{"title":"Comparative Discrimination of Life's Simple 7, Life's Essential 8, and Life's Crucial 9: Evaluating the impact of added complexity on mortality prediction.","authors":"Xu Zhu, Iokfai Cheang, Yiyang Fu, Sitong Chen, Gengmin Liang, Huaxin Yuan, Ling Zhu, Haifeng Zhang, Xinli Li","doi":"10.1186/s12916-025-04116-9","DOIUrl":"https://doi.org/10.1186/s12916-025-04116-9","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular health (CVH) is a key determinant of mortality, but the comparative effectiveness of different CVH metrics remains uncertain. Life's Simple 7 (LS7) evaluates seven domains: smoking, body mass index, physical activity, total cholesterol, blood pressure, fasting glucose, and diet. Life's Essential 8 (LE8) adds sleep health, while Life's Crucial 9 (LC9) further includes mental health. This study aimed to assess whether the additional components in LE8 and LC9 enhance mortality prediction compared to LS7.</p><p><strong>Methods: </strong>Data from 22,382 participants in the NHANES 2005-2018 were analyzed. Cox proportional hazards regression models were used to evaluate the associations between the scores of these metrics and all-cause, cardio-cerebrovascular disease (CCD), and CVD mortality. The predictive performance of each metric was assessed via receiver operating characteristic (ROC) curves and area under the curve (AUC) values.</p><p><strong>Results: </strong>The participants had a mean age of 45.23 ± 0.23 years, and 51.53% were female. During a median follow-up of 7.75 (4.42-11.08) years, there were 1,483 all-cause deaths, 405 CCD deaths, and 337 CVD deaths. Compared with participants with LS7 scores ≤ 4, those with scores ≥ 11 had a 65% (HR = 0.35 [0.25-0.50]) lower risk of all-cause mortality, a 66% (HR = 0.34 [0.16-0.73]) lower risk of CCD mortality, and a 61% (HR = 0.39 [0.18-0.85]) lower risk of CVD mortality. Similar trends were observed for LE8 and LC9. The AUC for LS7 (0.68 [0.66-0.70]) was slightly greater than that for LE8 (0.67 [0.65-0.69], P = 0.007) and LC9 (0.67 [0.65-0.69], P = 0.019) in predicting all-cause mortality at 5 years; however, the overall predictive performance was nearly identical across all three metrics. Furthermore, the addition of LS7 (AUC = 0.84 [0.82-0.86], P < 0.001), LE8 (AUC = 0.84 [0.82-0.86], P < 0.001), and LC9 (AUC = 0.84 [0.83-0.86], P < 0.001) to the baseline model (AUC = 0.83 [0.82-0.85]) significantly improved all-cause mortality predictions at 5 years; however, the actual gains in predictive performance were marginal.</p><p><strong>Conclusions: </strong>LS7, LE8, and LC9 all predict mortality effectively. Given its simpler scoring and fewer components, LS7 demonstrates comparable predictive performance to LE8 and LC9, making it a more practical tool for clinical and public health applications.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"265"},"PeriodicalIF":7.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980736","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":"Gut-immune-brain interactions during neurodevelopment: from a brain-centric to a multisystem perspective.","authors":"Greta Volpedo, Antonella Riva, Lino Nobili, Federico Zara, Teresa Ravizza, Pasquale Striano","doi":"10.1186/s12916-025-04093-z","DOIUrl":"https://doi.org/10.1186/s12916-025-04093-z","url":null,"abstract":"<p><strong>Background: </strong>Neurodevelopmental disorders (NDDs) and epileptic syndromes are complex neurological conditions linked by shared abnormal neurobiological processes. Existing therapies mostly target symptoms, rather than addressing the underlying causes of the disease, leaving a burden of unmet clinical needs.</p><p><strong>Main body: </strong>Emerging evidence suggests a significant role for the gut microbiota and associated immune responses in influencing brain development and function, changing the paradigm of a brain-centric origin of NDDs. This review discusses the pivotal interactions within the gut-immune-brain axis, highlighting how microbial dysbiosis and immune signaling contribute to neurological pathologies. We also explore the potential of microbial management and immunomodulation as novel therapeutic avenues, emphasizing the need for a shift towards addressing the root causes of these disorders rather than just their symptoms.</p><p><strong>Conclusions: </strong>This integrated perspective offers new insights into the biological underpinnings of NDDs and epilepsy, proposing innovative biomarkers and therapeutic strategies.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"263"},"PeriodicalIF":7.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981613","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}
