Pharmacogenomics (PGx) uses genetic information to personalize medication, reducing adverse reactions and improving efficacy. Despite its promise, low public awareness and disparities in PGx acceptability among under-represented groups may exacerbate health inequalities. The objective of this study was to elucidate a British South Asian community's attitudes toward personalised prescribing. Adults of Bangladeshi or Pakistani ancestry from the Genes & Health (G&H) study completed a survey. Community feedback guided theme prioritization. Multivariable logistic regression analyses (controlling for age and gender) explored relationships among survey variables, and case-control Genome Wide Association Studies (GWAS) and candidate variant enrichment analysis examined the genetic architecture underlying herbal remedy use. Out of 553 respondents (57% female, mostly aged 25-54), 72% reported medication inefficacy, and 54% experienced side effects. Herbal remedies were widely used (66%), notably Black seed (39%), Turmeric (37%), and Ginger (36%). Participants who reported not using traditional or herbal medicines had higher medication adherence MARS-5 scores (Odds Ratio (OR) 1.10, 95% Confidence Interval (CI) 1.05-1.16, p < 0.0002). All three commonly used herbal remedies inhibit the pharmacogenomically variable CYP2C9 enzyme responsible for metabolising commonly used medications. 58% of respondents were willing to provide DNA samples for PGx testing, yet 70% agreed that they would be more likely to take medication as instructed if PGx results suggested the medicine would suit them. Concerns about PGx testing were common (27%), especially among non-English speakers. Most (69%) were concerned about misuse of PGx data, particularly by pharmaceutical companies (82%). Importantly, 87% demanded stronger PGx data protections compared to other health data. Compared to a national UK population, the surveyed subpopulation reported higher rates of adverse drug reactions (ADRs) and perceived medication inefficacy, yet fewer respondents indicated willingness to undergo PGx testing. This highlights the need for tailored implementation strategies and underscores the importance of engaging underrepresented populations in policy development. The inverse relationship between medication adherence and herbal remedy use indicates an association between cultural health practices and medication behaviours that merits further investigation. Increased awareness of the common use of these CYP2C9 inhibitors and further research into the genetic architecture underlying herbal remedy use are warranted.

There is an important need to develop clinical strategies to reduce the risk of incident kidney cancer, especially in patients with type 2 diabetes (T2D) often accompanied by chronic kidney disease. Here, we investigated whether sodium-glucose cotransporter 2 (SGLT2) inhibitor use is associated with reduced kidney cancer risk compared to dipeptidyl peptidase-4 (DPP-4) inhibitor use in patients with T2D, using a nationwide cohort of the Korean national health insurance claims and health examination database. After 1:1 propensity score matching, 57,103 SGLT2 inhibitor new users and 57,103 DPP-4 inhibitor new users were selected from 581,702 kidney cancer-free participants, aged 20 to 79 years, who started oral glucose-lowering drugs for T2D from 2014 to 2018. During 408,481 person-years of follow-up, 102 (25.0 per 100,000 person-years) new kidney cancer events occurred. SGLT2 inhibitor use was associated with a 40% reduced risk of kidney cancer compared with DPP-4 inhibitor use (18.9 vs. 30.8 per 100,000 person-years; hazard ratio [HR] 0.60, 95% CI 0.40 to 0.89). The reduced kidney cancer risk associated with SGLT2 inhibitor use versus DPP-4 inhibitor use was consistent even after additional adjustment for all variables composing the propensity scores (HR 0.60, 95% CI 0.40 to 0.90) and regardless of age, sex, body mass index, current smoking, hypertension, medication use, or diabetic complications including nephropathy (all p > 0.05 for interaction). When comparing SGLT2 inhibitor users with 1:1 propensity score-matched non-users, SGLT2 inhibitor use was associated with a 34% reduced risk of kidney cancer compared to non-use (HR 0.66, 95% CI 0.49 to 0.89). Our findings suggest a potential association between SGLT2 inhibitor use and a lower risk of kidney cancer, which needs to be further validated.

