BMC Medicine[JOURNAL]
Sun
200 papers
Ambient pollution components and sources are associated with hippocampal architecture and memory in pre-adolescents.
Rosario MA, Sukumaran K, Bottenhorn KL … +11 more , de Jesus A, Cadenas-Iniguez C, Ahmadi H, Habre R, Abad S, Pine JG, Barch DM, Schwartz J, Hackman DA, Chen JC, Herting MM
BMC Med · 2026 Jun · PMID 42271458 · Full text
BACKGROUND: Ambient air pollution poses significant risks to brain health. The hippocampus may be particularly vulnerable, yet the extent to which it is impacted in children remains unclear. METHODS: Using partial least...
BACKGROUND: Ambient air pollution poses significant risks to brain health. The hippocampus may be particularly vulnerable, yet the extent to which it is impacted in children remains unclear. METHODS: Using partial least squares correlation, we cross-sectionally analyzed air pollution, brain, and cognitive data from the Adolescent Brain Cognitive Development Study to examine how multi-pollutant exposure influences hippocampal structure and memory in 9-11-year-olds (n = 7,940). Annual average air pollution exposures included PM (total mass, 15 components, and 6 source factors), NO, and 8-hour maximum O. Hippocampal outcomes included microstructure measured using Restriction Spectrum Imaging and hippocampus longitudinal-axis (i.e., head, body, tail) volumes. We examined hippocampal-dependent list-learning using the Rey Auditory Verbal Learning Test. Models were adjusted for demographic, socioeconomic, and neuroimaging factors. RESULTS: PM total mass was associated with hippocampal microstructure, but not long-axis volume or list-learning ability. Component and source analyses provided greater specificity: higher bromine, sulfate, and vanadium exposure was related to microstructure (72% shared variance), while higher copper and zinc exposure correlated with smaller left head and right body and tail volumes (75% shared variance). Source models implicated biomass burning and traffic pollution in microstructure (61% and 32% shared variance) and industrial and traffic sources in smaller hippocampal volumes (77% shared variance). Higher exposure to several components were also linked to poorer list-learning (67% shared variance). CONCLUSION: Co-exposure to multiple pollutants is linked to differences in hippocampal structure and memory, showing that associations are driven not only by PM total mass but also by specific components and sources. This evidence underscores the necessity of targeting source-specific (e.g., biomass burning, traffic, and industrial emissions) and constituent components (e.g., metals) of air pollution during critical developmental windows to safeguard brain health.
Is there a bidirectional relationship between the number of unhealthy lifestyle factors and depressive symptoms in adolescents? Evidence from a longitudinal study.
Wang M, Qin A, Li S … +5 more , Lv C, Liu Z, Zheng S, Yu L, Zhang J
BMC Med · 2026 Jun · PMID 42271324 · Full text
BACKGROUND: Depression and unhealthy lifestyle factors are major public health concerns. Although individual unhealthy lifestyle factors have been associated with adolescent depressive symptoms, the longitudinal relation...
BACKGROUND: Depression and unhealthy lifestyle factors are major public health concerns. Although individual unhealthy lifestyle factors have been associated with adolescent depressive symptoms, the longitudinal relationships between depressive symptoms, the cumulative number of unhealthy lifestyle factors, and depressive symptom trajectories remain unclear. This study examined these associations among Chinese adolescents. METHODS: Three annual waves of longitudinal data (T1: 2022; T2: 2023; T3: 2024) were collected using self-administered paper-based questionnaires and multi-stage stratified cluster sampling. The study included 5,988 adolescents (mean baseline age, 12.75 years; 3,013 boys [50.3%]). Depressive symptoms were assessed using the 20-item Center for Epidemiologic Studies Depression Scale. Eight unhealthy lifestyle factors were assessed: smoking, alcohol consumption, physical inactivity, low fruit/vegetable intake, unhealthy diet, excessive screen time, sedentary behavior, and inadequate sleep. Random intercept cross-lagged panel models examined bidirectional associations between depressive symptoms and the number of unhealthy lifestyle factors, adjusting for age, gender, ethnicity, region, living with father/mother, living on campus, education level, and body mass index. Latent class linear mixed models identified depressive symptom trajectories, and generalized linear mixed models examined associations between these trajectories and the number of unhealthy lifestyle factors. RESULTS: Depressive symptoms at time T significantly predicted the number of unhealthy lifestyle factors at time T + 1, whereas the reverse associations were not significant. Three depressive symptom trajectories were identified: "low" (n = 4,401), "fluctuating" (n = 1,264), and "high peaking" (n = 323). Compared with the "low" group, adolescents in the "fluctuating" and "high peaking" groups had a significantly higher number of unhealthy lifestyle factors at T3 (AIRR = 1.128, 95% CI: 1.088-1.171; AIRR = 1.162, 95% CI: 1.092-1.236). However, the number of unhealthy lifestyle factors at T1 was not significantly associated with later depressive symptoms or depressive symptom trajectories. Sensitivity analyses supported this unidirectional temporal pattern. CONCLUSIONS: Depressive symptoms may precede the accumulation of multiple unhealthy lifestyle factors in adolescents, whereas the reverse direction was not supported. Adolescents with "fluctuating" or "high peaking" depressive symptom trajectories showed greater behavioral risk accumulation. Long-term monitoring and early intervention for depressive symptoms may help prevent recurrent symptoms and unhealthy lifestyle consequences.
The economic burden of depression disease for China, India and the USA in 2025-2050: a health-augmented macroeconomic modelling study.
Wu M, Li A, Meng K … +7 more , Yi Y, Zhang Z, Shi C, He Y, Ouyang X, Tan C, Wan X
BMC Med · 2026 Jun · PMID 42265677 · Full text
BACKGROUND: Depression is an increasingly severe public health challenge worldwide, causing substantial health losses and profoundly impacting national economies. As China, India and the USA bear the largest share of the...
