BMC Medicine最新文献

{"title":"Trimester-specific associations of maternal vitamin D metabolic markers with risks of small vulnerable newborns: a prospective birth cohort study.","authors":"Shanshan Wang, Yonghua Xiao, Hongjuan Liu, Mingqi Ran, Xinyu Lu, Yundi Mu, Ningning Cui, Jialin Sun, Xudong Wu, Jian Shen, Xuefeng Yang, Xiaomin Wu, Liping Hao","doi":"10.1186/s12916-026-05087-1","DOIUrl":"10.1186/s12916-026-05087-1","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D metabolites beyond total 25(OH)D may influence fetal development, yet their trimester-specific associations with small vulnerable newborns (SVN) remain underexplored. This study examined longitudinal associations of multiple vitamin D metabolic markers with SVN-related outcomes and identified key determinants during pregnancy.</p><p><strong>Methods: </strong>In this prospective cohort of 2,505 mother-infant pairs from China, serum levels of five vitamin D metabolites 25(OH)D<sub>2</sub>, 25(OH)D<sub>3</sub>, total 25(OH)D, 3-epi-25(OH)D<sub>3</sub>, and 24,25(OH)<sub>2</sub>D<sub>3</sub>] were quantified using HPLC-MS/MS. Two vitamin D metabolite ratios (VMR), VMR1 [24,25(OH)<sub>2</sub>D<sub>3</sub>/25(OH)D<sub>3</sub>] and VMR2 [3-epi-25(OH)D<sub>3</sub>/25(OH)D<sub>3</sub>], were derived. Outcomes included low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA), and composite SVN. Associations were evaluated using multivariable logistic regression and restricted cubic spline models. Determinants, including dietary intake, supplementation, season of sample collection, and sociodemographic factors, were evaluated via multivariable linear regression.</p><p><strong>Results: </strong>Vitamin D deficiency decreased from 42.0% in the first trimester to 13.8% in the third trimester. Season and vitamin D intake were major determinants, with supplementation showing stronger correlations than diet. In early pregnancy, higher levels of 25(OH)D<sub>3</sub>, total 25(OH)D, 24,25(OH)<sub>2</sub>D<sub>3</sub>, and VMR1 were linked to lower risks of SVN-related outcomes, particularly PTB and SVN; however, several of these inverse associations were attenuated after FDR-based correction for multiple testing. In contrast, elevated 3-epi-25(OH)D<sub>3</sub> and VMR2 remained robustly associated with increased risks of SGA and SVN after correction. In mid-pregnancy, 25(OH)D<sub>3</sub> and total 25(OH)D were inversely associated with SGA, whereas 25(OH)D<sub>2</sub>, 3-epi-25(OH)D<sub>3</sub>, and VMR2 were positively associated with PTB, SGA or SVN. Nonlinear patterns included an S-shaped association between 3-epi-25(OH)D<sub>3</sub> and SGA and inverted U-shaped associations between 25(OH)D<sub>2</sub> and multiple outcomes (P <sub>nonlinearity</sub> < 0.05). In late pregnancy, associations were largely attenuated, with VMR2 showing only marginal inverse trends for SGA (P <sub>for trend</sub> = 0.058) and SVN (P <sub>for trend</sub> = 0.064).</p><p><strong>Conclusions: </strong>Trimester-specific vitamin D metabolic profiles showed differential associations with neonatal risks, with stronger corrected evidence for adverse associations related to epimerization-derived markers than for early inverse associations of conventional 25(OH)D metabolites. These findings support comprehensive vitamin D metabolic monitoring and further investigation of tailored supplementation strategies to improve maternal-feta","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-nucleus RNA sequencing reveals the pathological process and key transcription factor of sorafenib-induced cardiotoxicity.","authors":"Yani Wang, Zheming Yang, Jing Wang, Ziqi Liu, Yan Zhang, Xiaolin Zhang, Haixu Song, Chenghui Yan, Dan Liu, Yaling Han","doi":"10.1186/s12916-026-05060-y","DOIUrl":"10.1186/s12916-026-05060-y","url":null,"abstract":"<p><strong>Background: </strong>Sorafenib is a first-line treatment for advanced solid tumors. However, its clinical application is limited by cardiotoxicity. The underlying mechanisms remain unclear. We aimed to identify key mechanisms of sorafenib-induced cardiotoxicity using single-nucleus RNA sequencing (snRNA-seq) and experimental verification.