assessment of Sexual Health in Lichen Sclerosus

Samela, T.; Priori, R.; Colonna, L.; Zozi, L.; Gallo, V.; Assorgi, C.; Garcovich, S.; Paganelli, A.

2026-10-19 dermatology 10.64898/2026.10.16.26365725 medRxiv
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Introduction: Lichen sclerosus (LS) is a chronic inflammatory dermatosis predominantly affecting the anogenital region of both women and men. Sexual dysfunction remains among the most debilitating and overlooked consequences of the disease, as available patient-reported outcome measures are either restricted to one sex or capture sexual health only partially. The aim of the present work is to validate the Qualisex questionnaire (in its the Italian version) in patients with LS and to evaluate its psychometric properties, factor structure, convergent, discriminant validity, and sex symmetry. Methods: A cross-sectional study was conducted on 211 patients (167 women, 44 men; mean age 52.9 years) with a confirmed diagnosis of LS. Participants completed the Italian Qualisex, Skindex-29, DASS-21, and sexual-health-specific scales, the Female Sexual Function Index (FSFI) for women, and the International Index of Erectile Function (IIEF) for men. Construct validity was assessed via Principal Component Analysis (PCA), and reliability via Cronbach's alpha. Convergent and discriminant validities were evaluated against standard psychometric batteries. Results: Item 2 was removed due to low communality (0.167). PCA on the remaining 9 items revealed a two-factor structure accounting for 72.5% of total variance: Component 1 (Sexual Functioning and Satisfaction, 59.89%) and Component 2 (Partner Devaluation, 12.66%). Internal consistency was high (alpha= 0.911 overall; alpha= 0.841 in women; alpha= 0.899 in men). Qualisex scores correlated strongly with Skindex-29 Social Functioning (r = 0.582) and Emotions (r = 0.531) subscales, as well as FSFI (r = -0.391) and IIEF (alpha= -0.566). Discriminant validity was supported by low-to-moderate correlations with DASS-21 domains (r < 0.38). While FSFI and IIEF showed significant negative correlations with age (p = 0.002), Qualisex remained age-independent across sexes (p > 0.05). Conclusion. The 9-item Italian Qualisex is a reliable, sex-symmetrical, and age-independent patient-reported outcome measure for assessing sexual health impairment in LS, successfully isolating disease-specific distress from physiological aging and general distress.

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Trends and Disparities in Respiratory Failure Mortality with Co-Listed Atrial Fibrillation and Flutter Among U.S. Adults Aged >= 65 Years, 1999 to 2024, with AAMR Forecasts Through 2035: A CDC Wonder Analysis

Seher, W.; Masood, H. A.; Jamil, A.; Fiza, S.; Jehangir, A.; Hafeez, R.; Arbab, M.; Ahmad, R.; Ullah, H.; Sharma, S. P.

2026-10-16 respiratory medicine 10.64898/2026.10.15.26365608 medRxiv
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Abstract Background: Respiratory failure (RF) and atrial fibrillation/flutter (AF/AFL) often occur together in older adults, but long-term national mortality trends for the two conditions combined have not been described. We examined trends and disparities in deaths with co-listed RF and AF/AFL among U.S. adults aged 65 years and older from 1999 to 2024, and projected rates through 2035. Methodology: We used the CDC WONDER Multiple Cause of Death database to identify deaths with ICD 10 codes J96 (RF) and I48 (AF/AFL) listed together. Age-adjusted mortality rates (AAMRs) per 100,000 were standardized to the 2000 U.S. population and stratified by sex, race/ethnicity, census region, urbanization, state, and place of death. Joinpoint regression was used to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). Forecasts for 2025 to 2035 were generated with an exponential smoothing (ETS) model. Results: A total of 433,598 deaths were recorded. The overall AAMR rose from 12.8 in 1999 to 66.7 in 2024 (AAPC 8.11%; 95% CI, 7.35 to 8.87; P < 0.0001). Three segments were identified: an increase from 1999 to 2018 (APC 7.73%), a sharp rise from 2018 to 2021 (APC 18.10%), and a decline from 2021 to 2024 (APC -5.25%). Males had a higher AAMR and a steeper increase than females (AAPC 8.44% vs 7.81%). Non-Hispanic White adults had the highest mean AAMR, Hispanic adults had the largest relative increase (AAPC 8.72%), and Non-Hispanic Asian/Pacific Islander adults had the smallest (AAPC 6.23%). The Midwest had the fastest regional growth (AAPC 9.35%). From 1999 to 2020, non-metropolitan areas increased faster than metropolitan areas (AAPC 10.09% vs 8.21%). State AAMRs ranged from 24.7 in Ohio to 85.1 in Louisiana. Most deaths occurred in hospital inpatient settings (64.1%), followed by nursing homes (14.1%) and the home (11.9%). The model projects an AAMR of 122.96 per 100,000 by 2035 (95% prediction interval, 85.42 to 160.50). Conclusions: Mortality involving RF with AF/AFL among older U.S. adults increased more than fivefold over 25 years, with a marked surge during the COVID 19 period and only a partial decline afterward. Differences by sex, race/ethnicity, region, and urbanization point to groups that may benefit from earlier detection and coordinated cardiopulmonary care.