BACKGROUND: Depression is an increasingly severe public health challenge worldwide, causing substantial health losses and profoundly impacting national economies. As China, India and the USA bear the largest share of the global depression burden and have different developmental and demographic profiles, quantifying the condition's long-term macroeconomic effects in these countries is crucial for gaining insight into the relationship between mental health and economic development worldwide. METHODS: We used a health-augmented macroeconomic model to assess the macroeconomic impact of depression, comparing the difference in gross domestic product (GDP) between a status quo scenario and a counterfactual scenario in which depression was assumed to be completely eliminated between 2025 and 2050. The model incorporated human and physical capital channels, capturing productivity losses, reduced labour supply and declines in household savings caused by medical expenditures. Data were drawn from multiple publicly available sources, including literature, the Global Burden of Disease Study and the World Bank. RESULTS: From 2025 to 2050, the cumulative macroeconomic burden of depression is projected to reach INT $3,340 billion across the three countries. The USA is expected to bear the largest total and per capita losses, at INT $1,416 billion and INT $4,110 per person respectively. India would follow with INT $1,100 billion and INT $762 per person, while China would account for INT $873 billion and INT $615 per person. CONCLUSIONS: Across different economic models, depression has a significant and sustained negative impact on long-term macroeconomic development. Policymakers should take prompt action to implement effective prevention and management strategies to curb the growing health and economic impacts of depression.
Spectral focused imaging enables enhanced colorectal adenoma detection: a multicenter, parallel randomized controlled trial.
Zhang QW, Liao J, Zeng X … +9 more , Yi N, Li N, Zhang T, Liu M, Ye G, Yao P, Chou J, Hu C, Li XB
BMC Med · 2026 Jun · PMID 42260471 · Full text
BACKGROUND: The adenoma detection rate (ADR) indicates colonoscopy quality. White light imaging (WLI) often fails to identify small/flat adenomas. Spectral focused imaging (SFI) utilizes multiple narrow-band wavelengths...
BACKGROUND: The adenoma detection rate (ADR) indicates colonoscopy quality. White light imaging (WLI) often fails to identify small/flat adenomas. Spectral focused imaging (SFI) utilizes multiple narrow-band wavelengths to enhance mucosal visualization. Here, the diagnostic performance of SFI and high-definition WLI were first compared, focusing on ADR. METHODS: This prospective, parallel-arm, randomized controlled trial was undertaken in eight endoscopy centers. Participants (aged 45-85 years) were randomly allocated (1:1) to SFI and high-definition WLI groups. The primary endpoint was ADR, while secondary endpoints included the polyp detection rate (PDR), advanced ADR (aADR), and the average adenoma number per colonoscopy. Exploratory subgroup analyses compared detection of lesions differing in size, morphology, and anatomical location. RESULTS: Six hundred and ninety-eight patients were allocated to groups (SFI: n = 350; WLI: n = 348). The ADR was markedly greater in the SFI group (38.29% vs. 30.46%; P = 0.030), as were secondary measures: PDR (56.29% vs. 47.99%; P = 0.028), aADR (6.57% vs. 3.16%; P = 0.036), and adenoma number per colonoscopy (0.74 vs. 0.51; P = 0.021). Exploratory subgroup analysis indicated that SFI was superior in detecting right-sided adenomas (17.71% vs. 11.78%; P = 0.027), diminutive lesions ≤ 5 mm (28.86% vs. 19.54%; P = 0.004), and flat adenomas (22.86% vs. 16.67%; P = 0.040). CONCLUSIONS: SFI was significantly more effective in adenoma detection relative to high-definition WLI, particularly for right-colon and small/flat lesions. These findings support the use of SFI in routine endoscopy to enhance colonoscopy quality and detection of colorectal adenomas. TRIAL REGISTRATION: ClinicalTrials, NCT06603948.
Blood-based DNA methylation marker model for short-term and long-term lung cancer risk prediction.
Bhardwaj M, Sun YQ, Frick C … +5 more , Schöttker B, Røe OD, Holleczek B, Mai XM, Brenner H
BMC Med · 2026 Jun · PMID 42251373 · Full text
BACKGROUND: Screening heavy smokers with low-dose computed tomography (LDCT) has been shown to reduce lung cancer (LC) mortality, however, identifying the specific high-risk population that benefits most, a critical requ...
BACKGROUND: Screening heavy smokers with low-dose computed tomography (LDCT) has been shown to reduce lung cancer (LC) mortality, however, identifying the specific high-risk population that benefits most, a critical requirement for implementing effective and cost-efficient screening, remains challenging. METHODS: We developed and validated a blood-based DNA methylation marker model (BBDMM) for all participants, including both ever and never smokers, using the LC risk-informative CpG sites from epigenome-wide association studies (EWAS). The model was developed and internally validated in 2,459 participants from ESTHER, a population-based cohort from Germany. Subsequently, BBDMM was externally validated in exactly same 233 participants drawn from the Norwegian HUNT2 and HUNT3 cohorts with long- and short-term follow-ups and cases identified up to 18 and 6.7 years before LC diagnosis, respectively. RESULTS: The BBDMM predicted LC incidence with an area under the curve (AUC) of 0.84 [95% confidence interval (95% CI), 0.80-0.87] in the derivation set. In the independent external validation sets, AUCs of 0.85 (95% CI, 0.80-0.90) and 0.85 (95% CI, 0.80-0.90) were observed in HUNT2 and HUNT3, respectively. CONCLUSIONS: The BBDMM identified future lung cancer cases with promising potential and the model discrimination was highly stable at different time points. These markers may contribute to the evolution of a blood-based test for predicting LC risk.
PROTAC-mediated PCSK9 degradation attenuates atherosclerosis and improves plaque composition via suppression of NF-κB/TNF-α pathway.
Wang X, Liu Y, Zhang QP … +9 more , Zhang MC, Xia MD, Yang P, Chen SL, Guo WM, Liu M, Tang ZH, Fan G, Yang J
BMC Med · 2026 Jun · PMID 42249453 · Full text
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical therapeutic target for managing hyperlipidemia and atherosclerosis. We developed Cadd4, a synthetic proteolysis-targeting chimera (PROTAC) e...
