EBioMedicine最新文献

{"title":"Machine learning for population-level risk prediction of future cholangiocarcinoma.","authors":"Felix van Haag, Jan Clusmann, Paul-Henry Koop, Ryan Goodson, Ilya Tryakin, Shun-Ichi Wakabayashi, Tobias Seibel, Niharika Jakhar, Helen Ye Rim Huang, David Y Zhang, Inuk Zandvakili, Takefumi Kimura, Nobuharu Tamaki, Arunkumar Krishnan, Pedro Miguel Rodrigues, Jesus Maria Banales, Alessio Gerussi, Anna Saborowski, Daniel Rader, Jakob Nikolas Kather, Kai Markus Schneider, Carolin Victoria Schneider","doi":"10.1016/j.ebiom.2026.106433","DOIUrl":"10.1016/j.ebiom.2026.106433","url":null,"abstract":"<p><strong>Background: </strong>The poor prognosis of cholangiocarcinoma (CCA) is largely driven by rapid, asymptomatic disease progression, which usually results in a late diagnosis in the absence of established screening strategies. An early, cost-effective, and universally applicable risk assessment strategy would therefore be valuable.</p><p><strong>Methods: </strong>We developed machine learning (ML) models on prospective, multimodal data from 487,495 UK Biobank (UKB) participants, of whom 649 developed CCA during follow-up. Data from England (80%) were utilised for ML development via five-fold cross-validation, and then all models were tested on withheld data from Scotland, Wales, and Newcastle (20%). Iterative ablation studies reduced inputs from >150 features across demographic data, lifestyle, health records, blood parameters, genomics, and metabolomics to models built on five and ten routinely available clinical parameters. These were externally validated in the Penn Medicine Biobank (PMBB; n = 2638; 28 CCA), All of Us Research Program (AOU; n = 330,433; 362 CCA), Japan Medical Data Centre Claims Database (JMDC; n = 8,425,522; 723 CCA) and TriNetX (n = 728,886; 1592 CCA).</p><p><strong>Findings: </strong>We show that ML models integrating biliary-disease associated health records and Gamma glutamyltransferase can stratify risk of future CCA. Evaluation on the UKB test set as well as three independent cohorts revealed robust performance and generalisability across ethnicities. We achieved AUROCs of 0.71 [95% CI: 0.703-0.711], 0.77 [95% CI: 0.764-0.778 ], 0.796 [95% CI: 0.795-0.798] and 0.8 [95% CI: 0.794-0.805] for UKB, PMBB, AOU, and JMDC respectively, with respective AUPRCs of 0.014 [95% CI: 0.009-0.018], 0.042 [95% CI: 0.037-0.048], 0.038 [95% CI: 0.033-0.042] and 0.001 [95% CI: 0.001-0.001]. In AOU, application of the Youden J-optimised threshold yielded a number needed to screen of 79. Separate models for intra- and extrahepatic CCA did not improve performance. In line with the pathophysiology, performance declined for longer intervals between assessment and event. A group-level analysis in the TriNetX cohort revealed hazard ratios of up to 82.5 [95% CI: 26.4-257.96]. We provide extensive interpretability results and release all source codes used to develop the presented models.</p><p><strong>Interpretation: </strong>We provide a comprehensive framework for early CCA risk stratification in the general population, identifying key predictors, and demonstrating the potential of data-driven models in personalised screening for hepatobiliary cancer.</p><p><strong>Funding: </strong>German Cancer Aid (grant #70115730), Junior Principal Investigator Fellowship programme of RWTH Aachen Excellence strategy.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106433"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725480","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":"Alignment of registered cell therapy trial protocols with regulatory guidance on preclinical evidence: a systematic, cross-sectional, protocol-level analysis.","authors":"Matthew S Jeffers, Wimonchat Tangamornsuksan, Brian Dorus, Patrick Bedford, Jonathan Kimmelman, Daniel I McIsaac, Dean A Fergusson, Manoj M Lalu","doi":"10.1016/j.ebiom.2026.106456","DOIUrl":"10.1016/j.ebiom.2026.106456","url":null,"abstract":"<p><strong>Background: </strong>Cell therapies often advance into clinical trials based on supportive preclinical evidence, yet it remains unclear whether such evidence is presented in trial protocols in ways that explicitly justify translation to humans. We assessed whether preclinical efficacy evidence in cell therapy trial protocols aligns with regulatory guidance principles (e.g., mechanism of action, evidence of disease modification, clinically relevant model selection).