Frontiers in Nutrition

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).

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.

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.

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.

Background: Iron deficiency (ID) and iron deficiency anaemia (IDA) have global and severe health implications, and disproportionately impact women of reproductive age. Current methods of supplementing diets with iron are challenged by poor adherence and palatability, reducing effectiveness of these treatment strategies. The aim of this study is to evaluate the efficacy of a novel home beverage fortification with a mineral-enriched powder, designed to enhance bioavailability and ease of use, for the treatment of ID in women of reproductive age. Methods: This single-centre, randomised, double-blinded placebo-controlled trial will enrol 150 eligible biologically female participants with ID. Participants will be randomly assigned to the active intervention (iron/zinc-enriched powder) or control group (placebo powder) over 6 months. Primary outcomes will include change in serum ferritin (SF) concentrations and proportion of participants who remain iron deficient at 6-months. Secondary outcomes will include change in SF and haemoglobin (Hb) concentrations across timepoints, and levels of metabolites and key circulating pro-inflammatory biomarkers, changes in dietary intakes, self-reported perceptions of health, barriers to use of the powder, adherence and palatability, safety outcomes, and cost-effectiveness. Exploratory outcomes will assess the gut microbial metagenome and metabolome. Discussion: Fortification, an effective approach for the prevention of ID/IDA, has advantages over some methods of supplementation because it uses low levels of iron, minimising unpleasant side effects, does not risk toxicity, and has high acceptability and compliance rates. This mineral-enriched powder uses electrolytic iron and zinc sulphate monohydrate of a small particle size, which is less irritating to the gut, and facilitates bioavailability. Findings from the study will be shared with those affected by and involved in treating these conditions, as a novel intervention that is both effective and acceptable among women of reproductive age would help to improve treatment compliance, and ultimately, reduce ID/IDA burden. Trial registration: This trial is registered at clinicaltrials.gov (NCT05990166): https://clinicaltrials.gov/study/NCT05990166, August 2023.

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.

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.

Objectives: To compare high-sensitivity C-reactive protein (hsCRP) profiles in Korean and US adults with low-density lipoprotein cholesterol (LDL-C) below 100 mg/dL and examine differences after adiposity adjustment. Study design: Cross-sectional analysis of national health examination surveys. Methods: We analysed the Korea National Health and Nutrition Examination Survey 2022-2024 (n=5,785) and US National Health and Nutrition Examination Survey August 2021-August 2023 (n=1,056). Eligible adults had Sampson-calculated LDL-C below 100 mg/dL and hsCRP of 10 mg/L or less; elevated hsCRP was defined as 2-10 mg/L. We estimated survey-weighted prevalence differences and adjusted prevalence ratios (PRs). Results: LDL-C distributions closely overlapped (weighted medians, 79.7 vs 80.1 mg/dL), whereas median hsCRP was 0.50 vs 1.34 mg/L. Elevated-hsCRP prevalence was 12.2% in Korea and 35.7% in the United States (difference, 23.5 percentage points; 95% CI, 19.4-27.7); the age-sex-standardised difference was 23.4 percentage points. Among 6,235 common complete cases, the age-sex-adjusted US-versus-Korea PR was 2.86 (95% CI, 2.48-3.30), decreasing to 1.66 (1.40-1.98) after waist circumference adjustment and 1.92 (1.62-2.26) after body mass index adjustment. Conclusions: Similar LDL-C distributions coexisted with markedly different hsCRP profiles. Waist adjustment attenuated the between-country contrast more than BMI adjustment, supporting joint consideration of inflammatory, lipid and anthropometric measures in population surveillance.

