BMC Medicine最新文献

{"title":"The effectiveness of digital therapeutics in improving sleep quality: a systematic review and network meta-analysis.","authors":"Zihang Tong, Guancheng Ye, Shun Fan, Yusheng Li, Jiacheng Zhang, Haining Zhang, Qiaoling Chen, Hongyi Wang, Huanan Li, Jingui Wang","doi":"10.1186/s12916-026-05129-8","DOIUrl":"10.1186/s12916-026-05129-8","url":null,"abstract":"<p><strong>Background: </strong>Insomnia is a prevalent global sleep disorder. Digital therapeutics, delivered via online platforms, offer novel intervention options. However, existing systematic reviews largely focus on validating individual digital therapeutics, with limited comparative evidence across different types within a unified network. This network meta-analysis aims to evaluate the comparative effectiveness of various digital therapeutics on sleep quality, thereby providing evidence-based guidance for clinical decision-making in insomnia management.</p><p><strong>Methods: </strong>PubMed, Cochrane Library, Embase, and Web of Science were systematically searched and included eligible randomized controlled trials (RCTs). Outcomes included the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), sleep diary and objective sleep parameters. Sleep diary parameters included subjective total sleep time (sTST), subjective wake after sleep onset (sWASO), subjective sleep onset latency (sSOL), and subjective sleep efficiency (sSE); objective sleep parameters included total sleep time (TST), wake after sleep onset (WASO), sleep efficiency (SE), and sleep onset latency (SOL). Furthermore, the minimal clinically important difference (MCID) was employed to evaluate the clinical relevance of all outcomes.</p><p><strong>Results: </strong>A total of 96 RCTs comprising 18,419 participants were included, assessing 6 digital therapeutics: digital cognitive behavioral therapy (dCBT), digital brief behavioral therapy (dBBT), digital mindfulness-based therapy (dMBT), circadian rhythm support (CRS), virtual reality (VR), and tele-neurofeedback (NFB). Quality assessment of the included studies revealed that 2 low risk, 79 some concerns, 15 high risk. Network meta-analysis indicated that, compared with control treatment (CT), dCBT likely resulted in a significant decrease in ISI score (MD: -4.24 points, 95% CI: -4.83 to - 3.65; moderate-certainty evidence), a reduction in PSQI score (MD: -2.28 points, 95% CI: -2.88 to - 1.68; low-certainty evidence), shortened sSOL (MD: -12.57 min, 95% CI: -15.14 to - 10.00; low-certainty evidence), improved sSE (MD: 7.27%, 95% CI: 5.77 to 8.77; low-certainty evidence), and reduced sWASO (MD: -17.19 min, 95% CI: -20.96 to - 13.41; low-certainty evidence). dMBT significantly reduced ISI score (MD: -2.28 points, 95% CI: -4.00 to - 0.55; low-certainty evidence) and shortened SOL (MD: -7.96 min, 95% CI: -15.50 to - 0.42; moderate-certainty evidence). Based on an inconsistency model, VR substantially reduced WASO (MD: -13.38 min, 95% CI: -24.40 to - 2.36; moderate-certainty evidence). Of these findings, only dCBT reached the MCID for ISI improvement. NFB, dBBT, and CRS did not demonstrate statistically significant effects relative to CT for any of the outcomes. Given the constraints in the number of studies and sample sizes, the findings derived from objective outcomes warrant cautious interpretation.</p><p><stro","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073171","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":"Public health policy should be grounded in established evidence that acknowledges uncertainty: a response to The Lancet series on ultra-processed foods.","authors":"Daniel B Ibsen, Michael Fridén, Georgia D Tomova, Natalia Ortega, Peter W G Tennant","doi":"10.1186/s12916-026-05214-y","DOIUrl":"10.1186/s12916-026-05214-y","url":null,"abstract":"<p><strong>Background: </strong>The recent three-part Lancet series on ultra-processed foods (UPFs) argued that the displacement of traditional diets by UPFs is a major driver of poor diet quality and diet-related chronic diseases, which is becoming a major public health challenge worldwide. This Debate article aims to highlight key uncertainties surrounding that evidence base and the causal interpretation of the reported associations.