EBioMedicine最新文献

{"title":"Exploring electroencephalographic chronic pain biomarkers: a mega-analysis.","authors":"Felix S Bott, Paul Theo Zebhauser, Vanessa D Hohn, Özgün Turgut, Elisabeth S May, Laura Tiemann, Cristina Gil Ávila, Henrik Heitmann, Moritz M Nickel, Melissa A Day, Divya B Adhia, Yoni K Ashar, Tor D Wager, Yelena Granovsky, David Yarnitsky, Mark P Jensen, Joachim Gross, Markus Ploner","doi":"10.1016/j.ebiom.2025.105955","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105955","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain is associated with alterations in brain function, offering promising avenues for advancing diagnostic and therapeutic strategies. In particular, these alterations may serve as brain-based biomarkers to support diagnosis, guide treatment decisions and monitor clinical courses of chronic pain.</p><p><strong>Methods: </strong>Motivated by this potential, this study analysed associations between chronic pain and changes of large-scale brain network function using resting-state electroencephalography (EEG) from 614 individuals with chronic pain, collected by research groups from Australia, Germany, Israel, New Zealand, and the US.</p><p><strong>Findings: </strong>Employing a discovery-replication approach, we found limited replicability of associations between pain intensity and brain network connectivity. However, a mega-analysis combining all datasets revealed robust associations between pain intensity and large-scale brain network connectivity at theta frequencies and including the limbic network. Additionally, multivariate analyses identified connectivity patterns spanning theta, alpha, and beta frequencies with strong evidence for associations with pain intensity. Variations and ablations of model features yielded deeper insights into the relative importance of distinct electrophysiological brain features in assessing chronic pain.</p><p><strong>Interpretation: </strong>Our findings highlight challenges and provide guidance for developing EEG-based, scalable, and affordable biomarkers of chronic pain.</p><p><strong>Funding: </strong>This project was funded by the Deutsche Forschungsgemeinschaft and the Technical University of Munich.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105955"},"PeriodicalIF":10.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study of susceptibility to acute respiratory distress syndrome.","authors":"Beatriz Guillen-Guio, Eva Suarez-Pajes, Eva Tosco-Herrera, Tamara Hernandez-Beeftink, Jose Miguel Lorenzo-Salazar, Diana Chang, Rafaela González-Montelongo, Luis A Rubio-Rodríguez, Olivia C Leavy, Richard J Allen, Almudena Corrales, Raquel Cruz, Miguel Bardají-Carrillo, Angel Carracedo, Eduardo Tamayo, V Eric Kerchberger, Lorraine B Ware, Brian L Yaspan, Markus Scholz, André Scherag, Jesús Villar, Louise V Wain, Carlos Flores","doi":"10.1016/j.ebiom.2025.105951","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105951","url":null,"abstract":"<p><strong>Background: </strong>Acute respiratory distress syndrome (ARDS) is a severe inflammatory process of the lung, often due to sepsis, and poses significant mortality burden in intensive care units. Here we conducted a genome-wide association study (GWAS) of ARDS to identify genetic risk loci that can help guide the development of new therapeutic options.</p><p><strong>Methods: </strong>We performed a case-control GWAS in 716 cases with ARDS, mainly associated with severe infections, and 4399 at-risk controls from three independent studies. Results were meta-analysed across the three studies, with significance set at p < 5 × 10^-8. Suggestive associations were declared for variants exhibiting consistent direction of effects, likely to replicate and nominal significance (p < 0.05) in all three studies. Prioritised loci were subjected to Bayesian fine mapping, in-silico functional assessments, and gene-based rare variant collapsing analysis using whole-exome sequencing data. Two independent studies with 430 ARDS cases and 1398 at-risk controls served as validation samples.</p><p><strong>Findings: </strong>We identified a variant near HMGCR that showed genome-wide significant association with ARDS and had been previously linked to cholesterol metabolism. This locus was associated with ANKDD1B expression in artery. The rare exonic variant analysis showed associations between HMGCR and ARDS at nominal level (p < 0.05). While no nominal significance was achieved in the two additional validation cohorts, this variant exhibited a consistent direction of effects across all 5 studies.