Background. Metabolic syndrome is a cluster of cardiometabolic risk factors that may increase the risk of cardiovascular disease and type 2 diabetes, and African studies report a higher prevalence in women than in men. Prevention may depend, in part, on whether women recognise the condition and its modifiable risk factors. Relatively little appears to be known about this among women using primary-level health facilities in fast-growing peri-urban areas of Ghana. Objective. To assess knowledge of metabolic syndrome, describe lifestyle risk behaviours, self-reported cardiometabolic conditions and preventive practices, and examine selected lifestyle correlates of self-reported diabetes and hypertension among women attending Kasoa Polyclinic, Ghana. Methods. A descriptive cross-sectional survey was conducted in June and July 2024 among 174 women aged 18-45 years recruited by convenience sampling. A structured, interviewer-assisted questionnaire covered knowledge, lifestyle behaviours, self-reported diagnoses and preventive practices. Data were summarised as frequencies and percentages, and associations were examined with Pearson's chi-square test. Results. Only 37 women (21.3%) described metabolic syndrome as a condition that raises the risk of heart disease and type 2 diabetes, 40 (23.0%) identified central (apple-shaped) fat as the high-risk pattern and 31 (17.8%) knew that dietary recommendations exist. Most reported no weekly physical activity (116; 66.7%), daily sugary drinks (109; 62.6%), daily processed or fast food (100; 57.5%), high stress (103; 59.2%), and less than six hours' sleep (94; 54.0%). Self-reported diagnoses were hypertension in 60 (34.5%) and type 2 diabetes in 49 (28.2%). Fifty-nine (33.9%) had never received advice on prevention and 105 (60.3%) did not monitor their weight or waist. Self-reported diabetes was associated with short sleep (36.2% among those sleeping under six hours; p = 0.035) and with stress level (p = 0.028), being most frequent among women reporting low stress. Self-reported hypertension was more common with high stress (42.7%; p = 0.022) and with some physical activity (p = 0.005). Conclusion. Women attending this polyclinic appeared to have limited understanding of metabolic syndrome and a high burden of modifiable risk behaviours. Routine counselling on diet, activity, sleep, and weight monitoring at the polyclinic may be warranted. The bivariate, self-reported associations should be interpreted cautiously.

Background Influenza vaccines have seen many changes over recent years in terms of both policy recommendations and product types. Immune responses and vaccine effectiveness vary by vaccine strain composition and product type. This study aimed to explore this variation on a regional level through examining spatial and temporal autocorrelations of vaccine uptake of different product types within Michigan from 2017 to 2021. Methods Influenza vaccine administration data from the 2017/18 to 2021/22 seasons were obtained from the Michigan Care Improvement Registry. Population size estimates for 2017 and 2019 were obtained from the Michigan Department of Health and Human Services. Age-standardized and age-stratified vaccination rates were computed. Disparate county-level vaccine uptake clusters were constructed using spatial autocorrelation indicators and spatiotemporal clusters were identified using scan statistics. Linear mixed effect models were used to study the impact of social vulnerability and urbanicity level on seasonal influenza vaccination rate. Results Vaccination incidence rates for adjuvanted, recombinant, and nasal sprays vaccines and for any vaccines increased significantly through the study period. County-level spatiotemporal clusters of type-specific uptake rates were identified. Most notably, we identified an emerging cluster with high uptake of adjuvanted vaccine radiating from Ottawa County, located in suburban Grand Rapids, and the disappearance of high uptake cluster for high-dose vaccine uptake in the area. Vaccination rates by any product type were found to vary seasonally and showed weak negative association with more rural regions. The overall vaccination rates appear to be lower among counties with higher social vulnerability in certain urbanicity levels, but social vulnerability and urbanicity were not significantly associated with overall vaccination rate during the study period. Conclusions Vaccine type-specific uptake was spatially and temporally diverse in Michigan between 2017 and 2022. Mid and Northern Michigan had consistently relatively lower vaccination rate compared to other regions in Michigan.

