BMC Medicine[JOURNAL]
Sun
200 papers
Modelling the epidemic dynamics of HPV among women in China and optimization of ongoing cervical cancer elimination strategies.
Li Y, Lin YF, Cai B … +4 more , Chen F, Zhang Q, Liu S, Zhen J
BMC Med · 2026 Apr · PMID 42021319 · Full text
BACKGROUND: The infection of high-risk human papillomavirus (hr-HPV) and related cervical cancer have greatly threatened women's health. However, the benefits of ongoing strategies in China remains unclear. Insufficient...
BACKGROUND: The infection of high-risk human papillomavirus (hr-HPV) and related cervical cancer have greatly threatened women's health. However, the benefits of ongoing strategies in China remains unclear. Insufficient vaccine supply and excessive screening workload have hindered the widespread implementation of HPV immunization plans. METHODS: We constructed stratified mathematical models to simulate the transmission of hr-HPV among women under ongoing public health strategies, and calculated the incremental cost-utility ratio (ICUR) to compare the health-economics benefits among different intervention pathways, including different vaccine type and dose schedules, commonly recommended screening algorithms as well as an artificial intelligence (AI)-assisted thin-layer cytology test (TCT) method. The model parameters were calibrated according to real-world HPV prevalences, incorporating segmented model assumptions reflecting the levels of COVID-19 lockdown. RESULTS: The model shows that ongoing strategies in China are projected to reduce cervical cancer prevalence continuously and demonstrate cost-utility (ICUR: 27,592.62 USD/quality-adjusted life-year [QALY], 26,902.80-28,282.44) when increasing the participation rate to achieve the global goal by 2030. HPV vaccination provides substantial health benefits but cannot improve the cost-utility at current cost. Offering single dose of 2vHPV vaccine to girls before the age of 14 and reallocating excess doses to women under 25 yields a lower ICUR compared to two- or three-dose scenarios. Cervical screening can significantly reduce the ICUR. Among the screening methods, HPV testing demonstrates higher cost-utility, while AI-TCT outperforms all recommended traditional pathways. CONCLUSIONS: The ongoing strategies demonstrate substantial health and economic benefits in achieving the 2030 global target; however, neither screening nor vaccination alone can deliver optimal effectiveness. The findings highlight the importance of combining vaccination and screening, and provide evidence for the promotion of single-dose vaccination and AI-TCT projects to alleviate resource burdens.
Predicting amyotrophic lateral sclerosis stage based on multi-parameter ultrasound: development and validation of an interpretable machine learning model.
Yang T, Wang Y, Dong N … +14 more , Ding J, Yan X, Luo J, Chen P, Qiu Y, Lin T, Tong J, Mao J, Dai Y, Shentu H, Tang S, Sheng L, Zhao M, Yang G
BMC Med · 2026 Apr · PMID 42021292 · Full text
BACKGROUND: Amyotrophic lateral sclerosis (ALS) lacks sensitive, objective staging tools to guide clinical management and trials. Existing methods have limited granularity and rely on subjective assessment, while biomark...
BACKGROUND: Amyotrophic lateral sclerosis (ALS) lacks sensitive, objective staging tools to guide clinical management and trials. Existing methods have limited granularity and rely on subjective assessment, while biomarker and imaging approaches can be invasive or impractical for serial use. Ultrasound is a safe, portable imaging modality that can detect neuromuscular changes, but it has not yet been applied to ALS staging. We developed and validated an interpretable ultrasound model for clinical staging and risk stratification in ALS. METHODS: We enrolled 300 ALS patients, classified as early-stage (King's stages 1-2; n = 148) or late-stage (3-4; n = 152). Each patient underwent ultrasound of key muscle groups, including the diaphragm (excursion and thickening), geniohyoid (shear-wave velocity), and peripheral skeletal muscles (thickness and cross-sectional area). Six machine learning models were trained to predict early vs late stage from these ultrasound metrics combined with clinical factors. Performance was evaluated on a test set using area under the curve (AUC), F1 score and Brier score. Feature importance was analyzed with SHapley Additive exPlanation (SHAP) values. RESULTS: In the test set, the random forest achieved an AUC of 0.843, an F1 score of 0.727, and a Brier score of 0.177, with sensitivity 0.80 and specificity 0.68. SHAP analysis identified diaphragm excursion during deep breathing (DEDB) as the top predictor, followed by masseter muscle thickness (MMT) and geniohyoid shear-wave velocity (GHSWVmean). Higher DEDB, MMT and GHSWVmean values predicted earlier stage, whereas lower peripheral muscle thickness and older age indicated late-stage disease. CONCLUSIONS: Multiparameter ultrasound combined with machine learning offers a non-invasive, bedside tool for ALS staging. The model's accuracy and interpretability enable objective tracking of disease progression and may support timely interventions and patient stratification in clinical practice and trials. Leveraging widely accessible ultrasound technology, this approach is feasible for routine ALS care and research.
Correction: Vegetable intake and the risk of bladder cancer in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study.
Yu EY, Wesselius A, Mehrkanoon S … +15 more , Goosens M, Brinkman M, van den Brandt P, Grant EJ, White E, Weiderpass E, Le Calvez-Kelm F, Gunter MJ, Huybrechts I, Riboli E, Tjonneland A, Masala G, Giles GG, Milne RL, Zeegers MP
BMC Med · 2026 Apr · PMID 42021259 · Full text
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Prenatal exposure to flood and risk of low birth weight: a multi-country study from 36 African countries.
Li Q, Li Q, Yin Z … +4 more , Zhen S, Xiao Z, Xu H, Liang F
BMC Med · 2026 Apr · PMID 42015216 · Full text
BACKGROUND: 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 be...