</p><p><strong>Methods: </strong>SnRNA-seq was performed on cardiac tissue from a mouse model of sorafenib-induced cardiotoxicity. Bioinformatics analyses included weighted gene co-expression network analysis (WGCNA), differentially expressed gene (DEG) analysis, intercellular communication inference, and transcriptional regulatory network analysis. We conducted functional verification both in vivo and in vitro.</p><p><strong>Results: </strong>SnRNA-seq demonstrated that cell clustering and component analysis confirmed the reduction in cardiomyocytes (CMs) and endothelial cells (ECs), along with an increase in immune cell populations. DEG enrichment analysis indicated that the upregulated DEGs in CMs, ECs, and fibroblasts (FBs) were consistently enriched in pathways associated with cardiomyopathy, whereas the downregulated DEGs were enriched in myocardial remodeling and repair processes. Gene set scoring revealed activation of fibrosis and inflammation programs in CMs and FBs. Cell communication analysis revealed a widespread disruption of cellular crosstalk in sorafenib-induced cardiotoxicity and identified key ligand-receptor pairs contributing to pro-inflammatory and pro-fibrotic phenotypes. Meanwhile we identified the common transcription factors and main effect genes in the three main effector cells during sorafenib-induced cardiotoxicity. Augur analysis and WGCNA consistently identified CMs as the most significantly affected cell type. Transcriptional regulatory network analysis highlighted melanocyte-inducing transcription factor (MITF) as a core transcription factor involved in sorafenib-induced cardiotoxicity. Functional validation showed that MITF expression was significantly increased in cardiac tissues and CMs after sorafenib treatment and that knockdown of MITF attenuated sorafenib-mediated CM hypertrophy in vitro.</p><p><strong>Conclusions: </strong>By constructing the first snRNA-seq data for sorafenib-induced cardiotoxicity, we identified MITF as a key transcription factor associated with sorafenib-induced cardiotoxicity. Our study provides potential therapeutic targets for mitigating sorafenib-induced cardiotoxicity.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medical, socioeconomic, and geographic disparities in primary health care access and utilization: a population-based study of 8038 individuals aged one year and older in rural Uganda.","authors":"Saadiyah Mayet, Christin Puthur, Betty Nabatte, Benjamin Tinkitina, Christopher K Opio, Yin-Cong Zhi, Narcis B Kabatereine, Goylette F Chami","doi":"10.1186/s12916-026-05061-x","DOIUrl":"10.1186/s12916-026-05061-x","url":null,"abstract":"<p><strong>Background: </strong>There is limited data on trends in primary health care (PHC) access and utilisation in rural sub-Saharan Africa, with a particular lack of knowledge on disparities beyond geographic barriers.</p><p><strong>Methods: </strong>A cross-sectional study was conducted within the community-based cohort, SchistoTrack. 2191 households were randomly sampled from 52 rural villages in Pakwach, Buliisa, and Mayuge Districts in Uganda. All household members aged one year and older were surveyed between 2022-2024, resulting in 8038 individuals with baseline health access information. Key outcomes included any care sought within the month preceding the study, type of care sought, and usual source of care. Using logistic regressions with standard errors clustered by household and village, we examined a comprehensive and diverse set of medical, socioeconomic, and geographic determinants.</p><p><strong>Results: </strong>Only 8.2% (659/8038) of participants sought any care, with only 67.5% (445/659) of those participants seeking PHC. Having current symptoms, a previously diagnosed disease, older age, and being female were positively associated (Odds ratios (ORs) 1.02-2.85) with higher odds of seeking any care in the past month. Among participants who sought care, living in a Western district (Pakwach or Buliisa) was associated with higher odds (ORs 9.40-10.77) of seeking care from PHC centres than living in the Eastern study district (Mayuge). Current alcohol use among adults aged 20 years and older was associated with lower odds of seeking PHC (OR 0.43). Distance to a PHC centre and living in the Western districts were negatively (OR 0.72) and positively associated (ORs 4.70-5.64) with having PHC as the usual source of care for the household.