Hypothyroidism has been associated with increased skin cancer risk, whereas greater genetic susceptibility to hypothyroidism is associated with lower risk. These opposing associations suggest that the average risk associated with hypothyroidism may conceal substantial heterogeneity among patients, and that genetic background could help identify those at highest risk. In this study, we analyzed more than 650,000 individuals across All of Us and FinnGen cohorts to determine whether a hypothyroidism polygenic risk score (H-PRS) stratifies skin cancer risk among patients with autoimmune hypothyroidism and whether integration of a skin cancer polygenic risk score (SC-PRS) further refines risk. In FinnGen, autoimmune hypothyroidism was associated with increased skin cancer hazard (hazard ratio [HR] = 1.10; 95% CI [1.06, 1.15]), whereas H-PRS was inversely associated with risk (HR=0.97 per 1-SD increase; 95% CI [0.95, 0.98]). The hypothyroidism x H-PRS interaction was also negative (HR=0.94; 95% CI [0.91, 0.98]), indicating greater hypothyroidism-associated risk at lower H-PRS. The hypothyroidism and H-PRS associations replicated in All of Us, and similar H-PRS risk gradients were observed for melanoma, basal cell carcinoma, and squamous cell carcinoma in both cohorts. Among hypothyroid patients, predicted 10-year risk increased with higher SC-PRS and lower H-PRS. Combined clinical-genetic profiles had HRs ranging from 2.32 at the 20th H-PRS/80th SC-PRS percentiles to 3.37 at the 5th/95th percentiles, exceeding published point estimates for the established dermatological risk factors. Among women aged 55, representing the more commonly affected sex at approximately the median age of diagnosis, 10-year risk of skin cancer was 14.9% (95% CI [8.4%, 20.9%]) in the highest-SC-PRS/lowest-H-PRS quartiles versus 2.8% (95% CI [1.0%, 4.7%]) in the opposite quartiles. Overall, these findings support PRS-guided risk stratification for targeted skin cancer prevention and surveillance.

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.

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.

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.

Introduction: Pesticide exposure has been associated with poorer mental health, yet little is known about whether seasonal fluctuations in agricultural pesticide use are associated with cyclical changes in mood among people living in agricultural communities. We evaluated associations between 10 peak and off-peak pesticide spray seasons and ecological momentary assessment (EMA)-derived mood in a floricultural region in Ecuador. Methods: 496 participants completed repeated EMA surveys across 10 assessment administrations over 2.5 years (2022-2024), including one single-assessment administration and nine 10-day bursts (Nobservations=14,332). Mood outcomes included negative affect (sadness, anxiety, stress, anger, tiredness, difficulty concentrating; overall mean=2.79, Standard Deviation [SD]=1.32), positive affect (happiness, motivation; overall mean=4.21, SD=1.60), and behavioral dysregulation (aggression and impulsivity, overall mean=1.86, SD=1.29). Generalized linear mixed models estimated pooled, between-person and within-person associations between peak pesticide spray seasons and mood, adjusting for demographic and longitudinal factors Effect modification by sex, floricultural occupation, and cohabitation with a floricultural worker was assessed. Results: Peak spray seasons were associated with higher negative affect ({beta}=0.11 [0.06, 0.16]) and behavioral dysregulation ({beta}=0.10 [0.05, 0.15]) but not positive affect ({beta}=0.01 [-0.05, 0.07]). Associations were driven by within-person changes. Sex modified associations with negative affect, which were stronger in males than females. Floricultural occupation modified associations, with poorer mood, greater behavioral dysregulation and lower positive affect among floricultural workers than non-workers. Discussion: Peak pesticide spray seasons were associated with worsening of negative affect and behavioral dysregulation. EMA may provide a sensitive approach for detecting short-term neurobehavioral changes associated with seasonal pesticide exposure.

People experiencing homelessness (PEH) have substantially lower quality-adjusted life expectancy and substantially higher healthcare spending compared to housed populations. California has the largest population of PEH in the United States, and an estimated ten percent of PEH have co-occurring opioid use disorder (OUD). We developed a lifetime, individual-level microsimulation of the 18,928 PEH with OUD in California to evaluate the health and economic effects of expanding access to housing through a Housing First approach, which does not require OUD treatment or abstinence. Increases in permanent housing and shelter access were based on Los Angeles County's Measure A goals, and we accounted for both housing and healthcare costs. Expanding housing access increased mean age at death by 0.34 years, reduced fatal overdoses for the cohort by 39, and produced an incremental cost-effectiveness ratio of $31,083 per quality-adjusted life-year gained, well below conventional willingness-to-pay thresholds. We provide evidence that housing is a high-value health intervention for PEH with OUD in California. Policymakers should support Housing First programs as part of integrated responses to the intertwined crises of homelessness and opioid use.