BACKGROUND: 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. METHODS: 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. RESULTS: 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, mothers of advanced maternal age (≥ 35 years), 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. CONCLUSIONS: Our findings highlight the urgency of addressing health disparities stemming from prenatal floods and extreme environmental events for neonatal health promotion.
The role of continuous glucose monitoring for diagnosis of gestational diabetes: exploring the potential.
Crowley M, Newman C, Dunne FP
BMC Med · 2026 Apr · PMID 42015100 · Full text
The diagnosis of gestational diabetes relies upon an oral glucose tolerance test which has established limitations and suboptimal levels of patient adherence. Despite use of different diagnostic criteria globally, rates...
The diagnosis of gestational diabetes relies upon an oral glucose tolerance test which has established limitations and suboptimal levels of patient adherence. Despite use of different diagnostic criteria globally, rates of GDM are increasing in line with increasing rates of obesity. There is a clinical need to establish an alternative methodology to diagnose GDM. Recent studies have examined the diagnostic role of continuous glucose monitoring with particular emphasis on glucometrics that correlate with adverse pregnancy outcome and may indicate CGM-based diagnostic thresholds for GDM. Additionally, CGM metrics associated with pharmacotherapy necessity have been identified. Given this work is observational and non-interventional, more robust data in the form of randomised control trials are required. Identification of diagnostic thresholds for GDM diagnosis will likely be outcome based and rely on a large international multicentre analysis.
Sunshine duration and episodes of mental disorders and the inverse effect modification by ambient temperature.
Bai L, Chen J, Ma Y … +10 more , Yang C, Liu D, Jiang Y, Liu H, Wei C, Li Y, Lei J, Su H, Yang J, Wu S
BMC Med · 2026 Apr · PMID 42010637 · Full text
BACKGROUND: Although sunshine duration (SSD) has been associated with episodes of mental disorders, the existing evidence remains conflicting, and previous studies have overlooked the role of ambient temperature-a factor...
BACKGROUND: Although sunshine duration (SSD) has been associated with episodes of mental disorders, the existing evidence remains conflicting, and previous studies have overlooked the role of ambient temperature-a factor intertwined with sunlight exposure-in this association. The present study aimed to investigate the associations of SSD over short periods with risks of depressive, anxiety and schizophrenia episodes, and estimate the possible effect modification by ambient temperature. METHODS: Based on hospital admission data from the urban basic medical health insurance systems in China across 268 Chinese cities from January 1, 2013, to December 31, 2017, we conducted a nationwide time-stratified case-crossover study. The primary outcomes were episodes of depressive disorder, anxiety disorder, and schizophrenia. The individuals hospitalized for episodes of depressive disorder, anxiety disorder, and schizophrenia were included based on ICD-10 diagnosis codes. In addition to daily SSD, SSD increases between neighboring days (SDIN) over consecutive days were calculated to capture multi-day relative increases in SSD. Individuals served as their own controls, and the estimations were obtained using the conditional logistic regression models. RESULTS: A total of 330,610, 221,332, and 817,296 hospital admissions for depressive disorder, anxiety disorder, and schizophrenia were included, respectively. After considering the effect modification by temperature, significant negative associations between SSD and hospital admissions for depressive disorder and schizophrenia were found mainly in the cool season: per 1-h increase in 13-day moving average SSD was associated with decreases of 3.33% (95% CI: -5.85%, -0.73%) and 2.60% (95% CI: -4.21%, -0.96%) in hospital admissions for depressive disorder and schizophrenia, respectively. Ambient temperature showed inverse modification on the SSD-admission associations. When stratified by temperature, significant negative associations between SSD and hospital admissions for depressive disorder and schizophrenia were observed in low temperature stratum (< median), whereas no significant association was found in the high temperature stratum (≥ the median). Additionally, increases in 13-day moving average SDIN were associated with significant additional decreases in admissions for depressive disorder and schizophrenia. CONCLUSIONS: Shot-term exposure to increasing SSD was associated with decreases in episode risks of depressive disorder and schizophrenia, and such associations were more apparent at low temperatures. Increasing the duration of sunlight exposure and reducing exposure to increasing temperature, especially in the cool season, may help reduce the burdens of depressive disorder and schizophrenia.
Development, integration, retention, and career progression of physician associates/assistants in UK NHS hospitals and clinical teams: a multiple-case qualitative study.
Zhao Y, Swainston R, Tooman T … +8 more , Walker KA, Williams R, McGivern G, Wong G, English M, Leckcivilize A, Nagraj S, ROADMAP-PA collaborator group
BMC Med · 2026 Apr · PMID 42010541 · Full text
BACKGROUND: The NHS has introduced a range of new and extended roles in recent decades. Physician associates / assistants (PAs) have become one of the most politically scrutinised of these roles. In 2024, the UK governme...
