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Metabolomics- and proteomics-based multi-omics integration reveals early metabolite alterations in sepsis-associated acute kidney injury.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-11 DOI: 10.1186/s12916-025-03920-7
Pengfei Huang, Yanqi Liu, Yue Li, Yu Xin, Chuanchuan Nan, Yinghao Luo, Yating Feng, Nana Jin, Yahui Peng, Dawei Wang, Yang Zhou, Feiyu Luan, Xinran Wang, Xibo Wang, Hongxu Li, Yuxin Zhou, Weiting Zhang, Yuhan Liu, Mengyao Yuan, Yuxin Zhang, Yuchen Song, Yu Xiao, Lifeng Shen, Kaijiang Yu, Mingyan Zhao, Lixin Cheng, Changsong Wang
{"title":"Metabolomics- and proteomics-based multi-omics integration reveals early metabolite alterations in sepsis-associated acute kidney injury.","authors":"Pengfei Huang, Yanqi Liu, Yue Li, Yu Xin, Chuanchuan Nan, Yinghao Luo, Yating Feng, Nana Jin, Yahui Peng, Dawei Wang, Yang Zhou, Feiyu Luan, Xinran Wang, Xibo Wang, Hongxu Li, Yuxin Zhou, Weiting Zhang, Yuhan Liu, Mengyao Yuan, Yuxin Zhang, Yuchen Song, Yu Xiao, Lifeng Shen, Kaijiang Yu, Mingyan Zhao, Lixin Cheng, Changsong Wang","doi":"10.1186/s12916-025-03920-7","DOIUrl":"10.1186/s12916-025-03920-7","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication in patients with sepsis and is associated with high mortality. Therefore, early recognition of SA-AKI is essential for administering supportive treatment and preventing further damage. This study aimed to identify and validate metabolite biomarkers of SA-AKI to assist in early clinical diagnosis.</p><p><strong>Methods: </strong>Untargeted renal proteomic and metabolomic analyses were performed on the renal tissues of LPS-induced SA-AKI and sepsis mice. Glomerular filtration rate (GFR) monitoring technology was used to evaluate real-time renal function in mice. To elucidate the distinctive characteristics of SA-AKI, a multi-omics Spearman correlation network was constructed integrating core metabolites, proteins, and renal function. Subsequently, metabolomics analysis was used to explore the dynamic changes of core metabolites in the serum of SA-AKI mice at 0, 8, and 24 h. Finally, a clinical cohort (28 patients with SA-AKI vs. 28 patients with sepsis) serum quantitative metabolomic analysis was carried out to build a diagnostic model for SA-AKI via logistic regression (LR).</p><p><strong>Results: </strong>Thirteen differential renal metabolites and 112 differential renal proteins were identified through a multi-omics study of SA-AKI mice. Subsequently, a multi-omics correlation network was constructed to highlight five core metabolites, i.e., 3-hydroxybutyric acid, 3-hydroxymethylglutaric acid, creatine, myristic acid, and inosine, the early changes of which were then observed via serum time series experiments of SA-AKI mice. The levels of 3-hydroxybutyric acid, 3-hydroxymethylglutaric acid, and creatine increased significantly at 24 h, myristic acid increased at 8 h, while inosine decreased at 8 h. Ultimately, based on the identified core metabolites, we recruited 56 patients and constructed a diagnostic model named IC3, using inosine, creatine, and 3-hydroxybutyric acid, to early identify SA-AKI (AUC = 0.90).</p><p><strong>Conclusions: </strong>We proposed a blood metabolite model consisting of inosine, creatine, and 3-hydroxybutyric acid for the early screening of SA-AKI. Future studies will observe the performance of these metabolites in other clinical populations to evaluate their diagnostic role.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"79"},"PeriodicalIF":7.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398204","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}
引用次数: 0
Assessment of psychosocial aspects in adults in post-COVID-19 condition: the EURONET-SOMA recommendations on core outcome domains for clinical and research use.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-11 DOI: 10.1186/s12916-025-03927-0
Stefan Salzmann, Lars de Vroege, Petra Engelmann, Per Fink, Susanne Fischer, Stephan Frisch, Lise Kirstine Gormsen, Katharina Hüfner, Willem J Kop, Ferenc Köteles, Nadine Lehnen, Bernd Löwe, Christoph Pieh, Victor Pitron, Charlotte Ulrikka Rask, Markku Sainio, Rainer Schaefert, Meike Shedden-Mora, Anne Toussaint, Roland von Känel, Ursula Werneke, Winfried Rief