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical therapeutic target for managing hyperlipidemia and atherosclerosis. We developed Cadd4, a synthetic proteolysis-targeting chimera (PROTAC) engineered to selectively induce proteasomal degradation of the PCSK9 protein. In this study, we investigate Cadd4's anti-atherosclerotic properties and concurrently evaluate the feasibility and safety of its long-term therapeutic administration. METHODS: Cadd4-mediated PCSK9 degradation was assessed in mouse monocyte-macrophage leukemia cells(RAW264.7), mouse aortic vascular smooth muscle cells (MOVAS) and human umbilical vein endothelial cells (HUVECs) using immunofluorescence. Its anti-inflammatory effects were examined in lipopolysaccharide (LPS)-stimulated cells via quantitative real‑time PCR (qRT-PCR) and western blot. In vivo efficacy was assessed in apolipoprotein E-deficient (ApoE) mice maintained on a high-fat diet (HFD). Animals received intraperitoneal injections of Cadd4 (20 mg/kg every two days) or subcutaneous injections of alirocumab (3 mg/kg weekly) for 12 consecutive weeks. RESULTS: Cadd4 induced dose-dependent PCSK9 degradation in all three cell types tested and significantly attenuated LPS-induced inflammatory responses. Notably, a 2-week intraperitoneal administration of Cadd4 led to a marked reduction in PCSK9 expression in both the liver and aorta of treated mice. In HFD-fed ApoE mice, 12-week administration of Cadd4 significantly decreased atherosclerotic plaque area, enhanced collagen deposition within plaques and suppressed intra-plaque inflammation. Importantly, compared with alirocumab, Cadd4 demonstrated superior efficacy in suppressing matrix metalloproteinase (MMP) expression and increasing collagen content, effects that are likely mediated via inhibition of the NF-κB/TNF-α signaling pathway. Of note, Cadd4 mediated PCSK9 modulation did not alter plasma lipid profiles in this model. Collectively, these anti-atherosclerotic effects underscore the lipid-independent anti-inflammatory activity and plaque composition-improving capacity of Cadd4. CONCLUSIONS: Cadd4 potently induces PCSK9 degradation in arterial tissues, mitigates atherosclerotic progression and improves plaque composition via lipid-independent inhibition of the NF-κB/TNF-α pathway. These findings underscore the therapeutic promise of Cadd4 as a candidate for managing atherosclerotic cardiovascular disease.
Associations between retinal morphological features and risk of depression and anxiety disorders.
Li Y, Zhang Y, Yim C … +10 more , Kam KW, Ho M, Zhang XJ, Ip P, Ng MPH, Young AL, Tham CC, Pang CP, Chen LJ, Yam JC
BMC Med · 2026 Jun · PMID 42249369 · Full text
BACKGROUND: Understanding how retinal morphological features are associated with the risk of developing depression and anxiety disorders holds significant implications for public health and early detection strategies. Th...
BACKGROUND: Understanding how retinal morphological features are associated with the risk of developing depression and anxiety disorders holds significant implications for public health and early detection strategies. This study aims to investigate the association between optical coherence tomography (OCT)-detected retinal features and the incidence of depression and anxiety. METHODS: This cohort study was conducted using data from UK Biobank participants aged 40-70 years who underwent retinal OCT imaging at recruitment. Baseline retinal morphological features, including the retinal nerve fibre layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL), photoreceptor layer (PRL), retinal pigment epithelium (RPE), and macular thickness, were segmented from macular-centered OCT images. Depression and anxiety disorders were identified using International Classification of Diseases (ICD) codes. Cox proportional hazards regression models were used to assess the association of retinal features with incident depression and anxiety, with the full model adjusting for demographic, lifestyle, and comorbid factors. RESULTS: A total of 36,220 participants were included (mean [SD] age, 55.90 [8.22] years, 47.8% male). Over a median follow-up duration of 12.5 years, 1340 new cases of depression and 1373 new cases of anxiety were observed. In fully adjusted Cox hazard regression models, each standard deviation (SD) increase in GCIPL and macular thickness was associated with a lower risk of incident depression (HR [95%CI], 0.92 [0.87, 0.97]; and 0.91 [0.86, 0.96], respectively). The associations of GCIPL and macular thickness with incident depression were more pronounced among females. On the other hand, there was no association between retinal features and incident anxiety disorders in the fully adjusted model. CONCLUSIONS: Thinner GCIPL and macular thickness were independently associated with increased risk of depression, especially in females. Our findings highlight a potential role of OCT-detected retinal features as additional biomarkers for at-risk stratification of depression.
A large-scale single-nucleus resource reveals a cardiomyocyte-like fibroblast and stage-specific remodeling across cardiomyopathies.
Tang Q, Li X, Fan X … +10 more , Zheng C, Ma H, Luo R, Tang Y, Liu S, Fan C, Zhang Y, Zhang W, Wu X, Li X
BMC Med · 2026 Jun · PMID 42243863 · Full text
BACKGROUND: Cardiomyopathies represent a heterogeneous group of myocardial disorders with distinct phenotypes and outcomes, yet their cell-type-specific mechanisms and differences remain incompletely defined. METHODS: He...
BACKGROUND: Cardiomyopathies represent a heterogeneous group of myocardial disorders with distinct phenotypes and outcomes, yet their cell-type-specific mechanisms and differences remain incompletely defined. METHODS: Here, we present the Cardiac Cell Atlas, a large-scale single-nucleus transcriptomic atlas of 525 cardiac tissue samples (20 newly generated and 505 publicly available) spanning dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), left ventricular non-compaction (LVNC), and non-failing controls, integrating > 2 million nuclei. RESULTS: This resource delineates both shared remodeling signatures and divergent trajectories across cardiomyopathies. We identified a previously unrecognized fibroblast (FB) subpopulation expressing cardiomyopathy genes (TNNT2, RYR2, MYBPC3), positioned between fibroblasts and ventricular cardiomyocytes (VCM) and segregating into FB-like (SORBS2) and ventricular VCM-like (SORBS2) states, the latter with reparative potential. Notably, HCM was dominated by compensatory hypertrophic remodeling, whereas DCM showed progressive cardiomyocyte loss and maladaptive FB expansion, consistent with their distinct clinical outcomes. Left ventricular ejection fraction (LVEF)-associated pseudotime staging revealed dynamic remodeling: early HCM showed enriched VCM-FB-endothelial(EC) signaling and effective compensation, while early DCM lacked EC involvement, predisposing to dysfunction. At mid-stage, signaling declined in HCM but intensified in DCM as ECs became active remodelers, whereas late-stage disease in both subtypes exhibited global signaling loss, with residual maladaptive extracellular matrix(ECM)-receptor activity persisting in DCM. CONCLUSIONS: Together, the Cardiac Cell Atlas provides a comprehensive reference for human cardiac cell states and interactions, advancing mechanistic understanding and informing clinical strategies for risk stratification, stage-specific intervention, and improved outcomes in HCM and DCM. The web portal of Cardiac Cell Atlas together with all the datasets are publicly available at http://113.54.15.143:8000/app/index/.