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Development of a Communication Characteristics Module for Autistic Adults and the Creation of a Communication Profile Variable

Kripke-Ludwig, R.; Vera, J. W.; Moura, I.; Kapp, S. K.; Siddeek, Z.; Maslak, J.; Wallington, A. F.; Rosa, S. D. R.; Kripke, C. C.; Nicolaidis, C.

2026-10-19 rehabilitation medicine and physical therapy 10.64898/2026.10.15.26365687 medRxiv
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Purpose Autistic adults have diverse communication characteristics that are not well captured by standard demographic measures. Communication affects self-determination, relationships, access to healthcare, and services. Characterizing communication differences may improve research and intervention targeting for meaningful subgroups of autistic adults. Methods The Academic Autism Spectrum Partnership in Research and Education (AASPIRE) Outcomes Project team used a community based participatory research (CBPR) approach to develop a self- or caregiver-report module to characterize communication among autistic adults. The 10-item module asks about receptive and expressive communication, literacy, speech reliability, usage of digital communication, use of alternatives to speech, and communication fluency. It can be completed directly, with or without support, or via a caregiver. We used baseline survey data from 844 autistic adults to evaluate the module and derived a five-level variable, Communication Profile, from selected module items to stratify participants. We examined completion feasibility, response consistency, and construct validity. We also assessed test-retest reliability in a 15% random subsample who completed a 2-week retest following the 6-month survey, with oversampling of caregiver-report respondents. Results The Communication Characteristics module demonstrated high completion feasibility, minimal systematic error, and strong construct validity. The Communication Profile variable stratified participants into five meaningful communication profiles and demonstrated strong construct validity and substantial test-retest reliability ({kappa} = .69). Conclusion The Communication Characteristics module and Communication Profile variable provide a valid approach for characterizing communication diversity among autistic adults for research, clinical, and service settings. The full AASPIRE Measurement Toolkit is available at https://aaspire.org/measurement. Lay Summary Autistic people communicate in many different ways, and their communication may change in different situations. We developed and tested a set of survey questions to describe an individuals communication. We also used the results to describe 5 groups of autistic people based on how they communicate, without treating these groups as different types of autism.

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Autistic Adults' Perceptions of the Adequacy of their Supports and Disability-Related Information: Instrument Validation & Preliminary Correlates

Schuck, R. K.; Moura, I.; Baker-Ericzen, M. J.; Yang, L.-Q.; McDonald, K.; Kapp, S.; Uljarevic, M.; Love, J.; Vera, J. W.; Horner-Johnson, W.; Kripke-Ludwig, R.; Siddeek, Z.; Nicolaidis, C.

2026-10-21 psychiatry and clinical psychology 10.64898/2026.10.19.26365938 medRxiv
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Autistic adults face considerable challenges in receiving adequate support, from both paid/formal (such as from disability services) and unpaid/informal (for example, from friends and family) sources. Having adequate support can lead to better health and well-being outcomes. However, most instruments designed to assess adequacy of support were not made specifically for/with autistic adults. This paper presents a psychometric validation of the AASPIRE Adequacy of Supports and Information Scale (AASIS), a community-informed adaptation of a previously developed instrument (the Quality of Care and Support scale; Lucas-Carrasco et al., 2011), designed to be relevant and accessible to autistic adults. We also used the AASIS to explore correlates of perceptions of support in a sample of 798 autistic adults. Our confirmatory factor analysis supported a two factor structure for the AASIS (factor one: Supports; factor two: Information). Further testing confirmed the instrument was invariant across several groups, including race/ethnicity, gender, intellectual disability, communication fluency, and self versus proxy-report. Regression analyses suggested that the way in which participants joined the study (i.e., through community advertisements or via established healthcare/disability services) impacted whether they viewed their support as adequate. Additionally, a higher number of adverse childhood events and greater experience of discrimination were related to worse perceptions of support adequacy across both factors. Our findings support the preliminary validity of the AASIS across a variety of autistic people, though further testing is warranted. Findings also point to the importance of addressing the needs of autistic people who are minoritized and/or who have complex trauma histories.

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Beyond the Percentile: CDC-referenced BMI-for-Age and Brain Structure Across Childhood and Adolescence

Beck, D.; Westlye, L. T.; Tamnes, C. K.