</p><p><strong>Methods: </strong>We systematically searched ClinicalTrials.gov for cell therapy trials with available protocols. The primary outcomes were the proportions of protocols explicitly reporting 20 predefined preclinical evidence elements corresponding to regulator-derived translational principles. Secondary outcomes included the types and sources of evidence used to justify trial initiation and differences in reporting across trial contexts.</p><p><strong>Findings: </strong>We identified 305 eligible trials with protocols, of which 209 (68·5%) incorporated preclinical evidence. Reporting was uneven across domains of translational principles: at least one therapeutic mechanism of action element was explicitly reported in 95% of trials (95% confidence interval [CI], 91-97, n = 198/209), preclinical evidence of disease modification in 70% (95% CI, 63-76, n = 146/209), evidence informing trial intervention parameters in 69% (95% CI, 62-75, n = 144/209), and explicit justification of model relevance in 24% (95% CI, 19-31, n = 51/209). Protocol-level reporting of translational principles was generally higher in trials incorporating large-animal or original preclinical data, and lower in trials citing prior human data or sponsored by industry. Preclinical evidence was more often used to demonstrate biological plausibility than to justify key aspects of trial design.</p><p><strong>Interpretation: </strong>Although key translational principles are partially reflected in current practice, domains central to translational validity remain underrepresented. While additional preclinical evidence may be available in investigator brochures or regulatory submissions, publicly available protocols are important documents through which investigators formalise and communicate the rationale for trial initiation. Strengthening how preclinical evidence is structured in protocols may improve trial justification, regulatory evaluation, and support more reliable clinical translation.</p><p><strong>Funding: </strong>Canadian Stem Cell Network Impact Awards: Ethical, Legal, and Social Impact Stream.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106456"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849798","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":"An integrated reference atlas of human skeletal muscle.","authors":"Christopher Nelke, Franziska Babilon, Christina B Schroeter, Anne-Katrin Güttsches, Paula Quint, Karsten Krause, Gerd Meyer Zu Hörste, Benedikt Schoser, Jörg H W Distler, Sven G Meuth, Felix Kleefeld, Tobias Ruck","doi":"10.1016/j.ebiom.2026.106465","DOIUrl":"10.1016/j.ebiom.2026.106465","url":null,"abstract":"<p><strong>Background: </strong>Single-cell and single-nucleus RNA sequencing have transformed our understanding of human skeletal muscle biology, yet reproducibility and cross-study comparison remain limited by the lack of a unified reference framework and consistent cell-type annotation.</p><p><strong>Methods: </strong>We systematically searched for scRNA-seq and snRNA-seq datasets from adult human skeletal muscle. Seven eligible studies were retrieved and harmonised. We benchmarked multiple integration strategies to construct a joint reference atlas and derived modality-aware marker panels. Selected findings were validated by immunofluorescence in muscle biopsies.</p><p><strong>Findings: </strong>We generated a harmonised atlas comprising 122,000 cells and 630,000 nuclei from 88 healthy individuals and resolved 17 major skeletal muscle cell populations, spanning mononuclear compartments and multinucleated myofibers. Cross-modality analysis identified tissue- and modality-aware marker panels and nominated both established and previously unrecognised markers. NOVA1 emerged as a selective marker of fibro-adipogenic progenitors and was validated at the transcript and protein levels. Focusing on myonuclei, pseudotime modelling reconstructed differentiation trajectories from quiescent muscle stem cells to mature type I and type II myofibers and revealed lineage-specific programs, including transient activation of protocadherin-γ genes during type I myofiber differentiation. We further provide an interactive web application for marker-based cell-type prediction using the reference atlas.