Impact of reduced-frequency monitoring among users of HIV pre-exposure prophylaxis on sexually transmitted infections and associated care: secondary outcomes of a randomized controlled trial.
Wijstma ES, Groot Bruinderink ML, Jongen VW … +12 more , Boyd AC, Blitz L, van Bokhoven C, Woudstra J, Vermey K, Boers S, Götz HM, van Harreveld F, Prins M, Hoornenborg E, Davidovich U, Schim van der Loeff MF
BMC Med · 2026 Jun · PMID 42243843 · Full text
BACKGROUND: Oral HIV pre-exposure prophylaxis (PrEP) users are generally screened for sexually transmitted infections (STIs) every 3 months. The need for such frequent screening is debatable. We compared STI diagnoses an...
BACKGROUND: Oral HIV pre-exposure prophylaxis (PrEP) users are generally screened for sexually transmitted infections (STIs) every 3 months. The need for such frequent screening is debatable. We compared STI diagnoses and associated care between PrEP users who underwent 6-monthly versus 3-monthly PrEP monitoring. METHODS: We conducted a secondary analysis of the EZI-PrEP study- a 2 × 2 factorial randomized controlled trial examining 6-monthly versus 3-monthly and online versus in-clinic PrEP monitoring among men who have sex with men (MSM) and transgender or gender-diverse persons in the Netherlands (2021-2024). Participants were followed for 24 months. Scheduled PrEP monitoring included bacterial STI screening (i.e., Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), syphilis). Unscheduled STI testing in-between monitoring visits was permitted. This secondary analysis compared several outcomes between the 6-monthly and 3-monthly monitoring groups, using Poisson regression: (i) visit rates as number of visits per person-year (PY), (ii) STI detection rates as number of STI diagnoses per 100PY (to assess STI detection and potential (over)treatment), and (iii) STI positivity as number of STI diagnoses per 100 visits (as proxy for diagnostic delay). We stratified outcomes by visit type (i.e., scheduled/unscheduled) and adjusted for sexual behavior. RESULTS: 451 participants (99% MSM) were followed for median 22.7 months (IQR 19.2-23.8). Compared to 3-monthly PrEP monitoring, 6-monthly monitoring led to 31% fewer visits in total (rate ratio = 0.69, 95%CI = 0.64-0.74), but 67% more unscheduled visits (rate ratio = 1.67, 95%CI = 1.42-1.98). The STI detection rate was 18% lower in the 6-monthly monitoring group (adjusted rate ratio = 0.82, 95%CI = 0.70-0.95). STI positivity at PrEP monitoring visits did not differ between monitoring groups (6-monthly: 23.8 STIs/100 visits; 3-monthly: 23.2 STIs/100 visits; adjusted positivity ratio = 1.09, 95%CI = 0.90-1.30). CONCLUSIONS: Reduced-frequency PrEP monitoring resulted in fewer total clinic visits, but more self-initiated STI testing. Furthermore, fewer STIs were diagnosed during follow-up, yet the number of STIs detected per scheduled monitoring visit was similar between groups. These findings suggest that less frequent PrEP monitoring could reduce the burden of PrEP care and the number of STIs that are detected and treated, without leading to a substantial rise in STIs. TRIAL REGISTRATION: The trial has been registered with ClinicalTrials.gov, trial number NCT05093036 (https://clinicaltrials.gov/study/NCT05093036).
Evidence of unreliable data and poor data provenance in clinical prediction model research and clinical practice.
Gibson AD, White NM, Collins GS … +1 more , Barnett AG
BMC Med · 2026 Jun · PMID 42243840 · Full text
BACKGROUND: Clinical prediction models are often created using large routinely collected datasets. It is essential that prediction models are developed with appropriate data and methods and transparently reported to ensu...
BACKGROUND: Clinical prediction models are often created using large routinely collected datasets. It is essential that prediction models are developed with appropriate data and methods and transparently reported to ensure that decisions are based on reliable predictions. Kaggle is a popular competition and data repository website where users learn and apply analysis skills on a range of datasets. METHODS: We identified two large, publicly available Kaggle datasets, on stroke and diabetes, that lack clear data provenance, but are widely used in clinical prediction models in peer reviewed publications. We used exploratory analyses to examine the quality of data and reporting of information using nine items from the TRIPOD+AI statement checklist. RESULTS: Data provenance assessment using nine TRIPOD+AI items revealed major deficiencies, with minimal details for either dataset including no information on when, where, why or how the data were collected. The authenticity of both datasets could not be verified and have no reliable provenance of authenticity and should not be used for informing research or practice. From these two datasets, we found 125 clinical prediction model studies. Three prediction models had evidence of use in clinical practice, one model was cited in a medical device patent, and the models were cited in 86 review articles. CONCLUSIONS: We recommend that journals and data repositories mandate data provenance reporting to safeguard published research. Prediction models based solely on inauthentic or unreliable datasets should never be used to directly inform decisions on patient care.
CD81 restricts decidual IGF2-mediated smooth muscle cell dedifferentiation during spiral artery remodeling in preeclampsia.
Cao C, Dai Y, Wang Z … +9 more , Lei Y, Gu N, Zhou H, Duan H, Shen L, Li T, Zhao G, Liu D, Hu Y
BMC Med · 2026 Jun · PMID 42243812 · Full text
BACKGROUND: Preeclampsia (PE) is a pregnancy-specific complication characterized by defective spiral artery remodeling, notably due to the abnormal retention of differentiated vascular smooth muscle cells (VSMCs). Althou...