</p><p><strong>Interpretation: </strong>A common variant near HMGCR was associated with ARDS risk, suggesting a link between cholesterol metabolism and ARDS risk. Validation in independent studies is needed.</p><p><strong>Funding: </strong>Wellcome Trust, National Institute for Health Research Leicester Biomedical Research Centre, National Heart, Lung, and Blood Institute, ATS Research Program, Gobierno de Canarias, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Instituto Tecnológico y de Energías Renovables, Cabildo Insular de Tenerife, Instituto de Salud Carlos III, Agencia Estatal de Investigación, German Ministry of Education and Research, Thuringian Ministry of Education, Science and Culture, the Thuringian Foundation for Technology, Innovation, and Research, German Sepsis Society.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105951"},"PeriodicalIF":10.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poor sleep health is associated with older brain age: the role of systemic inflammation.","authors":"Yuyang Miao, Jiao Wang, Xuerui Li, Jie Guo, Maria M Ekblom, Shireen Sindi, Qiang Zhang, Abigail Dove","doi":"10.1016/j.ebiom.2025.105941","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105941","url":null,"abstract":"<p><strong>Background: </strong>Poor-quality sleep has been linked to increased dementia risk. We investigated the relationship between healthy sleep pattern and older brain age, and the extent to which this is mediated by systemic inflammation.</p><p><strong>Methods: </strong>The study included 27,500 adults from the UK Biobank (mean age 54.7 y, 54.0% female). The presence of five self-reported healthy sleep characteristics (early chronotype, 7-8 h daily sleep, no insomnia, no snoring, no excessive daytime sleepiness) were summed into a healthy sleep score (0-5 pts) and used to define three sleep patterns: healthy (≥4 pts), intermediate (2-3 pts), and poor (≤1 pt). Low-grade inflammation was estimated using the INFLA-score, a composite index of inflammatory biomarkers. After a mean follow-up of 8.9 y, brain age was estimated using a machine learning model based on 1079 brain MRI phenotypes and used to calculate brain age gap (BAG; i.e., brain age minus chronological age). Data were analysed using linear regression and generalised structural equation models.</p><p><strong>Findings: </strong>At baseline, 898 (3.3%) participants had poor sleep, 15,283 (55.6%) had intermediate sleep, and 11,319 (41.2%) had healthy sleep. Compared to healthy sleep, intermediate (β = 0.25 [0.11, 0.40], P = 0.010) and poor (β = 0.46 [0.05, 0.87], P < 0.001) sleep were associated with significantly higher BAG. In mediation analysis, INFLA-score mediated 6.81% and 10.42% of the associations between intermediate and poor sleep and higher BAG.</p><p><strong>Interpretation: </strong>Poor sleep health may accelerate brain ageing. This may be driven by higher levels of systemic inflammation.</p><p><strong>Funding: </strong>Alzheimerfonden; Demensfonden; Loo and Hans Osterman Foundation for Medical Research; the Knowledge Foundation; Swedish Research Council.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105941"},"PeriodicalIF":10.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation mediates the immunosuppressive tumour microenvironment in metastatic endometrial clear cell carcinoma.","authors":"Huiqing Jia, Yang Chen, Guofeng Ma, Sicong Xu, Xiangyan Zhang, Lianpeng Chang, Ping Yang, Yujing Xiao, Xuefeng Xia, Shukun Zhang, Huaxiao Tang, Yilin Mou, Lina Zhang, Haoyan Wang, Jing Bai, Xin Yi, Xiaoming Xing","doi":"10.1016/j.ebiom.2025.105954","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105954","url":null,"abstract":"<p><strong>Background: </strong>Endometrial clear cell carcinoma (ECCC) is a rare and highly aggressive histological subtype of endometrial cancer with marked metastatic potential. The molecular characteristics and underlying mechanisms governing its metastatic behaviour remain poorly understood. This study aimed to delineate molecular distinctions between metastatic (Pm) and non-metastatic (Pn) primary ECCC tumours, elucidate DNA methylation-mediated regulatory mechanisms driving metastasis, and identify potential epigenetic biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>This multicentre study involved 51 individuals diagnosed with ECCC, leading to the establishment of two independent cohorts: a sequencing cohort (n = 35) for integrated whole-genome methylation and transcriptomic analysis, and a tissue microarray (TMA) cohort (n = 16) to validate key findings.