</p><p><strong>Interpretation: </strong>This integrated reference atlas and accompanying annotation tool establish a standardised framework for human muscle transcriptomics, promoting consistent cell-type assignment and providing a baseline for future studies of muscle development, ageing, and disease.</p><p><strong>Funding: </strong>Else Kröner-Fresenius-Stiftung and the German Research Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106465"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863117","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":"Intratumoural plasma cells mediate a pro-inflammatory response to kinase inhibition and successful immune checkpoint blockade therapy in malignant peripheral nerve sheath tumours.","authors":"Joshua J Lingo, Ryan Reis, Altay Koyas, Ellen Voigt, Zeb R Zacharias, Chantal Allamargot, Emma L Hornick, Juan A Raygoza Garay, Courtney A Kaemmer, Elizabeth C Elias, Ali Jabbari, Connor R Wilhelm, Alexander W Boyden, Nitin J Karandikar, Patrick Breheny, David K Meyerholz, Rebecca D Dodd, Jon C D Houtman, Benjamin W Darbro, Dawn E Quelle","doi":"10.1016/j.ebiom.2026.106413","DOIUrl":"10.1016/j.ebiom.2026.106413","url":null,"abstract":"<p><strong>Background: </strong>The role of intratumoural plasma cells in immune checkpoint blockade (ICB) therapy has never been tested although their presence is linked with improved response and survival in people with cancer. Malignant peripheral nerve sheath tumours (MPNSTs) are deadly sarcomas with minimal responsiveness to ICB therapies. Strikingly, drugs inhibiting cyclin-dependent kinases 4/6 (CDK4/6) and MEK sensitise de novo MPNSTs to immunotherapy targeting programmed death-ligand 1 (PD-L1), which correlates with increased intratumoural plasma cells. Here, we tested if plasma cells mediate MPNST response to anti-PD-L1 therapy and how they modulate tumour immune responsiveness to CDK4/6-MEK inhibition.</p><p><strong>Methods: </strong>Anti-tumour activity of PD-L1 inhibition, with or without CDK4/6-MEK inhibition, was measured in de novo MPNSTs within wild-type versus plasma cell-deficient mice. Plasma cell-dependent effects of CDK4/6-MEK inhibition on priming the MPNST immune environment were determined by single cell transcriptomics and immune cell analyses.</p><p><strong>Findings: </strong>Plasma cell-deficient MPNSTs failed to respond to anti-PD-L1 monotherapy and were no longer sensitised by CDK4/6-MEK inhibition to immunotherapy. Following kinase inhibitor treatment, plasma cells were necessary for a pro-inflammatory response marked by increased tumour infiltration and activation of natural killer (NK) and CD8+ T cells, major histocompatibility class I antigen presentation, and decreased M2 macrophages. By comparison, elevated CD4+ T cell and B cell infiltration dominated the plasma cell knockout phenotype.</p><p><strong>Interpretation: </strong>Plasma cells favourably remodel the tumour immune environment for anti-tumour immunity and are critical for successful ICB therapy in MPNSTs. These findings may inform ICB treatment strategies and patient stratification for therapy of many tumour types.</p><p><strong>Funding: </strong>This research was supported by University of Iowa Sarcoma Research Program awards, the Gilbert Family Foundation, and NIH grants T34-GM141143, T32-GM067795, F31-CA281312, P30-CA086862, and R01-NS119322.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106413"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653073","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":"Superior precision of clinical predictions after CD3-relativisation to align flow cytometry data.","authors":"Gunther Glehr, Katharina Kronenberg, Fabiola Arella, Michael Kapinsky, David Segundo, María Iglesias-Escudero, Maria Xydia, Hendrik Veltman, Tobias Schmidt, Viola Hähnel, Víctor J López-Madrona, Thomas Dienemann, Hans Jürgen Schlitt, Edward Kenneth Geissler, Gero Brockhoff, Silvia Gregori, Philipp Beckhove, Rainer Spang, Eva Martínez-Cáceres, Marcos López Hoyos, Paloma Riquelme, James Alexander Hutchinson","doi":"10.1016/j.ebiom.2026.106427","DOIUrl":"10.1016/j.ebiom.2026.106427","url":null,"abstract":"<p><strong>Background: </strong>Flow cytometry captures subtle changes in immune cell distributions caused by disease, but its full potential in medical decision-making is presently limited by technical variability across instruments, sites and time. To accelerate development of generalisable diagnostic, prognostic or predictive clinical tests, we assembled a benchmark flow cytometry dataset over 20 months using 6 cytometers at 4 independent laboratories in Spain and Germany. Cohorts were amalgamated using a new alignment strategy, CD3-relativisation.