BACKGROUND: The NHS has introduced a range of new and extended roles in recent decades. Physician associates / assistants (PAs) have become one of the most politically scrutinised of these roles. In 2024, the UK government-commissioned Leng Review highlighted national concerns around the clarity, governance, supervision, and career development of PAs, but offered limited guidance for NHS organisations to operationalise them. This study, initiated prior to and independent of the Leng Review, examined how NHS hospitals and clinical teams in England and Scotland develop, integrate, retain, and support PAs in practice. METHODS: We conducted a multiple-case qualitative study across five NHS organisations in England and Scotland. Semi-structured interviews (n = 126) and one focus group (n = 8) were undertaken with PAs, consultants, resident doctors, other team members, senior organisational leaders, and stakeholders involved in workforce planning, supervision, and governance. Data were analysed thematically using a framework informed by prior scoping review and organised across macro (system), meso (organisational), and micro (individual/team) levels, with within- and cross-case comparisons. RESULTS: We identified 12 themes across macro, meso, and micro levels of the health system. At the macro-system level, labour market dynamics, fluctuating policy and regulatory signals, and wider public and professional debates, influenced organisational confidence in the PA role. At the meso-organisational level, PA role implementation was sometimes driven by well-intentioned local leaders responding to service needs but with short-term business case logics and pragmatic pressures, rather than long-term workforce planning. Governance arrangements were often developed retrospectively and inconsistently communicated. At the micro-team level, PAs' interpersonal skills and contribution to continuity of care were widely valued, though progression remained highly variable and reliant on local supervision and individual negotiation. CONCLUSIONS: The development, integration, retention, and career progression of PAs in hospitals are shaped by interacting system, organisational, team and individual influences. Many of these challenges reflected wider NHS workforce implementation dynamics, rather than features unique to PAs. To continue to support safe, effective, and sustainable use of PAs, and other new and extended roles, organisations and clinical teams need strong workforce planning, local change management processes, and fair career pathways.
Epigenome-wide analysis of DNA-methylation signatures following climate-related disasters.
Huang W, Xu R, Wu Y … +9 more , Yang Z, Ye Z, Wong EM, Southey MC, Hopper JL, Abramson MJ, Li S, Li S, Guo Y
BMC Med · 2026 Apr · PMID 42010415 · Full text
BACKGROUND: Floods and tropical cyclones (TCs), two of the most frequent and costliest climate-related disasters worldwide, have been linked to sustained health risks extending beyond acute hazards. However, evidence on...
BACKGROUND: Floods and tropical cyclones (TCs), two of the most frequent and costliest climate-related disasters worldwide, have been linked to sustained health risks extending beyond acute hazards. However, evidence on the underlying epigenetic mechanisms remains scarce. We aimed to characterize DNA methylation patterns associated with exposure to floods and TCs of varying intensities. METHODS: We collected peripheral blood samples from 479 women (132 twin pairs and 215 of their sisters) across Australia. Blood-derived DNA methylation profiles were assessed using the Illumina HumanMethylation450 BeadChip array. Daily flood and TC exposure data for the 6 years preceding each blood draw were obtained from the Dartmouth Flood Observatory and the International Best Track Archive for Climate Stewardship, respectively, and linked to participants based on residential addresses. Using a within-sibship analytical framework that accounted for shared familial factors and other relevant covariates, we examined associations between flood and TC exposures of varying intensities and site-specific methylation at each cytosine-guanine dinucleotide (CpG). Differentially methylated regions (DMRs) were identified using a combination of the comb-p and DMRcate algorithms. RESULTS: There were 164 CpGs and 219 DMRs associated with flood and TC exposures (Bonferroni-adjusted p value < 0.05), mapping to 242 genes enriched in pathways related to inflammation and immune regulation. These genes have been implicated in a wide range of human diseases or phenotypes. The number of differentially methylated CpGs increased with more recent and higher-intensity exposures. Intensity-dependent gene regulation was observed, with genes such as AMT and C22orf45 consistently implicated across various exposure levels, whereas RNF39 and ACY3 emerged only at higher intensities. CONCLUSIONS: Exposures to floods and TCs were associated with differentially DNA methylated signals across the human genome, exhibiting intensity-dependent patterns. The identified signals and related gene pathways may shed light on the biological mechanism underlying the profound health effects of climate-related disasters.
Redeemed prescription medicines to measure quality of life of patients with long-term conditions: a national cross-sectional study.
Larsen HHP, Siersma V, Willadsen TG … +4 more , Lyhnebeck AB, Prior A, Waldorff FB, Holm A
BMC Med · 2026 Apr · PMID 42002791 · Full text
BACKGROUND: The prevalence of multimorbidity is increasing and is associated with polypharmacy (PP) and a reduced quality of life (QoL). Polypharmacy consistently correlates with poorer outcomes; however, its relationshi...
BACKGROUND: The prevalence of multimorbidity is increasing and is associated with polypharmacy (PP) and a reduced quality of life (QoL). Polypharmacy consistently correlates with poorer outcomes; however, its relationship with QoL in a broad general practice population is underexplored. For the general practitioner, QoL assessment is resource-intensive; therefore, this study examines whether the number of redeemed unique prescription medications can serve as an indicator for QoL in patients with multimorbidity managed in general practice. METHODS: This nationwide cross-sectional study was conducted with data from questionnaires sent to 160,584 adults from 250 general practices who consulted their general practitioner for an annual chronic disease consultation in 2022. Questionnaire data were linked with socioeconomic and medication data from Danish Registries. We examined the association between the number of redeemed unique prescription medicines and six domains of QoL with linear models and tested for effect modification with multivariable linear models. The multivariable models were adjusted for the covariates sex, age, education, and cohabitation. The number of unique prescription medications that constitute a minimal clinically important difference (MCID) was calculated. Further, we presented associations between redeemed unique prescription medications and QoL stratified by the covariates. RESULTS: All 35,977 patients who participated in the survey were included in this study, with 18,665 (51.9%) being female. A linear association was found between redeemed unique prescription medications and more burdened QoL in all six domains. The largest association (2.95; 95% CI 2.87-3.03) and lowest MCID (4.4 redemptions) were found in the domain of physical ability. Stratified analyses appeared visually parallel with no clinically meaningful effect modification by any covariate in any QoL domain. CONCLUSIONS: Findings indicate a potential use of redeemed prescriptions as an indicator for the physical ability domains of QoL in clinical practice. The study found no clinically relevant effect modification.
Association between bariatric surgery and long-term ability to perform household tasks in the Swedish Obese Subjects study: a controlled prospective cohort study.