</p><p><strong>Findings: </strong>Tumours exhibiting metastasis were found to possess a profoundly immunosuppressive tumour microenvironment (TME), evidenced by reduced density of tumour-infiltrating lymphocytes (TILs), especially within subsets of anti-tumour immune cells. Further analysis highlighted differential hypermethylation events in Pm tumours that acted as crucial epigenetic switches regulating immune responses. Specifically, methylation at ETS1-binding sites influenced ETS1 regulon activity, thus broadly regulating immune response processes. Epigenetic silencing of key genes in the T cell receptor (TCR) signalling pathway, such as LCK, CD3E, and ZAP70, impaired T cell activation and inhibited the activity of interacting immune pathways. Additionally, we developed a Lasso-derived metastatic risk score model, incorporating TME features (TIL density) and epigenetic predictors (LCK methylation), which demonstrated strong predictive performance (area under the curve [AUC] = 0.859).</p><p><strong>Interpretation: </strong>This study illuminated the \"epigenetic-immune axis\" as a central regulatory mechanism driving ECCC metastasis. DNA methylation systematically silenced immune response genes by targeting ETS1-binding sites and TCR signalling components, thus reconstructing the immunosuppressive TME to facilitate metastasis. The development of the metastatic risk score model and identification of LCK as a potential therapeutic target provide valuable strategies for precision treatment decisions and advancing targeted epigenetic-immune therapies in ECCC.</p><p><strong>Funding: </strong>This work was supported by the National Natural Science Foundation of China, Joint Foundation Programme, Qingdao Municipal Science and Technology Bureau Municipal Science, Shenzhen Science and Technology Programme, and the Affiliated Hospital of Qingdao University Young Investigator Fund.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105954"},"PeriodicalIF":10.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and epigenetic profiles of circulating NK cells in spontaneous HIV-1 controllers.","authors":"Alisa Huber, Albert L Groenendijk, Adriana Navas, Nadira Vadaq, Suzanne D E Ruijten, Vasiliki Matzaraki, Ezio T Fok, Aysel Gurbanova, Wilhelm A J W Vos, Marc J T Blaauw, Louise E van Eekeren, Maartje C P Jacobs-Cleophas, Janneke Stalenhoef, Marvin Berrevoets, Renate van der Molen, Arnold van der Meer, Marien I de Jonge, Joost H A Martens, Casper Rokx, Annelies Verbon, Jan van Lunzen, Hans J P M Koenen, Mihai G Netea, Andre J A M van der Ven, Leo A B Joosten, Jéssica C Dos Santos","doi":"10.1016/j.ebiom.2025.105948","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105948","url":null,"abstract":"<p><strong>Background: </strong>NK cells play a key role in eliminating HIV-infected cells, but it is unclear whether there are specific NK cell receptor signatures in spontaneous HIV controllers.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis of circulating NK cell phenotypes in people living with HIV (PLHIV), divided into spontaneous HIV controllers (HIC), normal progressors on antiretroviral therapy (non-HIC), and first-degree HIV-negative family members. Using supervised and unsupervised flow cytometry, we assessed NK cell markers and receptors. We performed an epigenetic analysis of H3K4me3 chromatin enrichment in NK cells from both HIC and non-HIC and measured IFNγ, Perforin and CD107a expression in NK cells upon stimulation with IL-2/IL-15, K562 cells, and IFNα. Additionally, we conducted a genome-wide association study (GWAS) and quantitative trait locus (QTL) mapping using data from HIC and non-HIC part of the 2000HIV study.</p><p><strong>Findings: </strong>HIV controllers had higher levels of CD56^bright NK cells and increased expression of NKp46, NKp30, and DNAM-1. The genetic association between protective MHC class I alleles and the NK cell receptor KIR2DL2/3 supports a genetic predisposition to HIV control. Unsupervised clustering identified an HIV-induced NK cell population, separate from CMV-induced NK cells. Epigenetic analysis revealed greater H3K4me3 marks in genes involved in immune response pathways, including IFNα, IL-15, and IL-2. The memory-like NK cell subpopulation was characterised by elevated expression of NKG2C and ILT2, with reduced KIR2DL2/3 in HIC. These memory NK cells were more responsive to stimulation with IFNα, resulting in increased production of IFNγ in HIC.</p><p><strong>Interpretation: </strong>These results suggest that spontaneous HIV control is associated with an NK cell memory phenotype, shaped by HIV infection, epigenetic modifications, and genetic factors.