Cerebral Cortex Communications

A central question in psycholinguistics in visual word recognition is whether morphologically complex words are obligatorily decomposed into stems and affixes during visual word recognition or whether whole-word access can occur when forms are frequent and familiar. The present study investigated how morphological complexity and lexical frequency jointly shape neural responses by leveraging Korean nominal inflection, whose transparent stem-suffix structure permits a clean dissociation between base (stem) frequency and surface (whole-word) frequency. Twenty-five native Korean speakers completed a rapid event-related fMRI lexical decision task involving simple and inflected nouns that varied parametrically in both frequency measures. Representational similarity analysis (RSA) revealed robust encoding of surface frequency--but not base frequency--in the inferior frontal gyrus (IFG) pars opercularis and supramarginal gyrus (SMG), with significantly stronger correlations for inflected than simple nouns. Univariate analyses converged with this result: surface frequency selectively increased activation for inflected nouns in inferior parietal regions, whereas base frequency showed no reliable effects in any ROI. These findings challenge models positing obligatory pre-lexical decomposition, instead supporting accounts in which morphological processing is shaped by post-lexical, usage-driven lexical statistics. Taken together, our findings shed light on a distributed perspective on morphological processing, suggesting that structural and statistical factors jointly constrain access to morphologically complex forms.

BACKGROUNDMild traumatic brain injury (mTBI) is a signature injury in civilian and military populations that remains invisible to detection by conventional radiological methods. Diffusion MRI has been identified as a potential clinical tool for revealing subtle microstructural alterations associated with mTBI. OBJECTIVEThis study evaluates whether a comprehensive and powerful diffusion MRI (dMRI) technique called mean apparent propagator (MAP) MRI can detect sequelae of mTBI. METHODSWe analyzed data from 417 participants of the GE/NFL prospective mTBI study which included 143 matched controls (mean age, 21.9 {+/-} 8.3 years; 76 women) and 274 patients with acute mTBI and GCS [≥]13 (mean age, 21.9 {+/-} 8.5 years; 131 women). All participants underwent MRI exams at up to four visits including structural high-resolution T1W, T2W, FLAIR-T2W, and dMRI, in addition to clinical assessments of post-concussive physical symptoms (RPQ-3), psychosocial functioning and lifestyle symptoms (RPQ-13), and postural stability (BESS). The dMRI data for each subject were co-registered across all visits and analyzed using the MAP-MRI framework to measure and map the distribution of net microscopic displacements of diffusing water molecules in tissue and ultimately compute the microstructural MAP-MRI tissue parameters including propagator anisotropy (PA), Non-Gaussianity (NG), return-to-origin probability (RTOP), return-to-axis probability (RTAP), and return-to-plane probability (RTPP). We quantified voxel-wise and region-of-interest (ROI)-based changes in these parameters across all four visits. RESULTSMAP-MRI parameter values were within the expected ranges and showed relatively little variation across visits. We found no significant differences in the longitudinal trajectories of these parameters between mTBI patients and controls. At acute post-injury timepoints, RPQ-3 and RPQ-13 scores were increased in mTBI patients relative to controls, while BESS scores were not significantly different between groups. Analysis of dMRI metrics and clinical mTBI markers showed significant correspondence between MAP-MRI metrics in cortical gray matter, caudate and pallidum and BESS scores. CONCLUSIONWe developed and tested a state-of-the-art quantitative image processing pipeline for sensitive analysis and detection of subtle tissue changes in longitudinal clinical diffusion MRI data. The absence of a significant statistical difference between populations in the dMRI parameters in this study suggests that the mTBI corresponded to acute post-injury clinical symptoms but that the injury was not severe enough to cause detectable microstructural damage/alterations, and that increased diffusion sensitization combined with improved analysis techniques may be needed. CLINICAL IMPACTThese findings suggest that acute mTBI (GCS[≥]13) may not be detectable with diffusion MRI. TRIAL REGISTRATIONClinicalTrials.gov NCT02556177