{"title":"Assessment of psychosocial aspects in adults in post-COVID-19 condition: the EURONET-SOMA recommendations on core outcome domains for clinical and research use.","authors":"Stefan Salzmann, Lars de Vroege, Petra Engelmann, Per Fink, Susanne Fischer, Stephan Frisch, Lise Kirstine Gormsen, Katharina Hüfner, Willem J Kop, Ferenc Köteles, Nadine Lehnen, Bernd Löwe, Christoph Pieh, Victor Pitron, Charlotte Ulrikka Rask, Markku Sainio, Rainer Schaefert, Meike Shedden-Mora, Anne Toussaint, Roland von Känel, Ursula Werneke, Winfried Rief","doi":"10.1186/s12916-025-03927-0","DOIUrl":"10.1186/s12916-025-03927-0","url":null,"abstract":"<p><strong>Background: </strong>Harmonizing core outcome domains allows for pooling data, comparing interventions, and streamlining research evaluation. At the same time clinicians require concise and feasible measures for routine practice. Considering the heterogeneity of post-COVID-19 condition, a biopsychosocial approach requires sufficient coverage of the psychosocial dimension with assessments. Previous recommendations for core outcome sets have serious limitations regarding the psychosocial aspects of post-COVID-19 condition. This paper specifically focuses on psychosocial outcomes for adults with post-COVID-19 condition, providing both a comprehensive set of outcome domains for research and a streamlined clinical core set tailored for routine clinical use.</p><p><strong>Methods: </strong>In a structured Consensus Development Approach, the European Network to improve diagnostic, treatment, and healthcare for patients with persistent somatic symptoms (EURONET-SOMA) developed psychosocial core outcome domains and assessments regarding post-COVID-19 condition. The experts identified variables and instruments which should be considered in studies on adults suffering from post-COVID-19 condition, and which are feasible in the clinical setting and relevant for research.</p><p><strong>Results: </strong>We identified three higher-order dimensions with each encompassing several domains: The first higher-order dimension, \"outcomes\", encompasses (1) the classification/ diagnostics of post-COVID-19 condition, (2) somatic symptoms (including fatigue), (3) the psychopathological status and mental comorbidities, (4) the physical status and somatic comorbidities, (5) neurocognitive symptoms, and (6) illness consequences. The second higher-order domain \"mechanisms\" encompasses (7) cognitive components, (8) affective components, (9) behavioral components, (10) social components, and (11) psychobiological bridge markers (e.g., neuroimmunological and psychoneuroendocrinological variables). The third higher-order domain, \"risk factors\", includes factors such as (12) socioeconomic status and sociocultural factors, (13) pre-existing mental and somatic health issues, (14) personality factors (e.g., neuroticism), (15) adverse childhood experiences, (16) ongoing disability or pension claim, and (17) social media use. For each domain, specific instruments are suggested for research purposes and clinical use.</p><p><strong>Conclusions: </strong>The recommended core domains help to increase consistency in a biopsychosocial approach to post-COVID-19 condition across investigations, improve synergies, and facilitate decision-making when comparing different interventional approaches. It allows to better identify relevant subgroups in heterogeneous post-COVID-19 condition populations offering practical tools for routine clinical practice through the clinical core set.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"81"},"PeriodicalIF":7.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398192","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}
引用次数: 0
High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-07 DOI: 10.1186/s12916-025-03919-0
Julia Wicherski, Jonas Peltner, Cornelia Becker, Katrin Schüssel, Gabriela Brückner, Andreas Schlotmann, Helmut Schröder, Winfried V Kern, Britta Haenisch
{"title":"High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study.","authors":"Julia Wicherski, Jonas Peltner, Cornelia Becker, Katrin Schüssel, Gabriela Brückner, Andreas Schlotmann, Helmut Schröder, Winfried V Kern, Britta Haenisch","doi":"10.1186/s12916-025-03919-0","DOIUrl":"10.1186/s12916-025-03919-0","url":null,"abstract":"<p><strong>Background: </strong>Fluoroquinolone antibiotics have a high potential for serious adverse drug reactions, but real-world evidence in European patient cohorts is lacking. Therefore, we aim to examine the association between fluoroquinolone exposure and potentially life-threatening adverse events stratified by age and gender in Germany.