</p><p><strong>Methods: </strong>Four hundred and eighty-two clinical flow cytometry samples from 381 healthy donors and a further 100 samples from post-surgical patients admitted to intensive care were stained with a 10-colour T cell marker panel. To align data from different cohorts, we introduced CD3-relativisation, a method for normalising fluorescence intensities per-channel against CD3 signals. The quality of data alignment was evaluated using optimal transport distances (OTD), clustering consistency and predictive performance.</p><p><strong>Findings: </strong>Our fully annotated data resource (Zenodo 17094078) revealed systematic biases in flow cytometry measurements across time, locations and cytometers. CD3-relativisation minimised these biases without sacrificing biological information. Cell clustering performance and sample-to-sample variability improved after relativisation. Consequently, we were able to predict CMV-IgG serostatus, age and sex with superior precision without relying upon external calibrators, measurement of paired samples, batch definitions or data sharing. Models established in healthy control populations were transferable to a cohort of critically unwell, post-surgical patients.</p><p><strong>Interpretation: </strong>Our CD3-relativised benchmark dataset establishes a robust standard for evaluating computational methods in clinical cytometry, especially their stability over time and generalisability between instruments, laboratories and clinically heterogeneous populations.</p><p><strong>Funding: </strong>This work was supported by the BMS-Foundation (FA-19-009), BZKF (BF/04/R/Hutch), EU-H2020 (Immutol_101080562, exTra_101119855, PAVE_861190), BMBF (01KD2206I) and DFG (403161218).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106427"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720820","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":"Brain network biomarkers for diagnosis and clinical stratification in multiple sclerosis: a longitudinal study integrating individualised structural covariance MRI with high-density EEG.","authors":"Ruiping Gao, Xuegang Song, Hanyue Zheng, Yi Men, Jiajian Li, Yingtao Wang, Yuan Qi, Jun Sun, Yinan Zhao, Junwei Hao","doi":"10.1016/j.ebiom.2026.106438","DOIUrl":"10.1016/j.ebiom.2026.106438","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is increasingly recognised as a disorder of large-scale brain network reorganisation rather than a disease explained solely by focal demyelinating lesions. However, the relevance of structural network abnormalities to clinical heterogeneity and progression remains unclear.</p><p><strong>Methods: </strong>We analysed 3T magnetic resonance imaging (MRI) from two independent MS cohorts (total n = 635): Dataset 1 from the Chinese neuroimmunological diseases (NIDBase) cohort (163 MS and 248 healthy controls [HC]) and Dataset 2 from the UK Biobank (117 MS and 107 HC). A subset of Dataset 1 underwent 256-channel resting-state high-density electroencephalography (hd-EEG) (135 MS and 80 HC). We constructed structural covariance networks (iSCNs) from 3D T1-weighted MRI using Kullback-Leibler similarity across 170 Automated Anatomical Labelling atlas 3 (AAL3) regions. Patients were stratified by disability, cognition, and disease activity; a subgroup with no evidence of disease activity (NEDA) with 1-year follow-up MRI (n = 33) was analysed longitudinally. Linear support vector machine classifiers evaluated topological and connectivity features for diagnosis and clinical stratification.</p><p><strong>Findings: </strong>MS showed reproducible topological and connectivity abnormalities, involving thalamic and subcortical hubs and altered visual-network-related couplings. Disability showed the broadest abnormalities, whereas cognitive impairment and disease activity were associated with more selective changes. Patients meeting NEDA criteria showed subtle longitudinal nodal changes. Connectivity features performed best for MS-vs-HC discrimination, whereas topological features performed better for clinical stratification.