EBioMedicine最新文献

{"title":"Artificial intelligence for prediction of atrial fibrillation in the stroke unit: a retrospective derivation validation cohort study.","authors":"Maximilian Schoels, Laura Krumm, Alexander Nelde, Manuel C Olma, Christian H Nolte, Jan F Scheitz, Markus G Klammer, Christoph Leithner, Andreas Meisel, Franziska Scheibe, Michael Krämer, Karl Georg Haeusler, Matthias Endres, Christian Meisel","doi":"10.1016/j.ebiom.2025.105869","DOIUrl":"10.1016/j.ebiom.2025.105869","url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal atrial fibrillation (AF) is a major cause of stroke but is often undetected in routine clinical practice. Effective stratification is needed to identify patients with stroke who might benefit the most from intensified AF screening. Several artificial intelligence models have been proposed to predict AF based on ECG in sinus rhythm, but broad implementation has been limited. The most valuable input features and most effective model design for AF prediction are also unclear.</p><p><strong>Methods: </strong>We developed and tested AF prediction models utilising continuous electrocardiogram monitoring (CEM) recordings from the first 72 h after admission and multiple clinical input features from patients with stroke hospitalised at Charité, Berlin, Germany, between September 2020 and August 2023. We compared different models and input data to identify the best-performing model for prediction of AF. The relative contributions of different input data sources were assessed for explainability. A final model was externally validated using the first hour of monitoring data from the intervention group of the prospective multicentre MonDAFIS study.</p><p><strong>Findings: </strong>The derivation dataset included 2068 patients with acute ischaemic stroke, of whom 469 (22.7%) had AF, first detected before or during the index hospital stay (366 vs. 103). In predicting newly detected AF, a Bayesian fusion model emerged as best, achieving a ROC-AUC of 0.89 (95% CI: 0.80, 0.96). Model introspection indicated that HRV was the main driver of the model's predictions. A final, simplified tree-based ensemble model using age and HRV parameters of the first hour of CEM data achieved similar performance (ROC-AUC 0.88, 95% CI: 0.79, 0.95). The final model consistently outperformed the AS5F score in a real-world scenario external validation on the MonDAFIS dataset (1519 patients, thereof 36 (2.37%) with AF; ROC-AUC 0.79 vs. ROC-AUC 0.69, p = 4.69e-03).</p><p><strong>Interpretation: </strong>HRV appears to be the most informative variable for predicting AF. A computationally inexpensive model requiring only 1 h of single-lead CEM data and patients' age supports prediction of AF after acute ischaemic stroke for up to seven days. Such a model may enable risk-based stratification for cardiac monitoring, prioritising efforts where most needed to enhance AF screening efficiency and, ultimately, secondary stroke prevention.</p><p><strong>Funding: </strong>This study was supported by the German Federal Ministry of Education and Research and the German Research Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105869"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The sodium-glutamate antagonist riluzole improves outcome after acute spinal cord injury: results from the RISCIS randomised controlled trial analysed using a global statistical analytic technique.","authors":"Michael G Fehlings, Karlo M Pedro, Mohammed Ali Alvi, Ali Moghaddamjou, James S Harrop, Ralph Stanford, Jonathon Ball, Bizhan Aarabi, Paul M Arnold, James D Guest, Shekar N Kurpad, James M Schuster, Ahmad N Nassr, Karl M Schmitt, Jefferson R Wilson, Darrel S Brodke, Faiz U Ahmad, Albert Yee, Wilson Z Ray, Nathaniel P Brooks, Jason Wilson, Diana S-L Chow, Elizabeth G Toups, Kevin E Thorpe, Jiaxin Huang, Peng Huang","doi":"10.1016/j.ebiom.2025.105863","DOIUrl":"10.1016/j.ebiom.2025.105863","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Spinal cord injury (SCI) clinical trials typically rely on a single primary endpoint to assess drug efficacy. This strategy fails to adequately capture the full impact of treatment in heterogenous neurological conditions like SCI. A more patient-centric analysis requires assessment of neurological function, functional capacity, and quality of life, incorporating meaningful patient-reported outcomes. The global statistical test (GST) addresses this challenge using a unified statistical conclusion regarding the superiority of a treatment strategy over another by evaluating multiple trial endpoints simultaneously.