</p><p><strong>Main body: </strong>We discuss uncertainties related to three core questions central for making causal claims: what are UPFs, what are the mechanisms and what is the right comparison group? We argue that the breadth of the Nova classification system as an exposure framework encompasses nutritionally and functionally diverse foods that are unlikely to share common biological effects. This heterogeneity complicates causal inferences and risks conflating well-established dietary risk factors with more speculative attributes related to processing, additives, and food structure. Many of the proposed mechanisms linking UPFs to adverse health outcomes are not unique to ultra-processing and may operate similarly across foods regardless of processing level. While much emphasis has been given to the comparison between minimally processed and UPF, the comparison between processed food and UPF may better isolate the effects of ultra-processing. By embracing these uncertainties, we outline a way forward focusing on disaggregation of UPFs into specific components and characteristics.</p><p><strong>Conclusions: </strong>Advancing the evidence base in this way will support clearer attribution of risk and more targeted interventions. Public health policy should remain grounded in well-characterised dietary exposures while transparently acknowledging uncertainty around ultra-processing as an independent causal factor.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069135","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":"Major adverse cardiac events and mortality associated with ADHD and its treatment in adults with type 2 diabetes: a multi-national cohort study.","authors":"Zihan Dong, Yiling Zhou, Honghui Yao, Shengxin Liu, Aske Astrup, Anders Engeland, Le Gao, Malcolm B Gillies, Astrid Lunde, Yanli Zhang-James, Masako Araki, Isabell Brikell, Agnieszka Butwicka, Søren Dalsgaard, Brian M D'Onofrio, Stephen V Faraone, Soffia Gudbjornsdottir, Jan Haavik, Ralf Kuja-Halkola, Kari Klungsøyr, Henrik Larsson, Kenneth K C Man, Sallie-Anne Pearson, Dina Sarsembayeva, Melissa Vos, Ian C K Wong, Helga Zoega, Harold Snieder, Catharina A Hartman, Zheng Chang, Ebba Du Rietz","doi":"10.1186/s12916-026-05246-4","DOIUrl":"10.1186/s12916-026-05246-4","url":null,"abstract":"<p><strong>Background: </strong>Attention-deficit/hyperactivity disorder (ADHD) has been linked to elevated risk of type 2 diabetes (T2D). However, the impact of ADHD and ADHD medication use on prognosis and health outcomes in T2D remains unclear. This study investigates the associations of (1) ADHD and (2) ADHD medication use with rates of major adverse cardiac events (MACE) and all-cause mortality after a T2D diagnosis.</p><p><strong>Methods: </strong>This multinational cohort study used population-based data from Australia, Denmark, the Netherlands, Norway, Sweden, the United Kingdom, and the United States. Using a standardized analytical protocol, we identified adults with a first recorded T2D diagnosis during 2010-2020. Exposures were (1) ADHD, defined by a recorded ADHD diagnosis or ADHD medication dispensation, and (2) among adults with ADHD, the use of ADHD medication, both analysed as time-varying exposures. Main outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular disease-related death) and all-cause mortality after T2D diagnosis. Cause-specific Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs); results were pooled using random-effects meta-analyses and stratified by age and sex.</p><p><strong>Results: </strong>The cohort included 1,929,027 adults with T2D (909,176 [47.1%] males). In pooled analyses, adults with T2D and ADHD had a higher rate of all-cause mortality (HR, 2.42; 95% CI, 1.72-3.41), but not MACE (HR, 1.04; 95% CI, 0.81-1.35), after a T2D diagnosis compared with those without ADHD. Among adults with T2D and ADHD, ADHD medication use was associated with higher rate of MACE in those diagnosed with T2D before age 45 years (HR, 1.58; 95% CI, 1.18-2.10). These associations remained consistent, after adjusting for sex, age, calendar year at T2D diagnosis, psychiatric history, other psychotropic medication use, and cardiometabolic medication use.</p><p><strong>Conclusions: </strong>Adults with T2D and co-occurring ADHD were found to have increased risk of all-cause mortality after T2D diagnosis, while ADHD was not consistently associated with MACE across countries. ADHD medication use was linked to higher rate of MACE in adults with early-onset T2D. These findings suggest the potential need for integrated somatic-psychiatric care and careful consideration of ADHD medication use that may help reduce MACE and mortality, particularly in younger-onset T2D.