</p><p><strong>Conclusions: </strong>Medical and demographic factors influenced the decision to seek any care, but PHC usage was largely determined by regional and spatial disparities suggesting different avenues for targeted interventions seeking to increase general health access vs PHC usage.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of COVID-19 pandemic on childhood immunization coverage in Indonesia: lesson learned from a nationwide analysis of the Expanded Programme on Immunization.","authors":"Amalia Nurina, Evelyn Puspaningrum, Gertrudis Tandy, Debsy Pattilima, Badriul Hegar, Grace Wangge, Raph L Hamers, Iqbal Rf Elyazar, Henry Surendra","doi":"10.1186/s12916-026-05084-4","DOIUrl":"10.1186/s12916-026-05084-4","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic disrupted childhood immunization programmes in many countries worldwide. However, evidence on its impact in low and middle-income countries remains limited. This study examined the impact of the COVID-19 pandemic on childhood immunization coverage across 514 districts in Indonesia and identified district-level associated factors.</p><p><strong>Methods: </strong>We conducted a nationwide longitudinal analysis of the Expanded Programme on Immunization to compare immunization coverage before and after the pandemic. The outcome variable was the annual childhood immunization coverage (proportion of children aged 0-12 months who have received all recommended doses of childhood immunization as per the national immunization schedule). The independent variables include COVID-19 burden and vaccination rates, health system and human development indicators. Mixed-effect logistic regression was done to assess association between the independent and outcome variables.</p><p><strong>Results: </strong>At the national level, the coverage was 83.2% in pre-pandemic, 75.0% in the first year of pandemic, and 88.6%, in the second. In the first year, 69.3% of districts experienced significant decline, with a lower national coverage ratio of 0.92 (95% confidence interval 0.89-0.94). In the second year, 36.2% districts were still affected. The multivariable analysis showed that a significant decline in coverage during the first pandemic year was associated with high COVID-19 incidence (adjusted odds ratio 2.19, 95%CI 1.01-4.73 for the highest vs. lowest group), low midwife adequacy (5.84, 2.40-14.16 for the lowest vs. the highest group, 2.61, 1.26-5.40 for low-middle vs. the highest group), and a high proportion of health facility-based births (2.98, 1.49-5.98 for middle-high vs. the lowest group).</p><p><strong>Conclusions: </strong>The COVID-19 pandemic was negatively and unevenly associated with childhood immunization in Indonesia, with greatest impacts in districts facing a higher COVID-19 burden and weaker health system capacity. These findings underscore the need for targeted efforts to strengthen the local health system for future health crises.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and lipidomic analysis reveals lipid mediation of genetic risk in gestational diabetes.","authors":"Yao Dong, An-Qun Hu, Bai-Xue Han, Qing Li, Hai-Yan Liu, Jin-Jin Liu, Zong-Guang Li, Zi-Qiang Qian, Meng-Ting Cao, Long-Nan Pan, Yun-Yun Xu, Yao Pei, Fang Wu, Yan Tan, Yong-Fu Yu, Ying-Jie Zheng","doi":"10.1186/s12916-026-05083-5","DOIUrl":"10.1186/s12916-026-05083-5","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) is a complex metabolic disorder with a substantial genetic component; however, whether lipid species mediate the impact of genetic susceptibility on GDM risk remains unclear. This study aimed to characterize genetic architecture of GDM and evaluate whether lipid species mediate the genetic risk.</p><p><strong>Methods: </strong>A cohort and case-cohort design were implemented within the Anqing Pregnant Women Cohort. Maternal blood was collected at 15-20 gestational weeks, and GDM was diagnosed at 24-28 weeks. A Meta-GWAS of GDM was performed using regression-based methods, and polygenic risk score (PRS) was constructed. Lipidomic analysis was performed to identity differential lipid species. Risk Ratios (RRs) and 95% confidence interval (CI) were estimated via weighted Poisson regression. Weighted co-abundance network analysis (WGCNA) was applied to cluster lipids into co-abundance modules. Mediation analyses were used to estimate the extent to which lipid species statistically accounted for the association between genetic risk and GDM. A nested 5-fold cross-validation framework was used to explore predictive models and to evaluate the incremental value of PRS and lipid features.