</p><p><strong>Methods: </strong>We conducted an administrative cohort study using the active comparator new user design with a risk window up to 365 days between January 2013 and December 2019. Population-based longitudinal data from one of the largest German statutory health insurances were used. Episodes of newly dispensed fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin, norfloxacin, and enoxacin) were compared to other antibiotics (amoxicillin, amoxicillin clavulanic acid, azithromycin, cefuroxime, cephalexin, clindamycin, sulfamethoxazole-trimethoprim, and doxycycline). Endpoints were defined by incident diagnoses of aortic aneurysm/dissection, cardiac arrhythmia, hepatotoxicity, and all-cause mortality. Adjusted hazard ratios were estimated from piece-wise exponential additive mixed models with smooth non-linear effects for person-time and age and adjusted for comorbidities, year and quarter at index.</p><p><strong>Results: </strong>The cohorts comprised 15,139,840; 11,760,159; 11,027,175; and 15,305,757 antibiotic episodes. Patients during fluoroquinolone episodes were older (59 versus 51 years) and more often female (58% versus 54%). We counted 46,502; 446,727; 19,125; and 474,411 incident endpoints. Relative risk for all-cause mortality and hepatotoxicity was high for < 40-year- and 40-69-year-old females (aHR = 1.77, 95% CI 1.55-2.03 and aHR = 1.42, 95% CI 1.32-1.53), respectively. For aortic aneurysm/dissection a nominally increased relative risk for < 40-year-old females was found (aHR = 1.42, 95% CI 0.96-2.11), although 95% CI indicates that a small relative risk reduction is also supported by the data. Relative risk for cardiac arrhythmia was increased for men aged < 40 years (aHR = 1.14, 95% CI 1.08-1.20). High relative risks for each endpoint were also identified depending on choice of active comparator, and risks increased with higher defined daily doses and shorter follow-up.</p><p><strong>Conclusions: </strong>This study contributes real-world evidence to endpoint-specific differences of risks in patient subgroups which need to be considered to improve fluoroquinolone drug safety.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"76"},"PeriodicalIF":7.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370381","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}
引用次数: 0
A case-control study based on the National Health and Nutrition Examination Survey to evaluate the effects of human papilloma virus on bone health in women.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-07 DOI: 10.1186/s12916-025-03909-2
Xiang Li, Guangjun Jiao, Yunzhen Chen
{"title":"A case-control study based on the National Health and Nutrition Examination Survey to evaluate the effects of human papilloma virus on bone health in women.","authors":"Xiang Li, Guangjun Jiao, Yunzhen Chen","doi":"10.1186/s12916-025-03909-2","DOIUrl":"10.1186/s12916-025-03909-2","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus (HPV) infection and osteoporosis (OP) are global health concerns, with higher prevalence observed in women compared to men. However, the impact of HPV infection on bone health remains uncertain.</p><p><strong>Methods: </strong>This case-control study utilized data from the National Health and Nutrition Examination Survey (NHANES). Comparable datasets were created using nearest neighbor propensity score matching (PSM) at a ratio of 1:1. The association between HPV infection and bone mineral density (BMD) was analyzed using the Welch two-sample t-test. Furthermore, linear mixed models were employed for validation purposes. Restricted cubic spline (RCS) analysis and Kendall's tau-b tests were performed to explore the effect of different types of HPV infection on BMD.</p><p><strong>Results: </strong>Individuals with HPV infection (mean age 38.11 ± 11.32 years) had lower BMD in the femur and lumbar spine compared to uninfected individuals (mean age 37.92 ± 11.42 years). RCS analysis revealed that an increasing number of cooccurring HPV types in women was associated with lower BMD. Specifically, four HPV types were negatively associated with femur BMD, while 14 HPV types were negatively associated with lumbar spine BMD. Additionally, HPV types 53, 59, and 89 exhibited effects on both femur and lumbar spine BMD.</p><p><strong>Conclusions: </strong>HPV infection is associated with a decrease in BMD, and co-infection with multiple types of HPV implies even lower BMD. Appropriately designed trials are needed to determine if interventions targeted at preventing HPV infection can have a protective effect on BMD.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"75"},"PeriodicalIF":7.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370215","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}