BACKGROUND: The chromosome 9p21.3 locus is among the strongest genetic risk loci for cardiovascular disease (CVD), yet the regulatory mechanisms underlying this association remain poorly understood. Previous vascular disease studies focused predominantly on the role of this locus in smooth muscle cell (SMC) dysfunction, whereas its potential role in endothelial cells (ECs) remains less well characterized. Here, we sought to identify candidate regulatory variants at 9p21.3, their distal target genes, and effector transcripts that contribute to CVD-related phenotypes in ECs. METHODS: Promoter capture Hi-C was used to map chromatin interactions at 9p21.3 in primary human ascending aortic SMCs (n=6), supplementing the previously obtained ECs (n=16) dataset. To support the regulatory relevance of these interactions, expression quantitative trait locus analysis was performed in 136 vascular biopsies. Variant effects were prioritized in silico using AlphaGenome. The regulatory activity of the prioritized region was validated using CRISPR activation. RESULTS: Chromatin interaction mapping identified a complex regulatory architecture at the 9p21.3 locus involving 19 putative regulatory elements and 15 genes across ECs and SMCs. MIR31HG showed the most recurrent distal promoter connectivity with the 9p21.3 region. Consistent with the chromatin interaction map, expression of MIR31HG transcripts was associated with genetic variation at the 9p21.3 locus. In ECs, the lncRNA MIR31HG, but not miR-31, was responsive to hemodynamic flow. Depletion of MIR31HG in ECs was associated with endothelial activation. Epigenetic tracks and deep learning predictions highlighted an active enhancer element at 9p21.3, which was subsequently validated by CRISPR activation and increased MIR31HG expression, confirming its capacity to regulate MIR31HG over a large genomic distance of approximately 538 kb. CONCLUSIONS: Altogether, these data implicate lncRNA MIR31HG as a likely effector of the 9p21.3 CVD locus, linking the cis-regulatory element and heritable genetic variation in the respective region to endothelial activation through long-range enhancer regulation.

Background: Artificial intelligence (AI) may improve electrocardiographic differentiation of Takotsubo syndrome from acute anterior ST-segment elevation myocardial infarction (STEMI), but its impact on human diagnostic performance, the added value of visual explanations, and differences by reader background and experience remain uncertain. Methods: Using 12-lead electrocardiogram (ECG) images from two hospitals, we developed and externally validated an ensemble of three deep learning models after self-supervised pretraining and fine-tuning. The diagnostic task used ECGs recorded within 14 days after symptom onset, regardless of reperfusion status. We conducted a four-phase reader study. Phases 1-3 compared unaided interpretation, a reference sheet, and additional AI assistance. In Phase 4, readers evaluated a new ECG set after randomization to reference-sheet support alone, with AI predictions, or with AI predictions plus gradient-weighted class activation mapping (Grad-CAM) heatmaps. Diagnostic correctness was analyzed using generalized linear mixed-effects models. Exploratory analyses examined differences by cardiologist status and experience. Results: Development and external-validation cohorts, including healthy controls, comprised 832 and 95 participants, respectively. For Takotsubo-STEMI discrimination, external-validation accuracy was 0.914, with areas under the receiver operating characteristic and precision-recall curves of 0.970 and 0.984. Seventy healthcare providers completed the reader study. The estimated probability of correct diagnosis increased from 0.632 without assistance to 0.864 with AI assistance (odds ratio [OR], 3.71; P<0.001). In randomized Phase 4, AI assistance improved accuracy vs reference-sheet support alone (OR, 4.28; 95% CI, 3.08-5.95; P<0.001), and Grad-CAM provided additional benefit (OR, 1.53; 95% CI, 1.04-2.25; P=0.033). Exploratory analyses showed greater improvement among less experienced readers; with AI assistance, non-cardiologists outperformed cardiologists. AI-assisted readers remained less accurate overall than the model alone. Conclusions: An ECG image-based ensemble differentiated Takotsubo syndrome from anterior STEMI and improved reader accuracy. Visual explanations provided additional benefit, while experience-related differences highlight the importance of effective human-AI interaction.