</p><p><strong>Results: </strong>The Meta-GWAS of 536 GDM and 2,051 controls identified one genome-wide significant risk locus (LIPF) and eight suggestive loci, including two novel signals (IL17B, RPL15P2). Implicated genes were enriched in glycerolipid metabolism pathways. Lipidomic analysis in a case-cohort of 102 GDM and 111 controls identified 134 differential lipid species. WGCNA yielded 14 distinct co-abundance modules, five of which were significantly associated with GDM. Lipid mediators, including specific triacylglycerols, phosphatidylethanolamines, and hexosylceramides, collectively accounted for approximately 31.10% of the overall genetic effect on GDM. Modules enriched for these lipids showed varying degrees of statistical mediation for rs16885782 (CDKAL1), rs11236507 (DGAT2) and rs10830963 (MTNR1B), with mediation effect ranging from 10.30% to 22.07%. The incorporation of lipid biomarkers significantly improved GDM prediction (AUC = 0.849, P = 0.001), whereas further adding PRS did not show significant improvement (AUC = 0.858, P = 0.095).</p><p><strong>Conclusions: </strong>Genes involved in lipid metabolism are associated with GDM susceptibility. Lipids potentially mediate the genetic risk of GDM, and lipid biomarkers showed potential for improving predictive performance. These findings require further validation in independent cohorts.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating metabolomic signatures of ultra-processed and minimally processed food intake and risk of cardiovascular disease and type 2 diabetes: 20-year follow-up in the Whitehall II cohort.","authors":"Mengmei E Wang, Annie Britton, Michail Katsoulis, Kiara Chang, Eszter P Vamos, Clare H Llewellyn","doi":"10.1186/s12916-026-05081-7","DOIUrl":"10.1186/s12916-026-05081-7","url":null,"abstract":"<p><strong>Background: </strong>Higher intakes of ultra-processed food (UPF) and minimally processed food (MPF) are linked to increased and decreased cardiometabolic risks, respectively, though mechanisms underlying these associations remain less understood. We aimed to identify metabolomic signatures associated with UPF and MPF intakes, examine their prospective associations with cardiovascular disease (CVD) and type 2 diabetes (T2D), and quantify their mediation of processing-disease associations.</p><p><strong>Methods: </strong>In the Whitehall II cohort, UPF and MPF intakes in 6010 participants were derived using the Nova classification from 127-item food frequency questionnaires administered at phases 3 and 5 (1991-1994, 1997-1999), averaged across phases. Fasting plasma samples were analysed for 233 metabolites using nuclear magnetic resonance (NMR) spectroscopy. Metabolomic signatures for UPF and MPF intake were derived using elastic net regression. Cox models examined associations between metabolomic signatures and incident CVD and T2D. Mediation analyses quantified the proportion explained by metabolomic signatures.</p><p><strong>Results: </strong>We identified metabolomic signatures for UPF (34 metabolites) and MPF (50 metabolites). The UPF signature correlated positively with pro-inflammatory and atherogenic metabolites and inversely with omega-3 fatty acids and high-density lipoproteins; the MPF signature showed the opposite pattern. 1094 CVD and 853 T2D events occurred over 20 and 18 years median follow-up, respectively. Comparing the highest to lowest tertile, higher UPF signature scores were associated with greater risk of (hazard ratio [HR] = 1.19; 95% confidence interval [CI] 1.02-1.39) and T2D (HR = 1.20; 95% CI 1.03-1.42), whereas higher MPF signature scores were inversely associated with these outcomes (CVD: HR = 0.81; 95% CI 0.69-0.94; T2D: HR = 0.60; 95% CI 0.48-0.73). Associations between the signatures and outcomes were robust to additional adjustment for UPF or MPF intake. The signatures mediated 42.8-51.1% of processing-disease associations (51.1% for UPF-CVD, 46.6% for MPF-CVD, 42.8% for UPF-T2D, and 47.8% for MPF-T2D; all p < 0.05).