BMC MedicinePub Date : 2025-05-06DOI: 10.1186/s12916-025-04103-0
Qihua Zou, Yi Cao, Yulin Lai, Yu Fang, Yuchen Zhang, Panpan Liu, Lixia Lu, Hao Wu, Tianying Huang, Ning Su, Zhihua Li, Xicheng Wang, Xiaopeng Tian, Lirong Li, Yingxian Liu, Qingqing Cai, Yi Xia
{"title":"Nimotuzumab combined with docetaxel and cisplatin as first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma: a multicenter, phase 2 trial.","authors":"Qihua Zou, Yi Cao, Yulin Lai, Yu Fang, Yuchen Zhang, Panpan Liu, Lixia Lu, Hao Wu, Tianying Huang, Ning Su, Zhihua Li, Xicheng Wang, Xiaopeng Tian, Lirong Li, Yingxian Liu, Qingqing Cai, Yi Xia","doi":"10.1186/s12916-025-04103-0","DOIUrl":"https://doi.org/10.1186/s12916-025-04103-0","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the efficacy and safety of nimotuzumab combined with docetaxel and cisplatin (TPN) as the first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC).</p><p><strong>Methods: </strong>In this multicenter, open-label, phase 2 trial (ClinicalTrials.gov identifier: NCT03708822), patients with RM-NPC received intravenous nimotuzumab (200 mg on days 1, 8, and 15), docetaxel (75 mg/m<sup>2</sup> on day 1), and cisplatin (75 mg/m<sup>2</sup> on day 1) every 3 weeks for 6 cycles. The primary endpoint was the objective response rate (ORR), and the secondary endpoints included the disease control rate (DCR), duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>Between October 15, 2018, and July 20, 2022, 52 patients were enrolled. The ORR and DCR in the intention-to-treat population were 65.4% and 90.4%, respectively. With a median follow-up of 38.1 months, the median PFS and OS were 7.4 and 40.4 months, respectively. The majority of adverse events were grades 1-2. Grade 3/4 adverse events were neutropenia (42.3%), leukopenia (32.7%), febrile neutropenia (11.5%), nausea (7.7%), fatigue (5.8%), infection (5.8%), thrombocytopenia (1.9%), and anorexia (1.9%). There was no treatment-related death. Low baseline plasma Epstein-Barr virus (EBV) DNA level and the clearance of plasma EBV DNA after 2 cycles of treatment were associated with longer PFS. Additionally, patients who received ≥ 2400 mg of nimotuzumab and ≥ 4 cycles of docetaxel plus cisplatin had superior ORR and survival.</p><p><strong>Conclusions: </strong>First-line therapy with the TPN regimen showed promising efficacy with a well-tolerated safety profile in RM-NPC patients.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT03708822.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"264"},"PeriodicalIF":7.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953750","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}
BMC MedicinePub Date : 2025-05-06DOI: 10.1186/s12916-025-04090-2
Julia Misonow, Karin Wolf-Ostermann, Janissa Altona, Annika Schmidt, Susanne Stiefler, Serhat Guenay, André Kratzer, Antonia Keck, Carolin Donath, Elmar Graessel
{"title":"A complex intervention to reduce hospital admissions for people living with dementia in shared-housing arrangements in Germany: results of the multicenter, cluster-randomized controlled DemWG-study.","authors":"Julia Misonow, Karin Wolf-Ostermann, Janissa Altona, Annika Schmidt, Susanne Stiefler, Serhat Guenay, André Kratzer, Antonia Keck, Carolin Donath, Elmar Graessel","doi":"10.1186/s12916-025-04090-2","DOIUrl":"https://doi.org/10.1186/s12916-025-04090-2","url":null,"abstract":"<p><strong>Background: </strong>People living with dementia (PlwD) have a 1.4 times higher risk of hospitalization than people living without dementia. Hospital admissions lead to negative consequences for PlwD and people living with mild cognitive impairment (PlwMCI). Housing models such as shared-housing arrangements (SHAs), which are predominantly used by PlwD, enable care-dependent people to experience daily life as ordinary as possible. However, studies are needed to show how complex non-pharmacological interventions affect hospital admissions, especially in the SHAs setting.