Background: The relationship between recent viral infection and subsequent susceptibility to, or protection against, other viruses remains unclear, particularly across ages and symptom status. Methods: A prospective cohort study enrolled participants aged 6 months to 49 years in Washington and Oregon, USA, 2022-2024. Weekly nasal swabs were tested for SARS-CoV-2, respiratory syncytial virus (RSV), and influenza A/B; additional swabs were collected during symptomatic illness and were also tested for parainfluenza (PIV) 1-4, endemic human coronaviruses (hCOV), adenovirus, human metapneumovirus, human rhinovirus (hRV), and enteroviruses. Proportional hazards regression models were used to characterize associations between incident symptomatic infection (illness) and history of recent illness due to other viruses (within 1-7, 8-14, 15-30, 31-60, 61-90, 91-180 days), adjusted for geographic region, age, sex, daycare/school/work attendance, household size, and number of children in the household. For SARS-CoV-2, influenza, and RSV, these analyses were repeated to study incidence of infection (including asymptomatic cases). Findings: Of 3,560 participants, 2,969 (83%) had [&ge;]1 illness over 4,299 person-years. Adjusted hazard ratios (aHRs) in the short term ([&le;]2 weeks) after an illness were predominantly below 1, indicating that recent viral illness was often associated with lower risk of subsequent illness with other viruses. Across age groups, recent hRV illness was associated with lower risk of hCOV, PIV, and RSV illness (aHRs 0.07-0.27). SARS-CoV-2 illness was associated with a higher short-term risk of adenovirus and PIV illness (aHRs 3.20-3.33). In children aged 6 months-4 years, recent influenza illness was associated with higher short-term risk of SARS-CoV-2 illness. Including asymptomatic infections generally attenuated these associations. Interpretation: Some viral illnesses may alter short-term susceptibility to subsequent viral illnesses. Interactions may differ by age and symptom status. Funding: US Centers for Disease Control and Prevention; Washington State Department of Health.

Biomedical artificial intelligence (AI) increasingly relies on heterogeneous data sources, yet differences in data structure, terminology, evidence quality, and provenance complicate their integration into reliable knowledge resources. Here, we develop an evidence-aware framework for processing and integrating heterogeneous pharmacovigilance data from FDA Adverse Event Reporting System (FAERS) reports, biomedical literature, clinical trials, and electronic health records in Mass General Brigham. The framework combines large language model (LLM)-based information extraction, ontology-driven semantic normalization, cross-source evidence assessment, statistical and machine learning-based prioritization, and ingredient-based adverse drug event (ADE) relationship inference to transform heterogeneous evidence into a structured and evidence-based knowledge resource. The constructed knowledge system contains 11,588 drug nodes, 44,843 ingredient nodes, 3,275 ADE nodes, 993 indication nodes, and more than 2.47 million relationships, with each drug-ADE relationship assigned a confidence score. We further developed a drug-level web interface for accessing the knowledge resource and validated its utility in downstream AI tasks. Specifically, incorporating the developed knowledge resource improved the comprehensiveness, relevance, and overall quality of LLM-based drug-specific ADE synthesis and improved the precision and F1 score of clinical ADE relation extraction. These results demonstrate that AI-assisted processing combined with evidence-aware curation can transform heterogeneous biomedical evidence into reusable, AI-ready knowledge with explicit provenance and evidence strength information. The framework provides a general strategy for integrating heterogeneous biomedical data to support reproducible knowledge construction and downstream biomedical AI applications.