Brembeck P, Andersson-Assarsson JC, Peltonen M … +10 more , Taube M, Sjöholm K, Ahlin S, Adméus L, Konttinen H, Larsson I, Engström M, Henning B, Carlsson LMS, Svensson PA
BMC Med · 2026 Apr · PMID 42001100 · Full text
BACKGROUND: Obesity negatively impacts quality of life and reduces the ability to perform daily activities. While bariatric surgery typically results in sustained weight loss, its long-term impact on functional abilities...
BACKGROUND: Obesity negatively impacts quality of life and reduces the ability to perform daily activities. While bariatric surgery typically results in sustained weight loss, its long-term impact on functional abilities remains insufficiently studied. The aim of this study was to investigate the long-term association between bariatric surgery and the ability to perform household tasks. METHODS: The ability to perform household tasks was assessed using the standardized Home Management category of the Sickness Impact Profile (SIP) scale in 1641 bariatric surgery patients and 1656 usual obesity care controls from the Swedish Obese Subjects study. Assessments were conducted at baseline and multiple follow-ups over a 20-year period. Patients (aged 37-60 years, BMI ≥ 34 kg/m for men and ≥ 38 kg/m for women) were recruited between 1987 and 2001. Analyses were adjusted for sex, and baseline age, BMI, cohabitation status, and weekly working hours as well as year of study inclusion. RESULTS: At baseline, the score of the Home Management category of the SIP scale was higher in the surgery group than in controls, indicating greater home management dysfunction. Within the first year, however, the surgery group showed significant improvement, attaining a lower score than the control group (4.9 ± 12.4 vs. 7.0 ± 14.1; p < 0.001). This improvement persisted throughout 20 years of follow-up, with an adjusted score difference of - 3.2 (95% CI: - 3.9 to - 2.6; p < 0.001). Dysfunction in home management followed similar trajectories over time in both sexes but women consistently reported greater dysfunction than men. In the surgery group, individuals who regained weight reported significantly higher dysfunction in home management during 20 years of follow-up than those who maintained weight (adjusted score difference 1.3, 95% CI: 0.2 to 2.4; p = 0.020). CONCLUSIONS: Bariatric surgery was associated with improved home management within the first year compared with usual obesity care, and this benefit was sustained over time. These findings suggest that significant sustained weight loss provides lasting improvements in daily functioning. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01479452.
Viral shedding dynamics in coxsackievirus A6 hand, foot, and mouth disease: a prospective, individual-level analysis.
Meng J, Cheng Y, Chen Z … +6 more , Zheng Y, Ding L, Li X, Tsamlag L, Ciren P, Long L
BMC Med · 2026 Apr · PMID 42001055 · Full text
BACKGROUND: Coxsackievirus A6 (CVA6) has emerged as the predominant cause of hand, foot, and mouth disease (HFMD) in China since the introduction of enterovirus A71 (EV-A71) vaccination. A precise definition of the infec...
BACKGROUND: Coxsackievirus A6 (CVA6) has emerged as the predominant cause of hand, foot, and mouth disease (HFMD) in China since the introduction of enterovirus A71 (EV-A71) vaccination. A precise definition of the infectious period is critical for effective containment; however, data on the duration and kinetics of CVA6 shedding remain scarce. We therefore aimed to characterize the viral shedding dynamics of CVA6 and to identify the determinants of viral clearance. METHODS: We conducted a prospective longitudinal study enrolling pediatric inpatients with laboratory-confirmed CVA6 HFMD between June 2022 and August 2023. Serial pharyngeal swabs were collected every other day during hospitalization and weekly after discharge until two consecutive negative tests were obtained. Shedding duration was analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Viral load was quantified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and its dynamics were modeled using mixed-effects models. RESULTS: Among 88 patients, the median duration of viral shedding was 16 days (95% CI: 14-22), with more than 50% remaining PCR-positive beyond current isolation recommendations. Viral load levels were highest in the first week following symptom onset and tended to show a general progressive decline over the subsequent 5 weeks. Agranulocytosis was associated with prolonged shedding (HR = 0.41, 95% CI: 0.21-0.81, p = 0.010), whereas lymphocytosis accelerated clearance (HR = 1.83, 95% CI: 1.03-3.25, p = 0.039). Elevated aspartate aminotransferase (AST) level was independently associated with higher viral load (β = 0.016, SE = 0.006, p = 0.012). CONCLUSIONS: CVA6 infection is characterized by prolonged viral shedding, which is modulated by host immune and hepatic factors. These findings highlight the need for evidence-based, serotype-specific public health guidelines in the post-EV-A71 vaccine era.
Mental health and wellbeing interventions for uniformed service personnel: a mixed methods systematic review.
Eaton J, Ellard H, Freeman A … +4 more , Anderson AM, Chesters H, Arthurs OJ, Simpson A
BMC Med · 2026 Apr · PMID 41998682 · Full text
BACKGROUND: Uniformed service personnel are routinely exposed to occupational trauma in their roles which contribute to elevated rates of mental health conditions. A wide range of mental health and wellbeing intervention...
