{"title":"Cryoablation-induced modulation of Treg cells and the TGF-β pathway in lung adenocarcinoma: implications for increased antitumor immunity.","authors":"Shicheng Lin, Dianna Liu, Tianyu Liang, Yaoxue Zhuang, Xiaofan Wang, Shengmao Ma, Quanwang Li, Kaiwen Hu","doi":"10.1186/s12916-025-03926-1","DOIUrl":"10.1186/s12916-025-03926-1","url":null,"abstract":"<p><strong>Background: </strong>Cryoablation plays a key role in the comprehensive management of lung adenocarcinoma, characterized by its ability to activate antitumor immunity. This study aimed to explore the impact of cryoablation on the local immune microenvironment, focusing on regulatory T cells (Tregs) and the TGF-β pathway.</p><p><strong>Methods: </strong>Single-cell sequencing was employed to identify differences in immune cell populations and related pathway expression between lung adenocarcinoma tissues and adjacent noncancerous tissues. Prospective observations of changes in Tregs in the peripheral blood pre- and post-cryoablation for lung adenocarcinoma were conducted at Dongfang Hospital, Beijing University of Chinese Medicine. Bulk RNA-seq analysis of mouse tumor tissues was performed to predict the potential mechanisms underlying cryoablation-induced antitumor immunity. Finally, these predictions were validated through in vitro and in vivo experiments employing cell cryoablation and mouse subcutaneous tumor transplantation models.</p><p><strong>Results: </strong>Single-cell RNA sequencing analysis revealed intricate interactions between Tregs subpopulations and the regulation of the immune response in lung adenocarcinoma, highlighting the involvement of the TGF-β pathway. A significant decrease in the level of Tregs was noted at 30 days post-cryoablation compared to pre-surgical and 3-day post-surgery levels. The cellular and murine cryoablation models validated the inhibitory effect of cryoablation on Tregs and its potential to stimulate antitumor immunity. Additionally, the results of bulk RNA-seq demonstrated the role of cryoablation in regulating postoperative immunity via the TGF-β pathway. Cryoablation decreased the expression levels of TGF-β1, suppressed the phosphorylation of Smad2 and Smad3, and downregulated the expression of FOXP3, thereby inhibiting the conversion of CD4 + T cell precursors into Tregs. Moreover, cryoablation enhanced the expression of interferon-gamma (IFN-γ), thereby promoting its antitumor activity.</p><p><strong>Conclusions: </strong>This study revealed the effective modification of the lung adenocarcinoma microenvironment by cryoablation through the suppression of Tregs and activation of antitumor immunity via the TGF-β pathway. These findings hold implications for optimizing cryoablation-based therapies and guiding future clinical trials on lung adenocarcinoma treatment.</p><p><strong>Trial registration: </strong>This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR2000038580, Sep 24, 2020).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"89"},"PeriodicalIF":7.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413336","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 : 2025-02-12DOI: 10.1186/s12916-025-03906-5
Duncan K Gathungu, Viona N Ojiambo, Mark E Kimathi, David Kaftan, Hae-Young Kim, Daniel T Citron, Ingrida Platais, Daniel Briedenbecker, Clark Kirkman, Samuel M Mwalili, Anna Bershteyn
{"title":"Mitigating HIV risk associated with widow cleansing and wife inheritance using combined biomedical and structural interventions in western Kenya: a mathematical modeling study.","authors":"Duncan K Gathungu, Viona N Ojiambo, Mark E Kimathi, David Kaftan, Hae-Young Kim, Daniel T Citron, Ingrida Platais, Daniel Briedenbecker, Clark Kirkman, Samuel M Mwalili, Anna Bershteyn","doi":"10.1186/s12916-025-03906-5","DOIUrl":"10.1186/s12916-025-03906-5","url":null,"abstract":"<p><strong>Background: </strong>In parts of Africa, women who become widowed lose housing, bank accounts, and other property and must re-marry to avoid extreme poverty. To re-marry, some women are required to undergo widow \"cleansing\"-condomless sex with a man who removes \"impurities\" ascribed to her from her husband's death-and are \"inherited\" as a wife of a brother-in-law. This study explores how HIV biomedical and structural interventions could reduce HIV-related harms associated with these practices.