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073168","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":"3D bioprinted human vascular organoid sheets promote functional ischemic repair and exhibit adaptive in vivo remodeling.","authors":"Xinyu Fu, Li Yan, Zhaosen Chen, Bohan Dou, Dezhi Zhou, Xinyao Zhou, Kengyuan Qu, Che Gao, Peiliang Wang, Fengzhi Zhang, Zihao Zou, Taoxia Wang, Guiying Li, Liliang Ouyang, Jie Na","doi":"10.1186/s12916-026-05256-2","DOIUrl":"10.1186/s12916-026-05256-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ischemic vascular diseases remain a major clinical challenge, creating a need for engineered vascular tissues that can establish functional vascular networks and promote durable tissue repair. Conventional vascular organoids offer limited control over cellular composition and spatial organization, while the fate and adaptive remodeling of graft-derived human vascular cells after transplantation remain poorly understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Human vascular organoid sheets (hVOS) were constructed by extrusion-based three-dimensional (3D) bioprinting of human pluripotent stem cell (hPSC)-derived endothelial cells (ECs) and smooth muscle cells (SMCs) at a defined ratio within a gelatin methacryloyl (GelMA)-based bioink under chemically defined conditions. Vascular organization and cellular states were characterized using functional assays, immunofluorescence imaging, and single-cell RNA sequencing (scRNA-seq). Therapeutic efficacy and graft remodeling were evaluated in a murine hindlimb ischemia model using laser speckle perfusion imaging, histological analysis, intravital two-photon imaging, and scRNA-seq of recovered graft-derived human cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Co-bioprinting ECs and SMCs accelerated vascular network formation and generated stable, interconnected vascular structures that underwent progressive maturation during culture. scRNA-seq identified diverse vascular and stromal populations and revealed transcriptional programs associated with vascular maturation, mechanotransduction, and hypoxic adaptation. Following transplantation, hVOS significantly improved blood perfusion, increased limb salvage, and promoted ischemic tissue repair. Intravital imaging detected circulating dextran within GFP-labeled hVOS-derived vascular structures at days 14 and 28, demonstrating perfusion of graft-derived vascular structures by the host circulation. Post-transplantation scRNA-seq revealed substantial adaptive remodeling of graft-derived ECs toward venous-biased and inflammatory states, accompanied by activation of NF-κB- and stress-associated programs. Transplanted SMCs and fibroblasts also exhibited coordinated transcriptional changes associated with wound healing and extracellular matrix remodeling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;hVOS provide a reproducible and design-flexible 3D-bioprinted vascular tissue platform that enables controlled multicellular organization and formation of prevascularized constructs while supporting vascular integration and ischemic tissue repair in vivo. Single-cell analyses further reveal substantial adaptive remodeling of graft-derived vascular and stromal cells following transplantation. These findings support hVOS as a versatile platform for vascular regenerative medicine and for investigating the in vivo behavior of engineered human vascular tissues. Graphical abstract illustrating the generation and therapeutic application of human vascular organoid sheets ","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073595","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":"Biological signature of dietary patterns in older adults: findings from a population-based study.","authors":"Rachel Ann DaCosta, Caterina Gregorio, Amaia Calderón-Larrañaga, Alice Margherita Ornago, Anja Mrhar, Rosario Ortolá, Claudia Fredolini, Davide Liborio Vetrano, Adrián Carballo-Casla","doi":"10.1186/s12916-026-05202-2","DOIUrl":"10.1186/s12916-026-05202-2","url":null,"abstract":"<p><strong>Background: </strong>Diet quality is a key modifiable factor influencing age-related health outcomes, yet its impact on the biological mechanisms involved in the aging process is not fully understood. This study aimed to identify the blood-based biomarkers most strongly associated with adherence to diverse dietary patterns and to describe the pathophysiological domains they belong to.