BACKGROUND: Uniformed service personnel are routinely exposed to occupational trauma in their roles which contribute to elevated rates of mental health conditions. A wide range of mental health and wellbeing interventions may help uniformed service personnel manage their psychological responses to challenging incidents at work. Previous reviews of those interventions have focused on single groups of professionals or intervention types, limiting cross-sector insights. This review uses a mixed methods approach to synthesise evidence associated with mental health and wellbeing interventions across uniformed services. METHODS: The protocol was registered with PROSPERO (CRD42024605877). A mixed methods systematic review was conducted using the Joanna Briggs Institute (JBI) convergent segregated approach. Searches were conducted in Medline, CINAHL, Web of Science and PsycINFO (Dec 2024). Screening and quality appraisal (Mixed Methods Appraisal Tool) were performed independently by two reviewers. Due to heterogeneity, findings were narratively synthesised. Quantitative and qualitative results were integrated following the JBI approach. RESULTS: Eighty-six primary studies from 22 countries were included, covering a range of professions and intervention types. Synthesis of quantitative data from 82 studies showed that mindfulness-based training, resilience coaching, cognitive behavioural therapies and supported lifestyle activities demonstrated reduced symptoms of PTSD, anxiety and depression. However, interventions such as Critical Incident Stress Debriefing (CISD) and peer support yielded mixed results. Qualitative data from 9 studies were grouped into 5 categories: enhanced emotional insight, improved interpersonal relationships, perceived effectiveness, barriers to engagement and delivery challenges. Participants valued interventions that fostered self-awareness and support but cited stigma, guilt and logistical constraints as significant barriers. Integration of quantitative and qualitative findings revealed alignment in outcomes for several interventions, while highlighting evidence gaps, such as the lack of qualitative data for many interventions and limited exploration of cultural and organisational barriers. CONCLUSIONS: Mental health interventions for uniformed service personnel show promise but are influenced by delivery format, occupational culture and contextual factors. This review underscores the need for delivering interventions informed by ecological models, standardised outcome sets and deeper qualitative exploration into stigma and engagement barriers.
Integrated serum proteomic and liver genomic analyses identify molecular signatures associated with metabolic dysfunction-associated steatotic liver disease: a multi-cohort study.
Xu J, Gou W, Wang X … +7 more , Ru D, Hu W, Chen J, Li BY, Xi Y, Zheng JS, Chen YM
BMC Med · 2026 Apr · PMID 41998640 · Full text
BACKGROUND: Circulating proteomics acts as an intermediate phenotype linking genetic susceptibility to MASLD. However, current evidence rarely establishes a direct concordance between serum protein levels and hepatic gen...
BACKGROUND: Circulating proteomics acts as an intermediate phenotype linking genetic susceptibility to MASLD. However, current evidence rarely establishes a direct concordance between serum protein levels and hepatic gene expression. We aimed to perform a multi-cohort joint analysis of serum proteomics and transcriptomics to characterize essential molecular features for MASLD. METHODS: For the serum proteomic analysis of simple steatosis (MASL), we conducted a cross-sectional investigation in an MRI-based cohort (N/cases: 1048/428) and further examined the prospective association between protein features and MASL incidence (N/cases: 2945/1947) ascertained by ultrasonography over a median 9.8-year follow-up in the Guangzhou Nutrition and Health Study (GNHS) cohort. In parallel, we characterized fibrosis and MASH-related transcriptional features using liver transcriptomics from the MASH cohort (N = 94) and validated these gene signatures for MASH in liver transcriptomes from the independent Japanese and German populations (N = 98 and 59). RESULTS: The serum proteomic analysis identified the C3, C9, F9, VTN, AFM, APOD, APOF, and SHBG proteins were significantly associated with MASL risk (P < 0.05). Liver transcriptomic analysis revealed a coordinated downregulation of C9, C4BPB, C1RL, APOF, and ITIH4 in the high NAS group, implicating dysregulated complement activation as a critical mechanism driving disease progression. Furthermore, SHBG, A2M, GSN, C7, LUM, IGHG3, and IGFALS were associated with liver fibrosis stages, and pathways related to extracellular exosomes and vesicles were implicated in fibrotic development. Consistently, in the Japanese and Germany cohorts, APOF, GSN, and LUM exhibited aberrant expression in both MASH patients and those with high NAS scores. CONCLUSIONS: The multi-cohort study identified specific serum protein signatures associated with MASL risk, which correspond to dysregulated gene expression patterns in hepatocytes. These findings bridge the gap between systemic circulatory changes and intrahepatic pathological progression, providing not only robust non-invasive biomarkers for early stratification but also potential mechanistically-driven therapeutic targets for halting the progression of MASLD.
Genetic predisposition to high BMI, ultra-processed food consumptions in childhood, and adiposity in young adulthood: a 17-year prospective cohort study of 3061 individuals.
Zhou Z, Chen Q, Li Z … +18 more , Zhang S, Parra-Soto S, Wang A, Du M, Xu X, Fang Z, Lu Y, Zhao YC, Strawbridge RJ, Ip P, Satter N, Timpson NJ, Song M, Celis-Morales C, Gunter MJ, Pell JP, Giovannucci E, Ho FK
BMC Med · 2026 Apr · PMID 41992213 · Full text
BACKGROUND: Observational evidence suggests ultra-processed food (UPF) may contribute to obesity, but some people who consume a larger amount of UPF remain at normal weight. This study examined whether childhood UPF cons...
BACKGROUND: Observational evidence suggests ultra-processed food (UPF) may contribute to obesity, but some people who consume a larger amount of UPF remain at normal weight. This study examined whether childhood UPF consumption was associated with obesity in early adulthood and whether the association was modified by genetic susceptibility to body mass index (BMI). METHODS: This prospective cohort study included data from 3061 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) in England with follow-up from 7 to 24 years. UPF consumption was calculated from food diaries based on the NOVA classification. LDpred2 was used to construct a polygenic score (PGS) for body mass index (BMI). Linear regression models were used to estimate the association between UPF intake at 7 years and BMI at 24 years. The PGS-UPF interaction was examined to see whether genetic susceptibility modifies the association between childhood UPF consumption and early adulthood BMI. RESULTS: Each 10% increase in the proportion of total energy intake coming from UPF at 7 was associated with 0.21 (95% CI 0.05-0.37) kg/m higher BMI at 24, after adjusting for BMI at 7, age, sex, ethnicity, physical activity, socioeconomic position, and total energy intake. There is evidence for PGS-BMI interaction (0.19; 95% CI 0.02-0.36), and the UPF-BMI association was only retained in children with the highest genetic predisposition to higher BMI (0.74, 95% CI 0.07-1.42) in the subgroup analysis. CONCLUSIONS: UPF consumption in childhood is only associated with early adulthood obesity among children more genetically predisposed to higher BMI.