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The RISCIS trial (Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study) data was analysed using a multivariate nonparametric GST, integrating the total American Spinal Injury Association (ASIA) motor score (TOTM), Spinal Cord Independence Measure (SCIM), and SF-36 PCS (Short Form-36 Physical Component Scale) scores. In the RISCIS trial, patients with severe cervical SCI (AIS A, B, and C) were randomised to receive riluzole or placebo within 12 h of injury in a double blinded fashion. We compared six-month outcomes between groups using a modified O'Brien's rank sum test with sample variance adjustment. Higher summed ranks represent better global outcomes. The overall probability of improvement was computed using a summary estimate, the global treatment effect (GTE).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;A total of 131 patients (mean age 45.8 years old, 82% males) completed the six-month outcome assessment. Among these, 49.6% were classified as AIS A, 20.6% as AIS B, and 29% as AIS C. Riluzole was administered within 12 h from injury for 14 days in 65 patients, while 66 received a placebo. The unadjusted mean change from baseline to six months showed a favourable response in the riluzole group compared to placebo across TOTM (p = 0.28 by t-test; p = 0.26 by Wilcoxon test), SCIM (p = 0.04 by t-test; p = 0.02 by Wilcoxon test), or SF-36 PCS (p = 0.23 by t-test; p = 0.21 by Wilcoxon test) scores. Using the GST to simultaneously assess these measures, the riluzole group exhibited a higher rank sum compared to placebo [median rank sum = 207 (IQR: 166-246) in riluzole vs 185 (IQR: 146-236) in placebo, p = 0.04]. Subgroup analysis revealed the greatest treatment benefit among patients with AIS A injuries (GTE = 0.16, 95% CI: 0.01-0.31, p = 0.02). At six months, the probability that riluzole treatment resulted in overall better outcomes than placebo across all assessed outcomes was 58%.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Riluzole was associated with improved global outcomes in patients with severe traumatic SCI, based on a composite score integrating ASIA total motor scores, SCIM, and SF36 outcomes at six months. Riluzole is a promising therapeutic option in SCI, but further investigation through higher-quality studies incorporating multidimensional assessments is warranted.","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105863"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714978","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":"Decoding disease-specific ageing mechanisms through pathway-level epigenetic clock: insights from multi-cohort validation.","authors":"Pan Li, Jijun Zhu, Shenghan Wang, Haowen Zhuang, Shunjie Zhang, Zhongting Huang, Fuqiang Cai, Zhijian Song, Yuxin Liu, Weixin Liu, Sebastian Freidel, Sijia Wang, Emanuel Schwarz, Junfang Chen","doi":"10.1016/j.ebiom.2025.105829","DOIUrl":"10.1016/j.ebiom.2025.105829","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ageing is a multifactorial process closely associated with increased risk of chronic diseases. While epigenetic clocks have advanced ageing research, most rely on isolated CpG sites, limiting biological interpretability. We developed PathwayAge, a biologically informed model that captures coordinated methylation changes at the pathway level, providing interpretable insights into ageing biology and disease mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a cross-sectional study using genome-wide DNA methylation data from 10,615 individuals across 19 cohorts and 3413 Han Chinese participants, along with transcriptomic data from 3384 samples. A two-stage machine learning model aggregated CpG sites into GO or KEGG pathway-level features to predict chronological age. Model accuracy was assessed using mean absolute error (MAE) and Pearson correlation (Rho). Age acceleration residuals (AgeAcc) were computed and tested for associations with nine diseases using non-parametric statistics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;PathwayAge achieved high predictive accuracy (Rho = 0.977, MAE = 2.350) in cross-validation and across 15 independent blood-based validation cohorts (Rho = 0.677-0.979, MAE = 2.113-6.837), including a Chinese population (Rho = 0.972, MAE = 2.302). Compared to established clocks, PathwayAge showed improved performance in both age estimation and disease association analyses. Significant AgeAcc differences were observed across nine diseases, with disease-specific pathways confirmed by permutation tests (P &lt; 0.02). Top pathways implicated in ageing included autophagy, cell adhesion, synaptic signalling, and metabolic regulation. GO-based clustering revealed consistent ageing signatures across disease categories, including neuropsychiatric, immune, metabolic, and cancer-related conditions. Cross-omics validation using transcriptomic data further supported the model's biological relevance (Rho = 0.70, MAE = 7.21).