</p><p><strong>Methods: </strong>The longitudinal, multicenter, cluster-randomized, controlled, and prospective mixed methods study from April 1, 2019, to December 31, 2022, was part of the German DemWG study and included a waitlist control group design. The multicomponent complex intervention consisted of (a) education of nursing staff in the SHAs-at the beginning of the study, (b) digital education of general practitioners-at the beginning of the study, and (c) the multimodal, psychosocial group intervention MAKS-mk + -structured application of MAKS-mk + between t0 (baseline) and t1 (after 6 months). Longitudinal data were collected at three survey times t0-t2 (t2 at another 6 months follow-up). The primary outcome parameter-hospital admission-was assessed using the nursing documentation. Poisson-models with hierarchical random effects were used for statistical analysis.</p><p><strong>Results: </strong>Nationwide, 97 SHAs with 341 residents participated at t0. Within the longitudinal observation period (12 months, t0-t2), data from 236 participants at t1 and 168 participants at t2 with mild cognitive impairment or mild to moderate dementia were evaluated. In the intention-to-treat sample, the adjusted Poisson-model showed that participants in the intervention group (IG, n = 201) had a significantly lower number of hospital admissions at t1 than participants in the control group (CG, n = 140) (p-value = 0.048; CI = 0.22; 0.99). Beyond t1-\"open phase\" of the study, no further statistically significant long-term effects of the IG could be identified (p-value ≤ 0.498; CI = 0.25; 1.98).</p><p><strong>Conclusions: </strong>The complex intervention significantly reduced the number of hospital admissions for PlwD and PlwMCI in the \"structured phase\" of DemWG. This leads to significant improvements in the nursing care and living situation for PlwD and PlwMCI. Since the intervention has been proven to have positive effects and can be easily integrated into SHAs, regular and nationwide integration into everyday care should be given greater consideration.</p><p><strong>Trial registration: </strong>ISRCTN89825211 (Registered prospectively, 16 July 2019).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"262"},"PeriodicalIF":7.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981685","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}
BMC MedicinePub Date : 2025-05-02DOI: 10.1186/s12916-025-04085-z
Chenshan Huang, Yuanjiao Yan, Wilson Wai San Tam, Wenqian Sun, Yu Ye, Nafang Wang, Yanhong Shi, Ziping Zhu, Danting Chen, Lin Chen, Junyu Zhao, Rong Lin, Hong Li
{"title":"Effects of an integrated social-art intervention on cognitive and psychosocial outcomes among older adults with mild cognitive impairment in nursing homes: a mixed methods study.","authors":"Chenshan Huang, Yuanjiao Yan, Wilson Wai San Tam, Wenqian Sun, Yu Ye, Nafang Wang, Yanhong Shi, Ziping Zhu, Danting Chen, Lin Chen, Junyu Zhao, Rong Lin, Hong Li","doi":"10.1186/s12916-025-04085-z","DOIUrl":"https://doi.org/10.1186/s12916-025-04085-z","url":null,"abstract":"<p><strong>Background: </strong>The rising prevalence of mild cognitive impairment (MCI) among older adults in nursing homes necessitates effective interventions to slow the progression to dementia. Integrated social-art interventions have shown promise in enhancing cognitive function and reducing social isolation. This study aimed to evaluate the effects of such an intervention on cognitive and psychosocial outcomes in older adults with MCI.