Clinical benefit of tenecteplase despite failed recanalization in late-window ischemic stroke: a post hoc analysis of the TRACE-3 trial.
Lu Z, Wang Z, Jin A … +11 more , Che F, Wang L, Zhou L, Dai H, Liu X, Cao Z, Wang L, Hao M, Ye W, Xiong Y, Wang Y
BMC Med · 2026 Apr · PMID 41992212 · Full text
BACKGROUND: The TRACE-3 trial established the efficacy of intravenous tenecteplase for patients with acute ischemic stroke and large vessel occlusion in the late time window. It remains unclear whether intravenous tenect...
BACKGROUND: The TRACE-3 trial established the efficacy of intravenous tenecteplase for patients with acute ischemic stroke and large vessel occlusion in the late time window. It remains unclear whether intravenous tenecteplase confers clinical benefits specifically in the subpopulation of patients who did not achieve successful large vessel recanalization. METHODS: This is a post-hoc analysis of the TRACE-3 trial, a multicenter randomized controlled trial comparing tenecteplase with standard medical therapy in patients with large vessel occlusion between 4.5 and 24 h of symptom onset. The analysis included participants who had failed recanalization (defined as an Arterial Occlusive Lesion [AOL] score of 0) on follow-up angiography at 24 h. Primary outcome of current study was functional independence (modified Rankin Scale [mRS] score 0-2) at 90 days. We assessed effect modification by baseline characteristics, including stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and collateral circulation status. RESULTS: Among 288 patients with failed recanalization (123 in the tenecteplase group and 165 in the control group), tenecteplase was associated with a significantly higher rate of functional independence at 90 days compared with standard medical therapy (42.3% vs. 29.7%; adjusted risk ratio [RR] 1.37, 95% CI [Confidence Interval] 1.00-1.86, P = 0.048). Tenecteplase also resulted in greater reduction in NIHSS scores at 7 days (adjusted β 0.31, P = 0.028). A significant interaction was observed between treatment effect and baseline stroke severity (P for interaction = 0.02). The benefit of tenecteplase was significant in patients with moderate-to-severe stroke (NIHSS ≥ 10; RR 2.75, 95% CI 1.30-5.79) but not significant in those with minor-to-moderate stroke (NIHSS < 10). Collateral status did not significantly modify the treatment effect (P for interaction = 0.35). CONCLUSIONS: In patients with ischemic stroke treated in the late time window, tenecteplase was associated with improved functional outcomes despite persistent large vessel occlusion. Our findings suggest that tenecteplase may confer therapeutic efficacy through mechanisms beyond proximal arterial reopening. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05141305.
Non-invasive diagnosis strategy integrating PSMA PET/CT and mpMRI for patients with suspected prostate cancer: a multi-center study.
Wang Y, Tang Y, Chen J … +7 more , Sha H, Qi L, Hu S, Chen M, Gu D, Chen S, Cai Y
BMC Med · 2026 Apr · PMID 41992197 · Full text
BACKGROUND: Multiparametric MRI (mpMRI) and ^68 Ga-PSMA PET/CT are widely used for prostate cancer (PCa) diagnosis but remain limited by false positives and modest specificity, particularly in distinguishing benign prost...
BACKGROUND: Multiparametric MRI (mpMRI) and ^68 Ga-PSMA PET/CT are widely used for prostate cancer (PCa) diagnosis but remain limited by false positives and modest specificity, particularly in distinguishing benign prostate diseases (BPDs) and clinically significant PCa (csPCa). Existing studies often rely on small, single-center cohorts with limited generalizability. This study aimed to develop and externally validate a multimodal radiomics model integrating PET/CT and mpMRI for automated PCa diagnosis, and to evaluate the impact of prostate VOI delineation strategies. METHODS: A total of 488 patients with suspected PCa who underwent both ^68 Ga-PSMA PET/CT and mpMRI (T2 and DWI) followed by biopsy were retrospectively enrolled from two centers (366 for model development and ten-fold internal validation; 41 for external validation cohort 1; 81 for external validation cohort 2). Radiomics features were extracted from both modalities, and six classical machine learning classifiers (LR, SVM, Random Forest, Extra Trees, XGBoost, LightGBM) were trained for three tasks: (1) csPCa diagnosis, (2) overall PCa detection, and (3) comparison between expert-drawn and deep learning generated prostate VOIs. Model performance was assessed using AUC, sensitivity, specificity, accuracy, PPV, and NPV. RESULTS: Among 407 patients, 137 had BPD, 25 had clinically insignificant PCa, and 250 had csPCa. The multimodal PET/mpMRI radiomics model achieved the best performance with LightGBM (AUC = 0.91 internally; 0.825 externally). Automatically segmented VOIs achieved comparable diagnostic accuracy to expert annotations, with AUC differences within 3-8%. CONCLUSIONS: The proposed multimodal PET/CT and mpMRI ML-based model enables accurate risk stratification for prostate cancer, with strong external generalizability. Automated prostate segmentation provides comparable diagnostic performance to expert manual delineation, facilitating clinical scalability.
Interpretable multimodal PET/CT-EHR fusion via mixture-of-experts for prognostic stratification in mantle cell lymphoma: a multicenter study.