BackgroundQuantitative cerebral blood flow (CBF) measured with [15O]water positron emission tomography (PET) is the reference standard for quantifying brain perfusion. However, clinical interpretation of individual CBF measurements is limited by the absence of large normative datasets accounting for physiological variability across the adult lifespan. Long-axial field-of-view PET enables high-sensitivity quantitative [15O]water perfusion imaging without arterial blood sampling, allowing normative characterization of cerebral perfusion at unprecedented scale. The aim of this study was to establish normative and covariate-adjusted models of cerebral blood flow across the adult lifespan using total-body [15O]water PET. MethodsQuantitative CBF measurements were obtained in 302 neurologically healthy adults (age 21-86 years) using total-body [15O]water PET. Linear mixed-effects models were used to evaluate the effects of age, sex, body mass index (BMI), and blood hemoglobin concentration on CBF and to generate normative prediction models across the adult lifespan. Between-subject and within-subject variability were estimated from repeated scans in a subset of participants (n=51). ResultsMean grey matter CBF was 46.1 mL/(min*dL), with substantial inter-individual variability but high within-subject reproducibility (intraclass correlation coefficients 0.78-0.89). Advancing age was associated with a decline in CBF of approximately 7% per decade (p_FDR < 10-12). Higher BMI was associated with lower CBF (approximately -6% per 10 kg/m2; p_FDR < 0.01). Women exhibited higher CBF than men (approximately 7.5%), but this difference was largely explained by lower blood hemoglobin concentration in women. Covariate-adjusted models were used to generate normative predictions and prediction intervals describing expected CBF across adulthood. ConclusionThis study establishes a normative database of quantitative cerebral blood flow across the adult lifespan using high-sensitivity [15O]water PET. Age, BMI, and hemoglobin are major determinants of inter-individual variability in CBF. The resulting generative models provide a quantitative reference framework for interpreting cerebral perfusion measurements and may enable automated detection of abnormal brain perfusion in clinical PET imaging.

Neural excitability fluctuates with sensory events, creating windows of opportunity to enhance brain stimulation. Repetitive transcranial magnetic stimulation (TMS), including intermittent theta burst stimulation (iTBS), is a promising treatment for neurological and psychiatric disorders, but does not account for fluctuations in neural excitability, likely contributing to variable outcomes. Sensory Entrained TMS (seTMS) leverages sensorimotor oscillations to enhance corticospinal responses, but the sustained effects as a repetitive protocol are unknown. We extend seTMS to iTBS, measuring motor-evoked potentials (MEPs) as a physiological readout. In a randomized crossover study comparing standard iTBS with sensory entrained iTBS (se-iTBS; n=20), we found that se-iTBS more than doubled the MEP effect (55% vs 26% MEP enhancement) and persisted for at least 30 minutes. Notably, at least 80% of participants showed larger responses with se-iTBS at all time points. se-iTBS may provide a robust and practical framework for optimizing TMS that bridges electrophysiological mechanisms and clinical applications.

Patterns of locus coeruleus (LC) activity and norepinephrine (NE) release during non-rapid-eye-movement (NREM) sleep suggest a critical role for the LC-NE system in offline modulation of forebrain circuits. NE transmission promotes synaptic plasticity and is required for memory consolidation, but the field has only begun to uncover how LC activity contributes to coordinated forebrain network dynamics. Hippocampal ripples, a hallmark of memory replay, are temporally coupled with thalamocortical oscillations; however, the circuit mechanisms underlying systems-level consolidation across larger brain networks remain incompletely understood. Here, using multi-site electrophysiology, we examined LC firing in relation to hippocampal ripples in freely behaving rats. LC activity and ripple occurrence were state-dependent and inversely related: heightened arousal was associated with increased LC firing and reduced ripple rates. At finer timescales, LC spiking decreased {approx}1-2 seconds before ripple onset, with the strongest modulation during awake ripples but minimal change during ripple- spindle coupling. These findings reveal state-dependent dynamics of LC-hippocampal interactions, positioning the LC as a key component of a cortical-subcortical network supporting systems-level memory consolidation.