</p><p><strong>Methods: </strong>We adapted EMOD-HIV, an HIV agent-based network transmission model previously calibrated and validated for the Nyanza region of western Kenya. Building on the model's pre-existing configuration of marriages, mortality, and widowhood, we added widow cleansing and wife inheritance with assumptions based on literature. Modeled HIV prevalence among inherited widows was validated to match observed data. We modeled the effect of widowed women, cleansers, and inheritors receiving biomedical HIV interventions (testing, treatment for those tested positive, and 1 year of pre-exposure prophylaxis (PrEP) initiated at cleansing for those tested negative) with or without structural interventions (female empowerment). We modeled low (30%) and high (70%) intervention uptake and reported HIV outcomes including cumulative infections over 2025-2050.</p><p><strong>Results: </strong>Modeled HIV prevalence among inherited widowed women was 59.8% (95% CI: 59.5-60.2%), comparable to observed prevalence of 64.1% (95% CI: 63.2-65.4%). Among all widowed women, biomedical interventions averted 2.0% (95% CI: 1.3-2.6%) of HIV infections with low uptake and 2.6% (95% CI: 2.0-3.2%) with high uptake. Combined biomedical and structural interventions averted 7.8% (95% CI: 7.2-8.4%) of HIV infections with low uptake and 16.1% (95% CI: 15.5-16.6%) with high uptake. Impacts were smaller for men, e.g., high-uptake structural and biomedical interventions averted 1.8% (95% CI: 1.5-2.2%) of infections among cleansers and 2.7% (95% CI: 2.4-3.0%) among inheritors.</p><p><strong>Conclusions: </strong>Widowed women are a vulnerable population with extremely high HIV prevalence. Combined biomedical and structural interventions focused on the practice of widow cleansing and wife inheritance have the potential to avert up to one-quarter of HIV infections among widowed women, and a smaller proportion among men participating in these practices.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"88"},"PeriodicalIF":7.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405724","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 : 2025-02-12DOI: 10.1186/s12916-025-03855-z
Mya Polkamp, Nhan H T Pham, Wilson K M Wong, Hrishikesh P Hardikar, Pooja S Kunte, Morven A Cameron, Anandwardhan A Hardikar, Mugdha V Joglekar
{"title":"Tear-fluid-derived biomarkers of ocular complications in diabetes: a systematic review and meta-analysis.","authors":"Mya Polkamp, Nhan H T Pham, Wilson K M Wong, Hrishikesh P Hardikar, Pooja S Kunte, Morven A Cameron, Anandwardhan A Hardikar, Mugdha V Joglekar","doi":"10.1186/s12916-025-03855-z","DOIUrl":"10.1186/s12916-025-03855-z","url":null,"abstract":"<p><strong>Background: </strong>Early identification and management of sight-threatening ocular complications of diabetes using imaging or molecular biomarkers could help prevent vision loss. However, access to specialized infrastructure and expertise is limited, especially in remote areas of the world. Tear-fluid may offer an easier, non-invasive, and localized screenshot of ocular disease. To the best of our knowledge, there is no systematic review and meta-analysis on tear-fluid-based biomarkers for ocular complications in diabetes.</p><p><strong>Methods: </strong>Articles were extracted from PubMed, Embase, Medline, and Web of Science using the MeSH and Emtree terms. The keywords include (diabetes), (diabetic retinopathy), (diabetes mellitus, type 1), (diabetes mellitus, type 2), (insulin-dependent diabetes), (insulin resistant diabetes), (tears), (lacrimal fluid), (biological marker), and (biomarker, marker). Concentrations of tear-fluid biomarkers in individuals with diabetes, diabetic ocular complications, and healthy controls were extracted and standardized mean differences (SMDs) and 95% CIs were calculated. Heterogeneity was assessed using subgroup and leave-one-out sensitivity analyses. Publication and risk of bias were performed using the Egger's test and Cochrane guidelines. The quality of evidence was evaluated using the Newcastle-Ottawa scale.