</p><p><strong>Methods: </strong>We analysed data from 1,769 participants aged ≥ 60 years from the population-based Swedish National Study on Aging and Care in Kungsholmen. Dietary intake was assessed using validated food frequency questionnaires. Diet quality was evaluated using adherence to the Alternative Mediterranean Diet (AMED), the Alternative Healthy Eating Index (AHEI), and the reverse-transformed Empirical Dietary Inflammatory Index (rEDII). Fifty-four blood biomarkers spanning metabolic, inflammatory, vascular, and neurodegenerative domains were analysed. Cross-sectional associations between adherence to the dietary patterns and standardized biomarker levels were examined using quantile regression, adjusted for sociodemographic and lifestyle factors.</p><p><strong>Results: </strong>After multiple comparison correction, at the median level of each biomarker distribution, higher adherence (1 standard deviation increment) to the AMED was directly associated with folic acid levels [beta coefficient (95% confidence interval) = 0.066 (0.033, 0.099)] and inversely with glial fibrillary acidic protein [-0.018 (-0.030, -0.006)]. Higher AHEI adherence showed direct association with folic acid levels [0.068 (0.035,0.100)] and inverse with growth differentiation factor 15 levels [-0.063 (-0.098, -0.029)]. Higher adherence to the rEDII was inversely associated with leptin [-0.094 (-0.139, -0.049)], insulin [-0.086 (-0.130, -0.043)], growth differentiation factor 15 [-0.064 (-0.100, -0.027)], alkaline phosphatase [-0.078 (-0.122, -0.033)], tumour necrosis factor receptor superfamily member 1B [-0.047 (-0.076, -0.019)], and leukocytes [-0.058 (-0.092, -0.024)]. Associations remained consistent across multiple sensitivity analyses.</p><p><strong>Conclusions: </strong>Higher diet quality is associated with favourable levels of blood-based biomarkers in older adults, with distinct associations within the metabolic and inflammatory domains, supporting the role of diet in promoting healthier aging.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058464","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":"Effectiveness of structured lactation support and human donor milk banking in German NICUs: a stepped-wedge cluster-randomized trial.","authors":"Juliane Köberlein-Neu, Nicola Gabriela Dymek, Viola Zimmer, Trutz Bommhardt, Anna Katharina Stirner, Isabella Güldenring, Tim Ohnhäuser, Daniel Wiesen, Till Dresbach, Nadine Scholten","doi":"10.1186/s12916-026-05211-1","DOIUrl":"10.1186/s12916-026-05211-1","url":null,"abstract":"<p><strong>Background: </strong>Although exclusive human milk feeding is beneficial for very low birth weight infants, rates remain suboptimal globally. This hybrid type 1 effectiveness-implementation trial evaluated structured lactation support combined with human donor milk banking in neonatal intensive care units (NICUs), primarily assessing effectiveness, with secondary assessment of implementation and economic outcomes.</p><p><strong>Methods: </strong>We conducted a stepped-wedge cluster-randomized trial in 15 German Level I NICUs (April 2022-March 2024). The Neo-MILK intervention comprised structured lactation counselling, multilingual materials, mobile app support for mothers/parents, and human donor milk banking. Implementation strategies included video-based staff training, guidelines, commitment nudges for medical staff, and support for human donor milk bank establishment. The primary outcome was exclusive mother's own milk feeding at NICU discharge. Secondary outcomes included feeding status categories, clinical complications, length of stay, and maternal outcomes. Implementation outcomes were acceptability, feasibility, appropriateness, fidelity, and sustainability. Prespecified subgroup analyses examined birth weight (< 1,000 g vs. ≥1,000 g) and illness severity (CRIB ≥ 11 vs. <11). Economic evaluation employed time-driven activity-based costing and budget impact analysis.