</p><p><strong>Conclusions: </strong>Metabolomic signatures of UPF and MPF intake showed opposing associations with CVD and T2D risk, partially mediating these processing-disease associations. These findings suggest biological pathways linking UPF intake to adverse cardiometabolic outcomes, though the unexplained proportion indicates additional mechanisms may contribute.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of acute kidney injury in African children hospitalized with malaria: a multinational individual participant data meta-analysis.","authors":"Caitlin Bond, Anthony Batte, Folake Afolayan, Nicholas M Anstey, Quique Bassat, Philip A Bejon, James A Berkley, Rhys D R Evans, Stuart L Goldstein, Michael T Hawkes, Olayinka Ibrahim, Peace Imani, Chandy C John, Kevin C Kain, Claire Liepmann, Kevin Marsh, Ruth Namazzi, Margaret Nakuya, Nicole O'Brien, Lere P Oluwadare, Robert O Opoka, Jonathan Sserunkuuma, Hunter Wynkoop, Andrea L Conroy","doi":"10.1186/s12916-026-05072-8","DOIUrl":"10.1186/s12916-026-05072-8","url":null,"abstract":"<p><strong>Background: </strong>Historically, acute kidney injury (AKI) has been an underappreciated complication in children with severe malaria. We conducted an individual patient data meta-analysis to model the impact of AKI and its complications on inpatient mortality in African children hospitalized with malaria.</p><p><strong>Methods: </strong>Studies were identified using MEDLINE, EMBASE, Scopus, and PubMed with no language restrictions, as well as through outreach at scientific meetings. Investigators were contacted about participation in the study. Eligible studies included African children hospitalized with Plasmodium falciparum malaria, a serum creatinine measurement, and mortality assessed. The primary exposure was AKI, defined using Kidney Disease Improving Global Outcomes (KDIGO) criteria based on serum creatinine. The primary outcome was all-cause in-hospital mortality, and dialysis requirement was a secondary outcome. Data were standardized and cleaned, and random-effects meta-analyses were conducted to generate pooled estimates.</p><p><strong>Results: </strong>We included 18 studies involving 8 countries and 13,528 children aged 3 months to 16 years over a 33-year period with 951 deaths (7%). The frequency of KDIGO-defined AKI was 47% (95% confidence interval: 46% to 48%), with 47% of children having KDIGO-defined Stage 1 AKI, 30% having Stage 2, and 23% having Stage 3 AKI. Overall, KDIGO-defined AKI was associated with a 2.87 increased odds of mortality (95% CI 2.28 to 3.61) with a monotonic increase in mortality across AKI stage. AKI was a robust risk factor for mortality across era, sex, region, and subgroups. The KDIGO AKI definition was operationalized using simplified age-based thresholds to support bedside recognition of AKI with comparable mortality performance. The WHO-defined AKI threshold (creatinine value >3 mg/dL) occurred in 3.4% (238) of children. All 238 cases identified by WHO criteria were classified as having AKI using KDIGO and age-based definitions, but WHO missed 93% (3059/3297) of additional AKI cases.</p><p><strong>Conclusions: </strong>AKI was strongly associated with mortality in African children hospitalized with malaria. Creatinine thresholds can be operationalized to facilitate early AKI recognition. These findings have clinical implications for the implementation of kidney-protective care and for enhanced monitoring of children with severe malaria.</p><p><strong>Other: </strong>Funded by National Institutes of Health (1R01AI165946), registered number PROSPERO (CRD42024560012).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From behavioral to structural correlates: a multi-phase analysis of global reported mpox.","authors":"Li Shen, Mengna Wei, Yu Chen, Rui Li, Zhenfan Xu, Yuetong Chen, Yaqin Su, Mengyan Ye, Zhenhua Lu, Jiayi Li, Jinzhan Chen, Junze Du, Yijie Yin, Ying Liu, Peng Li, Liqun Fang, Xiaojie Yuan, Wei Liu, Kun Liu","doi":"10.1186/s12916-026-05068-4","DOIUrl":"10.1186/s12916-026-05068-4","url":null,"abstract":"<p><strong>Background: </strong>Mpox epidemiology has expanded from endemic zoonotic spillover to sustained human-to-human transmission. While behavioral risk factors have been well recognized, how macro-level correlates of mpox burden vary across epidemic phases remains insufficiently quantified, limiting targeted public health responses.