引用次数: 0
Anxiety disorder, depression and coronary artery disease: associations and modification by genetic susceptibility.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-06 DOI: 10.1186/s12916-025-03915-4
Shinya Nakada, Joey Ward, Rona J Strawbridge, Paul Welsh, Carlos Celis-Morales, Frederick K Ho, Jill P Pell
{"title":"Anxiety disorder, depression and coronary artery disease: associations and modification by genetic susceptibility.","authors":"Shinya Nakada, Joey Ward, Rona J Strawbridge, Paul Welsh, Carlos Celis-Morales, Frederick K Ho, Jill P Pell","doi":"10.1186/s12916-025-03915-4","DOIUrl":"10.1186/s12916-025-03915-4","url":null,"abstract":"<p><strong>Background: </strong>Associations of anxiety disorder and depression with coronary artery disease (CAD) are heterogeneous between populations. This study investigated how genetic susceptibility to CAD alters these associations with incident CAD, comparing and combining anxiety disorder and depression.</p><p><strong>Methods: </strong>This is a prospective cohort study using UK Biobank. Diagnoses of anxiety disorder and depression were ascertained through linked hospital admission data. Incident CAD was ascertained through hospital admission and death certificate data after baseline. CAD polygenic risk score (PRS<sub>CAD</sub>) was obtained from CARDIoGRAMplus4 and categorised into low, intermediate, and high. Cox proportional hazard models were used to examine associations between anxiety disorder and depression and CAD.</p><p><strong>Results: </strong>Both anxiety disorder (HR 2.31, 95% CI 1.92-2.78) and depression (HR 2.15, 95% CI 1.90-2.24) were associated with CAD after adjusting for sociodemographic confounders. There was an addictive interaction between depression and PRS<sub>CAD</sub> (RERI 0.97, 95% CI 0.12-1.81) such that the association between depression and CAD was strongest among those with a high PRS<sub>CAD</sub> whilst there was no such evidence for anxiety disorder. Anxiety disorder only (HR 1.68, 95% 1.16-2.44), depression only (HR 2.13, 95% CI 1.72-2.64), and concomitant anxiety disorder and depression (HR 3.85, 95% CI 2.48-5.98) were associated with CAD even among people with a low PRS<sub>CAD</sub>. Adjusting for potential mediators attenuated all these associations across PRS categories.</p><p><strong>Conclusions: </strong>CAD genetic susceptibility might partly contribute to the clustering of depression and CAD but does not provide a full explanation, nor does it explain the association between anxiety disorder and CAD. Therefore, other mechanisms should be explored.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"73"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363702","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}
引用次数: 0
Helicobacter pylori SlyD stabilizes TPT1 via hnRNPK and enhances OCT1-mediated CDX2 transcriptional activation to drive gastric intestinal metaplasia.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-06 DOI: 10.1186/s12916-025-03911-8
Shuwen Zheng, Yingying Wang, Chuxuan Ni, Rui Guo, Xunan Qiu, Jijun Chen, Lu Wang, Xiaohu Sun, Moye Chen, Yunen Liu, Yuan Yuan, Yuehua Gong
{"title":"Helicobacter pylori SlyD stabilizes TPT1 via hnRNPK and enhances OCT1-mediated CDX2 transcriptional activation to drive gastric intestinal metaplasia.","authors":"Shuwen Zheng, Yingying Wang, Chuxuan Ni, Rui Guo, Xunan Qiu, Jijun Chen, Lu Wang, Xiaohu Sun, Moye Chen, Yunen Liu, Yuan Yuan, Yuehua Gong","doi":"10.1186/s12916-025-03911-8","DOIUrl":"10.1186/s12916-025-03911-8","url":null,"abstract":"<p><strong>Background: </strong>Gastric intestinal metaplasia (GIM) represents an important precancerous lesion in intestinal-type gastric cancer, triggered by persistent Helicobacter pylori (H. pylori) infection. In a previous study, we unveiled SlyD as a novel virulence factor of H. pylori, establishing its role in GIM induction through TPT1. However, the underlying mechanism remains undetermined.</p><p><strong>Methods: </strong>Gastric epithelial cells were stimulated with H. pylori 26695, a SlyD inactivated mutant (ΔSlyD), and purified HpSlyD protein, respectively. Real-time qPCR and western blot were subsequently used to assess the expression levels of hnRNPK, TPT1, OCT1, and GIM markers. RNA sequencing was employed to identify differentially expressed genes associated with H. pylori SlyD infection. Protein stability was evaluated using cycloheximide. Molecular interactions were investigated through co-immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. Additionally, molecular docking was utilized to predict TPT1 inhibitors. Immunohistochemistry staining was conducted to validate hnRNPK, TPT1, OCT1, and CDX2 expression in gastric tissue samples from both human and Mongolian gerbils.