</p><p><strong>Results: </strong>Nine hundred eleven papers were identified, 19 of which met the study criteria and were included in the meta-analysis. Participants (n = 1413) belonged to three groups: healthy controls (Controls), diabetes without any complications (Diabetes), and diabetes with ocular complications (Complications). Actual concentrations were reported for TNF-α, VEGF, IL-1RA, IL-1β, IL-6, IL-8, lactoferrin, lysozyme, and MCP-1 in at least three different studies. Meta-analyses demonstrated that TNF-α concentration was significantly higher in the tear-fluid of Complications group when compared to Controls (SMD = - 1.08, 95% CIs = - 1.78, - 0.38, p = 0.003) or when compared to Diabetes (SMD = - 0.78, 95% CIs = - 1.48, - 0.09, p = 0.03). However, it was not different when Controls were compared to Diabetes (SMD = - 1.00, 95% CIs = - 2.27, 0.28, p = 0.13). VEGF demonstrated a similar trend indicating specificity of tear-fluid TNF-α and VEGF for diabetic ocular complications.</p><p><strong>Conclusions: </strong>Across all biomolecules meta-analyzed in this study, TNF-α and VEGF were identified as the most important biomarkers that could potentially offer a non-invasive tear-fluid-based assessment of progression to ocular complications in diabetes, especially in rural and remote areas where diabetes-related expertise and infrastructure are limited.</p><p><strong>Trial registration: </strong>PROSPERO (CRD42023441867) https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=441867 .</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"84"},"PeriodicalIF":7.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405728","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 : 2025-02-12DOI: 10.1186/s12916-025-03932-3
Shoujiang You, Danni Zheng, Yanan Wang, Qiang Li, Tu N Nguyen, Ruth Peters, Xiaoying Chen, Xia Wang, Yongjun Cao, Diederick E Grobbee, Stephen Harrap, Giuseppe Mancia, Bryan Williams, Neil R Poulter, Liu Lisheng, Michel Marre, Pavel Hamet, Craig S Anderson, Mark Woodward, John Chalmers, Katie Harris
{"title":"Healthy lifestyle factors and combined macrovascular and microvascular events in diabetes patients with high cardiovascular risk: results from ADVANCE.","authors":"Shoujiang You, Danni Zheng, Yanan Wang, Qiang Li, Tu N Nguyen, Ruth Peters, Xiaoying Chen, Xia Wang, Yongjun Cao, Diederick E Grobbee, Stephen Harrap, Giuseppe Mancia, Bryan Williams, Neil R Poulter, Liu Lisheng, Michel Marre, Pavel Hamet, Craig S Anderson, Mark Woodward, John Chalmers, Katie Harris","doi":"10.1186/s12916-025-03932-3","DOIUrl":"10.1186/s12916-025-03932-3","url":null,"abstract":"<p><strong>Background: </strong>To explore whether healthy lifestyle factors (HLFs) predict a lower risk of major macrovascular and microvascular events and death in people with type 2 diabetes (T2D) with a high risk of vascular complications.</p><p><strong>Methods: </strong>Post hoc analyses of 11,133 participants with T2D in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial who were assigned a score ranging from 0 to 4 based on the number of baseline HLFs: never smoked, moderate-to-vigorous physical activity, ideal waist/hip ratio, and low-to-moderate alcohol consumption. Multivariable Cox models were used to determine associations of 0, 1, 2, and ≥ 3 HLFs with vascular events and all-cause mortality.</p><p><strong>Results: </strong>Compared to participants with no HLFs, hazard ratios for participants with 3 or 4 HLFs were 0.68 (95% confidence interval [CI] 0.57-0.81) for the composite of major macrovascular or microvascular events, 0.58 (0.46-0.75) for major macrovascular events, 0.78 (0.61-0.99) for microvascular events, and 0.48 (0.37-0.63) for all-cause mortality during a median follow-up of 5 years. Each increment in HLF score was significantly associated with lower rates of these outcomes. There was no heterogeneity in the effect on any outcome by HLF across randomized intensive blood glucose control and blood pressure lowering treatments.