Journal of Leukocyte Biology

Rationale: Sepsis is a life-threatening syndrome causing significant morbidity and mortality especially in the aging population. Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition of clonal expansion of hematopoietic stem cells harboring somatic mutations associated with increased incidence of chronic illness and all-cause mortality. Objective: Evaluate the association of pre-illness CHIP with mortality and morbidity in patients admitted to the ICU with sepsis. Methods: We performed a retrospective study using a de-identified electronic health record linked with a DNA biorepository. We identified adult patients with sepsis who had DNA collected prior to ICU admission. We tested the association between CHIP status, determined from whole-genome sequencing, and ICU mortality, organ support-free days, and long-term survival adjusting for age, sex, race and Sequential Organ Failure Assessment (SOFA) score on ICU admission. Measurements and Main Results: Pre-illness CHIP was associated with increased sepsis mortality (OR = 1.54, 95% CI 1.13 to 2.07, P = 0.005) and fewer days alive and free of organ support (-1.7 days, 95% CI -3.2 to -0.2, P = 0.028) after adjusting for age, sex, race, and SOFA score. In sepsis survivors, CHIP was also associated with increased long-term mortality after discharge (HR 1.40, 95% CI 1.01 to 1.93, P = 0.041). Conclusions: Pre-illness CHIP was independently associated with increased mortality and morbidity in critically-ill adults with sepsis. These findings suggest that CHIP is a risk factor for sepsis severity. Elucidating the mechanism underlying this association could uncover new therapeutic interventions for sepsis.

Children with acute lymphoblastic leukemia (ALL) are treated with multiagent chemotherapy that causes profound changes to the immune system. There are limited data on how disease and therapy impact antigen-specific immune memory, leading to inconsistent guidelines on best practices for revaccination of this population. Here, to inform vaccine guidance, we investigated whether immunity derived from routine childhood measles and varicella zoster virus (VZV) vaccines is maintained during and after therapy for childhood ALL. We report that antibodies against measles and VZV were significantly reduced in children with ALL (n=45) compared to healthy controls (n=13), particularly in older children in whom a longer time had passed since their most recent vaccine dose. However, the avidity of the measles and VZV-specific antibodies was indistinguishable between groups. Despite changes to the composition of the T cell compartment, both overall and antigen-specific T cell function were preserved in children with ALL. These data provide compelling evidence for revaccination of children following ALL treatment. Intact T cell responses suggest that post-treatment revaccination would be effective.

Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has transformed outcomes for children with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), yet the influence of molecular subtype on outcomes remains unclear. We evaluated the impact of cytogenetic and molecular signatures on complete response (CR), overall survival (OS), and leukemia-free survival (LFS) after CD19 CAR-T therapy in eighty-six pediatric patients with R/R B-ALL treated with tisagenlecleucel. CR was assessed 30 days after infusion. Cytogenetic data were available for 84 patients and molecular profiling for 62. Survival analyses included 72 patients who received CD19 CAR-T as the sole cellular therapy. Seventy-seven patients achieved CR (89.5%). Pre-infusion bone marrow blasts of [&ge;]20% were associated with lower CR rates (53.8% vs 95.9%, p<0.0001) and significantly reduced OS and LFS (both p<0.0001). Among molecular markers, RAS mutations correlated with inferior OS (p=0.0222) and LFS (0.0402). In multivariate analysis, bone marrow blasts >20% and RAS mutations independently predicted inferior OS. Post CAR-T, CD19 negative relapses showed almost twice higher prevalence of RAS mutations (66% vs 37.5%). These findings highlight RAS mutations as a key molecular predictor of outcome after CD19 CAR-T therapy and suggest emergence of unique risk stratification for patients receiving CD19-targeting therapy.