</p><p><strong>Results: </strong>H. pylori SlyD upregulates TPT1 and induces the expression of GIM markers through hnRNPK. The interaction between hnRNPK and TPT1 enhances TPT1 protein stability, with H. pylori SlyD intensifying this association. TPT1 promotes the expression of GIM markers mediated via OCT1, which binds to CDX2 promoter region, thereby modulating its transcriptional activity. Dihydroartemisinin has the potential to target TPT1, inhibiting the H. pylori SlyD-induced expression of GIM markers.</p><p><strong>Conclusions: </strong>In vitro and in vivo experiments verified that H. pylori SlyD enhances TPT1 stability through hnRNPK, leading to OCT1-mediated transcriptional activation of CDX2 and the initiation of the GIM process. Our study offers novel perspectives on the pathogenesis of H. pylori-related gastric precancerous conditions.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"71"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363708","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}
引用次数: 0
Socioeconomic factors and sex effects of postpartum maternal depression on offspring internalizing symptoms: a systematic review and meta-analysis.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-06 DOI: 10.1186/s12916-025-03877-7
Yang Geng, Wenlan Liu, Zhiying Yu, Hui Zhang, Yun Li, Weihua Zhao
{"title":"Socioeconomic factors and sex effects of postpartum maternal depression on offspring internalizing symptoms: a systematic review and meta-analysis.","authors":"Yang Geng, Wenlan Liu, Zhiying Yu, Hui Zhang, Yun Li, Weihua Zhao","doi":"10.1186/s12916-025-03877-7","DOIUrl":"10.1186/s12916-025-03877-7","url":null,"abstract":"<p><strong>Background: </strong>Postpartum maternal depression and socioeconomic factors are established risk factors for the mental health of offspring. It has been consistently unclear as to whether female or male offspring are more vulnerable to the effects of postpartum maternal depression at different stages of the child's life course. To determine whether the characteristics of postpartum maternal depression with a history of prenatal depression influence sex differences in offspring internalizing symptoms across childhood and adolescence, socioeconomic factors should be considered.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, PsycINFO, CNKI, and SinoMed databases from inception to November 28, 2023, and selected longitudinal cohort studies that quantified sex differences in internalizing symptoms of children and adolescents. Pooled standardized mean differences (SMDs) were calculated using random-effects models. ROBINS-E tool was used to rate the quality of evidence.</p><p><strong>Results: </strong>Twenty-eight studies were eligible between 1997 and 2023, including 24,022 mother-child dyads. Sex-difference trajectories of offspring internalizing symptoms were identified after exposure to postpartum maternal depression, ranging from a lack of significant sex differences in childhood to a higher prevalence observed among girls than boys in adolescence (SMD, 0.25, 95% CI, 0.13-0.38). Economic income and maternal education affected the associations between the magnitude and concurrent recurrence of postpartum depression and significant sex differences in adolescent internalizing symptoms, respectively. After adjusting for socioeconomic factors, early nonconcurrent recurrence of postpartum depression was associated with greater odds of internalizing symptoms among adolescent girls than among boys (β = 0.03, 95% CI, 0.01-0.06); however, there was no statistical significance after adjusting for prenatal depression.</p><p><strong>Conclusions: </strong>Socioeconomic factors differentially impacted the association between postpartum maternal depression and significant sex differences in adolescent internalizing symptoms. Independent of socioeconomic factors and prenatal depression, postpartum maternal depression was not associated with significant sex differences in adolescent internalizing symptoms. Therefore, the significant sex effects of postpartum maternal depression are more likely due to complex interactions between maternal depression and the intrauterine and postpartum environments that shape offspring sex-difference trajectories, with consequences occurring for later internalizing symptoms in adolescence.</p><p><strong>Trial registration: </strong>PROSPERO, CRD42022301445.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"69"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363712","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}