</p><p><strong>Conclusions: </strong>HLFs are associated with lower risks of major macrovascular and microvascular events and lower rates of death in high-risk adults with T2D.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"87"},"PeriodicalIF":7.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405723","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 : 2025-02-12DOI: 10.1186/s12916-025-03907-4
Samuel M Mwalili, Duncan K Gathungu, Josiline Chemutai, Evalyne Musyoka, Daniel Bridenbecker, Clark Kirkman, David Kaftan, Hae-Young Kim, Ingrida Platais, Anna Bershteyn
{"title":"Estimated contributions and future mitigation strategies for HIV risk around funeral practices in western Kenya: a mathematical modeling study.","authors":"Samuel M Mwalili, Duncan K Gathungu, Josiline Chemutai, Evalyne Musyoka, Daniel Bridenbecker, Clark Kirkman, David Kaftan, Hae-Young Kim, Ingrida Platais, Anna Bershteyn","doi":"10.1186/s12916-025-03907-4","DOIUrl":"10.1186/s12916-025-03907-4","url":null,"abstract":"<p><strong>Background: </strong>A disco matanga, or \"disco funeral,\" is a celebration of a decedent's life that is culturally important in parts Africa, often involving overnight travel and alcohol consumption. These are known risk factors for HIV, which is prevalent in many areas where disco matanga is practiced. However, the contribution of disco matanga to HIV transmission is not well-understood. We used agent-based network modeling to estimate how disco matanga impacted HIV transmission, and to explore the impact of relevant biomedical, biobehavioral, and structural interventions to reduce HIV risk.</p><p><strong>Methods: </strong>We adapted EMOD-HIV, a previously validated network-based model of HIV in the Nyanza region of Kenya, to incorporate disco matanga assumptions informed by literature review. Occurrence of disco matanga was modeled to occur following any death in the population. We compared past HIV incidence (1980-2024) with and without incorporating disco matanga, and future HIV incidence (2025-2050) with different interventions for disco matanga attendees: (1) biomedical (HIV prophylaxis), (2) biobehavioral (reduction in condomless sex partners), (3) structural (female empowerment to avoid unwanted sex). We estimated HIV infections and deaths averted in the overall population, with sensitivity analysis around intervention uptake.</p><p><strong>Results: </strong>Over 1980-2024, disco matanga contributed 7.8% (95% CI: 5.5-9.3%) of all HIV infections, an effect that peaked at 9.9% (95% CI: 6.4-12.0%) in the year 2004, coinciding with a peak in all-cause mortality due to HIV/AIDS. Biomedical prevention at disco matanga could avert up to 9.7% (95% CI: 8.9-10.5%) of adult HIV infections and 2.3% (95% CI: 1.9-2.6%) of deaths; biobehavioral 2.9% (95% CI: 2.1-3.6%) of infections and 0.9% (95% CI: 0.6-1.2%) of deaths; and structural 1.2% (95% CI: 0.5-1.8%) of infections and 0.5% (95% CI: 0.2-0.7%) of deaths. Results were highly sensitive to intervention uptake.</p><p><strong>Conclusions: </strong>We conducted the first modeling study, to our knowledge, simulating the interactions between disco matanga, HIV/AIDS, and intervention options. We found that biomedical, biobehavioral, or structural interventions implemented during disco matanga could substantially reduce HIV transmission and mortality in the Nyanza region. Research is needed to understand the feasibility and acceptability of HIV interventions tailored to local cultural practices.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"85"},"PeriodicalIF":7.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405722","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 : 2025-02-12DOI: 10.1186/s12916-025-03921-6