Waldenstrom macroglobulinemia (WM) is a rare indolent neoplasm characterized by presence of more than 10% lymphoid cells in BM that exhibit plasmacytoid or plasma cell differentiation that secretes an IgM monoclonal protein. This is a retrospective analysis of 89 patients of WM that describes the clinical and laboratory characteristics, treatment patterns and outcome of patients of WM. The median age of the entire cophort was 66 years with male predominance (67.4%). Most common presentations were symptoms pertaining to anemia (77.5%) and constitutional symptoms (33.7%). Median bone marrow lymphoplasmacytic cells were 41%. Positivity for MYD88 and CXCR4 mutations were seen in 81.8% and 2.4% cases. BR was the most common regimen used (52.8%). Overall response rates were seen at 87.8%. Median overall survival, progression free survival and time to next treatment is 8.49 years, 2.15 years and 3.88 years. BR regimen was associated with highest event free survival.

BackgroundTo date, accessible diagnostic tools to identify whether a patients pneumonia is a bacterial, or viral infection, are not accurate or timely enough to prevent preemptive antibiotic administration. Relying on single biomarkers or clinical presentations has been insufficient. We aimed to incorporate a wide range of novel biomarkers and clinical presentations in a multivariable model and validate its capacity to differentiate cases of bacterial and viral pneumonia. MethodsData from 457 children aged 2-59 months, admitted to Kilifi County Referral Hospital, Kenya, with bacterial (n = 229) and viral (n = 228) infections, were used to develop and validate a predictive multivariable Poisson regression model to differentiate pneumonia etiology. The Receiver Operating Characteristic curve was used to assess biomarker performance and validate the model internally. ResultsSixty-three percent (63%) of the children presented with severe pneumonia. 72% with viral pneumonia had severe pneumonia, compared to 54% with bacterial pneumonia who had severe pneumonia. In crude analyses, chest-wall indrawing, cough, convulsions, crackles, angiotensinogen, and Serpin Family A Member 1 were significantly associated with pneumonia etiology, controlling for age. However, only chest-wall indrawing remained significant in multivariable analyses after controlling for age. The model demonstrated fair, but inadequate, discrimination, with an Area Under the Curve of 0.61. ConclusionAmong the children admitted to hospital with WHO defined pneumonia, a wide range of biomarkers and clinical presentations still failed to distinguish bacterial from viral pneumonia.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are complex chronic conditions that often follow infectious triggers with overlapping clinical features but poorly defined pathophysiological relationships. This study aimed to identify disease-specific immune signatures through multiparameter immunophenotyping of monocytes, dendritic cells, and T-cell subsets. A total of 207 participants were included (ME/CFS: n = 103; long COVID: n = 63; healthy controls: n = 41). Peripheral blood mononuclear cells were analyzed using multiparameter flow cytometry. Statistical analyses included non-parametric testing, age-adjusted ANCOVA, correlation network analysis, and principal component analysis (PCA). Long COVID was characterized by increased M2-like monocyte polarization, elevated CD80 expression across monocyte subsets, expansion of dendritic cells, and reduced expression of activation markers, indicating persistent immune activation with features of immune exhaustion. In contrast, ME/CFS exhibited reduced costimulatory molecule expression, impaired CCR7-mediated immune cell trafficking, and less coordinated activation patterns, consistent with a state of immune suppression. Correlation network analysis revealed more extensive and integrated immune interactions in long COVID, while PCA identified distinct immunophenotypic components and enabled moderate discrimination between the two conditions. These findings demonstrate that ME/CFS and long COVID are characterized by distinct immune profiles, supporting the concept of divergent immunopathological mechanisms. The identified signatures may contribute to biomarker development and guide targeted therapeutic approaches.