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;PathwayAge represents an interpretable, biologically grounded framework for estimating epigenetic age. By integrating pathway-level methylation signals, it uncovers mechanistic links between ageing and disease, with potential applications in biomarker development and precision ageing medicine.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;This research was supported by the Greater Bay Area Institute of Precision Medicine (Grant No. I0007), the National Social Science Foundation of China (Grant No. 32370639), and was further supported by the Shanghai Key Laboratory of Psychotic Disorders Open Grant (Grant No: 21-K01). ES received funding from the Hector II Foundation and the German Federal Ministry of Education and Research (BEST project, Grant No: 01EK2101B), and was endorsed by the German Center for Mental Health (DZPG). ES received speaker fees from bfd Buchholz-Fachinformationsdienst GmbH and editorial fees from the Lundbeck Foundation. SW received funding from the Str","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105829"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567312","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":"Effect of long-term azithromycin treatment on gut microbial diversity in children and adolescents with HIV-associated chronic lung disease.","authors":"Trym Thune Flygel, Ahmed Bargheet, Regina Esinam Abotsi, Shantelle Claassen-Weitz, Victoria Simms, Erik Hjerde, Kilaza Samson Mwaikono, Grace Mchugh, Dan Hameiri-Bowen, Veronika Kuchařová Pettersen, Rashida Abbas Ferrand, Mark Nicol, Jorunn Pauline Cavanagh, Trond Flaegstad, Evgeniya Sovershaeva","doi":"10.1016/j.ebiom.2025.105832","DOIUrl":"10.1016/j.ebiom.2025.105832","url":null,"abstract":"<p><strong>Background: </strong>HIV-associated chronic lung disease (HCLD) is common in children and adolescents growing up with HIV. The use of azithromycin (AZM) reduces the rate of acute respiratory exacerbations in this population, however, impact of this treatment on the gut microbiota and associations with blood-derived inflammatory markers have not been studied.</p><p><strong>Methods: </strong>Children and adolescents with HCLD in Harare, Zimbabwe and Blantyre, Malawi were recruited in a double-blind, placebo-controlled trial of once-weekly AZM or placebo for 48 weeks (BREATHE trial, NCT02426112). Rectal swabs were collected at inclusion (N = 346), 48 weeks (treatment end, N = 313), and 72 weeks (six months after treatment cessation, N = 244). The bacterial composition of fecal swabs was determined using 16S rRNA gene sequencing. Plasma biomarkers at inclusion and 48 weeks were measured using Luminex multiplex bead assay.</p><p><strong>Findings: </strong>At 48 weeks, bacterial α-diversity was significantly lower in the AZM group, with 27 bacterial genera showing differential abundance between the study groups. The placebo group exhibited higher interconnectivity between bacterial genera at 48 weeks compared to the AZM group. Correlations between the top seven differentially abundant genera and biomarkers observed at inclusion were no longer significant at 48 weeks in both groups. Depletion of Campylobacter persisted for six months after cessation of AZM treatment.</p><p><strong>Interpretation: </strong>Long-term AZM treatment in HCLD patients affects their gut bacterial composition at least 6 months after its cessation. The consequences of reduced bacterial diversity, such as altered interaction with the immune system and risk of resistance, need further investigation to understand how to optimise gut health during long-term antibiotic treatments.</p><p><strong>Funding: </strong>The study was funded by the Norwegian Research Council and Helse Nord (HNF 1387-17).