</p><p><strong>Methods: </strong>An explanatory sequential mixed-methods study was conducted, comprising a cluster randomized controlled trial (RCT) and a descriptive qualitative study. Four nursing homes in two districts of a city in southeastern China were randomly assigned (1:1) to either the intervention or the control group. The intervention group received a 14-week, 28-session integrated social-art program structured around theme-based group activities, while the control group received usual care, including assistance with daily living activities, basic medical care, recreational activities, and environmental cleaning. Quantitative outcomes were measured at baseline (T0), immediately post-intervention (T1), and at 24-week follow-up (T2), with global cognitive function as the primary outcome, and specific cognitive functions, psychosocial indicators, functional abilities, and quality of life as secondary outcomes. Qualitative interviews were conducted post-intervention to explore the reasons underlying the observed variations in efficacy.</p><p><strong>Results: </strong>Eighty older adults with MCI (median age 86.50 years) participated, with an average attendance rate of 86.25% in the intervention group. Intention-to-treat analyses revealed a significant improvement in global cognitive function at T1 in the intervention group compared to the control group (β = 2.85; 95%CI [1.27, 4.44], P < 0.001); however, this effect was not sustained at T2. No significant improvements were observed in psychosocial indicators, functional abilities, or quality of life (P > 0.05). Qualitative findings indicated that structured, sequential tasks and professional guidance contributed to short-term cognitive gains, whereas age-related health issues and limited ongoing engagement impeded the durability of these benefits.</p><p><strong>Conclusions: </strong>The 14-week integrated social-art intervention appears feasible and may promote short-term cognitive activation in institutionalized older adults with MCI, though its benefits were not sustained at follow-up. Future research should investigate strategies for maintaining cognitive improvements and explore modifications to enhance broader clinical outcomes in this vulnerable population.</p><p><strong>Trial registration: </strong>The trial was prospectively registered at the Chinese Clinical Trials Registry with the registration number ChiCTR2200061681 on 30 June 2022.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"256"},"PeriodicalIF":7.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963686","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}
BMC MedicinePub Date : 2025-05-02DOI: 10.1186/s12916-025-04099-7
Jie Xia, Siqi Yang, Jiao Li, Yao Meng, Jinpeng Niu, Huafu Chen, Zhiqiang Zhang, Wei Liao
{"title":"Normative structural connectome constrains spreading transient brain activity in generalized epilepsy.","authors":"Jie Xia, Siqi Yang, Jiao Li, Yao Meng, Jinpeng Niu, Huafu Chen, Zhiqiang Zhang, Wei Liao","doi":"10.1186/s12916-025-04099-7","DOIUrl":"https://doi.org/10.1186/s12916-025-04099-7","url":null,"abstract":"<p><strong>Background: </strong>Genetic generalized epilepsy is characterized by transient episodes of spontaneous abnormal neural activity in anatomically distributed brain regions that ultimately propagate to wider areas. However, the connectome-based mechanisms shaping these abnormalities remain largely unknown. We aimed to investigate how the normative structural connectome constrains abnormal brain activity spread in genetic generalized epilepsy with generalized tonic-clonic seizure (GGE-GTCS).</p><p><strong>Methods: </strong>Abnormal transient activity patterns between individuals with GGE-GTCS (n = 97) and healthy controls (n = 141) were estimated from the amplitude of low-frequency fluctuations measured by resting-state functional MRI. The normative structural connectome was derived from diffusion-weighted images acquired in an independent cohort of healthy adults (n = 326). Structural neighborhood analysis was applied to assess the degree of constraints between activity vulnerability and structural connectome. Dominance analysis was used to determine the potential molecular underpinnings of these constraints. Furthermore, a network-based diffusion model was utilized to simulate the spread of pathology and identify potential disease epicenters.