Mycetoma is a neglected tropical disease caused by various bacterial and fungal pathogens that has a significant health impact across a broad geographically defined "mycetoma belt" spanning South America, Africa and Asia. Histologically, mycetoma is characterised by invasive and destructive granuloma development in the skin, deep tissues and bone, leading to tissue destruction, deformities and high morbidity. The presence of macroscopic, highly compacted pathogen microcolonies, or "grains," is a key diagnostic feature, and the formation of grains supports pathogen persistence and disease chronicity. However, there is a paucity of information on immune responses in mycetoma patients and on the relative importance of phylogeny and/or grains in establishing the local immune landscape. Here, we used spatial proteomics to examine the distribution of 43 immune-related proteins in surgical biopsies from 11 patients with mycetoma of bacterial (Actinomycetoma; Actinomadura pelletierii and Streptomyces somaliensis; n=6) and fungal (Eumycetoma; Madurella mycetomatis; n=5) origin. Using mixed-effects modelling, an exploratory analysis across species and pathogen classes revealed few significant differences in immune marker expression. In contrast, and independently of pathogen class, the cellular infiltrate closest to grain boundaries had higher per-cell expression of CD66b+, ARG1, and VISTA. The preferential accumulation of CD66b+ARG1+VISTA+ cells at grain boundaries was confirmed by quantitative immunofluorescence analysis. Hence, the local tissue microenvironment surrounding the mycetoma grain represents a specialised immunosuppressive niche, with parallels to the tumour microenvironment.

Background: How post-COVID-19 condition (PCC) differs from post-acute infection syndromes (PAIS) caused by other respiratory viruses remains uncertain. Comparing these conditions may clarify whether post-acute symptoms reflect specific consequences of SARS-CoV-2 infection or broader post-viral mechanisms. Methods: We conducted a systematic review and meta-analysis of cohort studies comparing persistent symptoms or conditions in adults after SARS-CoV-2 infection with those following other acute respiratory viral infections. PubMed, Embase, and Scopus were searched. Random-effects models were used to estimate pooled risks. Results: Among 9,371 records screened, 22 studies were included and 14 contributed to the meta-analysis. Increased risk after SARS-CoV-2 infection was observed for pulmonary embolism, abnormal breathing, fatigue, hemorrhagic stroke, memory loss/brain fog, and palpitations; heart rate abnormalities showed borderline significance. For most other outcomes pooled estimates were inconclusive. Conclusions: Only a subset of outcomes appears more frequent after SARS-CoV-2 infection, suggesting many symptoms attributed to PCC may reflect broader post-viral syndromes.

Background. Young sexual and gender minorities of color face compound health risks shaped by interlocking systems of racism, cisgenderism, and class inequality. Spatial health research documents that place shapes health, but existing methods cannot specify the mechanisms through which spatial configurations produce different health outcomes for differently positioned people. This gap prevents targeted intervention. ObjectiveTo develop and pilot test the Spatial Intersectionality Health Framework (SIHF), which specifies three mechanisms through which space produces intersectional health inequities: Layered (multiple oppressive systems activating simultaneously), Positional (the same space producing different health pathways by intersectional position), and Conditional (nominally protective spaces carrying hidden costs for specific positions). We also introduce and validate Intersectional Geographically-Explicit Ecological Momentary Assessment (IGEMA) as the methodology operationalizing SIHF across three data levels. MethodsThe GeoSense study enrolled 32 young sexual and gender minorities of color (ages 18-29) in New York City. IGEMA was implemented across three integrated levels: (1) GPS mobility tracking via participants personal smartphones, linked to census tract structural exposure indices across n=19 participants; (2) ecological momentary assessment of intersectional discrimination with multilevel modeling of mood, stress, and sleep outcomes; and (3) map-guided qualitative interviews with SIHF mechanism coding and intercoder reliability assessment across 92 coded records from 18 participants. This study was conducted as the pilot for NIH R01HL169503. ResultsAll three SIHF mechanisms were empirically detectable. A compound structural gendered racism index outperformed every single-axis alternative in predicting daily mood (b=-0.048, p=.001) and stress (b=0.121, p<.001). The Positional mechanism accounted for 71% of coded harm experiences. Intercoder reliability for mechanism assignment reached kappa=0.824 at Stage 2 reconciliation. Daily intersectional discrimination predicted greater sleep disturbance (b=1.308, p=.004). ConclusionsSIHF and IGEMA together provide an empirically testable framework for specifying how space produces intersectional health inequities. Mechanism specification, not spatial location alone, is the condition for designing research and intervention that reaches the source of harm for multiply marginalized populations.