</p><p><strong>Methods: </strong>Using World Health Organization (WHO) global daily mpox surveillance data from January 1, 2022 to April 30, 2025, we calculated country-period reported mpox incidence and developed a phase-sensitive analytical framework integrating multi-domain macro-level variables across distinct epidemic phases. Five ensemble machine learning models (eXtreme Gradient Boosting, Gradient Boosting Decision Tree, Light Gradient Boosting Machine, Random Forest, Categorical Boosting) were optimized, and their outputs were interpreted using SHapley Additive exPlanations (SHAP) values to identify the changing correlates of mpox burden across phases.</p><p><strong>Results: </strong>Reported mpox incidence exhibited four temporal-epidemiological phases, comprising localized sporadic emergence, accelerated global spread, sustained dissemination, and region-specific resurgence. SHAP-based interpretation revealed a phase-dependent shift in model-associated correlates, from behavioral factors in earlier phases, such as close-contact networks and population mobility, to later structural vulnerability indicators related to socioeconomic disparities and health-system capacity. The LGBT+ (lesbian, gay, bisexual, transgender, and other sexual and gender minorities) Legal Index was the strongest overall predictor, accounting for 13.5% of the overall SHAP importance. Its association with reported mpox incidence was context-dependent, with positive contributions occurring in legally inclusive settings and negative contributions observed in restrictive settings, a pattern consistent with differential case ascertainment and reporting visibility.</p><p><strong>Conclusions: </strong>Our findings highlight a transition from behavioral to structural indicators in global mpox burden, uncovering phase-specific and geographic heterogeneity. These results support phase-tailored interventions that combine early targeted prevention with later health-system strengthening, equitable surveillance, community support, and stigma reduction.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of fluid restriction in acute bacterial meningitis: A systematic review.","authors":"M Netravathi, Debjyoti Dhar, Thuppanattumadam Ananthasubramanian Sangeeth, Nicoline Schiess, Francesco Venuti, Nicolò Binello, Kavita Kothari, Tarun Dua","doi":"10.1186/s12916-026-05075-5","DOIUrl":"10.1186/s12916-026-05075-5","url":null,"abstract":"<p><strong>Background: </strong>Acute bacterial meningitis (ABM) is a neurological emergency that requires prompt and appropriate antibiotics and corticosteroids. Previously fluid restriction was recommended in the treatment of ABM in view of studies reporting hyponatremia which was due to elevated antidiuretic hormone (ADH) levels.</p><p><strong>Aims: </strong>The primary objective was to study the effects of adjuvant fluid restriction in patients of ABM on mortality, neurological and audiological parameters.</p><p><strong>Methods: </strong>Electronic search was performed on the PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Epistemonikos, Web of science, Cochrane Central Register of Controlled Trials (CENTRAL) and Clinical trial registry for studies published from 1946 to 6th Feb 2024. The systematic review included all studies that were Randomized controlled trials (RCT) wherein fluid restriction was employed in patients with ABM. Data were uploaded into the rayyan tool, and the review authors independently screened the articles. Quality of the studies was assessed using the Cochrane 'Risk of bias 2' (ROB2) tool. Risk ratios (RR) with 95% confidence intervals (CI) were used to measure treatment effect and the GRADE framework was used to evaluate the certainty of evidence for each outcome.