引用次数: 0
Adverse events in the nervous system associated with blinatumomab: a real-world study.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-06 DOI: 10.1186/s12916-025-03913-6
Wen Gao, Jingwei Yu, Yifei Sun, Zheng Song, Xia Liu, Xue Han, Lanfan Li, Lihua Qiu, Shiyong Zhou, Zhengzi Qian, Xianhuo Wang, Huilai Zhang
{"title":"Adverse events in the nervous system associated with blinatumomab: a real-world study.","authors":"Wen Gao, Jingwei Yu, Yifei Sun, Zheng Song, Xia Liu, Xue Han, Lanfan Li, Lihua Qiu, Shiyong Zhou, Zhengzi Qian, Xianhuo Wang, Huilai Zhang","doi":"10.1186/s12916-025-03913-6","DOIUrl":"10.1186/s12916-025-03913-6","url":null,"abstract":"<p><strong>Background: </strong>Nervous system toxicity (NST) is a frequent and serious adverse event (AE) associated with blinatumomab, the first bispecific antibody drug targeting CD19 and CD3. Real-world data are needed to better understand the incidence and characteristics of NST in clinical practice.</p><p><strong>Methods: </strong>Data were obtained from the FDA Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence interval progressive neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms were utilized for data mining.</p><p><strong>Results: </strong>A total of 5,962 blinatumomab-related cases were analyzed. NSTs were more frequent in males (44.01%) and younger individuals (18-45 years, 28.39%), with a higher prevalence in the USA (77.99%). Forty-three signals of NST were identified, of which neurotoxicity, neurological symptoms, agnosia, intention tremor, and immune effector cell-associated neurotoxicity syndrome had the highest ROR values. Concomitant use of medication for age, musculoskeletal system, genitourinary system, and sexual hormones were independent risk factors for NST, and age was an independent protective factor for fatal NST. The median time to onset (TTO) for neurological events was 3 days (range, 1 ~ 21). The highest fatality rate for neurological events was observed for increased intracranial pressure disorders, which also had the highest co-occurrence rate with cytokine release syndrome (CRS).</p><p><strong>Conclusions: </strong>Age is an independent protective factor for fatal NST, and CRS leads to a higher fatality rate for NST patients treated with blinatumomab. Thorough medication evaluation should be conducted before administering blinatumomab, especially for high-risk patients with preexisting neurological conditions.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"72"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363700","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}
引用次数: 0
Assessing brain-muscle networks during motor imagery to detect covert command-following.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-06 DOI: 10.1186/s12916-025-03846-0
Emilia Fló, Daniel Fraiman, Jacobo Diego Sitt
{"title":"Assessing brain-muscle networks during motor imagery to detect covert command-following.","authors":"Emilia Fló, Daniel Fraiman, Jacobo Diego Sitt","doi":"10.1186/s12916-025-03846-0","DOIUrl":"10.1186/s12916-025-03846-0","url":null,"abstract":"<p><strong>Background: </strong>In this study, we evaluated the potential of a network approach to electromyography and electroencephalography recordings to detect covert command-following in healthy participants. The motivation underlying this study was the development of a diagnostic tool that can be applied in common clinical settings to detect awareness in patients that are unable to convey explicit motor or verbal responses, such as patients that suffer from disorders of consciousness (DoC).</p><p><strong>Methods: </strong>We examined the brain and muscle response during movement and imagined movement of simple motor tasks, as well as during resting state. Brain-muscle networks were obtained using non-negative matrix factorization (NMF) of the coherence spectra for all the channel pairs. For the 15/38 participants who showed motor imagery, as indexed by common spatial filters and linear discriminant analysis, we contrasted the configuration of the networks during imagined movement and resting state at the group level, and subject-level classifiers were implemented using as features the weights of the NMF together with trial-wise power modulations and heart response to classify resting state from motor imagery.