</p><p><strong>Funding: </strong>The authors are part of the 2000HIV study, which is supported by ViiV Healthcare.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105948"},"PeriodicalIF":10.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seizure detection using wearable electrocardiogram connected to a smartphone: a phase 3 clinical validation study.","authors":"Jesper Jeppesen, Jakob Christensen, Oliver Ahrenfeldt Petersen, Sarah Fenger, Sidsel Armand Larsen, Stephan Wüstenhagen, Stefan Rahr Wagner, Peter Johansen, Sándor Beniczky","doi":"10.1016/j.ebiom.2025.105952","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105952","url":null,"abstract":"<p><strong>Background: </strong>Automated seizure detection is needed for patient safety and for objective seizure quantification. Wearable seizure detection devices hold great potential to improve patient care. Our objectives were to assess the accuracy of a wearable ECG-device connected to a smartphone, in detecting epileptic seizures in patients with autonomic ictal changes, and evaluate its capability to automatically determine impairment of consciousness.</p><p><strong>Methods: </strong>We conducted a phase 3, prospective, blinded, multicentre, clinical validation study of real-time seizure detection using a predefined algorithm. We recruited consecutive patients admitted to Epilepsy Monitoring Units. Eligible patients experienced seizures with autonomic ictal manifestations, defined as ictal heart rate change exceeding 50 beats per minute, inferred from the first recorded seizure. Patients wore an ECG-device connected to a smartphone. The algorithm, based on heart rate variability, used a personalised detection threshold determined from the first 24 h of recording. During daytime, seizure detection triggered automated behavioural-testing on the smartphone to confirm detection and assess consciousness.</p><p><strong>Findings: </strong>Of 101 enrolled patients, 36 experienced seizures, with 42 seizures recorded from 17 eligible patients. Overall sensitivity across all 42 seizures was 90·5% (95% CI: 77·4-97·3%), median sensitivity per patient was 100% (95% CI: 100-100%). All bilateral tonic-clonic seizures were detected, while sensitivity for other focal seizures was 82·6% (95% CI: 61·2-95·1%), median per patient: 100% (95% CI: 60-100%). Mean false alarm rate was 2·5/day (median per patient: 1·1/day, 95% CI: 0-2·8/day, zero during the night). Device deficiency time was 1·8% and signal loss was 4·5% (median per patient: 0·3% and 0·5% respectively). Use of the behavioural-testing application successfully cancelled all false alarms and accurately identified impairment of consciousness.</p><p><strong>Interpretation: </strong>The wearable ECG device connected to a smartphone accurately detected focal and generalised seizures, and assessed impairment of consciousness.</p><p><strong>Funding: </strong>Independent Research Fund Denmark (grant number 0134-00400B).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105952"},"PeriodicalIF":10.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral blood neutrophil proteomic profiling with transcriptomic data integration reveals biomarkers for tuberculosis infection diagnosis.","authors":"Jiarong Yang, Zizheng Lv, Liguo Liu, Han Zhang, Jie Hu, Xingzhu Geng, Henan Xin, Zisen Liu, Lei Gao, Xiaobing Zhang, Yanli Xu, Rongmei Liu, Qi Jin, Jianhua Zheng","doi":"10.1016/j.ebiom.2025.105945","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105945","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) is one of the deadliest infectious diseases worldwide, causing millions of new cases and deaths annually. Rapid and accurate TB diagnostics are essential for TB control, yet current methods do not fully meet global needs. Peripheral blood neutrophils play a critical role in TB infection and represent a promising source of diagnostic markers.</p><p><strong>Methods: </strong>We conducted a cross-sectional proteomic analysis to characterise neutrophil protein profiles in individuals with active TB (ATB), latent TB infection (LTBI), and healthy controls (HC). Stringent criteria were applied to identify differentially expressed proteins (DEPs) among these groups. Transcriptomic data were integrated to perform pathway enrichment analysis of DEPs. Three DEPs (B2M, TXN, and PRDX5) were further validated as candidate diagnostic biomarkers for Mycobacterium tuberculosis (MTB) infection using automated western blotting in a cohort of 319 individuals, including 71 ATB, 142 LTBI, and 106 HC.