</p><p><strong>Results: </strong>Two articles with 407 participants were included in the meta-analyses and both of them had children less than 7 years old. Fluid restriction probably had little or no difference on mortality at admission compared with normal fluid maintenance (RR:1.19; 95% CI 0.77 to 1.85) and also on neurological sequalae (RR 1.31, 95% CI 0.74 to 2.30). A single study reported on mortality and neurological sequelae based on hyponatremia status and there was no difference in between the fluid restricted group and standard maintenance groups.</p><p><strong>Conclusions: </strong>There are only two studies on the efficacy of Fluid restriction as an adjuv-ant therapy in the treatment of acute bacterial meningitis. Fluid restriction does not appear to significantly alter the mortality or neurological sequelae compared to maintenance therapy.</p><p><strong>Trial registration: </strong>Prospero id: CRD42024533368.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical trial landscape of cell therapy for spinal cord injury: from integrated practices to future developments.","authors":"Jun Kang, Senyu Yao, Songfu Zou, Yangfan Yu, Xu Huang, Ziqi Xie, Yaobang Lin, Bin Liu, Mao Pang, Limin Rong","doi":"10.1186/s12916-026-05078-2","DOIUrl":"10.1186/s12916-026-05078-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Spinal cord injury (SCI) precipitates a multiphasic secondary injury cascade that establishes a hostile, inhibitory microenvironment, rendering the condition refractory to conventional surgical stabilization and rehabilitation. While cell-based therapies offer promise for neural reconstruction, their clinical translation is impeded by protocol heterogeneity and fragmented safety data. To address this, we mapped clinical trials for SCI to quantify patient demographic parameters, identify lineage-specific adverse-event patterns, evaluate objective motor and sensory efficacy outcomes, and analyze methodological trial designs to formulate concrete structural recommendations for future advanced-phase trials.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analyzed clinical trials from the Web of Science Core Collection (SCIE and ESCI) published since 2005. The dataset comprised 116 eligible studies involving patients with SCI receiving cellular therapies with reported safety outcomes. We employed a dual-method approach combining manual extraction of clinical characteristics (demographics, interventions, adverse events, efficacy outcomes) with quantitative data analysis. Statistical associations between therapeutic variables (cell type, route, dosage) and safety profiles were evaluated using Fisher's exact test.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The clinical landscape is predominantly defined by early-phase (Phase 1: 59.5%), single-arm investigations (63.8%) utilizing autologous bone marrow-derived cells. Reflecting a cautious paradigm to minimize severe complications, patient selection frequently targeted the hemodynamically stable chronic phase (58.3%) and thoracic SCI (21.6%). Safety analyses revealed lineage-specific profiles: mesenchymal stromal cells were significantly associated with transient fever (P  = 0.038), whereas intrathecal administration correlated with procedural symptoms such as headache (P &lt; 0.001). The observation of higher systemic adverse event rates in low-dose cohorts was likely confounded by the mandatory concurrent immunosuppressive regimens required for specific allogeneic lineages, rather than the absolute cell dose. Regarding therapeutic efficacy, outcomes were critically influenced by the chronological phase of injury. Patients treated in the acute or subacute phases exhibited higher rates of neurological improvement, though distinguishing this from spontaneous recovery remains challenging, whereas chronic phase interventions demonstrated more limited primary sensorimotor gains. Additionally, intrathecal administration showed an advantage in preserving sensory pathways due to minimized structural disruption, while dose requirements could not be generalized and varied fundamentally based on specific cellular mechanisms of action.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;While the baseline safety of cellular transplantation for spinal cord injury is established, clinical translation remains hindered by methodol","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}