BACKGROUND: Preeclampsia (PE) is a pregnancy-specific complication characterized by defective spiral artery remodeling, notably due to the abnormal retention of differentiated vascular smooth muscle cells (VSMCs). Although elevated CD81 levels in the placenta and maternal circulation contribute to this impairment, the definite mechanisms remain elusive. This study aimed to investigate how CD81 overexpression in extravillous trophoblasts (EVTs) contributes to defective VSMC dedifferentiation within uterine spiral arteries, as well as the involved molecular mechanisms. METHODS: Placental basal plates from severe preeclampsia (sPE) patients and non-PE controls were immunostained for CD81 and VSMC markers. A placental restricted CD81 overexpression mouse model was constructed to evaluate PE-like phenotype and placental pathology. Primary decidual stromal cells (DSCs) and natural killer (dNK) cells were applied to investigate how CD81-overexpressing EVTs interact with them to suppress VSMC dedifferentiation. Additionally, antagonistic and rescue experiments were conducted to identify the function of the key molecules involved. RESULTS: The proportion of retained differentiated VSMCs in spiral arteries was significantly higher in sPE patients than in normal pregnancies, and was positively correlated with CD81 expression on EVTs. Similarly, pregnant mice with placental restricted CD81 overexpression exhibited PE-like phenotype and showed persistent VSMC retention in spiral arteries. In vitro, conditioned medium (CM) from DSCs pretreated with medium from CD81-overexpressing EVTs increased the expression of differentiated VSMC markers, which was associated with reduced insulin-like growth factor 2 (IGF2) levels in DSCs. Notably, exogenous IGF2 supplementation reversed this effect. CONCLUSIONS: CD81 upregulation on EVTs prevents VSMC dedifferentiation through a DSC-dependent mechanism. This study represents a pioneering effort to reveal the crucial role of interplay between EVTs, DSCs, and VSMCs in facilitating VSMC dedifferentiation, thereby enabling the completion of spiral artery remodeling.
Mapping shared and specific cortical after-effects of repetitive TMS on brain function.
Lv Y, Feng Z, Fan F … +8 more , Wang J, Wu J, Cui Z, Xia M, Ji GJ, Geng X, Sai L, Zou Q
BMC Med · 2026 Jun · PMID 42237355 · Full text
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is widely used to modulate brain activity and treat neurological and psychiatric disorders, yet how diverse stimulation protocols shape cortical function-an...
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is widely used to modulate brain activity and treat neurological and psychiatric disorders, yet how diverse stimulation protocols shape cortical function-and whether they share common principles-remains unclear. METHODS: We combined resting-state fMRI acquired before and after single-session rTMS across nine distinct protocols targeting specific cortical regions to comprehensively map changes in the local amplitude of hemodynamic fluctuations. RESULTS: We found that after-effects co-varied across protocols, with similarity patterns constrained by structural and functional connectivity. Strikingly, a shared spatial pattern emerged across all protocols, closely aligned with the brain's sensory-association hierarchy. Both shared and protocol-specific effects exhibited significant correspondence with the distribution of neurotransmitter systems. Mapping to the Neurosynth cognitive atlas revealed many-to-many correspondences between rTMS effects and cognitive domains, primarily driven by stimulation of parietal and motor regions. These rTMS-induced changes also overlapped with functional abnormalities in major depressive disorder and Parkinson's disease, highlighting the parietal cortex as a potential transdiagnostic target. Key results were independently replicated in two datasets of multi-session rTMS. CONCLUSIONS: These findings reveal a unified organizational framework for rTMS after-effects, grounded in cortical hierarchy, neurochemistry, and cognitive activations, offering potential guidance for neuromodulations of brain disorders.
CIITA/PRMT5 promote CD4Gzma T cell activation via H3R2me2-mediated endothelial expression of MHC class II in smoking-induced atherosclerosis.
Chen Y, Luo X, Xu B … +21 more , Zhu X, Mou J, Wang M, Gu Q, Wang Y, Bai X, Zhang S, Wang S, Lv Y, Weng X, Liu X, Li M, Huang X, Zhao C, Zeng M, Liu M, Qu S, Sun Q, Hu S, Yu B, Jia H
BMC Med · 2026 Jun · PMID 42237295 · Full text
BACKGROUND: Smoking is considered as the major risk factor for the progression of atherosclerosis (AS), whereas the underlying immunological mechanism remains unclear. METHODS: ApoE mice were treated with cigarette tar v...
BACKGROUND: Smoking is considered as the major risk factor for the progression of atherosclerosis (AS), whereas the underlying immunological mechanism remains unclear. METHODS: ApoE mice were treated with cigarette tar via inhalation in vivo, mouse arterial endothelial cells (MAECs) and human coronary artery endothelial cells (HCAECs) were treated with cigarette tar in vitro. Single cell RNA sequencing (scRNA-seq) was utilized to explore the molecular mechanism of CD4 Granzyme A (Gzma) T cells activation in smoke-related atherosclerotic progression. RESULTS: Cigarette tar significantly aggravated the development of atherosclerotic lesion in ApoE mice. Results of scRNA-seq and validation experiments further indicated that cigarette tar inhalation significantly increased the proportion of CD4Gzma T cells, a T cell subset which could lead to endothelial cells (ECs) damage. Concurrently, a significant reduction in the proportion of ECs was observed. Of note, cigarette tar enhanced interaction of ECs and CD4Gzma T cells via mediating major histocompatibility complex II (MHC II) signaling pathway activation rather than other antigen-presenting cell types. Mechanistically, class II major histocompatibility complex transactivator (CIITA), a key transcriptional regulator of MHC II genes expression, was identified to connect with protein arginine methyltransferases-5 (PRMT5), scoring highest via utilizing mass spectrometry analysis, which triggered symmetrical dimethylation modification of H3R2 and promoted MHC II expression. Meanwhile, CIITA knockout/knockdown, and PRMT5 inhibition/knockdown inhibited the infiltration of CD4Gzma T cells and MHC II expression of ECs, alleviating the atherosclerotic lesion severity. Additionally, findings from the in vitro co-culture experiment provided additional confirmation that activated CD4Gzma T cells possessed the capability to induce cytotoxicity in ECs. CONCLUSIONS: Cigarette tar augments the expression of MHC II in ECs via promoting CIITA nuclear translocation and PRMT5-mediated methylation modification. This process activates CD4Gzma T cells, which subsequently mediate ECs injury in turn, thereby contributing to the progression of AS. Therefore, CIITA and PRMT5 represent potential therapeutic targets for interventions aimed at mitigating smoke-related AS.