Shramana Deb, Ritwick Mondal, Purbita Sen, Dipanjan Chowdhury, Shramana Sarkar, Granthik Banerjee, Vramanti Sarkar, Anjan Chowdhury, Julián Benito-León
{"title":"Neuroinflammatory disorders of the central nervous system associated with monkeypox virus: a systematic review and call to action.","authors":"Shramana Deb, Ritwick Mondal, Purbita Sen, Dipanjan Chowdhury, Shramana Sarkar, Granthik Banerjee, Vramanti Sarkar, Anjan Chowdhury, Julián Benito-León","doi":"10.1186/s12916-025-03921-6","DOIUrl":"10.1186/s12916-025-03921-6","url":null,"abstract":"<p><strong>Background: </strong>Monkeypox virus (MPXV) has emerged as a significant global health concern with outbreaks worldwide. While MPXV is primarily known for its dermatological and systemic manifestations, it can also cause central nervous system (CNS) complications. This systematic review describes the demographic, clinical, diagnostic, and therapeutic characteristics of MPXV-associated CNS neuroinflammatory disorders.</p><p><strong>Methods: </strong>We systematically reviewed the literature to identify cases of MPXV-associated CNS neuroinflammatory disorders. Data on demographics, systemic and neurological manifestations, diagnostic methods, treatment strategies, and outcomes were extracted and analyzed.</p><p><strong>Results: </strong>Eighteen cases of MPXV-associated neuroinflammatory disorders were identified. The mean age of patients was 27.8 years (range: 28 days to 43 years), with a male predominance (66.7%). Diagnosis included The most common diagnoses were acute disseminated encephalomyelitis in nine cases (50.0%), encephalitis/meningoencephalitis in seven cases (38.9%, isolated transverse myelitis in one case (5.6%), and transverse myelitis with encephalitis in one case (5.6%). The latency between the onset of systemic symptoms and neurological involvement averaged 6.2 days. MPXV detection was confirmed in 13 of 18 (72.2%) cases, primarily using quantitative real-time polymerase chain reaction from various biological specimens. Among the 12 cases with documented treatment, the most commonly administered therapies were tecovirimat (58.3%) and intravenous methyl-prednisolone (66.7%). Outcomes were reported in 17 cases, with complete recovery in 29.4%, partial recovery in 41.2%, and death in 29.4% of patients.</p><p><strong>Conclusions: </strong>MPXV-associated neuroinflammatory disorders of the CNS are rare but cause significant complications. The findings underscore the need for clinical vigilance, advanced diagnostic approaches, and targeted therapeutic strategies. Further research is essential to elucidate mechanisms underlying MPXV neurovirulence and develop effective treatments for these life-threatening conditions.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"86"},"PeriodicalIF":7.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405726","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 : 2025-02-11DOI: 10.1186/s12916-025-03914-5
Louise E van Eekeren, Nadira Vadaq, Marc J T Blaauw, Albert L Groenendijk, Wilhelm A J W Vos, Erni J Nelwan, Annelies Verbon, Janneke E Stalenhoef, Marvin A H Berrevoets, Jan van Lunzen, Mihai G Netea, Gert Weijers, Niels P Riksen, Joost H W Rutten, Quirijn de Mast, Eric T T L Tjwa, Leo A B Joosten, André J A M van der Ven
{"title":"Distinct metabolic perturbations link liver steatosis and incident CVD in lean but not obese PWH.","authors":"Louise E van Eekeren, Nadira Vadaq, Marc J T Blaauw, Albert L Groenendijk, Wilhelm A J W Vos, Erni J Nelwan, Annelies Verbon, Janneke E Stalenhoef, Marvin A H Berrevoets, Jan van Lunzen, Mihai G Netea, Gert Weijers, Niels P Riksen, Joost H W Rutten, Quirijn de Mast, Eric T T L Tjwa, Leo A B Joosten, André J A M van der Ven","doi":"10.1186/s12916-025-03914-5","DOIUrl":"10.1186/s12916-025-03914-5","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a key risk factor for cardiovascular disease (CVD), potentially driven by shared metabolic mechanisms. Metabolic perturbations associated with MASLD and CVD remain underexplored in people with HIV (PWH).