Quantitative measures for tracking functional health have generally been lacking. Intrinsic capacity (IC) has been proposed as an appropriate measure, but its metrics have been derived in small datasets and sparse longitudinal data. Using harmonized measures of cognition, locomotion, sensory function, vitality, and psychological well-being from 501,615 UK Biobank participants and followed for a median of 15.5 years, we derived domain-specific and composite IC scores. We examined associations with incident disease, cause-specific mortality, multimorbidity, lifestyle and socioeconomic factors, and multi-omic profiles from Olink proteomics, NMR metabolomics, clinical biochemistry, and blood-cell traits. We found that composite IC declined non-linearly with age, and within-person decline was steeper than the cross-sectional age measures. Participants with greater baseline morbidity, those who subsequently developed incident disease, and those who died earlier in follow-up showed lower IC trajectories across adulthood. The IC domains were only modestly correlated with one another, supporting multidimensionality, yet higher overall IC was associated with lower risk of most diseases examined. The dominant IC domain varied by endpoint, with cognition informative for dementia, sensory function for hearing loss, psychological capacity for depression, locomotion for osteoarthritis, and vitality for cardiometabolic outcomes. IC was also associated cross-sectionally with physical activity, insomnia, smoking, medication burden, and socioeconomic disadvantage. More proteins were found predictive for vitality, and enrichment converged on immune/inflammatory and metabolic pathways. Blood-based surrogates recapitulated part of the phenotypic signal, particularly for vitality. Overall, this IC framework captures longitudinal health trajectories and broad disease vulnerability in a large middle- to older-aged cohort and supports IC as a clinically meaningful, multidomain phenotype of aging and identifies blood-based correlates that may facilitate at-scale future monitoring of aging-related function declines.

BackgroundThe rapid growth of the worlds urban population has contributed to the expansion of informal urban settlements in many cities across the world. In these settings, lack of safe sanitation combined with high population density and poverty contributes to heightened health risks for often vulnerable populations. The aim of this study was to evaluate the effect of a shared, onsite sanitation intervention on the nutritional status of children in Maputo, Mozambique. MethodsThe Maputo Sanitation (MapSan) trial was a controlled before-and-after study to evaluate the effect of a shared, onsite sanitation intervention on child health in Maputo, Mozambique. Here, we report the effects on childhood stunting, wasting and underweight, and height-for-age, weight-for-height and weight-for-age z-scores. Children were enrolled aged 1-48 months at baseline and outcomes were measured before and 12 and 24 months after the intervention, with concurrent measurement among children in a comparable control arm. The primary analysis was intention-to-treat. The trial was registered at ClinicalTrials.gov, number NCT02362932. ResultsWe enrolled 757 and 852 children in the intervention and control groups respectively. There was no evidence for an effect of the intervention on any outcome at 12 or 24 months of follow-up except for wasting where there was very weak evidence for an effect (adjusted prevalence ratio: 0.497; 95% CI: 0.22-1.11; p=0.09). In two exploratory analyses - one including only those children born into compounds post-intervention and a second excluding children in control compounds which had independently improved their sanitation facilities during follow-up - we found that stunting increased in the intervention group whilst wasting decreased. ConclusionsThis study contributes to the growing evidence on the role of sanitation in shaping child health outcomes in informal urban settlements. We found no evidence for an effect on stunting and weak evidence for an effect on wasting. More research is needed to understand how sanitation can reduce childhood undernutrition in complex urban environments.