Background: Developing generalizable neuroimaging models is often hindered by limited labeled data which has led to an increased interest in unsupervised inverse learning. Existing approaches often neglect geometric principles and struggle with diverse pathologies. We propose a symmetry-informed inverse learning foundation model to address these shortcomings for robust and efficient anomaly detection in brain MRI. Methods: Our framework employs a reconstruction-to-embedding pipeline, trained exclusively on healthy brain MRI slices. A 2D U-Net uses a novel, symmetry-aware masking strategy to reconstruct a disorder-free slice. Difference maps are embedded into a 1024-dimensional latent space via a Beta-VAE. Anomaly scoring is performed using Mahalanobis distance. We evaluated generalization by fine-tuning on external lesion datasets, BraTS Africa (SSA), and the ADNI-derived Alzheimer disease cohort (Alz). Results: On the source metastasis (Mets) dataset, the framework achieved high performance (AB1+MSE: 99.28% accuracy, 99.79% sensitivity). Generalization to the external lesion dataset (SSA) was robust, with the Symmetry ROC configuration achieving 91.93% accuracy. Transfer to the Alzheimer dataset (Alz) was more challenging, achieving a peak accuracy of 70.54% with a high false-positive rate, suggesting difficulty in separating subtle, diffuse changes. Conclusion: The symmetry-informed inverse learning framework establishes a robust foundation model for neuroimaging, showing strong performance for focal lesions and successful generalization under domain shift. Limitations in diffuse neurodegeneration underscore the necessity for richer representations and multimodal integration to improve future foundation models.

Brain activity comprises both rhythmic (periodic) and arrhythmic (aperiodic) components. These signal elements vary across healthy aging, and disease, and may make distinct contributions to conscious perception. Despite pioneering techniques to parameterize rhythmic and arrhythmic neural components based on power spectra, the methodology for quantifying rhythmic activity remains in its infancy. Previous work has relied on parametric estimates of rhythmic power extracted from specparam, or estimates of rhythmic power obtained after detrending neural spectra. Variation in analytical choices for isolating brain rhythms from background arrhythmic activity makes interpreting findings across studies difficult. Whether these current approaches can accurately recover the independent contribution of these neural signal elements remains to be established. Here, using simulation and parameter recovery approaches, we show that power estimates obtained from detrended spectra conflate these two neurophysiological components, yielding spurious correlations between spectral model parameters. In contrast, modelled rhythmic power obtained from specparam, which detrends the power spectra and parametrizes brain rhythms, independently recovers the rhythmic and arrhythmic components in simulated neural time series, minimising spurious relationships. We validate these methods using resting-state recordings from a large cohort. Based on our findings, we recommend modelled rhythmic power estimates from specparam for the robust independent quantification of rhythmic and arrhythmic signal components for cognitive neuroscience.

Mechanistic understanding and biomarkers of gonadotropin-releasing hormone antagonist treatment effect in paedophilic disorder are absent but may enhance outcomes and reduce sexual-offending risk. 52 help-seeking self-referred Swedish men with paedophilic disorder enrolled in a double-blinded, placebo-controlled, randomized clinical trial. Participants underwent task-based fMRI before, and two weeks after, subcutaneous injection of 120mg of degarelix or equal volume of placebo. fMRI blood-oxygen-level-dependent activation was compared between child and adult (child>adult) stimuli in task-derived regions of interest. Primary outcome was within region-of-interest child>adult activation change, whereas secondary outcomes correlated region-of-interest child>adult activation change to change in clinical measurements of risk, paedophilic interest, sexual preoccupation, hyper- and hyposexuality. 19 degarelix and 22 placebo participants had sufficient fMRI data quality. Reductions in paedophilic interest were strongly correlated with increased child>adult cerebellar (vermis) region-of-interest activation following degarelix (r=-0.740, p<0.001) but not placebo (r=0.183, p=0.41; between-group correlation coefficient z=3.347, p<0.001). Treatment did not significantly change child>adult region-of-interest activity. Post hoc analysis indicated that baseline autism symptoms correlated with degarelix-induced changes in paedophilic interest (r=0.717, p<0.001; between-group correlation coefficient z=2.958, p=0.003) and cerebellar activation (r=-0.581, p=0.01; between-group correlation coefficient z=-1.930, p=0.05). Increased child>adult cerebellar activation was associated with degarelix-induced reductions of paedophilic interest, suggesting cerebellar activity as mechanistically important to, and a prospective biomarker of, degarelix treatment effect. Additionally, autism symptoms may inform treatment prediction. Together, these findings have mechanistic and clinical implications for degarelix treatment of paedophilic disorder. EU clinical trials register identifier: 2014-000647-32 https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000647-32/SE, registered on 05/06/2014.