Placental signaling pathways regulate nutrient transport and fetal growth, with potential long-term consequences for offspring metabolic health. Most prior human studies have focused on individual placental markers, limiting insight into the role of coordinated activity across multiple pathways in relation to offspring outcomes. Our objective was to identify patterns across placental nutrient signaling pathways and assess whether the latent placental signaling patterns were associated with early childhood adiposity, and secondarily, explore associations of adiposity-associated patterns with metabolic biomarkers. Among 108 mother-child pairs from the Healthy Start cohort, we quantified 33 placental signaling proteins and their phosphorylated-to-total protein ratios involved in nutrient sensing, insulin/growth factor signaling, stress/inflammation, and mitochondrial biogenesis using Simple Western assays of term placental villus tissue. We applied unsupervised methods to identify latent patterns and LASSO regression was used to select patterns associated with %fat mass at age 4. Multivariable linear regression was used to estimate associations adjusting for offspring age, sex, and maternal pre-pregnancy BMI. These same models were used in exploratory analysis of fasting levels of adiponectin, leptin, insulin, glucose, and lipids at age 4. We identified two placental signaling patterns associated with %fat mass. The insulin-mTOR-energy sensing pattern was associated with lower childhood %fat mass (β = -2.46, 95% CI - 4.84, - 0.09) and adiponectin, and the stress-inflammatory MAPK pattern was associated with higher %fat mass (β = 1.28, 95% CI 0.05, 2.51), leptin, and triglycerides; however, the FDR p-values ranged from 0.06 to 0.13. Two placental signaling patterns were associated with childhood %fat mass and metabolic markers. These findings indicate that capturing placental activity across several signaling pathways may yield insights into early origins of adiposity and metabolic health.

The EAT Lancet diet is increasingly recognized for its simultaneous benefits to human and planetary health. Its key components are known to exert anti-inflammatory and antiplatelet effects; however, the potential association between adherence to the EAT‑Lancet diet and incident venous thromboembolism (VTE), as well as the underlying biological mechanisms, remains unclear. This prospective study involved 201,695 UK Biobank participants who were free of VTE at baseline, and integrated large-scale Olink plasma proteomics to identify diet-related molecular signatures. Adherence to the EAT-Lancet diet was quantified using two validated indices. Cox models were employed to evaluate associations between EAT-Lancet diet, plasma proteins, and incident VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]). Mediation analyses quantified the role of plasma proteins. During a median follow-up of 13.77 years, participants in the highest adherence group of the Stubbendorff index showed lower risks of VTE (HR = 0.809, 95% CI: 0.750-0.874), DVT (HR = 0.856, 95% CI: 0.781-0.938), and PE (HR = 0.754, 95% CI: 0.678-0.838). Consistent protective associations were observed with the Knuppel index. Mediation analyses identified 94 shared plasma protein mediators, with mediation proportions ranging from - 4.77% to 8.45% of the association, among which FABP4, LEP, and ENPP6 were the top-ranked mediators. The overall proteomic signature mediated 59.19% (95% CI: 27.02%-92.15%) and 40.10% (95% CI: 14.53%-65.96%) of the associations between the Stubbendorff and Knuppel index and incident VTE, respectively. Higher adherence to the EAT-Lancet diet is significantly associated with a reduced risk of incident VTE, DVT, and PE, with plasma proteins potentially mediating this effect.

Climate change is increasing the frequency, duration, and severity of floods escalating worldwide, exposing pregnant women to growing health risks. While previous literature has demonstrated an association between prenatal flood exposure and low birth weight (LBW) in offspring, evidence in low- and middle-income countries (LMICs) remains limited. In this cross-sectional study, birth records from the Demographic and Health Surveys (DHS) were geospatially matched with flood data from the Dartmouth Flood Observatory (DFO). A total of 290,008 singleton live births across 36 African LMICs were analyzed. Logistic regression models were employed to estimate odds ratios (ORs) for the association between prenatal flood exposure and LBW prevalence. The burden of LBW attributable to prenatal flood exposure was estimated across 28 of 36 African LMICs. We observed positive associations between prenatal flood exposure and LBW (OR: 1.076, 95% CI: 1.028 to 1.128), with the effect sizes escalating progressively across severity exposure levels (P for trend = 0.003). Higher odds ratios were found among urban residents, mothersof advanced maternal age (≥ 35years), and households utilizing unsafe water or flush toilets. We estimated that prenatal flood exposure was associated with approximately 234 excess LBW cases per 1,000 births per decade, totaling 467,904 (95% CI: 180,434 to 751,720) over the 21-year study period (from 2000 to 2020) across 28 African LMICs. Our findings highlight the urgency of addressing health disparities stemming from prenatal floods and extreme environmental events for neonatal health promotion.