</p><p><strong>Results: </strong>Among 1,627 very low birth weight infants (831 intervention, 796 control), the intervention increased exclusive mother's own milk feeding at discharge by 11%-points (95% CI: 3.0 to 19.0; p = 0.007) from a 43% baseline. Exclusive formula feeding decreased correspondingly. Subgroup analyses showed no significant effects in extremely low birth weight infants (< 1,000 g) or high-risk infants (CRIB ≥ 11). Clinical complications and length of stay showed no differences. Acceptability, appropriateness, and feasibility were high. Fidelity was sufficient, with prepartal counselling delivered as intended in 71% of cases. Human donor milk banks were established in 40% of sites. Sustainability indicators were promising, with 61% of staff reporting routine integration. Economic evaluation suggested potential net savings nationally in the base-case scenario.</p><p><strong>Conclusions: </strong>Structured lactation support with human donor milk banking increased exclusive mother's own milk feeding across Level I NICUs, with no observed increase in complications or costs. Implementation appeared feasible, with indications of sustainability. Variable uptake and differential effects in highest-risk subgroups highlight the need for ongoing organizational support and tailored strategies to further optimize effectiveness.</p><p><strong>Clinical trial registration: </strong>German Clinical Trials Register DRKS00025058.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988087","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":"Personal-MetaboHealth, an actionable health check in middle age, is improved by an effective lifestyle intervention in those at risk.","authors":"Niels van den Berg, Gabriela Natalle Lopes, Fatih A Bogaards, Marian Beekman, Edson Amaro Junior, P Eline Slagboom, Joris Deelen","doi":"10.1186/s12916-026-05178-z","DOIUrl":"10.1186/s12916-026-05178-z","url":null,"abstract":"<p><strong>Background: </strong>MetaboHealth represents a novel indicator of overall health in middle age and may potentially be suitable as actionable health check in prevention strategies. MetaboHealth is a blood-based metabolomic composite score that predicts a wide range of age-related conditions and mortality in large European cohorts.</p><p><strong>Methods: </strong>Here, we investigated whether MetaboHealth can be personalised and limited to clinically validated, i.e. CE-marked, metabolic biomarkers. Next, we assessed whether the updated MetaboHealth score predicts all-cause mortality and cardiometabolic disease incidence and can be improved by a lifestyle intervention. To personalise MetaboHealth, we scaled the metabolic biomarkers using a Dutch reference population (i.e. the Biobanking and BioMolecular Research Infrastructure Netherlands) and, in addition, based the score solely on clinically validated metabolic biomarkers.</p><p><strong>Results: </strong>The novel version of the score, Personal-MetaboHealth, retained predictive accuracy for all-cause mortality and showed an even stronger association with incident cardiometabolic disease in the Leiden Longevity Study (LLS) in which 2,404 participants were followed for up to 22 and 16 years for mortality and morbidity, respectively. The association of Personal-MetaboHealth with all-cause mortality remained robust after adjusting for smoking quantity, alcohol consumption, and medication use, while the cardiometabolic disease association was attenuated due to smoking quantity. Each unit increase in Personal-MetaboHealth was associated with a 13.69 year later onset of the first cardiometabolic disease in the LLS. Next, we showed that Personal-MetaboHealth can be improved by a 3-month combined lifestyle intervention in middle aged individuals (Growing Old Together study), specifically in those at risk, i.e. with an unhealthy score at baseline.</p><p><strong>Conclusions: </strong>Personal-MetaboHealth thus offers a potential actionable health check in middle age for early prevention and extension of healthy lifespan.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900487","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":"Endocannabinoid dynamics across marathon and ultramarathon running: evidence from two field studies.","authors":"Michael Siebers, Dana Huvermann, Christoph Siebers, Deborah Canales-Romero, Alexandra Florea-Ghile, Lina Keite, Lucas John, Moritz Munk, Roman Bizjak, Jens Witzel, Sebastian Schulz, Johannes Kirsten, Laura Bindila, Anke Hinney, Marijke Grau, Daniel A Bizjak, Harald Engler, Johannes Fuss","doi":"10.1186/s12916-026-05186-z","DOIUrl":"10.1186/s12916-026-05186-z","url":null,"abstract":"<p><strong>Background: </strong>Endocannabinoid (eCB) signaling has been implicated in the physiological and affective responses to endurance exercise, including phenomena such as the runner's high. However, although humans have the capacity to run for several hours and even days, evidence regarding eCB signaling is largely limited to exercise bouts shorter than 60 min. Consequently, the temporal dynamics of eCB signaling during prolonged running and the accompanying acute affective responses remain unclear.