</p><p><strong>Results: </strong>Kinesthetic motor imagery produced decreases in the mu-beta band compared to resting state, and a small correlation was found between mu-beta power and the kinesthetic imagery scores of the Movement Imagery Questionnaire-Revised Second version. The full-feature classifiers successfully distinguished between motor imagery and resting state for all participants, and brain-muscle functional networks did not contribute to the overall classification. Nevertheless, heart activity and cortical power were crucial to detect when a participant was mentally rehearsing a movement.</p><p><strong>Conclusions: </strong>Our work highlights the importance of combining EEG and peripheral measurements to detect command-following, which could be important for improving the detection of covert responses consistent with volition in unresponsive patients.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"68"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363704","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}
引用次数: 0
Prevalence of cardiovascular symptoms in post-acute COVID-19 syndrome: a meta-analysis.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-06 DOI: 10.1186/s12916-025-03908-3
Li-Wei Huang, Hua-Min Li, Bei He, Xiao-Bo Wang, Qi-Zhi Zhang, Wen-Xing Peng
{"title":"Prevalence of cardiovascular symptoms in post-acute COVID-19 syndrome: a meta-analysis.","authors":"Li-Wei Huang, Hua-Min Li, Bei He, Xiao-Bo Wang, Qi-Zhi Zhang, Wen-Xing Peng","doi":"10.1186/s12916-025-03908-3","DOIUrl":"10.1186/s12916-025-03908-3","url":null,"abstract":"<p><strong>Background: </strong>Since its emergence in 2019, COVID-19 has continued to pose significant threats to both the physical and mental health of the global population, as well as to healthcare systems worldwide (Raman et al., Eur Heart J 43:1157-1172, 2022). Emerging evidence indicates that COVID-19 may lead to post-acute COVID-19 syndrome (PACS) with cardiovascular implications, potentially driven by factors such as ACE2 interaction with viruses, systemic inflammation, and endothelial dysfunction. However, there remains a limited amount of research on the cardiovascular manifestations of PACS, which may delay the development of optimal treatment strategies for affected patients. Therefore, it is crucial to investigate the prevalence of cardiovascular sequelae in COVID-19 patients and to determine whether COVID-19 infection acts as an independent risk factor for these outcomes.</p><p><strong>Methods: </strong>This meta-analysis adhered to PRISMA guidelines and was registered in PROSPERO (CRD42024524290). A systematic search of PubMed, Embase, and the Cochrane Library was conducted up to March 17, 2024. The primary outcomes included hypertension, palpitations, and chest pain, with pooled effect estimate reported as proportions and odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity and subgroup analysis were performed to assess the robustness of the results and to identify sources of heterogeneity.</p><p><strong>Results: </strong>A total of 37 studies, encompassing 2,965,467 patients, were included in the analysis. Pooled results from case-control studies revealed that, compared to the control group, the ORs of chest pain in the COVID-19 group was 4.0 (95% CI: 1.6, 10.0). The ORs for palpitation and hypertension were 3.4 (95% CI: 1.1, 10.2) and 1.7 (95% CI: 1.6, 1.8), respectively. The proportions of PACS patients experiencing chest pain, palpitation, and hypertension as sequelae were 22% (95% CI: 14%, 33%), 18% (95% CI: 13%, 24%), and 19% (95% CI: 12%, 31%), respectively.</p><p><strong>Conclusions: </strong>Our findings indicate that 15% of COVID-19 patients experience cardiovascular sequelae. Furthermore, COVID-19 infection significantly increases the likelihood of developing these sequelae compared to uninfected individuals. Future research should prioritize investigating the underlying pathological mechanisms and developing targeted preventive and management strategies.</p><p><strong>Trial registration: </strong>CRD42024524290.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"70"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363710","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}
引用次数: 0
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