</p><p><strong>Findings: </strong>Hundreds of DEPs were identified across the three groups. Integrated transcriptomic analysis revealed significant enrichment of DEPs in the NOD-like receptor signalling pathway. Receiver operating characteristic analysis of the three-protein combination (B2M, TXN, and PRDX5) yielded an area under the curve of 0.9847, with a sensitivity of 95.11% and a specificity of 96.23% for detecting MTB infection.</p><p><strong>Interpretation: </strong>This study presents a comprehensive proteomic profile of neutrophils under different MTB infection states, and this three-protein combination may assist in the diagnosis of MTB infection.</p><p><strong>Funding: </strong>This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-037) and the National Science and Technology Major Project of China (20212017ZX10201301-002-003).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105945"},"PeriodicalIF":10.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence for tracking social behaviours and supporting an autism spectrum disorder diagnosis: systematic review and meta-analysis.","authors":"Carter Sun, Alistair McEwan, Kelsie A Boulton, Eleni Andrea Demetriou, Ayesha K Sadozai, Amit Lampit, Adam J Guastella","doi":"10.1016/j.ebiom.2025.105931","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105931","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence (AI) holds promise for developing tools that can track social behaviours and support clinical assessments and outcomes in Autism Spectrum Disorders (ASD). This review evaluated existing AI algorithms for extracting facial information during social interaction assessments and contributing to diagnostic accuracy for ASD assessment and response to therapy.</p><p><strong>Methods: </strong>Systematic review of studies on human participants with an ASD diagnosis, sourced from Medline, Embase, Scopus, Web of Science, IEEE Xplore, and ACM Digital Library, evaluated the diagnostic accuracy of AI algorithms in ASD classification and their use in tracking social development through facial information for clinical application in social interactions. Bivariate and multi-level models addressed dependencies, heterogeneity, moderators (modalities, algorithms, tasks), and applied robust variance estimation. Publication bias was evaluated with funnel plots. The QUADAS-2 tool assessed the risk of bias and applicability. This study was registered on PROSPERO (CRD42021249905).</p><p><strong>Findings: </strong>Of 40,570 studies identified, 38 met the review criteria, and seven provided sufficient data for meta-analysis. The pooled diagnostic odds ratio of 15.917 (95% CI [4.775-53.059]), and bivariate analysis estimated an area under the receiver operating characteristic curve of 0.862. Accuracy improved with facial features, unstructured play, support vector machines, and decision tree-based algorithms. AI methods can analyse social behaviours, including eye gaze on social stimuli, emotional expression, and joint attention in ASD assessments. AI-enabled robots have also been used to guide therapy.</p><p><strong>Interpretation: </strong>This study shows that AI can accurately and objectively augment ASD assessments, track social behaviours, and enhance therapy outcomes. Further validation in diverse populations is needed to ensure clinical applicability and ethical use.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105931"},"PeriodicalIF":10.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Once-daily dolutegravir/lamivudine fixed-dose formulations in children living with HIV: a pharmacokinetic and safety sub-study nested in the open-label, multicentre, randomised, non-inferiority D3/PENTA 21 trial.","authors":"Lisanne A H Bevers, Gabriela Toledo, Muzamil Kisekka, Elizabeth Kaudha, Grace M Ahimbisibwe, Isabelle Deprez, Tiyara Arumugan, Ebrahim Variava, Avy Violari, Iona White, Dickson Bbuye, Annet Nanduudu, Enoch Mulwanyi, Pauline Amuge, Diana A Rutebarika, Adeodata Kekitiinwa, Cissy Kityo, Philippa Musoke, Moherndran Archary, Justine Boles, Margaret J Thomason, Saskia N de Wildt, Carlo Giaquinto, Angela Colbers, David M Burger, Ann M Buchanan, Man K Chan, Tom G Jacobs, Anna Turkova","doi":"10.1016/j.ebiom.2025.105929","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105929","url":null,"abstract":"<p><strong>Background: </strong>Two-drug regimen dolutegravir/lamivudine (DTG/3TC) is recommended as an alternative to standard three-drug regimens in adult treatment guidelines. This nested pharmacokinetic sub-study within the D3/Penta 21 randomised trial (#NCT04337450) assessed DTG and 3TC concentrations and safety in virologically-suppressed children, switching to once-daily DTG/3TC fixed-dose formulations.