Maternal diabetes and obesity are established risk factors for adverse offspring health. Emerging evidence suggests that these fetal programming effects vary by sex, yet it remains unclear whether these factors independently or interactively influence early brain development. This prospective study included 1,965 infants from six international cohorts. Infant MRI was used to derive subcortical volumes (thalamus, amygdala, hippocampus, pallidum, putamen, caudate). ComBat harmonization was applied. Multiple linear regression tested main and interaction effects of maternal obesity, maternal diabetes, and sex, controlling for covariates with false discovery rate (FDR) corrections. Of the sample, 46% were female (N = 909), 9% were exposed to maternal diabetes (N = 172), 22% to maternal obesity (N = 386), and 3% to both (N = 61). MRI scans were performed at 25.9 ± 18.8days. Maternal diabetes was associated with smaller thalamic volume (standardized β = -0.09, 95%CI -0.16 to -0.01, FDR P = 0.020), but this association was attenuated after adjusting for maternal obesity. Maternal obesity was associated with smaller hippocampal (standardized β = -0.13, 95%CI -0.21 to -0.05, FDR P = 0.009) and thalamic volumes (standardized β = -0.09, 95%CI -0.14 to -0.03, FDR P = 0.007). Sex-specific associations were observed. In females, maternal obesity was associated with smaller hippocampal (standardized β = -0.24, 95%CI -0.36 to -0.13, FDR P < 0.001) and amygdala volumes (standardized β = -0.18, 95% CI = -0.30 to -0.06, FDR P = 0.016). A three-way interaction (diabetes x obesity x sex) was observed for thalamus volume (standardized β = -0.50, 95%CI -0.81 to -0.18, FDR P = 0.017). In males, combined exposure had lower thalamic volume compared to those with one or neither exposure (all Ps < 0.05). In females, maternal obesity (standardized β = -0.12, 95%CI -0.20 to -0.04, FDR P = 0.015) and diabetes (standardized β = -0.16, 95%CI -0.30 to -0.02, FDR P = 0.042) showed independent associations with thalamic volume, without a significant interaction (standardized β = 0.23, 95%CI -0.01 to 0.46, FDR P = 0.092). Maternal obesity shows stronger associations with infant subcortical volumes than maternal diabetes. It is associated with smaller hippocampal and amygdala volumes in females, while combined exposure to maternal diabetes and obesity is associated with smaller thalamic volumes in males. These findings highlight the role of maternal metabolic health and infant sex in early neurodevelopment.

Bangladesh has a noticeable rise in vector-borne diseases (VBD) attributed to climate change. Accurately mapping, predicting, and identifying the risk factors of VBD is essential for prevention and control strategies. Therefore, this study aimed to investigate the spatiotemporal pattern and associated meteorological factors of VBD in Bangladesh. This study used district-level reported cases of VBD (dengue, chikungunya, malaria, filariasis, and yellow fever) obtained from the Bangladesh Bureau of Statistics. Simultaneously, meteorological data (temperature, relative humidity, wind speed, and precipitation) were sourced from NASA from 2017 to 2020. A combination of exploratory spatial analysis, spatial regression, and advanced tree-based machine learning models was utilized for prediction, risk factor identification, and correlation analysis. Dengue was the most prevalent vector-borne disease during the study period, peaking in 2019, while malaria and filariasis showed variable incidence across districts. Dhaka, Pirojpur, Jessore, Bandarban, Rangamati, and Narail districts exhibited higher incidence rates of VBD. The spatial regression model identified mean temperature as a major risk factor for VBD (β = 16.64, s.e. = 6.39). Additionally, the optimal XGBoost model also highlighted mean temperature as the primary determinant, alongside other climatic and socioeconomic factors such as GDP, population size, and healthcare infrastructure, underscoring the complex interplay between health infrastructure and socioeconomic drivers for Bangladesh's VBD from 2017 to 2020. The study's findings, incorporating the One Health perspective, provide insights for planning early-warning, prevention, and control strategies using machine learning to combat infectious diseases in Bangladesh and similar endemic countries. Precautionary measures and intensified surveillance must be implemented in certain high-risk districts nationwide.

School aversion is increasingly recognized in adolescents and has been linked to emotional distress, suicide risk, and academic failure. However, studies rely on correlational analysis, making it unclear which risk factors truly cause school aversion. To address this gap, we combined directed acyclic graph (DAG)-based modeling, DoWhy-based causal effect estimation, and counterfactual simulation to explore psychosocial pathways related to school aversion in clinically referred adolescents. Participants were clinically referred adolescents from mental health services who completed standardized psychosocial assessments. Variables were obtained through validated instruments and clinical intake records, covering demographics, adversity, personality, and symptoms. Causal inference was conducted through a combined framework of DAG learning, DoWhy estimation with backdoor propensity-score weighting and logistic-model-based counterfactual simulation. All analyses were performed using Python 3.11.8, with pgmpy, DoWhy, and scikit-learn as core libraries. A total of 423 adolescents were assessed, with 57.7% showing school aversion or refusal and 39.7% reporting suicidal thoughts or attempts. DAG modeling identified several school aversion-adjacent relationships, with family structure, bullying, and digital addiction retained as primary school-aversion-centered pathways in downstream analyses, whereas trauma remained a nearby contextual factor. DoWhy analysis showed that the retained associations were SchoolAversion → Bullying [average treatment effect (ATE) = 0.046, p = 0.001] and SchoolAversion → DigitalAdd (ATE = 0.036, p = 0.008), while family structure showed a significant negative effect on school aversion (ATE = -0.162, p = 0.031). Counterfactual simulation showed that removing bullying or digital addiction had relatively small effects on school aversion. In exploratory counterfactual simulations, SchoolAversion → Suicide showed a risk difference of 0.266 (bootstrap95% CI 0.182 to 0.346). Among clinically referred adolescents, school aversion appeared not only as an outcome linked to upstream psychosocial context, but also as a central factor associated with downstream bullying, digital addiction, and suicide risk in the present framework. This integrated causal framework may help refine risk screening and intervention prioritization in clinical populations, while further validation in non-clinical and longitudinal samples is needed.