</p><p><strong>Interpretation: </strong>The iSCN approach identified reliable patterns of topological and connectivity impairment across MS and its clinical stratifications, providing insight into MS neuropathology and guiding future diagnostic and therapeutic biomarker development.</p><p><strong>Funding: </strong>This work was funded by Beijing Research Ward Excellence Program (BRWEP2024W022010104, BRWEP2024W022010109), Beijing Scholar program (No. 106), the Project for Innovation and Development of Beijing Municipal Geriatric Medical Research Center (11000023T000002041657), Dengfeng Talent Program (DFL20220701), National Natural Science Foundation of China (82571539, 82501612), Xuanwu Hospital Talent Convergence Program-Leading Talents (HZ2021ZCLJ008), the Beijing Hospitals Authority's Ascent Plan (DFL20240801), and Beijing \"Huizhi\" Talent Program, Cultivation Program-Leading Talents (HZ2025PYLJ003).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106438"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789593","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":"Determining intracellular and extracellular activities of azithromycin against azithromycin-resistant Salmonella Typhi and their association with clinical treatment responses.","authors":"Ngo Ngoc Phuong Thuy, Voong Vinh Phat, Sabina Dongol, Nguyen Hoang Thu Trang, Sumit Bista, Quynh Nguyen, Chau Vinh, Guy E Thwaites, Buddha Basnyat, Christopher M Parry, Stephen Baker, Maia A Rabaa, Jay C D Hinton, Abhilasha Karkey, Pham Thanh Duy","doi":"10.1016/j.ebiom.2026.106447","DOIUrl":"10.1016/j.ebiom.2026.106447","url":null,"abstract":"<p><strong>Background: </strong>The spread of extensively drug-resistant (XDR) Salmonella Typhi variants in South Asia has severely limited treatment options for typhoid fever, a life-threatening systemic infection affecting millions. Azithromycin has become the last effective oral drug against XDR typhoid; however, despite increasing azithromycin resistance, limited data exists concerning the correlation between in vitro susceptibility and clinical treatment efficacy.</p><p><strong>Methods: </strong>We developed a THP-1 macrophage infection model to evaluate time- and concentration-dependent azithromycin activity against intracellular and extracellular S. Typhi, including azithromycin-susceptible (MIC ≤16 mg/L) and azithromycin-resistant isolates (MIC ≥ 32 mg/L). The accumulation of azithromycin in THP-1 macrophages was quantified using LC-MS/MS. Pharmacological modelling was used to estimate key parameters (E_max, E_min, C_s, C_si), and compare azithromycin efficacy between intracellular and extracellular compartments. When available, in vitro findings were correlated with clinical treatment responses.</p><p><strong>Findings: </strong>Azithromycin accumulated in THP-1 macrophages at concentrations 20-72 fold higher than in extracellular medium after 24 h. This intracellular accumulation was associated with concentration-dependent killing of S. Typhi in the intracellular assays, while only bacteriostatic effects were observed extracellularly. Importantly, pharmacological modelling data estimated that azithromycin concentrations ranging from 46.86 to 123.78 mg/L were sufficient to inhibit intracellular growth of azithromycin-susceptible isolates. In contrast, concentrations exceeding 460.63 mg/L were required to suppress intracellular growth of azithromycin-resistant isolates, substantially higher than the C_max typically observed in human white blood cells (114.0-146.0 mg/L) following a 3 day course of oral azithromycin. Notably, among those with available data, three patients infected with azithromycin-resistant S. Typhi failed to respond clinically to azithromycin treatment.</p><p><strong>Interpretation: </strong>We have established a THP-1 macrophage model to characterise the intracellular pharmacodynamics of azithromycin. Our findings indicate that azithromycin is likely ineffective for treating infections caused by azithromycin-resistant S. Typhi, warranting further clinical validation.</p><p><strong>Funding: </strong>Wellcome International Training Fellowship.