Jiang C, Zhang Z, Jiang Z … +6 more , Ding C, Teng Y, Gao L, Jiang M, Qu L, Tian R
BMC Med · 2026 Apr · PMID 41992190 · Full text
BACKGROUND: Mantle cell lymphoma (MCL) is a rare, biologically heterogeneous B-cell malignancy with highly variable outcomes. Existing prognostic tools are suboptimal. We developed an interpretable deep learning framewor...
BACKGROUND: Mantle cell lymphoma (MCL) is a rare, biologically heterogeneous B-cell malignancy with highly variable outcomes. Existing prognostic tools are suboptimal. We developed an interpretable deep learning framework integrating baseline [F]FDG PET/CT and electronic health record (EHR) data for individualized risk stratification. METHODS: In this multicenter study, 187 treatment-naïve MCL patients were analyzed. A mixture-of-experts (MoE) fusion network integrated multimodal representations from PET/CT and EHR data. Expert modules comprising vision encoders, radiomics extractors, and a medical language model were integrated through an attention-based gating mechanism to construct multimodal radiomic signatures (R-signatures) predictive of progression-free survival (PFS) and overall survival (OS). R-signatures were validated and incorporated with clinical and metabolic factors into multiparametric models. Deep learning model interpretability was evaluated using attention visualization, expert-level contributions and pathologic correlation. RESULTS: R-signatures robustly discriminated relapse (AUC = 0.893 training, 0.755 validation) and death (AUC = 0.804 and 0.844), and independently predicted adverse outcomes (PFS: HR = 27.70, P < 0.001; OS: HR = 6.86, P = 0.001). Multiparametric models integrating R-signatures with total lesion glycolysis, β2-microglobulin, WBC, and Ki-67 outperformed conventional indices (C-indices: PFS 0.892 training, 0.781 validation; OS 0.877 training, 0.862 validation). Time-dependent ROC analyses consistently showed AUCs approaching or exceeding 0.800. Calibration and decision curve analyses confirmed excellent agreement and superior clinical net benefit. Attention maps localized high-weighted regions to hypermetabolic tumor areas, with higher R-signature values in blastoid and pleomorphic variants versus classical histology (P = 0.028 and P = 0.010). CONCLUSIONS: This interpretable PET/CT-EHR fusion framework substantially improves prognostic precision in MCL, providing a noninvasive, clinically translatable tool for risk-adapted management.
Epigenetic aging markers in the association between frailty and mortality among U.S. adults.
Beydoun MA, Noren Hooten N, Beydoun HA … +4 more , Georgescu MF, Tsai J, Evans MK, Zonderman AB
BMC Med · 2026 Apr · PMID 41987221 · Full text
BACKGROUND: Frailty reflects diminished physiological reserve and increased vulnerability to adverse health outcomes. It has been linked to biological aging, including epigenetic age acceleration (EAA), a DNA methylation...
BACKGROUND: Frailty reflects diminished physiological reserve and increased vulnerability to adverse health outcomes. It has been linked to biological aging, including epigenetic age acceleration (EAA), a DNA methylation-based marker of aging, but the extent to which EAA accounts for the frailty-mortality association remains unclear. METHODS: We analyzed three U.S. cohorts-NHANES (1999-2002), HRS (2016), and HANDLS (2004-2009)-with mortality follow-up through 2019-2022. Frailty was defined using harmonized adaptations of the Fried phenotype and FRAIL scale. EAA was derived from five epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, DunedinPoAm). Additive Bayesian networks, Cox proportional hazards models, and counterfactual four-way decomposition were used to assess potential mediation and moderation of the frailty-mortality association by EAA, adjusting for age, sex, race/ethnicity, and socioeconomic status. RESULTS: Frailty was strongly associated with higher all-cause mortality in NHANES and HRS. GrimAge and DunedinPoAm showed the strongest mediation. In NHANES, GrimAge accounted for 33% (p < 0.001) and DunedinPoAm mediated 17% (p = 0.006) of the association. In HRS, DunedinPoAm mediated 9% (p = 0.040) and GrimAge 16% (p = 0.020). Other clocks showed limited mediation. HANDLS findings were consistent. Higher socioeconomic status was associated with slower aging and lower frailty risk. Female sex was inversely associated with multiple epigenetic clocks but positively associated with frailty. CONCLUSIONS: Epigenetic aging, particularly GrimAge and DunedinPoAm, may explain part of the frailty-mortality association, supporting a role for biological aging pathways linking frailty to mortality.
Development of a novel prognostic assessment tool for recurrent respiratory papillomatosis.
Yamada S, Ikegami T, Fukuhara T … +47 more , Horichi Y, Shinomiya H, Nibu KI, Ebisumoto K, Iijima H, Sakai A, Okami K, Wasano K, Nakanishi Y, Yoshizaki T, Nakagawa T, Hanazawa T, Okamura J, Ueki Y, Horii A, Kise N, Suzuki M, Kasuga M, Yokota S, Takumi Y, Ishinaga H, Kitano M, Ota I, Masui T, Yoshimi N, Sasaki Y, Noda Y, Morita S, Takahashi G, Takeuchi K, Nakamura Y, Ishida K, Sugawara K, Matsuda S, Makoshi Y, Sugiyama N, Kano K, Sahara S, Kita J, Morita K, Mochizuki D, Nakanishi H, Imai A, Misawa Y, Takizawa Y, Kawasaki H, Misawa K
BMC Med · 2026 Apr · PMID 41987216 · Full text
BACKGROUND: Recurrent respiratory papillomatosis (RRP), caused by the human papillomavirus (HPV), is associated with an unpredictable clinical course. Although the Derkay Score is widely used to determine clinical severi...