A biologically informed framework for instrument selection in dietary Mendelian randomization using chemosensory genetics.
Hwang LD, Lin C, Evans DM … +3 more , Martin NG, Reed DR, Joseph PV
BMC Med · 2026 Jun · PMID 42231279 · Full text
BACKGROUND: Mendelian randomization (MR) is increasingly used to strengthen causal inference in nutritional epidemiology. However, dietary MR studies often rely on instruments selected from genome-wide association studie...
BACKGROUND: Mendelian randomization (MR) is increasingly used to strengthen causal inference in nutritional epidemiology. However, dietary MR studies often rely on instruments selected from genome-wide association studies of self-reported intake based solely on statistical significance, increasing vulnerability to pleiotropy and reverse causation and potentially violating key MR assumptions. We aimed to develop and evaluate a biologically informed framework for selecting valid genetic instruments for dietary exposures, leveraging genes encoding taste and olfactory receptors that influence chemosensory perception and shape food preferences and dietary behaviour. METHODS: We prioritised 1,214 nonsynonymous variants (minor allele frequency ≥ 1%) across 30 taste and 295 olfactory receptor genes. Associations with 140 food-liking traits were tested in UK Biobank participants aged 37 to 73 years. Candidate variants were evaluated using a multi-stage filtering pipeline comprising replication in an independent younger cohort (Avon Longitudinal Study of Parents and Children, age 25), concordance between food liking and intake, exclusion of associations with socioeconomic status, assessment of food specificity accounting for linkage disequilibrium and co-consumption, and directionality testing to reduce reverse causation. Retained variants were used as instruments in MR analyses of cardiometabolic outcomes. RESULTS: We identified 268 variants within 101 olfactory and 16 taste receptor genes associated with 96 food-liking traits. Filtering yielded 24 candidate instruments for 20 foods. The instrument for onion liking satisfied all pre-defined criteria for classification as high confidence. As an illustrative MR application, genetically proxied onion liking was associated with lower systolic and diastolic blood pressure and reduced risk of type 2 diabetes, with no evidence of effects on body mass index, glycaemic traits, or serum lipid levels. CONCLUSIONS: Instrument selection guided by chemosensory genetics provides a scalable strategy for dietary MR that can improve instrument credibility and reduce susceptibility to pleiotropy and reverse causation. However, this approach prioritises biological specificity at the cost of fewer available instruments. This framework supports more robust causal evaluation of diet-disease relationships and strengthens inference in nutritional epidemiology and public health research.
Prenatal and/or childhood acid-suppressive medication use and risk of serious infections in children: A retrospective analysis of Taiwanese medical claims data.
Yao TC, Hsu YL, Huang JL … +6 more , Chang YC, Chang SM, Pan JJ, Hong X, Wang JY, Tsai HJ
BMC Med · 2026 Jun · PMID 42231258 · Full text
BACKGROUND: Recent studies suggest an increased risk of serious infections associated with proton pump inhibitor (PPI) use in young children, but no study simultaneously examined the impact of acid-suppressive medication...
BACKGROUND: Recent studies suggest an increased risk of serious infections associated with proton pump inhibitor (PPI) use in young children, but no study simultaneously examined the impact of acid-suppressive medication (ASM) use during pregnancy and childhood on infection risk in children. This study aimed to investigate the associations between prenatal and/or childhood exposure to ASMs and serious infections in children. METHODS: A national cohort study was conducted based on the entire medical claims data in Taiwan, comparing prenatal and/or childhood exposure to PPIs or histamine-2 receptor antagonists (H2RAs) with antacid exposure in an active-comparator design. We quantified the risks of hospitalization for overall serious infection and specific infections, including sepsis, acute bronchiolitis or bronchitis, pneumonia, acute gastroenteritis, pyelonephritis, cellulitis or soft-tissue infection, meningitis or encephalitis, and septic arthritis or osteoarthritis, among children with prenatal and/or childhood exposure to PPIs or H2RAs. Adjusted hazard ratios (AHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. RESULTS: Among 195,377 mother-child pairs prenatally exposed to PPIs or H2RAs (13.39% of the prenatal cohort) and 1,263,741 pairs exposed to antacids, prenatal exposure to PPIs or H2RAs was associated with an increased risk of overall serious infection compared with antacid exposure (AHR: 1.09; 95% CI: 1.06-1.12), as well as specific infections, including sepsis (AHR: 1.21; 95% CI: 1.03-1.12), acute bronchiolitis or bronchitis (AHR: 1.07; 95% CI: 1.03-1.11), pneumonia (AHR: 1.10; 95% CI: 1.04-1.15), acute gastroenteritis (AHR: 1.12; 95% CI: 1.06-1.18), and pyelonephritis (AHR: 1.10; 95% CI: 1.02-1.19). Subgroup analyses demonstrated consistent results for PPI and H2RA exposure when analyzed separately. Childhood exposure to PPIs or H2RAs was also associated with increased risks of serious infections, with the highest risks generally observed among children exposed during both prenatal and childhood periods (AHR 1.12 for overall serious infection; AHR 1.62 for sepsis; AHR 1.29 for acute bronchiolitis or bronchitis; AHR 1.06 for pneumonia; AHR 1.30 for acute gastroenteritis; and AHR 1.24 for pyelonephritis). CONCLUSIONS: This nationwide cohort study provides real-world evidence of an association between prenatal and childhood exposure to PPIs or H2RAs and an increased risk of serious infections in children.