</p><p><strong>Methods: </strong>We used data from the longitudinal multicenter 2000HIV study comprising 1895 virally suppressed PWH, out of which 970 had available liver and carotid artery measurements. Transient elastography with controlled attenuation parameter (CAP) was performed for the assessment of liver steatosis (CAP > 263 dB/m) and fibrosis (LSM ≥ 7.0). Historic and future incident CVD within 2-year follow-up, defined as myocardial infarction, stroke, peripheral arterial disease, and angina pectoris, were extracted from the medical files, while atherosclerotic plaque(s) in the carotid arteries were assessed using ultrasonography. Metabolic perturbations were analyzed using mass spectrometry-based untargeted metabolomics (n = 500 metabolites) and nuclear magnetic resonance spectroscopy for targeted lipids and other metabolites (n = 246 metabolites).</p><p><strong>Results: </strong>PWH with liver steatosis were more likely to have arterial plaques (47% vs. 36%; P value = 0.003) and CVD history (11% vs. 6.8%; P value = 0.021) than PWH without liver steatosis. These associations were only significant in lean PWH, in contrast to those with BMI ≥ 25 kg/m<sup>2</sup>. Metabolic pathways associated with liver steatosis and fibrosis primarily involved lipid and amino acid metabolism, and they were validated by targeted lipoproteomic measurements. Interestingly, metabolomic pathways and lipoproteomic signatures associated with MASLD were mostly distinct from those associated with CVD parameters. However, several metabolic pathways were shared, especially in lean PWH. These include arachidonic acid metabolism and formation of prostaglandin, purine metabolism, cholecalciferol metabolism, and glycine, serine, alanine, and threonine metabolism.</p><p><strong>Conclusion: </strong>Metabolic disturbances linked to liver steatosis and CVD diverge across BMI categories in PWH. Lean PWH, unlike their overweight/obese counterparts, show common metabolic perturbations between MASLD and CVD, particularly involving arachidonic acid metabolism. This suggests that lean PWH with liver steatosis may face a heightened risk of CVD due to shared metabolic pathways, potentially opening avenues for targeted interventions, such as aspirin therapy, to mitigate this risk.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"78"},"PeriodicalIF":7.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398196","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 : 2025-02-11DOI: 10.1186/s12916-025-03899-1
Shuhui Yin, Simu Huang, Peng Xue, Zhuoran Xu, Zi Lian, Chenfei Ye, Siyuan Ma, Mingxuan Liu, Yuanjia Hu, Peiyi Lu, Chihua Li
{"title":"Generative artificial intelligence (GAI) usage guidelines for scholarly publishing: a cross-sectional study of medical journals.","authors":"Shuhui Yin, Simu Huang, Peng Xue, Zhuoran Xu, Zi Lian, Chenfei Ye, Siyuan Ma, Mingxuan Liu, Yuanjia Hu, Peiyi Lu, Chihua Li","doi":"10.1186/s12916-025-03899-1","DOIUrl":"10.1186/s12916-025-03899-1","url":null,"abstract":"<p><strong>Background: </strong>Generative artificial intelligence (GAI) has developed rapidly and been increasingly used in scholarly publishing, so it is urgent to examine guidelines for its usage. This cross-sectional study aims to examine the coverage and type of recommendations of GAI usage guidelines among medical journals and how these factors relate to journal characteristics.</p><p><strong>Methods: </strong>From the SCImago Journal Rank (SJR) list for medicine in 2022, we generated two groups of journals: top SJR ranked journals (N = 200) and random sample of non-top SJR ranked journals (N = 140). For each group, we examined the coverage of author and reviewer guidelines across four categories: no guidelines, external guidelines only, own guidelines only, and own and external guidelines. We then calculated the number of recommendations by counting the number of usage recommendations for author and reviewer guidelines separately. Regression models examined the relationship of journal characteristics with the coverage and type of recommendations of GAI usage guidelines.