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105832"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567313","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":"CD4 T cell counts are inversely correlated with anti-gp120 cluster A antibodies in antiretroviral therapy-treated PLWH.","authors":"Mehdi Benlarbi, Jonathan Richard, Tommaso Clemente, Catherine Bourassa, William D Tolbert, Suneetha Gottumukkala, Marc Messier-Peet, Halima Medjahed, Marzena Pazgier, Frank Maldarelli, Antonella Castagna, Madeleine Durand, Andrés Finzi","doi":"10.1016/j.ebiom.2025.105856","DOIUrl":"10.1016/j.ebiom.2025.105856","url":null,"abstract":"<p><strong>Background: </strong>While antiretroviral therapy (ART) efficiently suppresses viral replication, inflammation and immune dysfunction persist in some people living with HIV-1 (PLWH). HIV-1 soluble gp120 (sgp120) has been detected in PLWH plasma and its presence is linked to immune dysfunction. It was reported that sgp120 binding to CD4 on uninfected bystander CD4⁺ T cells sensitises them to cellular death via antibody-dependent cellular cytotoxicity (ADCC) mediated by non-neutralising anti-cluster A antibodies (Abs) present in PLWH plasma.</p><p><strong>Methods: </strong>We included plasma from 520 PLWH on ART from three independent cohorts for measurements of anti-cluster A Abs and anti-CD4 binding site (anti-CD4BS) Abs. Associations between CD4⁺ T cell counts and anti-cluster A Abs was assessed using generalised least squares linear regression models, adjusting for potential confounders including age, sex, nadir CD4 and duration of ART. The role of anti-CD4BS Abs was evaluated using flow-cytometry based ADCC assays with primary CD4⁺ T cells.</p><p><strong>Findings: </strong>We observed that non-neutralising anti-cluster A Abs are negatively associated with CD4⁺ T cell counts. Anti-CD4BS antibodies blocked the coating of uninfected bystander cells by sgp120, thereby preventing their elimination by ADCC. Supporting a protective role of anti-CD4BS antibodies, their presence in PLWH plasma abrogated the negative association between CD4 counts and anti-cluster A Abs.</p><p><strong>Interpretation: </strong>Our results reveal that anti-cluster A Abs are associated with immune dysfunction in PLWH and anti-CD4BS antibodies might have a beneficial impact in these individuals.</p><p><strong>Funding: </strong>This study was supported by the Canadian Institutes of Health Research, the Canada Foundation for Innovation, the Fonds de Recherche du Québec-Santé, and the National Institutes of Health.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105856"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674175","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":"Moderate-intensity exercise training uniquely modulates circulating lipid species beyond classical lipid levels in humans.","authors":"Yu Zhang, Zhengzheng Zhang, Borja Martinez-Tellez, Xinyu Di, Alida Kindt, Isabelle Kohler, Francisco J Osuna-Prieto, Charles Clark, Nicolas Drouin, Amy Harms, Thomas Hankemeier, Jonatan R Ruiz, Lucas Jurado-Fasoli","doi":"10.1016/j.ebiom.2025.105849","DOIUrl":"10.1016/j.ebiom.2025.105849","url":null,"abstract":"<p><strong>Background: </strong>Regular physical exercise shows significant health-related benefits, potentially through the modulation of lipid metabolism in an intensity-dependent manner.</p><p><strong>Methods: </strong>In this study, we profiled 794 plasma lipid species across 18 subclasses following a 24-week supervised concurrent and randomised exercise intervention at moderate and vigorous intensities in 101 young, sedentary adults.</p><p><strong>Findings: </strong>Here, we demonstrate that moderate-intensity exercise, but not vigorous-intensity, significantly increased plasma levels of glycerophospholipids and triacylglycerol species. Interestingly, we also identified a sex-specific response to moderate-intensity exercise, with men exhibiting elevated glycerophospholipids and lysophospholipids species, and women showing significant increases in triacylglycerols species. Increments in glycerophospholipids species were associated with improvements in cardiorespiratory fitness, i.e., VO₂peak.</p><p><strong>Interpretation: </strong>Importantly, while traditional lipid markers, including total cholesterol or triglycerides remained unchanged after the exercise intervention, our findings suggest that exercise partially exerts its health benefits by selectively targeting and modifying specific lipid subtypes in an intensity, sex-dependent manner.</p><p><strong>Funding: </strong>The study was supported by the Junta de Andalucía, Consejería de Transformación Económica, Industria, Conocimiento y Universidades Dirección General de Investigación y Transferencia del Conocimiento (ref. P18-RT-4455, ref. SOMM17/6107/UGR, and DOC 01151) and European Regional Development Funds (ERDF), the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), and PTA-12264, Retos de la Sociedad (DEP2016-79512-R), the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016 Excellence actions: Unit of Excellence on Exercise and Health (UCEES).