Frontiers in Physics

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.

Background: Workplace discrimination and violence against health workers including sexual harassment is a societal problem worldwide. We aimed to assess the frequency, predictive factors, and effects of sexual harassment using a nationwide survey of physicians working in Switzerland. Materials and Methods: We conducted a self-administered questionnaire survey of physicians working in Swiss healthcare institutions. The questionnaire assessed experiences of sexual harassment at work, including frequency, types, and sources of harassment. It also asked about the impact of sexual harassment, whether incidents were reported, and what actions were taken following a report. Results: Among the 1837 physicians that participated in the survey, 575 (31.3%) had experienced sexual harassment at least once during their career. Among those reporting sexual harassment, 39.1% of women and 13.2% of men had experienced harassment at least once in their job. Women reported more verbal harassment, while men reported more physical harassment. Women were also more likely to face both forms combined. The main sources of harassment were colleagues of the same profession (46.7%), patients (42.3%), and superiors (41.0%). The most frequently reported impacts included stress (60.1%), emotional exhaustion (34.7%), reduced motivation at work (30%), and considering leaving the job (7.5%). Gender-men was associated with a lower likelihood of experiencing harassment 0.24 (0.18 to 0.31), whereas working in the German-speaking region was associated with a slightly higher likelihood of having experienced sexual harassment at least once (OR 1.35, 95% CI:1.02-1.81). Conclusions: Sexual harassment is common among physicians in Swiss healthcare institutions. It adversely affects the mental health and career trajectories of both men and women yet remains widely underreported due to fears of reprisals and inaction. Institutions should effectively intervene to ensure that reported incidents result in appropriate actions, and that those who report them receive adequate protection from reprisals.

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.

Violence against women is a key contributor to mental health gender disparities, with greater gender gaps observed in low-and middle-income countries. This study examines state-level associations between gender-based violence against women and mental health burden in India over time. We linked 1) annual state-level age-standardised disability-adjusted life year rates (ASDR) from the Global Burden of Disease study for overall mental health disorders, depressive disorders, anxiety disorders, bipolar disorder, schizophrenia and self-harm, with 2) annual state-level gender-based violence rates from the Open Government Data Platform, India. We used descriptive ecological analyses and multilevel modelling to estimate the state-level association between gender-based violence and sex-stratified mental health outcomes over time (2001 - 2021). Results showed higher state-level gender-based violence (GBV) rates were associated with higher state-level ASDR of schizophrenia ({beta}women = 0.39 [95%CI 0.25 - 0.52]; {beta}men = 0.42 [0.29 - 0.55]) and bipolar disorder ({beta}women = 0.02 [0.01- 0.03]; {beta}men = 0.04 [0.03 - 0.05]), after adjustment for state-level social development, but not with other outcomes. Higher GBV rates were associated with a lower gender disparity in depressive disorders. Longitudinal findings revealed that the state-level association between GBV rates and ASDR of overall mental health disorders strengthened over time ({beta}women = 5.08 [3.96 - 6.20]; {beta}men = 3.38 [2.60 - 4.15]), whereas the association weakened for self-harm and schizophrenia. Lagged findings suggested that with an increase in GBV rate, ASDR of overall mental health disorders increased for men over two years and for both sexes over five years. Our findings highlight the importance of considering state-level trends in GBV and related policies, and considering impacts of GBV on both men and women's mental health.

Community-led urban greening may contribute to neighborhood safety, but its relationship with crime remains uncertain. We examined whether Keep Indianapolis Beautiful Project GreenSpaces in Indianapolis were associated with changes in violence and total crime. We used a matched-pair difference-in-differences design comparing funded sites with matched unfunded applicant sites. The primary analysis included 29 matched pairs with two years of pre- and post-grant follow-up. Monthly Part I violent offenses and total crime within 600-m buffers were modeled using Poisson pseudo-maximum likelihood. In the first post-grant year, the violent-crime estimate was lower but imprecise (IRR, 0.903; 95% CI, 0.805-1.014). In the second post-grant year, the relative rate was lower (IRR, 0.830; 95% CI, 0.718-0.961). Total crime estimates showed no clear post-grant change. Additional analyses indicated some sensitivity to spatial scale, but no sustained divergence in pre-grant crime patterns. Analyses of short-term crime dependence showed clear month-to-month persistence in violent crime within sites but limited evidence of stable spatial dependence across nearby sites. Therefore, within the two-year post-grant period examined, Project GreenSpaces was associated most consistently with lower relative violent-crime rates in the second year, while no corresponding decrease was observed for total recorded crime. Longer follow-up is needed to determine whether these patterns persist or change as projects mature.