Wastewater surveillance (WWS) is established as a vital tool for monitoring polio and SARS-CoV-2 with potential to improve surveillance for many other infectious diseases. This study evaluated the feasibility of detecting measles virus (MeV) RNA in wastewater as part of a national WS preparedness trial in Brisbane, Australia, from March to June 2025. Composite and passive sampling methods were employed in parallel at three wastewater treatment plants serving populations between 230,000 and 584,000. Nucleic acids were extracted and analyzed using RT-qPCR targeting MeV N and M genes to distinguish wild-type and vaccine strains. MeV RNA were detected in both 24-hour composite and passive samples on May 26 to 27, 2025 from the largest catchment of 584,000 which also included an international airport. No measles cases were reported in this city or region within 4 weeks of the WS detections. These were confirmed as vaccine-derived measles virus (MeVV) strain via specific RT-qPCR assay. Extraction recoveries varied (11.5% to 70.5%), with passive sampling showing higher efficiency. This is the first report of use of passive samples for detection of MeV. These findings are consistent with other studies reporting WWS results of both MeVV genotype A and wild type genotype B and/or D. It demonstrates the potential for sensitive MeV WWS with rapid differentiation of MeVV from wild type MeV shedding, including in airport transport hubs and with different sample types. Use of WWS could strengthen measles surveillance by enabling rapid detection of MeV RNA and supporting outbreak preparedness and response. This requires optimised methods which are specific to or differentiate wild-type MeV from MeVV. Furthermore, the successful detection of MeV using passive sampling in this study highlights its potential for deployment in diverse global contexts which may include non-sewered settings.

BackgroundThe World Health Organization has developed several global template protocols for epidemiological investigations, including for household transmission investigations (HHTIs). These investigations facilitate rapid characterisation of novel or re-emerging respiratory pathogens and support evidence-based public health actions. Beyond technical readiness, community buy-in is central to the feasibility and acceptability of HHTIs. Research is needed to determine the perceived legitimacy among the community to inform local protocol adaptation and development of implementation plans that consider community attitudes and needs. MethodsIn 2025, we conducted a convenience survey of community members living in Victoria, Australia to explore: their understanding of emerging respiratory diseases; their willingness to take part in public health surveillance activities such as HHTIs; the acceptability of clinical and epidemiological data collection and respiratory/blood sample collection as main components of HHTIs, and; participant comfort towards including their companion animals in HHTIs. ResultsWe received 282 survey responses, of which 235 were included in the analysis dataset. Compared to the general Victorian population, our participants included a higher proportion of participants who reported being female, tertiary-educated, of Aboriginal and/or Torres Strait Islander heritage, born in Australia and speaking only English at home. Participants indicated overall high levels of comfort and acceptability towards participation in HHTIs, particularly in relation to clinical and epidemiological data collection, with lesser but still high levels of comfort with providing multiple respiratory specimens in a 14-day period. Participants were least comfortable with other specimens such as urine and blood. Involving companion animals in HHTIs was similarly acceptable as human-focused components. ConclusionsDespite our survey population being non-representative of the general Victorian population, our findings provide valuable descriptive insights into the acceptability of HHTIs in Victoria, Australia from which to benchmark future local and international surveys and community engagement activities.

BackgroundTimely cancer diagnosis in children and adolescents is critical to improving outcomes, yet substantial variation in diagnostic intervals persists across cancer types and care settings. We aimed to quantify time to diagnosis and assess variations by patient, demographic, and system-level factors. MethodsWe conducted a retrospective population-based study of children and adolescents aged 0-19 years diagnosed with one of 12 common cancers between 2010 and 2022 in Quebec, Canada. The diagnostic interval was defined as the time from first cancer-related healthcare encounter to diagnosis. We calculated medians and interquartile ranges (IQR) overall and by cancer type and used multivariable quantile regression to identify factors associated with time to diagnosis at the 25th, 50th, and 75th percentiles. ResultsAmong 2,927 individuals with cancer, diagnostic intervals varied by cancer type and age. Median intervals were longest for carcinomas (100 days; IQR 33-192) and shortest for leukemias (8 days; IQR 3-44). Compared with children living in Montreal, living in regional areas and other large urban centres was associated with longer 50th and 75th percentiles of time to diagnosis for hepatic and central nervous system (CNS) tumours. Diagnostic intervals were shorter in the post-pandemic period (2020-2022) across several cancer sites, with CNS tumours showing reductions across all quantiles. InterpretationDiagnostic timeliness differed by cancer type, age, and rurality, but not by sex, material, or social deprivation. The shorter diagnostic intervals observed in the post-pandemic period suggest that pandemic-related changes in care pathways may have expedited diagnosis for some cancers.