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106447"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789628","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":"Interfering with innate immunity: type I IFNs and avian influenza susceptibility.","authors":"Stuart G Tangye, Cindy S Ma","doi":"10.1016/j.ebiom.2026.106414","DOIUrl":"10.1016/j.ebiom.2026.106414","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106414"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648096","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":"Establishing the role of ZBTB20 mutations in GnRH deficiency and impaired neurogenesis in the subventricular zone: a human cohort and animal model study.","authors":"Jun Guan, Jingtan Zhu, Yuting Li, Min Nie, Jing Zhang, Zhiheng Chen, Huadie Liu, Dan-Na Chen, Ruizhi Zheng, Meichao Men, Jia-Da Li","doi":"10.1016/j.ebiom.2026.106416","DOIUrl":"10.1016/j.ebiom.2026.106416","url":null,"abstract":"<p><strong>Background: </strong>Congenital hypogonadotropic hypogonadism (CHH) arises from defective development or dysfunction of GnRH neurons. Olfactory bulb (OB) malformations frequently accompany CHH, a condition termed Kallmann syndrome (KS). Nevertheless, approximately 50% of CHH cases remain genetically undefined.</p><p><strong>Methods: </strong>Leveraging our 15-year effort in building one of Asia's largest CHH cohorts (812 unrelated patients, and 49 CHH families), we identified a pathogenic ZBTB20 mutation (p.R300C) in a four-generation CHH family with seven affected members. We generated nervous system-specific Zbtb20 conditional knockout (cKO) mice to assess phenotypic and mechanistic consequences. Molecular analyses, including transcriptional regulation assays, were performed to explore downstream pathways.</p><p><strong>Findings: </strong>Four additional heterozygous ZBTB20 variants were detected in the CHH cohort. Zbtb20 cKO mice recapitulated hallmark CHH features: GnRH neuron deficiency, hypogonadism, and infertility. Notably, migration of GnRH neurons in Zbtb20-deficient embryos was stalled along the defective terminal nerve (TN) scaffold. Furthermore, Zbtb20 deficiency impaired proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) and disrupted their migration via the rostral migratory stream (RMS) to the OB. We also identified Thbs4 as a key downstream target, as ZBTB20 transcriptionally activates Thbs4, which is critical for SVZ NSCs migration.</p><p><strong>Interpretation: </strong>Our study establishes ZBTB20 as a CHH-associated gene and demonstrates its essential role in SVZ-OB neurogenesis. Loss of ZBTB20 function leads to OB atrophy, disrupted terminal nerves, GnRH deficiency and CHH pathogenesis.</p><p><strong>Funding: </strong>This project is financially supported by National Natural Science Foundation of China, and the Natural Science Foundation of Hunan Province.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106416"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700919","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":"Hospital sinks and healthcare-associated infection: ecology, transmission, surveillance and mitigation.","authors":"Aoife Kearney, Kevin Chau, Shireen Kotay, Jessica Martin, Andrew Kirby, Amy J Mathers, Nicole Stoesser","doi":"10.1016/j.ebiom.2026.106415","DOIUrl":"10.1016/j.ebiom.2026.106415","url":null,"abstract":"<p><p>Hospital sinks are recognised polymicrobial reservoirs for multi-drug resistant organisms and have been implicated in patient transmission and outbreaks. Earlier studies on sink-associated microbes predominantly focused on specific species or resistance mechanisms (e.g. carbapenemases) using targeted microbiological methods. More recently, less selective approaches (e.g. metagenomic sequencing) have enabled broader characterisation of these microbial communities. This review summarises current evidence describing hospital sink-trap microbiomes, examining ecological determinants, surveillance strategies and interventions aiming to mitigate transmission from these reservoirs. We discuss biotic and abiotic factors that shape microbial selection/persistence, assess approaches to managing these reservoirs to reduce patient risk, and highlight priorities for future research to inform evidence-based practice in healthcare settings.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106415"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711650","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}