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).

Brazil experienced its worst dengue epidemic in 2024, with an increase in severe outcomes among elderly individuals, highlighting the need for vaccination strategies informed by population immunity. We reconstructed state- and age-specific immune profiles by fitting an age-structured catalytic model to dengue surveillance data from 2000-2025. This inferred immune profile was incorporated into an SIR-type transmission model to project disease burden and to evaluate the public health impact of vaccine allocation strategies. We observed substantial spatial heterogeneity in accumulated immunity, which was closely associated with projected burden and optimal allocation. Strategies prioritizing states with lower historical incidence and larger susceptible populations yielded greater benefits. Under limited vaccine supply, targeting children resulted in the greatest reductions in DALYs, whereas targeting elderly populations achieved smaller DALY reductions but larger reductions in mortality. We further showed that accelerated vaccine supply markedly increased impact, while allocation choices remained critical when availability was constrained.

To deal with the COVID-19 pandemic, Denmark implemented an aggressive program aimed at controlling the pandemic which included both testing and contact tracing programs. The large amount of data collected in Denmark on the pandemic and its integrated nature made it possible to investigate the effectiveness of the testing and contact tracing effort. The results of that investigation and a discussion of the effectiveness and limitations of the different control efforts are reported herein, as are lessons learned concerning possible improvements for the future. The analysis is limited to the period from the start of the COVID-19 pandemic in Denmark (late Feb. 2020) into May 2021, at which time the impact of vaccination intervention was already playing a role with ~25% of the Danish population at least partially vaccinated. From the available data sets we estimate the national Infection Detection Efficiency (IDE) starting around July 1, 2020, the time at which the national infection detection program started to be implemented in a more robust form. The results rely on daily COVID-19 hospital admissions, PCR test results, and anti-body prevalence values for the Danish population. We find that for the long-term average, the combined Danish national testing and contact tracing program identified on average about 55 to 60% of the infected individuals during the period from Sept. 1, 2020, into early May 2021. However, higher infection detection efficiencies were achieved in localized areas for short time intervals. Our investigations further indicate that the Danish testing and contact tracing program, which was among the most ambitious in the world, could have had a better balance between voluntary probing on the one hand and focused contact tracing and targeted testing on the other hand. As typically implemented, it proved to be largely ineffective in controlling the pandemic. However, in at least one case when it was implemented in an enhanced and focused mode, it was able to bring a large local outbreak that dominated the country's cases under control. We have compiled a list of lessons learned regarding the use of contact tracing procedures to control potential future pandemics before vaccinations become available.

Fetal development is highly sensitive to environmental influences, including maternal smoking during pregnancy (MSDP) and air pollution. The placenta may play a central role in mediating these effects through epigenetic mechanisms, including small non-coding RNAs (sncRNAs). While most studies have focused on microRNAs (miRNAs), other sncRNA classes remain poorly characterized. Here, we characterized the placental sncRNA landscape and investigated its associations with prenatal exposure to MSDP and air pollution. The sncRNA expression profile of 390 chorionic villi samples from the Barcelona Life Study Cohort (BiSC) was measured using small RNA sequencing and the seqBuster/seqCluster pipeline. MSDP was assessed via questionnaire, and prenatal exposure to black carbon (BC), particulate matter [≤]2.5 m (PM2.5), and nitrogen dioxide (NO2) was estimated using hybrid dispersion-land-use regression (LUR) spatiotemporal models. Associations were evaluated using linear regressions adjusted for relevant covariates. We identified 979 placental sncRNA clusters, assigned primarily to miRNAs (33.2%), piRNAs (26.4%), snoRNAs (12.2%), tRFs (7.8%), and others (20.4%). MSDP was associated with the downregulation of miR-421 and the upregulation of multiple snoRNAs from the imprinted DLK1-DIO3 locus (SNORD113-4, SNORD114-2, SNORD114-3, and SNORD114-17), as well as the piR-26394. No sncRNAs remained significantly associated with air pollution after multiple-testing correction, although several miRNAs showed suggestive associations. Overall, this study provides a comprehensive characterization of placental sncRNAs and identifies previously unreported smoking-associated sncRNAs within the imprinted DLK1-DIO3 locus, expanding our understanding of placental epigenetic responses to prenatal environmental exposures.