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105849"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648845","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":"Plasma proteomic signatures of dual cognitive and mobility decline in older adults.","authors":"Qu Tian, Erin E Greig, Michael R Duggan, Keenan A Walker, Luigi Ferrucci","doi":"10.1016/j.ebiom.2025.105858","DOIUrl":"10.1016/j.ebiom.2025.105858","url":null,"abstract":"<p><strong>Background: </strong>The simultaneous memory and gait decline is linked to greater dementia risk than memory decline alone. We aim to identify dual decline-related protein changes that may offer valuable insights into biological processes.</p><p><strong>Methods: </strong>We compared longitudinal changes in 7268 plasma proteomic markers in older adults experiencing dual decline, memory decline, and gait decline from no decline (reference) using linear mixed-effects regression and related to brain MRI and blood biomarkers.</p><p><strong>Findings: </strong>There were no baseline group differences in proteins. Longitudinally, only dual decline showed significant changes in 75 proteins, with PGP9.5 showing the most alteration (p-FDR < 0.05), implicated in synaptic function, proteostasis, and regulation of amyloid precursor protein and amyloid β protein. The top-enriched pathway pointed to mitochondrial protein degradation. Of 75, changes in select proteins were related to future cognitive impairment, brain atrophy patterns, and blood biomarkers of AD, neuroinflammation, and neurodegeneration, with TRI72 being the top significant protein related to cognitive impairment and pTau181 progression.</p><p><strong>Interpretation: </strong>Older adults experiencing dual decline exhibit longitudinal protein changes, indicating mitochondrial dysfunction, proteostasis, neuroinflammation, and immune responses.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105858"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768503","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":"Small vessels, big problem: a dive into the pulmonary microcirculation in pulmonary hypertension and methods for evaluation.","authors":"Misha Dagan, Shane Nanayakkara, William Chan, David C McGiffin, David M Kaye","doi":"10.1016/j.ebiom.2025.105867","DOIUrl":"10.1016/j.ebiom.2025.105867","url":null,"abstract":"<p><p>Pulmonary microvascular dysfunction is central to the pathophysiology of pulmonary hypertension (PH), yet remains challenging to evaluate in clinical practice. This review outlines current and emerging methodologies for assessing the pulmonary microcirculation, including advanced imaging, computational modelling, and invasive haemodynamic techniques. Exercise right heart catheterisation, waveform analysis, and vasoreactivity testing provide indirect insights into microvascular health, while novel invasive approaches, such as pulmonary flow reserve and pulmonary microvascular resistance indices, offer the potential for more precise functional characterisation. Computational models incorporating CT-derived anatomical data and patient-specific haemodynamics may enhance early detection and phenotyping of PH. Although many of these tools remain in the research domain, their refinement and integration into clinical workflows could enable earlier diagnosis, personalised risk stratification, and monitoring of therapeutic response. Ultimately, translating these innovations into practice may allow for targeted interventions that address microvascular dysfunction at an earlier stage of disease progression.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105867"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of amycretin, a unimolecular glucagon-like peptide-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats.","authors":"Rune Ehrenreich Kuhre, Borja Ballarín-González, Christian Lehn Brand, Tine Glendorf, Kim Grimstrup Madsen, Karina Rahr Hjøllund, Wouter Frederik Johan Hogendorf, David Højland Ipsen, Sofia Lundh, Thomas Kruse, Signe Beck Petersen, Anna Secher, Andreas Vegge, Kirsten Raun","doi":"10.1016/j.ebiom.2025.105862","DOIUrl":"10.1016/j.ebiom.2025.105862","url":null,"abstract":"<p><strong>Background: </strong>Amycretin is a novel unimolecular glucagon-like peptide-1 (GLP-1) and amylin receptor agonist. This study aimed to determine its role in mitigating diet-induced metabolic disorders, such as obesity, insulin resistance, and fatty liver disease, in mice and rats.