Walking impairments in Parkinsons disease (PD), including reduced speed, cadence, and stride length, and increased variability, impair mobility and raise fall risk. Conventional treatments may fail to address these deficits, underscoring the need for complementary non-invasive alternatives. This study examined whether combining rhythmic auditory cueing with transcranial direct current stimulation (tDCS) over the supplementary motor area (SMA), a critical region for internally-generated movement, would enhance gait performance in PD. Thirty-three participants with PD and thirty-two healthy controls completed two sessions (anodal vs. sham tDCS) with gait assessed during stimulation, immediately after stimulation, and 15 minutes after stimulation under two auditory conditions: walking in silence and walking to music paced 10% faster than baseline cadence. Spatiotemporal, variability, and stability gait parameters were analyzed using linear mixed-effects models. Rhythmic auditory cueing significantly increased cadence and speed during, immediately after, and especially 15 minutes after stimulation, suggesting sustained effects of rhythmic entrainment. Anodal tDCS produced faster cadence, as well as lower stride time variability and stride width, particularly in individuals with PD. Although both music and anodal tDCS affected gait, no interaction was observed, indicating independent effects. Individuals with PD had greater gait variability overall, and adjusted temporal gait parameters less to music than healthy controls did. Anodal stimulation reduced walking variability in PD, reducing the group differences observed under sham conditions. These findings suggest that rhythmic cueing and SMA stimulation target complementary mechanisms, highlighting the promise of combined tDCS-music interventions for gait rehabilitation in PD.

How embryonic cells generate large clones of cells in the adult represents a fundamental question in biology. Here, using melanocyte stem cells (McSCs) in the zebrafish as a model, we explore the function of the master melanocyte transcription factor (MITF) in safeguarding McSCs in embryonic development and their potential to pigment large clones in the adult. MITF is well known is for its role in the specification of melanoblasts from the neural crest (NC) and their differentiation into melanocytes, yet little is known about how this activity shapes the stem cell lineages. Here, we use live imaging coupled with single-cell transcriptomics and lineage tracing to show that MITF (mitfa in zebrafish) protects the melanocyte stem cell (McSC) fate in zebrafish. Utilizing a temperature sensitive mitfavc7 mutant, we show loss of Mitfa leads to a surprising premature and aberrant expansion of McSC progeny at the niche during embryogenesis, coupled with novel emergent transcriptional cell states. Linage tracing of McSCs from the embryonic to juvenile stages reveals Mitfa activity is subsequently required in regeneration by Schwann cell-like and melanocyte stem cell progenitors that serve as a reservoir for fast-responding pigment progenitors. Thus, the impact of Mitfa loss on the melanocyte lineage is cell-state and stage-specific. The emergent cell states upon mitfa loss may have important implications for our understanding the loss of MITF activity in human genetic disease and melanoma.

Dementia affects tens of millions of people worldwide, yet disease-modifying treatments remain strikingly limited. Although the recombinant zoster vaccine Shingrix has been associated with reduced dementia incidence, its potential influence on individuals already living with dementia is unknown. Here, we followed a propensity-score matched cohort of 68,960 US dementia patients using a nationwide electronic health record network, comparing Shingrix recipients within two years of diagnosis to recipients of any other vaccine. Shingrix was associated with substantially reduced all-cause mortality across the first three years of follow-up (hazard ratios 0.74, 0.88, and 0.89; P[&le;]0.006), robust across multiple sensitivity analyses. Furthermore, within-individual subgroup analyses of repeated Mini-Mental State Examinations conducted 3-6 years apart revealed significantly divergent cognitive decline rates across groups (time-by-group interaction P=0.002). Interval vaccination was associated with more stable cognition, contrasting with steeper declines in unvaccinated individuals. These findings support prospective evaluation of recombinant zoster vaccination as a potential strategy to improve outcomes in patients with established dementia.

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.

We used 2492 whole genome sequences from Laos to investigate the molecular epidemiology of SARS-CoV-2 from 2021 through 2024, covering the major waves of COVID-19 disease in Laos including time periods of travel restrictions and after relaxation of travel across international borders. We identify successive waves of COVID-19 caused by shifts in the dominant lineage, beginning with the Alpha variant in April 2021 and continuing through the Delta and Omicron variants. We quantify a shift from a small number of viral introductions responsible for widespread transmission in early waves to a larger number of introductions for each variant after travel restrictions were lifted, and identify potential routes of introduction into the country. Our study underscores the importance of genomic surveillance to public health responses to characterize viral transmission dynamics during pandemics.

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.