Brazil has one of the highest dengue burdens globally, with transmission influenced by climate events. Yet, the effects of compound climate extremes on dengue risk and prediction have not been quantified to date. Using a Bayesian spatiotemporal model of monthly dengue cases across 435 health regions from 2010 to 2025, we estimated relative risk associated with interacting long-lag and short-lag drought indicators and temperature anomalies across nine Koppen-Geiger climatic zones, adjusting for absolute temperature and El Nino-Southern Oscillation. Long-lag dry, mid-lag warm and short-lag wet conditions were associated with the highest relative risk in five climatic zones, with temperature anomalies modifying hydrometeorological dynamics more strongly in temperate than tropical areas. Climate covariates improved the prediction of case counts and outbreaks compared to baseline models at lead times of 1, 3, 6 and 12 months, and for the upcoming season 5 months ahead. Improvements were greatest in the Northeast, Southeast, and Midwest. Recent dengue incidence provided the greatest improvement at the 1-month lead, whereas combining incidence with climate information performed best at 3- and 6-month leads. We extended our framework to weekly state-level predictions of the season ahead to align with national public health planning. We proposed a multi-staged dengue forecasting approach to enhance early warning and response across Brazil.

Background: Commercial spaceflight now carries civilians on short missions, yet their stress-axis physiology is poorly described. Earlier shuttle data suggest that sympathetic responses predominate after short flights and glucocorticoid responses after long ones. The neutrophil-to-lymphocyte ratio (NLR) is a low-cost readout of both. Methods: Preregistered secondary analysis of open clinical laboratory data (NASA Open Science Data Repository OSD-569 and OSD-575) from the four Inspiration4 crew members, each sampled seven times: three draws before launch, one the day after return (R+1) and three during recovery (R+45 to R+194). Log-transformed NLR was modelled with a linear mixed model with a random intercept per crew member and Kenward-Roger inference. Lymphocyte and eosinophil counts and C-reactive protein were secondary outcomes with false discovery rate correction. Results: All 28 draws were analysed. NLR at R+1 did not differ from pre-flight (fold change 1.04; 95% CI 0.81 to 1.34; p = 0.73); two crew members increased (+25% and +46%) and two decreased (-27% and -11%). During recovery NLR was 23% lower than pre-flight (fold change 0.77; 95% CI 0.64 to 0.92; p = 0.005). No secondary outcome changed after correction; lymphocytes were 18% lower at R+1 (95% CI -35% to +4%; q = 0.31). Between-person differences explained 58% of the variance. An ordinary regression ignoring repeated measures missed the recovery effect (p = 0.08). Conclusions: A 3-day orbital flight produced no consistent leukocyte stress signature one day after return. The lower NLR during recovery suggests that pre-flight values, not recovery values, deviate from the resting state, which has implications for how baselines are defined in short-duration spaceflight studies.

PhenoAge, a blood-based biological aging clock, is associated with cancer outcomes, a finding taken as evidence that biological aging shapes prognosis. In 3,067 patients undergoing primary tumor resection, PhenoAge acceleration rose with tumor stage. One or two of its eight blood components, differing by cancer type, carried the prognostic signal, and replacing its general-population weights with equal weights did not weaken it. In cancer, PhenoAge may reflect disease burden rather than biological aging.