</p><p><strong>Methods: </strong>This study investigated eCB signaling during long-distance running and following a 45-minute break. Two studies were conducted: In Study 1, 19 trained runners completed both a marathon and a duration-matched walking session, with repeated blood sampling every 14 km during the marathon and after a 45-minute recovery. In Study 2, 36 ultramarathon runners completed races of 100 km, 160 km, or 230 km and provided blood samples before and after their respective races. Plasma concentrations of anandamide (AEA), 2-arachidonoylglycerol (2-AG), 1-AG, arachidonic acid (AA), and palmitoylethanolamide (PEA) were quantified by a standardized liquid chromatography/multiple reaction monitoring assay. Euphoria, anxiety, and pain were assessed as core features of the runner's high using visual analog scales.</p><p><strong>Results: </strong>AEA increased progressively throughout the marathon and remained elevated after 45 min, whereas walking elicited only modest changes. In line, after all ultramarathon distances AEA levels were increased compared with baseline. By contrast, an increase in 2-AG during exercise was observed only in the regular marathon, where concentrations rose significantly during the later stages of running and into early recovery. Elevated post-race 2-AG levels were also observed following all ultramarathon distances, consistent with a delayed, recovery-related response. Marathon running was associated with higher euphoria and lower anxiety than walking, while pain increased after 28 km of running. Ultramarathon running increased pain, reduced anxiety, and did not significantly alter euphoria post-exercise.</p><p><strong>Conclusions: </strong>Together, these findings show robust, time-dependent changes in circulating eCB concentrations during and after prolonged endurance running, as well as gradual increases in AEA during walking. These eCB dynamics occurred alongside acute affective changes during sustained endurance exercise.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872912","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":"Bladder cancer precision-cut tumor slices (PCTS) preserve functional immune microenvironment enabling ex vivo drug evaluation.","authors":"Sarah Richtmann, Maja Radak, Viktor Sincic, Jenny Hugoson, Nadja Werner, Valeriia Skoryk, Darcy Wagner, Fredrik Liedberg, Kristina Lundberg","doi":"10.1186/s12916-026-05173-4","DOIUrl":"10.1186/s12916-026-05173-4","url":null,"abstract":"<p><strong>Background: </strong>The development of effective cancer immunotherapies is hindered by the lack of preclinical models that faithfully preserve tumor-immune interactions. Current approaches provide limited representation of immune components, creating a critical translational gap between laboratory findings and clinical outcomes. Precision Cut Tumor Slices (PCTS) offer a promising solution by maintaining complete tumor architecture including native immune cell populations and spatial organization.</p><p><strong>Methods: </strong>We established a PCTS platform using fresh bladder cancer specimens and optimized culture conditions to preserve tissue integrity and cell viability. Comprehensive phenotyping was performed using flow cytometry to characterize tumor and immune cell populations. Immune functionality was validated through CD3/CD28 stimulation experiments measuring activation markers (CD69, CD137, HLA-DR) and cytokine secretion. Nine patient samples were treated with the PD-1 checkpoint inhibitor nivolumab to assess ex vivo effects. Additionally, multiplex immunofluorescence microscopy was employed on fixed PCTS as a readout for spatial distribution and cytotoxic effects of chemotherapy agents.