Association of borderline hypertension defined by ACC-AHA diagnostic criteria during pregnancy with neurodevelopment in infants.
Zhang Y, Du J, You X … +14 more , Sun T, Lv H, Jiang Y, Jiang T, Qin R, Xu X, Dou Y, Xu B, Jin G, Shen H, Hu Z, Lin Y, Kong X, Ma H
BMC Med · 2026 Jun · PMID 42226260 · Full text
BACKGROUND: The American College of Cardiology (ACC) and the American Heart Association (AHA) revised the diagnostic criteria for hypertension, recommending a lower threshold of 130/80 mmHg for nonpregnant adults. Howeve...
BACKGROUND: The American College of Cardiology (ACC) and the American Heart Association (AHA) revised the diagnostic criteria for hypertension, recommending a lower threshold of 130/80 mmHg for nonpregnant adults. However, this lower threshold has not been adopted in the global obstetrics field. It remains unclear whether applying this new definition to pregnant women would have implications for maternal health and offspring development. The present study aimed to examine potential relationships between maternal borderline hypertension and neurodevelopmental outcomes in infants. METHODS: This study is a secondary analysis conducted within the prospective Jiangsu Birth Cohort in China. A total of 3352 mothers with blood pressure (BP) records and 3641 of their children were included. Pregnant women were categorized as normotensive (systolic BP [SBP] < 130 mmHg and diastolic BP [DBP] < 80 mmHg), borderline hypertensive (SBP 130-139 mmHg and/or DBP 80-89 mmHg), or hypertensive (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg). Infant neurodevelopment was assessed using the Bayley-III screening test. General linear mixed-effects models and Poisson generalized linear mixed models were applied to evaluate potential associations between maternal borderline hypertension in different trimesters and offspring neurodevelopment, including continuous neurodevelopmental scores and the risk of non-typical development. RESULTS: Compared with offspring of normotensive mothers, those exposed to maternal borderline hypertension during the first trimester suggested a higher risk of non-typical development in receptive communication (risk ratio [RR], 1.25; 95% confidence interval [CI], 1.00, 1.55; P = 0.045), and exhibited lower expressive communication scores (β, -0.19; [95% CI, -0.38, -0.01]; P = 0.038).When borderline hypertension identified in the first trimester persisted into the second or third trimester, offspring exhibited a more significant reduction in expressive communication scores (β, -0.45; [95% CI, -0.79, -0.11]; P = 0.010). CONCLUSIONS: Maternal borderline hypertension, particularly when detected in the first trimester, was associated with lower infant neurodevelopmental scores and a higher risk of non-typical neurodevelopment. The impact appeared more pronounced when borderline hypertension persisted across trimesters. These findings suggest that closer monitoring and management of borderline hypertension during pregnancy may be beneficial for supporting optimal infant neurodevelopment, though further studies are needed to confirm these results.
Pre-diagnostic biomarkers and risk of stress-related disorders: a cohort study based on electronic health records.
Peltola AA, Khan E, Tirkkonen A … +3 more , von Bonsdorff MB, Jylhävä J, Lin J
BMC Med · 2026 Jun · PMID 42226210 · Full text
BACKGROUND: Stress-related disorders are associated with future somatic health conditions, suggesting these disorders involve systemic mechanisms. Yet, evidence from biomarkers remains fragmented across physiological sys...
BACKGROUND: Stress-related disorders are associated with future somatic health conditions, suggesting these disorders involve systemic mechanisms. Yet, evidence from biomarkers remains fragmented across physiological systems. We investigated whether routinely collected laboratory biomarkers are associated with stress-related disorder risk and analyzed their temporal trends before diagnosis. METHODS: We conducted a retrospective cohort study using electronic health records from Central Finland, collected between 2010 and 2023. Our analytical sample included 73,909 individuals: 6,758 cases and 67,151 controls matched on sex and birth year. Cases were diagnosed with stress-related disorders: acute stress reaction, posttraumatic stress disorder, adjustment disorder, other/unspecified reactions to severe stress, burnout, or stress not elsewhere classified. At baseline, participants were aged 34-92 years and were followed for an average of 4.6 ± 3.3 years. Ten routine biomarkers were examined: C-reactive protein, hemoglobin, glucose, glycated hemoglobin, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatinine, sodium, and potassium. Temporal trends were visualized using generalized additive models. Cox proportional hazards models, adjusted for comorbidities, prescribed medications, and care visit frequency, were used to estimate associations between the risk of stress-related disorder diagnosis and biomarker levels measured within one year prior. RESULTS: Three biomarkers were associated with the risk of stress-related disorder diagnosis in the multivariable model. Higher hemoglobin (HR 0.98 per g/L, 95% CI, 0.97-0.99) and higher potassium (HR 0.74 per mmol/L, 95% CI, 0.64-0.86) were associated with a reduced risk, while higher LDL-C was associated with an increased risk (HR 1.12 per mmol/L, 95% CI, 1.06-1.18). The multivariable model concordance was 0.67. In time-varying models extended over the full follow-up, only hemoglobin retained a significant association. CONCLUSIONS: Hemoglobin, potassium, and LDL-C showed modest but robust associations with stress-related disorder diagnosis. These findings point to physiological domains for future research into the somatic aspects of stress-related disorders.
Association between maternal preconception blood pressure and spontaneous abortion: a population-based cohort study in China.
Yin J, Feng S, Hu X … +13 more , Fu W, Li J, Lyu X, Zhao C, Wu H, Lei J, Zhang H, He Y, Wang Y, Peng Z, Zhang Y, Yang Y, Ma X
BMC Med · 2026 Jun · PMID 42226161 · Full text
BACKGROUND: Maternal preconception blood pressure (BP) is associated with various adverse pregnancy outcomes, but its relationship with spontaneous abortion (SA) remains controversial. We aimed to evaluate the relationsh...