Purpose: Posterior pharyngeal wall (PPW) thickening is a common structural manifestation of treatment-related internal lymphedema in patients with head and neck cancer and can be evaluated using lateral videofluoroscopic images acquired during modified barium swallow (MBS) studies. However, no standardized method currently exists for quantitative measurement. Methods: This two-phase methodological study first conducted a scoping review to characterize existing approaches to PPW thickness measurement and identify the principal factors contributing to variation in PPW thickness measurement. Eight studies were identified with variation observed across these measurement factors. An empirical reliability study was then performed using 107 MBS studies from 93 Head and Neck Cancer patients. Two independent raters annotated 10 anatomical landmarks on pre-swallow and post-swallow resting frames, and a computer-assisted algorithm quantitatively generated seven candidate PPW thickness measurements based on different vertebral reference points and measurement directions. Reliability was assessed intraclass correlation coefficients (ICCs). Results: Inter-rater reliability was highest for the measurement originating from the midpoint of C3 and extending perpendicular to the anterior C3 surface (ICC, 0.78; 95% CI, 0.72-0.83). Among the normalization references, C2-C4 vertebral length demonstrated greater reliability than C3 vertebral length, with an ICC of 0.88 (95% CI, 0.85-0.91). No significant differences were observed between pre-swallow and post-swallow PPW thickness measurements across the evaluated approaches. Conclusions: These findings provide a methodological foundation for more standardized and reliable quantification of PPW thickness, with potential to expand the role of MBS from the functional evaluation of swallowing to include quantitative characterization of pharyngeal structural abnormalities.

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.

Objectives: To determine how strongly clinical referral text, rather than image content, drives the decisions of multimodal large language models (LLMs) differentiating glioma from brain abscess on MRI. Materials and methods: This retrospective single-center study included 60 contrast-enhanced T1-weighted brain MRI examinations (30 gliomas, 30 abscesses; reference-standard diagnosis). One axial slice per case was paired with five referral texts (explicitly inflammatory to explicitly tumor-suggestive) under three prompt instructions and submitted 20 times each to GPT-4o, Claude Sonnet 5, Gemini 3.5 Flash, and Qwen 3.6 (72,000 answers). The primary outcome was the text-driven span (difference in tumor-call frequency between explicit inflammatory and explicit tumor text). Two blinded radiologists classified the images without text; sensitivity, specificity, and accuracy were compared descriptively. Results: Patients (29 women) had a mean age of 55.8 +/- 16.4 years. With neutral text, models answered tumor in 45-67% of queries (specificity, 0.38-0.78), versus 52% and 60% for radiologists (specificity, 0.77 and 0.63). The text-driven span was 0.79-1.00 (p < 0.001 for all models), whereas confirmed gliomas and abscesses differed by only 0.01-0.10 in three models and 0.25 in Gemini 3.5 Flash. Subtle wording produced at least 83% of the span in three models. An instruction to ignore the text reduced the span to 0.48-0.70 in three models and to 0.04 in Gemini 3.5 Flash, partly through reversion to a tumor default. Model accuracy was 0.52-0.73 versus 0.78 and 0.73 for radiologists. Conclusion: Multimodal LLMs deferred to referral text over imaging evidence in differentiating glioma from brain abscess, and prompt instructions did not reliably correct this.

Lesion network mapping (LNM) has provided a compelling framework in clinical neuroscience, linking focal brain damage at heterogeneous anatomical locations to shared functional networks across behavioural syndromes. Recently, the methodological specificity of LNM has come under discussion following observations that derived network maps tend to converge onto the normative connectome's generic degree distribution. While current efforts largely treat this convergence as a statistical inference challenge addressable via post-hoc spatial null models or individual-level analyses, we identify a foundational upstream measurement artifact operating within individual patients: the lesion "bystander effect". Because pathological lesions follow biological constraints rather than functional brain parcellations, a typical lesion encapsulates both a symptom-driving critical node and surrounding asymptomatic bystander tissue. By averaging connectivity profiles across the entire lesion mask, LNM mechanically dilutes focal clinical signals. Across empirical clinical cohorts, individual-level machine learning classifiers, synthetic within-cohort lesion unions, and whole-brain spherical simulations, we demonstrate that increasing lesion extent deterministically drives network maps toward the connectome degree vector following a mathematical power law. Fulfilling the clinical promise of LNM will therefore require computational strategies that isolate the causal functional core from surrounding bystander tissue prior to network projection.