</p><p><strong>Results: </strong>PCTS maintained viability of both cancer cells and diverse immune populations for up to six days. Functional validation demonstrated immune responsiveness upon T cell stimulation, with elevated activation markers and significantly increased secretion of inflammatory mediators including IFNγ and CXCL10, in treated as compared to control samples. The platform successfully addressed intra-tumor heterogeneity while maintaining experimental reproducibility across patient samples. Treatment with nivolumab revealed heterogeneous responses, with two out of nine samples (22%) demonstrating dose-dependent immune activation in the PCTS model, consistent with published response rates. Multiplex immunofluorescence analysis confirmed the ability to capture both immune-mediated responses and direct cytotoxic effects on cancer cells, enabling comprehensive evaluation of combination therapies.</p><p><strong>Conclusions: </strong>This validated PCTS platform represents a versatile human-derived tool for evaluating cancer immunotherapies while maintaining physiological tumor microenvironment complexity. The technical foundation established here enables future prospective studies correlating ex vivo responses with patient clinical outcomes, potentially advancing personalized treatment selection and reducing reliance on animal models in immunotherapy development.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872856","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":"24h movement behaviours in university students compared to working age and older adults: wearable-based evidence and cardiometabolic health implications.","authors":"Ju Lynn Ong, Shuo Qin, Tara H Martin, Xin Yu Chua, Chun Siong Soon, Gizem Yilmaz, Lieng Hsi Ling, Falk Müller-Riemenschneider, Woon-Puay Koh, Michael Wl Chee","doi":"10.1186/s12916-026-05192-1","DOIUrl":"10.1186/s12916-026-05192-1","url":null,"abstract":"<p><strong>Background: </strong>Physical inactivity, sedentary behaviour and inadequate sleep are established risk factors for non-communicable diseases. Although older adults are traditionally expected to be less active and more sedentary than young adults, contemporary social, occupational and educational environments may have changed this. Here, we characterised 24-hour movement behaviours (physical activity [PA], sedentary behaviour [SB], and sleep) across adulthood using wearable devices and examined their cardiometabolic correlates using a compositional data approach.</p><p><strong>Methods: </strong>Data were analysed from 1,967 adults across three Singaporean cohorts: university students (n = 500; mean[SD] age 19.9[1.3] years), working-age adults (n = 437; 41.1[10.0] years), and community-dwelling older adults (n = 1,030; 74.0[2.6] years). Each person contributed 4 weeks of Oura Ring recordings on time spent in PA, SB and sleep. BMI, body roundness index (BRI), pulse wave velocity (PWV), and a composite vascular health score (zComposite) were additionally assessed. Associations between reallocations of time across 24 h-movement behaviours and these cardiometabolic outcomes were estimated using compositional data regression models.</p><p><strong>Results: </strong>University students accumulated the most SB (mean 633.89 min/day) and the lowest PA (320.28 min/day) and sleep (431.75 min/day), whereas older adults accumulated the least SB (500.86 min/day) and greatest PA (420.28 min/day) and sleep (455.62 min/day). Working-age adults showed profiles in-between the students and older adults (SB: 581.28 min/day; PA: 346.55 min/day; sleep: 445.77 min/day). In compositional models, reallocating 30 min per day to PA from other behaviours was associated with lower BMI (-0.13 kg/m²), BRI (-0.04), PWV (-0.05 m/s), and zComposite (-0.01). Reallocating 30 min per day from SB to other behaviours was associated with lower BMI (-0.28 kg/m²) and BRI (-0.07). Reallocating 30 min per day to sleep from other behaviours was related to lower BMI (-0.21 kg/m²) and BRI (-0.05).</p><p><strong>Conclusions: </strong>University students exhibited lower physical activity and higher sedentary time than older adults. Reallocation of time toward greater PA, less SB and longer sleep was associated with lower cardiometabolic risk. These findings challenge conventional expectations about age-related inactivity and highlight young adulthood as a critical, under-recognised target for interventions to promote PA and reduce SB for long-term health.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962939","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}