ObjectivesWe determined the frequency of sexually transmitted infection (STI) testing among people accessing sexual health services (SHS) in England. MethodsWe assessed STI testing frequency in face-to-face and online SHSs in England using data from the GUMCAD STI surveillance system. We quantified different combinations of tests (e.g. single chlamydia test or full STI screen), number of tests completed in 2024 and test positivity by sociodemographic and behavioural characteristics, as well as clinical setting and outcomes. ResultsOverall, there were 2,222,028 attendances at SHS in England in 2024 that involved tests for chlamydia, gonorrhoea, syphilis and/or HIV. Most of these attendances involved tests for all four of these STIs. Most people accessing SHS in England tested once (80.1%), and a small minority (1.9%) tested at least quarterly (4+ times). Some groups had a comparably larger proportion of quarterly testers; these included gay, bisexual, and other men who have sex with men (GBMSM) (6.7%), London residents (3.6%), online testers (2.5%), people using HIV-PrEP (13%), and people with 5+ partners in the previous 3 months (10.6%). Only 10.5% of GBMSM reporting higher-risk sexual behaviours tested quarterly despite recommendations for quarterly testing in this group. ConclusionsThe majority of those who tested for STIs in England in 2024 only tested once. The minority who tested at least quarterly had a higher proportion of GBMSM, people using HIV-PrEP, London residents and people reporting higher risk behaviours. Quarterly testing often appears to be aligned with current testing recommendations in England; however, we also observed that only a low proportion of behaviourally high-risk GBMSM and HIV-PrEP users are meeting these recommendations. It is important to acknowledge groups with lower or higher testing frequency when developing interventions and updating guidelines related to STI testing. WHAT IS ALREADY KNOWN ON THIS TOPICThe effectiveness of asymptomatic testing for chlamydia and gonorrhoea in gay, bisexual and other men who have sex with men (GBMSM), and the potential impact of the consequent increased antibiotic use on rising antimicrobial resistance and individual harm has recently been questioned. Testing and treatment remains a key pillar of STI prevention and management; despite this, there is limited evidence of STI testing frequency within sexual services (SHS) on a national level. WHAT THIS STUDY ADDSThis analysis shows that the majority of people attending SHSs in England in 2024 tested once, and only a small proportion of behaviourally high-risk people tested frequently. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYAwareness of groups that are behaviourally high risk but testing infrequently is important to guide interventions and messaging regarding STI testing. The low levels of frequent testing, even among those who would be recommended quarterly testing under UK guidelines, provides important context for wider discussion around asymptomatic STI screening.

