AIDS and Behavior

Background Community-led interventions for female sex workers (FSW) can improve HIV prevention and treatment outcomes by lowering self-stigma and strengthening social cohesion to improve service uptake. In Zimbabwe, the AMETHIST intervention trial integrated peer-led microplanning with self-help groups for FSW and demonstrated improved HIV treatment outcomes. We investigated the role of social cohesion and self-stigma in explaining these findings. Method We conducted a mixed-method analysis of data collected during AMETHIST. We re-analysed qualitative data from interviews and group discussions to identify narratives linking self-stigma, engagement with microplanners and/or self-help groups and HIV service use. We analysed quantitative data from endline respondent-driven sampling surveys for differences in self-reported measures of social cohesion and self-stigma between trial arms, and between those who did and did not participate in intervention activities or access services. Results In both arms, FSW self-reported engaging with peer supporters, participating in self-help groups and accessing HIV services. Qualitative narratives suggested peer support and group participation could reduce self-stigma and support service uptake. Lower levels of self-stigma were seen in the intervention arm (58.6% vs 63.2%; aOR 0.77; 95% CI 0.61-0.86). Social cohesion exceeded 50% across the whole sample, but was not associated with study arm, nor with engagement in intervention-related activities. Discussion Although qualitative data suggested some FSW felt their uptake of services was influenced by intervention components, quantitative analyses did not suggest either variable was on the causal pathway to the outcomes of the intervention. A limitation may have been the measurement of these complex constructs and the high levels of social cohesion across both study arms.

Long-acting injectable human immunodeficiency virus (HIV) medicines expand treatment and prevention choices, but willingness to use them does not establish readiness to begin. We examined readiness to start these options, associated factors and conditions for acceptance among people living with HIV and pre-exposure prophylaxis (PrEP)-service clients in Uganda. This cross-sectional study analysed 225 participants at Mildmay Hospital and Kajjansi Health Centre IV in central Uganda. Readiness meant preferring initiation immediately or within three months. Modified Poisson regression estimated adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), including age-by-service-group interaction. Separate models examined informational, perceptual and financial factors, adjusting for service group, age and sex. Logistic marginal standardisation checked demographic and expanded age comparisons. Overall, 108 participants (48.0%) were ready to start injectable HIV treatment or prevention, 111 (49.3%) wanted more information about these options, and six (2.7%) preferred initiation in six to twelve months. Readiness was 80.8% among people living with HIV aged 15-24 years and 34.4% among those aged 25 years or older (aPR 2.35, 95% CI 1.63-3.38). Corresponding proportions among PrEP-service clients were 39.2% and 41.4% (aPR 0.95, 95% CI 0.60-1.50; interaction p=0.002). In separate adjusted models, clinic-staff information (aPR 1.94, 95% CI 1.42-2.66), belief in greater effectiveness (2.00, 1.43-2.80) and a one-point increase in benefit score (3.27, 2.36-4.55) were associated with higher readiness. A one-point increase in concern score (0.70, 0.60-0.80) and financial difficulty sometimes or more often (0.68, 0.48-0.96) were associated with lower readiness. Fewer side effects was the leading condition for accepting injectable HIV treatment or prevention across service and readiness groups. Nearly half of participants were ready to start, while a similar proportion wanted further information about injectable options. Programmes should assess intended initiation timing alongside willingness and address safety, appointment flexibility, privacy and affordability through counselling and service planning.

The efficacy of current antiretroviral interventions for prevention of vertical HIV transmission is both a triumph and a challenge for future efficacy studies of novel agents, including long-acting antiretroviral agents. Given the effectiveness of current antiretroviral interventions, standard randomized controlled trials to assess novel interventions targeted towards further reducing vertical HIV transmission may be infeasible due to required sample sizes. To address this study design challenge, we propose a novel augmented clinical trial design, where a randomized trial with an active comparator is augmented with a concurrent observational cohort to supplement the standard-of-care arm. The proposed design and analysis can overcome sampling biases, and an associated diagnostic can evaluate potential biases from unmeasured covariates. The proposed trial design is illustrated with an example and studied further using a simulation study. In the illustrative example, an augmented trial with a 3:1 allocation ratio in the trial component yielded an unbiased treatment effect estimate, as compared to the trial component alone, and the standard error was reduced substantially. Although the total sample size of the augmented trial was larger than a similarly powered 1:1 standard trial, the sample size of the augmented trial's trial component was half the size of the standard trial and within the range of historically similar trials, thereby providing both feasibility and potential cost advantages. Although limitations with this design remain, many of these limitations can be mitigated by careful study planning and coordination. Augmented trials provide a potentially applicable solution to studying the efficacy of long-acting antiretrovirals for infant postnatal prophylaxis against HIV.