</p><p><strong>Results: </strong>Brain activity abnormalities among patients with GGE-GTCS were primarily located in the temporal, cingulate, prefrontal, and parietal cortices. The collective abnormality of structurally connected neighbors significantly predicted regional activity abnormality, indicating that white matter network architecture constrains aberrant activity patterns. Molecular fingerprints, particularly laminar differentiation and neurotransmitter receptor profiles, constituted key predictors of these connectome-constrained activity abnormalities. Network-based diffusion modeling effectively replicated transient pathological activity spreading patterns, identifying the limbic-temporal, dorsolateral prefrontal, and occipital cortices as putative disease epicenters. These results were robust across different clinical factors and individual patients.</p><p><strong>Conclusions: </strong>Our findings suggest that the structural connectome shapes the spatial patterning of brain activity abnormalities, advancing our understanding of the network-level mechanisms underlying vulnerability to abnormal brain activity onset and propagation in GGE-GTCS.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"258"},"PeriodicalIF":7.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963688","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}
BMC MedicinePub Date : 2025-05-02DOI: 10.1186/s12916-025-04086-y
Yi Tao, Shi-Wei Jin, Zhe Wang, Mengmeng Pan, Wanyan Ouyang, Jie Xu, Yuanfang Liu, Yan Wang, Weiping Zhang, Jian Li, Jian-Qing Mi
{"title":"Exploring secondary extramedullary myeloma disease: a five-predictor scoring system with spotlight on double-hit cytogenetics.","authors":"Yi Tao, Shi-Wei Jin, Zhe Wang, Mengmeng Pan, Wanyan Ouyang, Jie Xu, Yuanfang Liu, Yan Wang, Weiping Zhang, Jian Li, Jian-Qing Mi","doi":"10.1186/s12916-025-04086-y","DOIUrl":"https://doi.org/10.1186/s12916-025-04086-y","url":null,"abstract":"<p><strong>Background: </strong>Extramedullary myeloma disease (EMD) can present at disease relapse (secondary EMD, sEMD) and confers an aggressive clinical course. Identifying predictive markers for sEMD is crucial for clinical management.</p><p><strong>Methods: </strong>Our study, spanning February 2013 to October 2022, identified sEMD in 77 (12.5%) of 618 newly diagnosed multiple myeloma patients. We categorized sEMD patients into bone-related extramedullary (EM-B) and extraosseous extramedullary (EM-E) relapse groups, as well as into early and late relapse groups based on the median interval from initial MM diagnosis, and assessed their overall survival (OS). We investigated independent predictors for the development of sEMD and focused on double-hit (DH) myeloma, one of the predictors of sEMD. Through the analysis of single-cell RNA from DH myeloma samples, we explored the potential mechanisms by which it may contribute to sEMD.</p><p><strong>Results: </strong>Median OS post-sEMD diagnosis was 11 months, with no significant OS difference between EM-B and EM-E relapse groups. A median interval of 22 months from initial MM diagnosis to sEMD relapse divided the 77 sEMD patients into early and late relapse groups, with early sEMD associated with significantly inferior OS post-sEMD (5.0 vs 27.0 months, p = 0.028). Driven by the prognostic difference of early vs late sEMD relapse, we used a time-to-event model and identified five independent predictors: double-hit (DH) cytogenetics, ≥ 3 osteolytic lesions, IgD subtype, and non-autologous stem-cell transplantation (ASCT) status, each scoring one point, alongside EM-E scoring two points. These predictors informed an additive score, stratifying patients into low (0-2 points) and high (3-5 points) risk categories for sEMD, showing a significant difference in 3-year sEMD rates (6.6% vs 52.8%, p < 0.001). Moreover, the single-cell RNA sequencing of newly diagnosed DH myeloma samples uncovered significant mitogen-activated protein kinase (MAPK) activation in DH cells and exhaustion in CD8 + memory and NK effector cells. Potential therapeutic targets such as EZH2 have emerged from this analysis.