BACKGROUND: Recurrent respiratory papillomatosis (RRP), caused by the human papillomavirus (HPV), is associated with an unpredictable clinical course. Although the Derkay Score is widely used to determine clinical severity, its prognostic value has rarely been evaluated. We developed a pathological severity score, the Hamamatsu Recurrent Respiratory Papillomatosis Pathological (HARRP) Score and combined it with the Derkay Score to develop a novel clinicopathological system-the Derkay-HARRP (D-H) Classification. We aimed to validate its prognostic value. METHODS: We retrospectively analyzed 125 patients who were clinically diagnosed with RRP from 16 Japanese institutions, randomly divided into validation (n = 38) and test (n = 87) cohorts. HPV-typing and immunohistochemistry for HPV-L1, HPV-E4, Ki-67, and p16 were performed. HPV particles were confirmed using the NanoSuit-correlative light and electron microscopy (CLEM) method. Receiver operating characteristic (ROC) curve analysis evaluated marker performance and defined recurrence cut-offs. HARRP and Derkay Scores were further assessed by ROC analysis and Cox proportional hazards models. We stratified patients using the D-H Classification and analyzed disease progression over time. RESULTS: No significant demographic differences were observed between the two cohorts. Positivity of HPV-L1, HPV-E4, and Ki-67 in the upper third of the epithelium was associated with recurrence. NanoSuit-CLEM confirmed HPV particles in HPV-L1-positive areas, supporting pathological relevance. The HARRP Score was calculated by assigning 1 point each for positivity of HPV-L1, HPV-E4, and ≥ 5% Ki-67-positive cells in the upper third of the epithelium. ROC analysis of the HARRP Score showed areas under the curve (AUCs) of 0.675 (validation) and 0.754 (test), whereas the Derkay Score showed AUCs of 0.709 and 0.834, respectively. The cut-off values were 1 and 4, respectively. Both scores were significant in the Cox analysis (p < 0.001). The D-H Classification stratified patients as Severe (both positive scores), Moderate (either positive), or Mild (both negative), with significant differences in relapse-free survival (p < 0.001). Severity tended to decrease with repeated surgeries and recurrence was rare in the Mild group. Findings remained consistent in HPV-positive cases only. CONCLUSIONS: Combination of the Derkay and HARRP Scores-the D-H Classification-provides a practical tool for risk stratification and personalized follow-up planning of patients with RRP.
Detection rate and mutational landscape in extracranial arteriovenous malformations: a cohort study.
Schmidt VF, Schanze D, Brill R … +29 more , Loeser JH, Uller W, Doppler M, Cangir Ö, Hengst S, Vielsmeier V, Pech M, Obereisenbuchner F, Schirren M, Sint A, Puhr-Westerheide D, Deniz S, Weiß JBW, Häberle B, Hartel A, Fröba-Pohl A, Haehl J, Holm A, Sporns PB, Scherf T, Ricke J, Lassmann S, Seidensticker M, Wohlgemuth WA, Kimm MA, Zenker M, Wildgruber M, Kapp FG, APOLLON Investigators
BMC Med · 2026 Apr · PMID 41987212 · Full text
BACKGROUND: This study aimed to assess the detection rate and spectrum of pathogenic variants (PVs) and candidate variants (variants of uncertain significance, VUS) in AVM patients. METHODS: In this retrospective multice...
BACKGROUND: This study aimed to assess the detection rate and spectrum of pathogenic variants (PVs) and candidate variants (variants of uncertain significance, VUS) in AVM patients. METHODS: In this retrospective multicenter cohort study, tissue and blood samples were collected from 114 patients with extracranial AVMs during treatment or when clinically indicated, for dedicated molecular genetic analyses. PVs (solved) and VUS were detected by targeted sequencing on DNA using gene panels analyzing genes suspected to be associated with AVMs. Unsolved cases were further categorized into unrestricted and restricted, with the latter reflecting methodological limitations. Subgroup analyses were carried out based on affected genes to explore associated genotype-phenotype correlations. RESULTS: PVs were identified in 80.7% (92/114) and VUS in 5.3% (6/114), resulting in a total detection rate of 86.0% (98/114). Unsolved cases accounted for 11.4% (13/114) including 6/13 (46.2%) with methodological restrictions. Somatic PVs were most frequent in KRAS (21.1%, 24/114), MAP2K1 (17.5%, 20/114), HRAS (8.8%, 10/114), and BRAF (7.9%, 9/114). Germline variants were found in RASA1 (7.0%, 8/114), PTEN (5.3%, 6/114), and EPHB4 (3.5%, 4/114). In a few cases, somatic variants in RASA1 (1.8%, 2/114) and PTEN (2.6%, 3/114) were identified. Additional PVs occurred in PIK3CA (3.5%, 4/114), SOS1 (2.6%, 3/114), GNAQ (1.8%, 2/114), and RIT1, RAF1, and GNA14 (each 0.9%, 1/114). Within the RAS/MAPK pathway, RAS variants (KRAS, HRAS) were linked to more severe clinical stages (65.6% vs. 40.0% MAP2K1 and 37.5% BRAF, p = 0.027) and higher relapse rates (55.6% vs. 43.8% MAP2K1 and 0% BRAF, p = 0.049). Germline variants showed a distinct distribution pattern with more syndromic presentations (61.1% vs. 15.6%, p < 0.001) compared to mosaic variants. CONCLUSIONS: Broad and sensitive testing enables a high detection rate of causative variants in AVMs. PVs and VUS detected reveal a broader genetic spectrum than previously recognized. Somatic RAS PVs were associated with more advanced disease stages and higher relapse rates than MAP2K1 and BRAF variants, while germline variants were more frequently linked to syndromic patterns.
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