</p><p><strong>Methods: </strong>Children aged 2-<15 years received either 5/30 mg DTG/3TC dispersible tablets (DT) or 50/300 mg film-coated tablets (FCT), using WHO weight band (WB)-aligned dosing: 10-<14 kg 4 DTs; 14-<20 kg 5 DTs; 20-<25 kg 6 DTs or 1 FCT; 25-<40 kg 1 FCT. A minimum of 8-evaluable pharmacokinetic curves per WB/formulation were targeted for 24 h pharmacokinetic profiling (t = 0, 1, 2, 3, 4, 6, and 24 h post-dosing) at steady state. The number of children with DTG C_trough <0.32 mg/L (EC90) and <0.064 mg/L (PA-IC90) were summarised. Safety was evaluated through 48 weeks in eligible children consented to the pharmacokinetic sub-study.</p><p><strong>Findings: </strong>Between 11th May 2022 and 31st May 2023, 82 children consented for the sub-study. Seventy-two were included in the pharmacokinetic analysis; median (IQR) age was 7.1 (4.9-10.0) years and weight 21.6 (17.7-24.8) kg. DTG geometric mean (GM) (%CV) C_trough and AUC_{0-24 h} were 0.82 (54) mg/L and 66.2 (35) h∗mg/L. 3TC GM-AUC_{0-24 h} was 16.2 (45) h∗mg/L. Three children had DTG C_trough<0.32 mg/L, all had DTG C_trough ≥0.064 mg/L. In children weighing 20-<25 kg WB and taking 1 FCT (50/300 mg) 3TC GM AUC_{0-24 h} was 19% higher than in children ≥25 kg (1 FCT). Of 82 children, 3 had 4 serious adverse events (SAEs) and 5 had 6 grade ≥3 adverse events (AEs). No AEs were related to DTG/3TC or resulted in treatment discontinuation. No 3TC-related AEs or laboratory abnormalities were observed in children taking FCT in the 20-<25 kg WB. PK parameters were comparable to historical paediatric data from ODYSSEY (DTG) and IMPAACT2019 (3TC) trials.</p><p><strong>Interpretation: </strong>The study demonstrated adequate DTG and 3TC exposures with reassuring safety profiles using WB-based dosing, supporting licencing applications for dispersible and film-coated DTG/3TC formulations for paediatric use.</p><p><strong>Funding: </strong>The D3/Penta 21 trial is sponsored by Fondazione Penta Onlus ETS (Penta) and funded by ViiV Healthcare.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105929"},"PeriodicalIF":10.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broadening dementia risk models: building on the 2024 Lancet Commission report for a more inclusive global framework.","authors":"Cyprian M Mostert, Chinedu Udeh-Momoh, Andrea Sylvia Winkler, Connor McLaughlin, Harris Eyre, Mohamed Salama, Kirti Ranchod, Dominic Trepel, George Vradenburg, William Hynes, Graham Fieggen, Shehzad Ali, Najat E L Mekkaoui, Alan Landay, Kirsten Bobrow, Levi Muyela, Kelly Atkins, Antonella Santuccione Chadha, Roberta Marongiu, Mariapaola Barbato, Sam Nightingale, John Joska, Alfred K Njamnshi, Mie Rizig, James G Kahn, Karen Blackmon, Zul Merali, Agustin Ibanez","doi":"10.1016/j.ebiom.2025.105950","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105950","url":null,"abstract":"<p><p>The 2024 Lancet Commission Report on dementia prevention has identified 14 modifiable risk factors that account for approximately 45% of global dementia cases. We used a global multidimensional approach that integrates gender equity considerations, poverty, wealth shocks, income inequality and HIV infection rates to identify additional risk factors beyond those reported in 2024 report. This methodological framework aims to enhance equitable prevention strategies to mitigate the global burden of dementia. We demonstrate that adding four additional risk factors: poverty, wealth shocks, income inequality, and HIV, while also considering the influences of sex and gender will improve the global applicability of the 2024 report. This is important because, despite dementia primarily affecting women, 57% of the risk factors identified in the 2024 report are more prevalent in men. Our analysis suggests that incorporating these four additional factors could potentially increase the proportion of preventable dementia cases to about 65%. This approach would also reshape the understanding of dementia risk, indicating that around 56% of modifiable risks disproportionately impact women. Expanding risk models in this manner is crucial for developing equitable and effective global dementia prevention strategies, particularly in underrepresented regions. We present these considerations as enhancements to the Commission's significant work.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105950"},"PeriodicalIF":10.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}