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

Retention in antiretroviral therapy (ART) programmes remains a major public health challenge in HIV care, with loss to follow-up (LTFU) and death threatening treatment success. Because these outcomes are competing events, conventional survival methods may yield biased estimates of their incidence and associated risk factors. To estimate the cumulative incidence of LTFU and mortality and identify factors associated with these outcomes among adults receiving ART in Northern Ghana using a competing-risks framework. We conducted a retrospective cohort study of 329 adults living with HIV who initiated ART at Nalerigu Baptist Medical Centre, Ghana, between January 2013 and December 2019. Fine--Gray subdistribution hazard models were used to evaluate predictors of LTFU and death while accounting for competing risks. Cause-specific Cox proportional hazards models were fitted as a sensitivity analysis. The incidence rates were 2.2 per 100 person-months (95% CI: 1.9--2.6) for LTFU and 0.74 per 100 person-months (95% CI: 0.57--0.98) for death. At 36 months, the cumulative incidence was 50.2% for LTFU and 16.0% for death. Patients residing closer to the clinic had a lower cumulative incidence of LTFU than those living farther away (SHR = 0.68, 95% CI: 0.49--0.93), whereas higher baseline weight was associated with increased LTFU (SHR = 1.02 per kg, 95% CI: 1.00--1.04). Mortality was lower among patients receiving efavirenz-based regimens (SHR = 0.27, 95% CI: 0.15--0.50), females (SHR = 0.39, 95% CI: 0.18--0.85), and those with higher baseline weight (SHR = 0.93 per kg, 95% CI: 0.90--0.96). Findings were broadly consistent in cause-specific Cox models. LTFU was substantially more frequent than mortality among adults receiving ART in Northern Ghana. Travel distance to the treatment facility was an important barrier to retention, while ART regimen, sex, and baseline weight were associated with mortality. Expanding access to ART services through decentralized and community-based models may improve retention and support efforts to achieve HIV control targets.

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

Since its inception in 2003, the United States President's Emergency Plan for AIDS Relief (PEPFAR) has played a central role in HIV/AIDS prevention and treatment across Sub-Saharan Africa. Following the January 2025 suspension of United States foreign aid, which includes PEPFAR funding, countries across Sub-Saharan Africa demonstrated varying governmental responses to the resulting HIV funding disruptions. This study evaluates whether national characteristics were associated with a country's ability to respond to this funding crisis. Countries in Sub-Saharan Africa receiving PEPFAR funding were classified into one of three response categories: Level 1 (minimal or no governmental response), Level 2 (government response without sufficient plans or resources to fully offset funding losses), or Level 3 (high governmental response with strategies to maintain HIV/AIDS prevention and treatment services). Response categories were compared with national Human Development Index (HDI), GDP per capita, HIV prevalence, total population living with HIV, annual HIV mortality, and historical PEPFAR funding. Univariable proportional-odds ordinal logistic regression was used to identify factors associated with response level. Five countries (17.2%) were classified as Level 1, 10 (34.5%) as Level 2, and 14 (48.3%) as Level 3. Higher HDI was significantly associated with stronger governmental response (OR = 4.05; 95% CI, 1.49-11.04; Holm-adjusted p = 0.0376). GDP per capita (OR = 2.35; 95% CI, 1.00-5.51; unadjusted p = 0.0489) and HIV prevalence (OR = 3.53; 95% CI, 1.03-12.11; unadjusted p = 0.0452) demonstrated positive associations before adjustment for multiple comparisons, but neither remained significant after Holm correction (adjusted p = 0.2261 for both). Historical PEPFAR funding, total population living with HIV, and annual HIV mortality were not significantly associated with response level after adjustment. Countries with higher levels of human development demonstrated stronger governmental responses to the 2025 PEPFAR funding disruptions. Several countries with minimal documented responses were also affected by active conflict or political instability, potentially compounding their vulnerability to treatment interruptions. These findings suggest that broader national development may play an important role in governmental responses to funding disruptions and highlight the need to strengthen resilient health systems, diversify HIV financing, and prioritize support for countries at greatest risk of future funding shocks.