Wearable-derived physiological features have been associated with disease risk, but most current studies focus on single conditions, limiting understanding of cross-disease patterns. This study adopts a trans-diagnostic approach to examine whether wearable data capture shared and condition-specific physiological signatures across multiple chronic conditions spanning physical and mental health, and then evaluates the utility of these features for disease classification. A total of 9,301 patients with at least 21 days of consecutive FitBit data from the All of Us Controlled Tier Dataset version 8 were analyzed. Disease subcohorts included cardiovascular disease (CVD), diabetes, obstructive sleep apnea (OSA), major depressive disorder (MDD), anxiety, bipolar disorder, and attention-deficit/ hyperactivity disorder (ADHD), chosen based on prevalence and relevance. Logistic regression and XGBoost models were fitted for each disease subcohort versus the control cohort. We found that compared to using just baseline demographic and lifestyle features, incorporating wearable-derived features enabled improved classification performance in all subcohorts for both models, except for ADHD where improvement was mainly observed for ROC-AUC in logistic regression model likely due to the smaller sample size in ADHD subcohort. The largest performance gains were observed in MDD (increase in ROC-AUC of 0.077 for Logistic regression, 0.071 for XGBoost; p < 0.001) and anxiety (increase in ROC-AUC of 0.077 for logistic regression, 0.108 for XGBoost; p < 0.001). This study provides one of the first comprehensive transdiagnostic evaluations of wearable-derived features for disease classification, highlighting their potential to enhance risk stratification in the real-world setting as a practical complement to clinical assessments and providing a foundation to explore more fine-grained wearable data. Author summaryWearable devices such as fitness trackers and smartwatches are becoming increasingly popular and affordable, providing continuous measurements of heart rate, physical activity, and sleep. Alongside the growing digitization of health records, this creates new opportunities for large-scale, real-world health studies. In this study, we analyzed wearable-derived physiological patterns across a range of chronic conditions spanning both physical and mental health to better understand how these signals relate to disease risk. We found that incorporating wearable-derived heart rate, activity and sleep features improved disease risk classification across several conditions, with particularly strong gains for major depressive disorder and anxiety. By examining how individual features contributed to model predictions, we also identified meaningful associations between physiological signals and disease risk. For example, both duration and day-to-day variation of deep and rapid eye movement (REM) sleep were associated with increased risk in certain conditions. Our study supports the development of real-time, automated tools to assess disease risk alongside clinical care.

Childhood socioeconomic position (SEP) can have lifelong effects on health. Many studies have used adult height as a surrogate marker for early-life conditions. In this study, we derived the non-genetic component of height, calculated as the residual from sex-specific standardized height regressed on genetically predicted height, as a surrogate for childhood SEP, using data from the Hispanic Community Healthy Study/Study of Latinos (2008-2011). A positive residual would indicate favorable early-life conditions promoting growth, while a negative residual indicates early-life adversity that may stunt the development. The height residual was associated with early-life variables such as parental education, year of birth, US nativity and age at first migration to the US (50 states/DC), supporting the validity of height residual as a surrogate for early-life conditions. Furthermore, a height residual was positively associated with better cardiovascular health (CVH) and cognitive function among middle-aged and older adults. Interestingly, among <35 years old, the height residual was negatively associated with the "Lifes Essential 8" clinical CVH scores. These results suggest the non-genetic component of height as a surrogate for childhood environment, with predictive value for CVH and cognitive function.

BackgroundAccelerometer-derived behavioral phenotype captures multidimensional aspects of human behavior extending well beyond physical activity, encompassing light exposure, step counts, physical activity patterns, sleep, and circadian rhythms. Whether these five domains constitute a unified behavioral architecture underlying cancer risk and whether circadian organization and light exposure confer incremental predictive value beyond movement volume alone remains to be comprehensively established. MethodsWe conducted an accelerometer-wide association study (AWAS) encompassing the complete accelerometer-derived behavioral exposome across five behavioral domains in UK Biobank participants with valid wrist accelerometry data. Incident solid cancers were designated as the primary endpoint, with prespecified site-specific solid cancers and hematological malignancy as secondary outcomes. Cox proportional hazards models with age as the timescale were used. The minimal covariate set served as the primary reporting tier, followed by sensitivity analyses additionally adjusting for adiposity/metabolic factors, independent activity patterns, shift work history, and accelerometry measurement quality. Nominal statistical significance was defined as two-sided P < 0.05 ResultsAmong 89,080 participants, 6,598 incident solid cancer events were observed over a median follow-up of 8.39 years. In the minimally adjusted model, the pan-solid-tumor association atlas was dominated by signals from activity volume, inactivity fragmentation, and circadian rhythm. Higher overall acceleration (HR per SD: 0.91, 95% CI: 0.89-0.94) and higher daily step counts (HR: 0.93, 95% CI: 0.90-0.95) were independently associated with reduced solid cancer risk, while inactivity fragmentation metrics were consistently linked to higher risk. Notably, circadian rhythms, most prominently cosinor mesor (Midline Estimating Statistic of Rhythm under cosinor model), emerged as leading inverse risk signals, underscoring the independent contribution of circadian behavioral architecture. Site-specific analyses revealed pronounced heterogeneity across tumor sites. Lung cancer exhibited a robust inverse activity-risk gradient, while breast cancer showed reproducible associations with MVPA. Most strikingly, nocturnal light exposure demonstrated a tumor-site-specific association confined to pancreatic cancer, a signal absent across all other sites examined. Associations for uterine cancer were predominantly inactivity-related and substantially attenuated following adjustment for adiposity and metabolic factors. ConclusionsAcross five accelerometer-derived behavioral domains, solid cancers as a whole were most consistently associated with a high-movement, low-fragmentation, and circadian-coherent behavioral profile. While site-specific heterogeneity exists, the broad cancer risk landscape is dominated by movement volume, inactivity fragmentation, and circadian rhythmicity. Light exposure, although more localized in its contribution, demonstrates a potentially novel and specific association with pancreatic cancer risk. These findings support a five-domain behavioral exposome framework for cancer epidemiology and, importantly, position circadian rhythm integrity and nocturnal light exposure as critically understudied dimensions warranting dedicated mechanistic investigation.