</p><p><strong>Conclusions: </strong>Our study introduces a five-predictor scoring system informed by the potential mechanisms underlying sEMD progression in DH myeloma, with the goal of delaying or possibly preventing sEMD.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"257"},"PeriodicalIF":7.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978383","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":"Molecular landscape of atherosclerotic plaque progression: insights from proteomics, single-cell transcriptomics and genomics.","authors":"Chaonan Wang, Yuyao Feng, Xiaoyan Liu, Haidan Sun, Zhengguang Guo, Jiang Shao, Kang Li, Junye Chen, Keqiang Shu, Deqiang Kong, Jiaxian Wang, Yiran Li, Xiangling Lei, Chen Li, Bao Liu, Wei Sun, Zhichao Lai","doi":"10.1186/s12916-025-04058-2","DOIUrl":"https://doi.org/10.1186/s12916-025-04058-2","url":null,"abstract":"<p><strong>Backgrounds: </strong>Atherosclerosis is a major contributor to cardiovascular diseases worldwide. Despite advancements in understanding its pathology, significant gaps remain in the molecular characterization of atherosclerotic plaques. This study addresses this gap by extensively profiling the proteomic landscape of carotid atherosclerotic plaques, classified under the American Heart Association (AHA) types IV to VI, to identify potential biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>The study employed an integrated approach using data-independent acquisition (DIA) proteomics, single-cell RNA sequencing, and Mendelian randomization (MR). A total of 87 human carotid plaques were analyzed to identify and quantify protein expression. These proteins were then mapped to specific regions within the plaques, such as the fibrous cap and lipid core, and further validated in independent samples and single-cell datasets. Furthermore, Mendelian randomization techniques were employed to assess causal relationships between identified proteins levels and ischemic stroke.</p><p><strong>Results: </strong>The proteomic analysis of the 87 carotid plaques revealed 6143 proteins, highlighting diverse expression profiles across different plaque stages. Notably, proteins like CD44 and GAL-1 were predominantly expressed in the fibrous cap, suggesting a role in plaque stability, while TREM2, SMAD3, and IL-6R showed higher expression in the lipid core, indicating involvement in inflammatory processes. These findings were further corroborated by single-cell RNA sequencing, revealing cell-specific expression patterns that align with the observed proteomic data. Additionally, MR analysis indicated the causal role of IL6R, CD44, and SMAD3 in ischemic stroke.</p><p><strong>Conclusions: </strong>This study provides valuable insights into the progression of atherosclerotic plaques, identifying key proteins that could serve as potential biomarkers and therapeutic targets. It enhances our molecular understanding of atherosclerosis and opens up new avenues for treatment. Additionally, our study demonstrates the accuracy and robustness of proteomics in prioritizing genes associated with plaque-related traits.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"254"},"PeriodicalIF":7.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974366","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":"COVID- 19 vaccination reduces new-onset fibromyalgia risk in survivors.","authors":"Aihui Liu, PeiLun Liao, Hongyang Jiang, Shan Huang, Shinan Li, James Cheng-Chung Wei, Zhenhua Ying","doi":"10.1186/s12916-025-04069-z","DOIUrl":"https://doi.org/10.1186/s12916-025-04069-z","url":null,"abstract":"<p><strong>Background: </strong>Numerous studies have demonstrated that COVID-19 is associated with an increased risk of new-onset fibromyalgia (FM), which not only significantly impacts patients' quality of life but also places a substantial burden on healthcare systems. However, no studies have yet investigated whether COVID-19 vaccination may mitigate the risk of developing new-onset FM in individuals who have survived COVID-19. This study aimed to assess the potential effect of COVID-19 vaccination in reducing the risk of new-onset FM among COVID-19 survivors.