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

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

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

Neuropsychiatric symptoms (NPS) are highly prevalent in Mild Cognitive Impairment (MCI), conceptualized as an intermediate clinical state between normal aging and dementia. Although neuroimaging studies have reported associations between NPS and brain alterations in MCI, longitudinal evidence on NPS and their relationship with multimodal MRI measures remains limited. We aimed to investigate (1) longitudinal changes in NPS, volumetric assessment and measurement of regional cerebral blood flow (CBF) within the medial temporal lobe (MTL); (2) associations between longitudinal changes in MRI measures and NPS; (3) whether baseline MRI measures predicted longitudinal changes in NPS. Thirty individuals with MCI aged over 65 years were recruited, of whom eighteen followed up for a mean period of 29 {+/-} 8.9 months. There were significant reductions in total grey matter and white matter volumes, together with volume loss in the bilateral hippocampus, bilateral parahippocampal gyrus and right entorhinal cortex (pFDR[&le;]0.05) over the follow up period. Volume loss in the right parahippocampal gyrus was associated with increase in aggression (pFDR<0.01), and CBF increase in the right hippocampus and parahippocampal gyrus was associated with worsening in agitation (pFDR<0.01). Furthermore, lower baseline volume of the right entorhinal cortex was associated with increase in aggression, and lower baseline CBF in the right hippocampus and parahippocampal gyrus was associated with worsening of agitation (pFDR<0.05). Our findings highlight the importance of identifying NPS in individuals with MCI and the role of structural and perfusion MRI measures as promising biomarkers for monitoring disease progression and improving risk prediction of conversion to dementia.

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

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

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

Background. In people with type 2 diabetes (T2D), postprandial glucose weighs on glycaemic control, and carbohydrate counting is difficult. Patients can describe their meal but rarely quantify it. Objective. To assess (1) whether a small open large language model (LLM), fine-tuned on public data, estimates the carbohydrate content of a meal described in words, and (2) what this carbohydrate adds to the prediction of the postprandial glucose rise in two public cohorts. Methods. Step 1: the Qwen3-4B LLM was fine-tuned with QLoRA on Nutrition5k dishes and compared with an automatically matched USDA food composition table and with Qwen3-4B and Qwen3-8B used without training, on test dishes (internal control) and on 100 real meals of ShanghaiT2DM patients, whose reference carbohydrate was computed from the recorded quantities. Step 2: the maximum glucose rise between 0 and 120 minutes ({Delta}Gmax) was predicted by personalised gradient boosting (M2), compared with a spline linear regression and with the Chronos-2 foundation model, using only information available at meal start and person-level cross-validation, in ShanghaiT2DM (people with T2D recruited in two Shanghai hospitals; carbohydrate estimated by the LLM) and CGMacros (free-living adults in Santa Barbara, California; carbohydrate entered in the dataset, no text). Step 3: the model was transferred between datasets. 95% confidence intervals (CI) were obtained by cluster BCa bootstrap (2,000 resamples). Results. On the 100 real meals, the carbohydrate mean absolute error (MAE) of the fine-tuned model was 12.2 [9.9, 15.2] g, almost half that of the table (22.6 g; paired difference -10.5 [-16.8, -6.0] g) and nearly a third of that of the same model without fine-tuning (34.3 g), with a bias of -10.3 g; on test dishes it was 2.2 [2.0, 2.5] g. Personalised gradient boosting (M2) reached a correlation between predicted and observed rises of r = 0.63 [0.55, 0.69] in CGMacros (1,286 meals, 45 adults) and 0.49 [0.42, 0.54] in ShanghaiT2DM (2,339 meals, 99 people with T2D), about twice the linear reference (r = 0.32 and 0.23); for a rise above 50 mg/dL, its area under the ROC curve (AUROC) was 0.80 and 0.74, versus 0.64 and 0.68 with pre-meal glucose alone. Adding carbohydrate to pre-meal glucose changed r by 0.095 [0.068, 0.128] in CGMacros and by 0.004 [-0.010, 0.017] in ShanghaiT2DM; difference between datasets: 0.091 [0.060, 0.126]. Applied from one dataset to the other, the model lost correlation ({Delta}r = -0.11 [-0.17, -0.05] towards ShanghaiT2DM and -0.12 [-0.19, -0.04] towards CGMacros). The full "text [-&gt;] LLM [-&gt;] glucose" chain was evaluated in ShanghaiT2DM only. Conclusion. An open 4-billion-parameter LLM, fine-tuned with QLoRA on public data and usable offline, almost halves the error of carbohydrate counting for real meals described in words compared with an automatically matched table, with an underestimation of large meals. Personalised gradient boosting, based on pre-meal glucose and the person's usual response, doubles the correlation of a linear reference for predicting the glucose rise in both cohorts. Carbohydrate improved this prediction in CGMacros but not in ShanghaiT2DM; the two datasets differ in many respects, and the cause of this gap is not established.