BackgroundEducation is an important determinant of health throughout the life course. However, less is understood about whether and how intergenerational educational mobility—comparing an individual’s own and their parents’ education—is associated with depressive symptoms among aging populations across diverse settings. This study examines this association and its mediating pathways.MethodsUsing data from six harmonized longitudinal aging studies: the US Health and Retirement Study (HRS) and its partner studies in England, European countries, South Korea, Mexico, and China, we conducted cross-sectional (n = 94,655) and longitudinal analyses (n = 56,817) to first establish the association across diverse populations, and then strengthen causal inference by examining whether educational mobility relates to depressive symptoms over time. Educational mobility was categorized as stably low, downwardly mobile, stably middle, upwardly mobile, and stably high group based on country- and cohort-specific percentiles. Depressive symptoms were assessed using the Euro-D or CES-D. We also examined the moderating role of gender in these associations. Mediating pathways through household wealth, social activeness, and multimorbidity were also explored.ResultsLongitudinal analyses revealed consistent gradient associations across countries. Compared to the stably low group, downwardly mobile (OR: 0.84, 95% CI: 0.76–0.93), stably middle (OR: 0.78, 95% CI: 0.72–0.84), upwardly mobile (OR: 0.74, 95% CI: 0.67–0.83), and stably high (OR: 0.65, 95% CI: 0.53–0.80) showed lower odds of depressive symptoms. Gender differences emerged in European countries and South Korea, where women had lower odds than men in downwardly mobile and stably high groups. Cross-sectional results showed similar but stronger patterns. Household wealth was the most consistent mediator, explaining 24–34% of the association in the USA and comparable proportions elsewhere except for South Korea. Social activeness and multimorbidity also showed important but varying mediating proportions across countries.ConclusionsAdvantaged educational mobility is associated with reduced depressive symptoms in mid- and later-life. Household wealth, social activeness, and multimorbidity contribute as important mediators. Future policies are needed to promote intergenerational educational equity and implement integrated strategies to reduce mental health disparities.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-026-04808-w.

BackgroundClearance of Plasmodium falciparum infection requires a TH1 immune response with production of pro-inflammatory cytokines, IgG1, and IgG3 responses. In contrast, infections with helminths are dominated by TH2/Treg immune responses characterized by production of anti-inflammatory cytokines, IgE, and IgG4, which could potentially interfere with malaria outcomes and immune responses.MethodsWe recruited 441 malaria-symptomatic children aged 2–10 years attending two hospitals in the Manhiça District (Mozambique) and assessed infection by rapid antigen diagnostic test, microscopy, and/or quantitative PCR. Using Luminex, we measured concentrations of 30 cytokines and IgA, IgM, IgE, IgG, and IgG1–4 levels against 12 P. falciparum antigens and total IgE.ResultsAmong 74 children diagnosed with malaria, 22% (16) were coinfected with STH, and 78% (58) had only P. falciparum. Soil-transmitted helminths (STH) coinfection associated with lower P. falciparum density (P = 0.005) and fever (P = 0.047). Coinfected children also had lower concentrations of plasma pro-inflammatory (IL-8, TNF, IFNα, IP-10, MCP1, MIG, MIP1β, and GM-CSF) and anti-inflammatory cytokines (IL-5, IL-10) (P < 0.05). Furthermore, antibody responses to a set of P. falciparum antigens, including SSP2 (IgG1, IgG4, IgG), PTRAMP (IgG3), MSP3 (IgG), RH5 (IgG1), and α-gal (IgG1), as well as total IgE, were elevated in STH coinfected children (P < 0.05).ConclusionsSTH infections were associated with decreased P. falciparum parasitemia, downregulation of inflammatory cytokines, and enhanced antibody responses, potentially resulting in milder malaria episodes, suggesting enhanced protective immunity.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-026-04827-7.