2026-10-20 pediatrics 10.64898/2026.10.18.26365816 medRxiv
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Importance: Pediatric obesity affects 1 in 5 US children and has been linked to brain structural differences. Most evidence is cross-sectional and models body mass index (BMI) linearly, with metrics that compress severe obesity. Objective: To examine associations between brain structure and BMI for age across the weight spectrum and Centers for Disease Control and Prevention (CDC) weight status categories, distinguishing between and within person associations, and their age and sex moderation. Design, Setting, and Participants: Longitudinal cohort study of youth aged 8 to 10 years at baseline in the US community based Adolescent Brain Cognitive Development Study (4 waves, 2016 to 2025; ages 8 to 18 years). Exposures: Extended CDC BMI-for-age z-score, grouped by wave-mean z-score: underweight (<5th percentile, n=297), healthy weight (5th to <85th, n=7,452), overweight (85th to <95th, n=1,919), and obesity ([&ge;]95th, n=1,842). Main Outcomes and Measures: Cortical thickness (12 regions) and subcortical volume (7 regions) from T1 weighted magnetic resonance imaging (MRI), defined a priori. Results: Among 11,510 participants contributing 32,212 observations (mean [SD] age, 12.6 [2.5] years; 52.2% male), higher between person BMI for age z was associated with lower frontal and temporal thickness (6 regions) and larger subcortical volume (5 regions; all q < .001), but associations were nonlinear (17 of 19 regions). Youth with obesity had lower thickness than healthy weight youth in 8 frontal and temporal regions (largest, -0.21 SD; q < .001), with dorsal frontal differences decreasing across adolescence; underweight youth had smaller subcortical volumes. Higher BMI for age z was associated with larger subcortical volume (all 7 regions) within the healthy weight category and lower cortical thickness (11 of 12 regions; fusiform: {beta} = -0.27; q < .001) within the obesity category, steeper than in healthy weight youth in 10 regions, but not in overweight or underweight youth. Within person associations did not reproduce the obesity associations, reversed from negative at age 10 to positive at age 16, and were more negative in female than male participants. Conclusions and Relevance: Youth with obesity had lower cortical thickness than healthy weight peers, but associations between brain structure and BMI for age differed between CDC weight status groups, suggesting a complex relationship between adiposity and brain structure.

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Municipality-level ecological analysis of COVID-19 mortality and infections in Austria, 2020 to 2023

Riedmann, U.; Stevenson, A. C.; Dibben, C.; Grant, W. B.; Sprenger, M.; Zgaga, L.; Woltsche, J.; Wolf, P.; Maerz, W.; Ioannidis, J.; Pilz, S.

2026-10-16 epidemiology 10.64898/2026.10.15.26365614 medRxiv
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Background: Previous studies indicated that regional fluctuations in COVID-19 impact were associated with socioeconomic, demographic and environmental factors early in the pandemic. It is unclear whether factors associated with regional COVID-19 mortality and SARS-CoV-2 infections changed over the course of the pandemic. Methods: We evaluated the association of ecological factors with municipality-specific COVID-19 mortality in the national population of Austria between January 2020 and June 2023. Analyses were conducted separately per calendar year and pooled across years via random-effects meta-analysis. Outcomes were analysed using univariable and multivariable zero-inflated negative binomial (ZINB) regression, including annually averaged environmental exposome exposure (including air pollution and UV radiation), socioeconomic, demographic and infection dissemination predictors with significance threshold set to p<0.005. Secondary analysis modelled SARS-CoV-2 infections using of negative-binomial model (NB). Two additional approaches for smaller predictor set selection were applied as sensitivity analyses. Results: Within the entire observation period 18,430 COVID-19 deaths were reported. In univariable analyses (pooled RR (99.5% CI)), COVID-19 mortality was significantly associated with the proportion of commuters (0.79 (0.73-0.86)), residents aged 75-84 (1.18 (1.01-1.37)) and [&ge;]85 years (1.29 (1.04-1.60)), residents with at most compulsory education (1.15 (1.02-1.29)), employed residents aged 15-64 (0.89 (0.85-0.93)), and homeowners (0.91 (0.83-0.99)), as well as with precipitation (0.94 (0.89-0.99)) and the average time with a mean temperature of 5-15 C (0.95 (0.90-0.99)). In multivariable analyses the share of population aged 85 or older (1.30 (1.09-1.54)) and home ownership (0.92 (0.87-0.98)) were independently significant. Mortality predictor estimates were relatively stable across pandemic years. Across 5,963,882 documented SARS-CoV-2 infections share of employed in 15- to 64-year-olds (1.01 (1.01-1.02)), part-time employment rate (1.01 (1.00-1.02)) and district level nursing care allowance recipiency (0.97 (0.95-0.98)) were associated with detected infections. Overnight stays, population 85 or older, income, compulsory education or less and air pollution all had multiple significant estimates with opposite directionality, leading to non-significant overall associations. Sensitivity analyses outcomes mirrored main analyses outcomes. Conclusions: Throughout the pandemic in Austria, demographic and socioeconomic factors were associated with COVID-19 mortality and infections, but many associations, especially for infections, were unstable over time. These findings underscore the importance of structural vulnerabilities in epidemic impact.