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

Background: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for EGFR-mutated non-small cell lung cancer (NSCLC) but have distinct toxicity profiles across generations. Aims: To investigate relationships between EGFR-TKI physicochemical, pharmacokinetic and pharmacological properties and drug-specific adverse drug reactions (ADRs) using national and global pharmacovigilance data. Methods: ADRs for erlotinib, afatinib and osimertinib were extracted from the UK MHRA Yellow Card scheme and WHO VigiAccess. Disproportionality analysis used reporting odds ratios (RORs). Signals were defined as ROR >2, lower 95% confidence interval >1 and >3 cases. Drug properties were curated from ChEMBL, emc, SmPC and EMA sources. Results: VigiAccess contained 88,662 individual case safety reports (163,619 ADRs) and Yellow Card contained 752 reports (1,814 ADRs). Four System Organ Class (SOC) signals were identified in VigiAccess and three in Yellow Card, with five additional Yellow Card Preferred Term signals. Eye disorders showed the strongest consistent association with erlotinib (VigiAccess ROR 4.33; Yellow Card ROR 4.18). Osimertinib was associated with pneumonitis (ROR 7.67) and pulmonary embolism (ROR 3.94). Afatinib showed psychiatric disorder signals in both databases (ROR 3.2-3.3) and diarrhoea (ROR 2.79). Neoplasm-related signals likely reflected confounding by indication. Conclusions: EGFR-TKIs demonstrate generation-specific pharmacovigilance profiles. Integration with drug properties supports mechanistic plausibility for several signals, while the atypical afatinib psychiatric association warrants further investigation. Findings are hypothesis-generating and require confirmation in controlled observational or mechanistic studies.

Schizophrenia spectrum disorders (SSD) have been linked to immune dysregulation and altered intestinal barrier function, although findings across studies remain inconsistent. The present study investigated circulating markers of intestinal permeability and immune activation in individuals with early-stage SSD and healthy controls and examined their associations with clinical outcomes. Serum concentrations of intestinal fatty acid-binding protein (iFABP), zonulin, soluble CD14 (sCD14), bactericidal/permeability-increasing protein (BPI), and lipopolysaccharide-binding protein (LBP) were measured in 36 patients with SSD at baseline and one-year follow-up and in 36 matched healthy controls. Linear mixed-effects models adjusted for age, sex, and body mass index (BMI) were used to evaluate group differences and longitudinal changes. No biomarker differences between patients and controls, and no longitudinal changes within patients, remained statistically significant after correction for multiple testing. Similarly, biomarker concentrations were not associated with symptom severity, global functioning, or neutrophil-to-lymphocyte ratio (NLR). Exploratory analyses identified a robust positive association between BMI and zonulin concentrations and additional associations among iFABP, LBP, and sCD14. Exploratory mixed-effects models identified a negative non-significant association between iFABP and sCD14 after adjustment for age, sex, and BMI. Overall, the findings do not support a generalized alteration of gut permeability or immune activation markers in SSD. Instead, they suggest that variation in gut-related biomarkers may be more strongly influenced by metabolic and individual factors than by diagnosis or current symptom severity.

Exposure to armed conflict can leave persistent effects on mental health, yet its neurophysiological correlates remain poorly characterized, particularly in populations exposed to prolonged violence outside narrowly defined post traumatic stress disorder samples. Here we examined resting state electroencephalographic activity in 122 Colombian adults, including 74 participants exposed to armed conflict and 48 controls. Eyes closed EEG was analysed for 240 seconds per participant. We quantified absolute and relative spectral power across delta, theta, alpha and beta bands and regional functional connectivity using weighted phase lag index in theta, alpha and beta. Group comparisons were adjusted for age, education, sex and assessment year, with correction across 78 EEG contrasts. Median occipital and global alpha power was lower in exposed participants, although adjusted estimates were close to the null and confidence intervals were broad. Temporal theta relative power was lower in exposed participants at nominal significance, but this association did not survive Holm correction. No spectral power or regional connectivity contrast remained significant after multiple testing correction. Exploratory associations between EEG measures and MoCA performance were modest in participants with confirmed scores. These findings provide a systematic characterization of resting EEG after exposure to armed conflict in a population shaped by prolonged violence and displacement. They also indicate that large or widespread alterations in resting spectral power and connectivity were not detectable with the current sample and analytical framework, while defining candidate signals and methodological priorities for larger studies of conflict related brain health.

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 [&le;]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.