</p><p><strong>Methods: </strong>We utilized the data resources from the TriNetX platform to compare 90,508 COVID-19 survivors who received the COVID-19 vaccine with 90,508 unvaccinated survivors. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and its corresponding 95% confidence interval (CI). The incidence was calculated using the Kaplan-Meier survival analysis method. Furthermore, we conducted detailed subgroup analyses and sensitivity analyses.</p><p><strong>Results: </strong>The cohort analysis of the present study revealed a significant reduction in the risk of new-onset FM among COVID-19 survivors who received the COVID-19 vaccine, compared to the unvaccinated group (HR 0.84; 95% CI 0.71-0.99). Notably, the results of the subgroup analysis indicated that the COVID-19 vaccine exerted a protective effect against the development of new-onset FM in males, individuals with a body mass index (BMI) < 30, and those with comorbid depression and anxiety.</p><p><strong>Conclusions: </strong>Our findings suggest that COVID-19 vaccination may play a protective role in reducing the risk of new-onset FM among COVID-19 survivors. The findings may indicate the importance of targeting vaccination to specific subgroups, such as males, individuals with lower BMIs, and those with mental health conditions, including depression and anxiety. This approach may enhance the protective effects of the vaccine and further reduce the incidence of long-term health complications associated with COVID-19. Further research is needed to validate these observations.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"255"},"PeriodicalIF":7.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062045","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}
BMC MedicinePub Date : 2025-04-30DOI: 10.1186/s12916-025-04050-w
Seika Lee, Marta A Kisiel, Pia Lindberg, Åsa M Wheelock, Anna Olofsson, Julia Eriksson, Judith Bruchfeld, Michael Runold, Lars Wahlström, Andrei Malinovschi, Christer Janson, Caroline Wachtler, Axel C Carlsson
{"title":"Using machine learning involving diagnoses and medications as a risk prediction tool for post-acute sequelae of COVID-19 (PASC) in primary care.","authors":"Seika Lee, Marta A Kisiel, Pia Lindberg, Åsa M Wheelock, Anna Olofsson, Julia Eriksson, Judith Bruchfeld, Michael Runold, Lars Wahlström, Andrei Malinovschi, Christer Janson, Caroline Wachtler, Axel C Carlsson","doi":"10.1186/s12916-025-04050-w","DOIUrl":"https://doi.org/10.1186/s12916-025-04050-w","url":null,"abstract":"<p><strong>Background: </strong>The aim of our study was to determine whether the application of machine learning could predict PASC by using diagnoses from primary care and prescribed medication 1 year prior to PASC diagnosis.</p><p><strong>Methods: </strong>This population-based case-control study included subjects aged 18-65 years from Sweden. Stochastic gradient boosting was used to develop a predictive model using diagnoses received in primary care, hospitalization due to acute COVID- 19, and prescribed medication. The variables with normalized relative influence (NRI) ≥ 1% showed were considered predictive. Odds ratios of marginal effects (OR<sub>ME</sub>) were calculated.</p><p><strong>Results: </strong>The study included 47,568 PASC cases and controls. More females (n = 5113) than males (n = 2815) were diagnosed with PASC. Key predictive factors identified in both sexes included prior hospitalization due to acute COVID- 19 (NRI 16.1%, OR<sub>ME</sub> 18.8 for females; NRI 41.7%, OR<sub>ME</sub> 31.6 for males), malaise and fatigue (NRI 14.5%, OR<sub>ME</sub> 4.6 for females; NRI 11.5%, OR<sub>ME</sub> 7.9 for males), and post-viral and related fatigue syndromes (NRI 10.1%, OR<sub>ME</sub> 21.1 for females; NRI 6.4%, OR<sub>ME</sub> 28.4 for males).</p><p><strong>Conclusions: </strong>Machine learning can predict PASC based on previous diagnoses and medications. Use of this AI method could support diagnostics of PASC in primary care and provide insight into PASC etiology.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"251"},"PeriodicalIF":7.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980482","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}