BACKGROUND: Maternal preconception blood pressure (BP) is associated with various adverse pregnancy outcomes, but its relationship with spontaneous abortion (SA) remains controversial. We aimed to evaluate the relationship between preconception BP and SA. METHODS: This population-based cohort study used data from participants in the National Free Preconception Examination Program between 2013 and 2019. Maternal preconception BP was categorized according to the 2017 ACC/AHA guidelines. The relationship between these BP categories and SA incidence was analyzed using multivariable logistic regression to generate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Additionally, restricted cubic splines were employed to assess the dose-response relationship between maternal BP and the risk of SA. RESULTS: The study included 7 067 998 women, of whom 208 508 (2.95%) experienced a SA. Maternal preconception elevated BP (aOR, 1.02; 95% CI: 1.00-1.05), stage 1 hypertension (aOR, 1.06; 95% CI: 1.04-1.08), and stage 2 hypertension (aOR, 1.25; 95% CI: 1.20-1.31) were all associated with an increased risk of SA, demonstrating a gradient relationship. Our results also show that there is a "J"-shaped dose-response relationship between maternal preconception BP and the risk of SA, with the lowest risk observed at a systolic BP of 110 mm Hg and a diastolic BP of 70 mm Hg. Sensitivity analyses excluding individuals with hypotension or self-reported hypertension yielded results consistent with the main analysis. CONCLUSIONS: Preconception elevated BP and stage 1 hypertension were associated with an increased risk of SA, although the strength of these associations was weaker than that observed for stage 2 hypertension. There was a "J"-dose-response relationship between maternal preconception BP and the risk of SA, with the lowest risk of SA at systolic BP of 110 mm Hg and diastolic BP of 70 mm Hg.
A novel and accurate EEG emotion classification model based on multiple attention local binary patterns.
Koksal H, Yildirim K, Nayak J … +6 more , Baygin M, Barua PD, Tasci B, Dogan S, Tuncer T, Acharya UR
BMC Med · 2026 Jun · PMID 42219487 · Full text
BACKGROUND: Electroencephalography (EEG) signals play a crucial role in understanding brain activity because they provide useful information about real emotions and intentions. Many machine learning models have been used...
BACKGROUND: Electroencephalography (EEG) signals play a crucial role in understanding brain activity because they provide useful information about real emotions and intentions. Many machine learning models have been used for automatic EEG-based emotion classification. However, previous studies remain limited by restricted feature representations and insufficient subject-independent validation. METHODS: In this work, we developed a novel EEG emotion dataset from 22 healthy participants. The dataset includes 14-channel EEG recordings with arousal and valence labels. We also proposed a new feature-extraction function named multiple attention local binary pattern (MATLBP), which generates five feature vectors from EEG signals. To improve the feature-engineering process, we designed an architecture with multi-level MATLBP-based feature extraction, multiple feature-selection methods, and a multi-classifier classification phase. We also used a channel-wise evaluation approach for all EEG channels. Then, iterative majority voting (IMV) was applied during classification to generate predicted vectors. Finally, the MATLBP-based feature-engineering architecture selected the best prediction vector as the final outcome. Thus, the proposed model can automatically select the most accurate result. RESULTS: The proposed framework was assessed on both the self-collected EEG dataset and the publicly available DREAMER dataset using leave-one-subject-out cross-validation. The model achieved accuracies of 93.38% for arousal and 88.64% for valence on the self-collected dataset. On the DREAMER dataset, it achieved accuracies of 93.56% for arousal, 97.22% for valence, and 86.73% for dominance. Relative to previously reported methods, the proposed approach demonstrated competitive performance under subject-independent validation conditions, with the additional advantage of reduced computational complexity. CONCLUSIONS: The proposed MATLBP-based framework provides an accurate and computationally efficient approach for subject-independent EEG emotion classification across the self-collected and DREAMER datasets. Its strong cross-subject performance and lightweight architecture indicate its potential use in affect-aware clinical decision-support systems, neurofeedback applications, and assistive technologies for individuals with impaired emotional expression. The primary limitation is potential optimistic bias due to model selection on the same dataset. Independent validation in larger, multicenter cohorts is needed to confirm generalizability.
Cognitive impairments and neurofunctional alterations in children with electrical status epilepticus during sleep: insights from WISC-IV and resting-state fMRI.
Mo T, Wang X, Luo J … +9 more , Lin J, Meng X, Hu Z, Chen L, Zhang L, Chen Y, Cao D, Liao J, Zeng H
BMC Med · 2026 May · PMID 42218544 · Full text
BACKGROUND: Electrical Status Epilepticus During Sleep (ESES) is a rare pediatric epilepsy syndrome characterized by sleep-induced epileptiform discharges, leading to cognitive and behavioral impairments. We aimed to inv...
BACKGROUND: Electrical Status Epilepticus During Sleep (ESES) is a rare pediatric epilepsy syndrome characterized by sleep-induced epileptiform discharges, leading to cognitive and behavioral impairments. We aimed to investigate the underlying neural mechanisms that are critical for advancing early diagnosis and targeted interventions. METHODS: Twenty-five children with ESES and 30 age- and sex-matched healthy controls were enrolled. Cognitive function was assessed via the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV), focusing on Full-Scale IQ (FSIQ), Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI). Resting-state functional MRI (rs-fMRI) was conducted to evaluate neural activity via regional homogeneity (ReHo) analysis. Correlations between ReHo values and cognitive scores were analyzed in the ESES group. RESULTS: Compared with healthy controls, children with ESES presented significantly lower FSIQ and PRI scores (P = 0.017, P = 0.016), indicating cognitive impairments in global intellectual abilities and perceptual reasoning. rs-fMRI revealed decreased ReHo in the left Superior Frontal Gyrus (premotor area), bilateral postcentral gyri (primary somatosensory cortex), right cerebellum posterior, and rolandic operculum. In contrast, increased ReHo was observed in the left precuneus and left middle frontal gyrus. ReHo in the right postcentral gyrus showed a positive correlation with FSIQ and VCI scores (r = 0.56, P = 0.01; r = 0.67, P < 0.001). CONCLUSIONS: ESES is associated with significant cognitive deficits, particularly in perceptual reasoning and verbal comprehension, alongside altered neural activity patterns. ReHo analysis revealed changes in local neural activity within key brain regions linked to cognitive function. These findings highlight the potential of rs-fMRI metrics as biomarkers for assessing cognitive impairments and guiding therapeutic interventions in ESES.
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