Chinese is one of the living languages with the highest homophone densities, making homophone processing a critical component of language comprehension and orthographic decoding, as well as an ideal model for examining its cognitive mechanisms. This study assessed mono- and bi-character homophone selection function in 129 Mandarin- and Cantonese-speaking participants, including 66 cognitively healthy individuals, 17 with semantic variant (sv) primary progressive aphasia (PPA), 23 with the nonfluent/agrammatic variant (nfv) PPA, and 23 with the logopenic variant (lv) PPA. All PPA variants showed impairment in homophone selection, with most significant deficits in svPPA and lvPPA. ROC analyses demonstrated its strong diagnostic utility for distinguishing PPA from controls. Voxel-based morphometry revealed that homophone performance correlated with gray-matter volume in left anterior and inferior temporal regions, with variant-specific patterns observed. These findings described the potential role of homophone selection in diagnosing PPA syndrome in Chinese speakers, illuminate crosslinguistic influences on language impairment in PPA, and provide novel insights into the cognitive processing of homophones.

Background and Objectives Transient ischemic attack (TIA) diagnosis is challenging because it relies mainly on clinical assessment and exclusion of common differential. Functional MRI (fMRI) may provide a diagnostic biomarker by detecting transient brain dysfunction not visible on conventional imaging. This pilot study aimed to characterize acute motor-task BOLD activation in patients with suspected DWI-negative TIA and compare functional patterns between confirmed TIA and alternative diagnoses. Secondary objectives were to assess longitudinal changes in activation and connectivity at 3 months. Methods In this prospective single-center study, adults presenting within 24 h of transient anterior-circulation neurological symptoms underwent conventional MRI and additional motor-task fMRI. Patients with acute DWI lesions were excluded. Final diagnosis was established after 3-month follow-up. Whole-brain analyses, individualized motor cortex region-of-interest (ROI) analyses, and generalized psychophysiological interaction (gPPI) connectivity analyses were performed during the acute phase and at 3 months. Results Eight patients were enrolled; six had complete longitudinal imaging data and were included in the final analyses. Final diagnoses were TIA (n=2), migraine aura (n=2), functional neurological disorder (n=1), and hypoglycemia (n=1). Whole-brain and ROI analyses showed reduced bilateral motor-related BOLD responses during the acute phase in both TIA patients and in the patient with hypoglycemia. In contrast, patients with migraine and functional neurological disorder exhibited less marked longitudinal changes. In TIA patients, motor cortex activation increased at 3 months, tending to normalize toward values observed in non-TIA participants. Connectivity analyses revealed heterogeneous patterns, but the 2 TIA patients demonstrated increased longitudinal connectivity between the motor cortex contralateral to symptoms and other sensorimotor regions, including supplementary motor, premotor, parietal, and postcentral cortices. Discussion These preliminary findings suggest that TIA may be associated with transient bilateral reductions in motor-network activity. Functional abnormalities appeared to improve over time, supporting the hypothesis of reversible network dysfunction. Although limited by the very small sample size, this study provides the first longitudinal assessment of emergency task-based fMRI in rigorously defined TIA and supports further investigation of acute functional MRI as a potential biomarker of transient cerebral dysfunction.

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.

Partitioned-heritability studies have shown which tissues carry the heritability of complex traits, but whether the regulatory layer whose annotations are most informative for heritability within a tissue differs between traits has not been tested, because measured annotations for different layers come from different sets of biosamples. Sequence-to-function models predict the allelic effect of every variant on several regulatory layers with a single model, so that layers can be compared on the same variants within the same tissues. We grouped AlphaGenome Atlas predictions into 12 lineages and six regulatory layers and partitioned the heritability of 11 complex traits with stratified LD score regression. Traits localized largely to the expected lineages, and within these lineages the most informative predicted layer differed between traits (P = 3.6 x 10^-8). Predicted chromatin-accessibility (DNase) effects were the most informative for height and bone mineral density, whereas predicted transcription-initiation (CAGE) effects were the most informative for Alzheimer's disease, most brain traits and cholesterol levels. The difference persisted across sensitivity analyses, and the predicted contrast held for three related traits whose layers had been predicted in advance (P = 2 x 10^-7). Predicted CAGE effects also remained informative after conditioning on fine-mapped eQTLs and measured regulatory annotations. These results identify differences across traits in the heritability information captured by predicted regulatory layers and offer testable hypotheses for investigating the regulatory basis of complex traits.