Background: Dengue is rapidly emerging in parts of Europe. How households value vector control attributes, and whether inferences depend on decision models or message framing, is unclear. Methods: We conducted a split-ballot online experiment among adults in Italy and France, as well as a hotspot subsample from Marche, Italy. National samples included 1,505 respondents in Italy and 1,501 in France; 183 respondents were recruited in Marche. Participants were randomised to a discrete choice experiment (random utility maximisation) or a regret-based choice experiment (random regret minimisation) and to one of three pre-task messages (control, loss aversion, community values). Each respondent completed 12 choice tasks comparing two dengue control programmes and an opt-out. We estimated mixed logit and mixed random-regret models with random parameters and treatment effects. Results: Across frameworks, nearby cases and high mosquito prevalence were the dominant drivers of programme uptake, whereas cost and operational burden were secondary. In pooled analyses, loss-aversion messaging increased the weight on high mosquito prevalence in both models (from 0.483 to 0.547 in the utility model; from 0.478 to 0.557 in the regret model). Cost effects were small nationally but larger in the hotspot subsample. Conclusions: Risk salience dominates preferences for dengue vector control in these European settings. Random utility and random regret models yield consistent rankings of attributes but differ in behavioural interpretation and some secondary effects; messaging effects were modest and context dependent.

BackgroundFamily-based HIV index case testing identifies family members with unknown HIV status and links them to care. Data are limited in southern Ethiopia. MethodsA facility-based cross-sectional study was conducted among 377 adults on antiretroviral therapy (ART) in Wolaita Zone, Southern Ethiopia, from November 2022 to May 2023. Participants were selected using systematic random sampling. Data were collected via interviewer-administered semi-structured questionnaire. Multivariable logistic regression identified factors associated with index case family testing. Adjusted odds ratios (AOR) with 95% confidence intervals (CI) were calculated, and statistical significance was declared at p < 0.05. ResultsThe proportion of index case family testing for HIV was 84.9% (95% CI: 81.2- 88.6). In multivariable analysis, urban residence (AOR = 2.8; 95% CI: 1.16-6.75), duration on ART greater than 12 months (AOR = 13.0; 95% CI: 4.6-36.9), disclosure of HIV status to family members (AOR = 5.6; 95% CI: 1.9-16.5), discussion of HIV status with family members (AOR = 6.6; 95% CI: 1.9-23.2), and being counselled by health professionals to bring families for testing (AOR = 6.3; 95% CI: 2.1-19.0) were significantly associated with index case family testing. ConclusionThe prevalence of family-based HIV index case testing in Wolaita Zone was 84.9%, below the national 95% target. Health professionals should strengthen counselling on ART adherence, status disclosure, family discussion, and active referral to improve testing uptake among family members of people living with HIV.