</p><p><strong>Methods: </strong>Preclinical studies were conducted to characterise amycretin activation of GLP-1, amylin and calcitonin receptors, and determine the effects of amycretin administration on the metabolic health of mice and rats. Investigations included measurements of body weight and body composition, energy intake and energy expenditure, insulin sensitivity, metabolic dysfunction-associated steatotic liver disease (MASLD), and access in the mouse brain.</p><p><strong>Findings: </strong>Amycretin activated human, mouse and rat GLP-1, amylin and calcitonin receptors in cell-based systems. In diet-induced obese (DIO) rats, amycretin administration for 21 days reduced total energy intake by 47% (95% CI (mean), kcal: vehicle: 2132-2493 vs. amycretin: 1044-1390) and lowered body weight by 18% (95% CI (mean), % change relative to pre-treatment: vehicle: 6.56-8.47 vs. amycretin: -10.48 to -12.74, p < 0.0001), while maintaining energy expenditure. Amycretin targeted key areas of the mouse brain that regulate food intake. Insulin sensitivity improved significantly with amycretin administration in DIO rats compared with vehicle controls, shown by higher glucose infusion rates during a hyperinsulinaemic euglycemic clamp. Additionally, amycretin improved histological hallmarks of MASLD, primarily by reducing steatosis.</p><p><strong>Interpretation: </strong>Amycretin had various beneficial effects on metabolic health in mice and rats; effectively reducing body weight, enhancing insulin sensitivity, and improving MASLD activity scores. Thus, amycretin could be a promising therapeutic option for metabolic diseases including obesity and type 2 diabetes, warranting further clinical trials assessing its efficacy in humans.</p><p><strong>Funding: </strong>Novo Nordisk A/S.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105862"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706829","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":"Maternal diet shapes infant microbiota and defensive capacity against infections in early life via differential human milk composition.","authors":"Karla Rio-Aige, Marta Selma-Royo, Raúl Cabrera-Rubio, Sonia González, Cecilia Martínez-Costa, Margarida Castell, María J Rodríguez-Lagunas, María Carmen Collado, Francisco J Pérez-Cano","doi":"10.1016/j.ebiom.2025.105850","DOIUrl":"10.1016/j.ebiom.2025.105850","url":null,"abstract":"<p><strong>Background: </strong>Maternal nutritional status and dietary profile during pregnancy and lactation have short- and long-term impacts on offspring health. However, there is an incomplete understanding of the mechanisms behind these health effects. This study aims to assess the effect of maternal diet on the health of offspring by examining to unravel the impact of maternal diet on offspring health outcomes and evaluate the link between maternal nutrition, human milk immune components and neonatal colonisation as potential mechanisms that mediate the influence of maternal diet in the incidence of infant infections.</p><p><strong>Methods: </strong>To assess this objective, we used two complementary approaches by which a clinical observational study based on the MAMI birth cohort guided a preclinical interventional analysis using a neonatal rat model of rotavirus-induced gastroenteritis.</p><p><strong>Findings: </strong>The findings in both approaches demonstrated that a maternal diet rich in plant-based protein, fibre and polyunsaturated fatty acids, was linked to reduced incidence and severity of infections in offspring that would be mediated by beneficial modulation of the gut microbiota and immune system. Specifically, in the suckling rats, a predominant Th1 immune response and an enhanced virus-specific response were observed. Moreover, human milk IgA and rat milk IgG2c played a key protective role that complemented the effects of maternal diet.</p><p><strong>Interpretation: </strong>These results strengthen the importance of maternal diet during pregnancy and lactation supporting infant health.</p><p><strong>Funding: </strong>The study was supported by LaMarató-TV3 (DIM-2-ELI, ref. 2018-27/30-31).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"118 ","pages":"105850"},"PeriodicalIF":10.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752694","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}