</p><p><strong>Results: </strong>A higher proportion of top SJR ranked journals provided author guidelines compared to the random sample of non-top SJR ranked journals (95.0% vs. 86.7%, P < 0.01). The two groups of journals had the same median of 5 on a scale of 0 to 7 for author guidelines and a median of 1 on a scale of 0 to 2 for reviewer guidelines. However, both groups had lower percentages of journals providing recommendations for data analysis and interpretation, with the random sample of non-top SJR ranked journals having a significantly lower percentage (32.5% vs. 16.7%, P < 0.05). A higher SJR score was positively associated with providing GAI usage guidelines for both authors (all P < 0.01) and reviewers (all P < 0.01) among the random sample of non-top SJR ranked journals.</p><p><strong>Conclusions: </strong>Although most medical journals provided their own GAI usage guidelines or referenced external guidelines, some recommendations remained unspecified (e.g., whether AI can be used for data analysis and interpretation). Additionally, journals with lower SJR scores were less likely to provide guidelines, indicating a potential gap that warrants attention. Collaborative efforts are needed to develop specific recommendations that better guide authors and reviewers.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"77"},"PeriodicalIF":7.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398200","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 : 2025-02-11DOI: 10.1186/s12916-025-03923-4
Shouling Wu, Yanxiu Wang, Jiangshui Wang, Jun Feng, Furong Li, Liming Lin, Chunyu Ruan, Zhifang Nie, Jinwei Tian, Cheng Jin
{"title":"Modifiable factors and 10-year and lifetime cardiovascular disease risk in adults with new-onset hypertension: insights from the Kailuan cohort.","authors":"Shouling Wu, Yanxiu Wang, Jiangshui Wang, Jun Feng, Furong Li, Liming Lin, Chunyu Ruan, Zhifang Nie, Jinwei Tian, Cheng Jin","doi":"10.1186/s12916-025-03923-4","DOIUrl":"10.1186/s12916-025-03923-4","url":null,"abstract":"<p><strong>Background: </strong>Preventing cardiovascular disease (CVD) in adults with hypertension is essential, but it remains uncertain whether optimizing modifiable factors can eliminate the excess CVD risk associated with new-onset hypertension.</p><p><strong>Methods: </strong>In this prospective cohort study, 29,597 adults with new-onset hypertension and no prior CVD (from 2006-2016 surveys) were each matched by age and sex to a normotensive control. Eight modifiable factors were assessed using the American Heart Association's Life's Essential 8 algorithm. We followed participants for incident CVD until December 2020, estimating 10-year and lifetime (age 25-95) CVD risks using the Fine-Gray competing risks model.</p><p><strong>Results: </strong>Over a median follow-up of 9.81 years, adults with new-onset hypertension had higher 10-year (8.97% vs. 6.31%) and lifetime CVD risks (45.55% vs. 34.98%) compared to normotensive controls. After adjusting for age, sex, and other unmodifiable factors, each additional favorable factor was associated with a stepwise reduction in CVD risk (P-trend < 0.05). Hypertensive participants with four or more favorable factors had a 17% lower 10-year CVD risk (HR 0.83; 95% CI 0.72-0.97) and a similar lifetime CVD risk (HR 0.90; 95% CI 0.78-1.05) compared to normotensive controls. Notably, the protective effect was weaker among those with early-onset (before age 45) hypertension than those with later-onset (age ≥ 60) hypertension (P-interaction < 0.05).</p><p><strong>Conclusions: </strong>In adults with new-onset hypertension, maintaining four or more modifiable factors at favorable levels was associated with a CVD risk comparable to that of normotensive individuals. However, young hypertensive adults may require more aggressive interventions to mitigate CVD risk.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"80"},"PeriodicalIF":7.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398208","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}