EBioMedicine最新文献

{"title":"Involvement of Mediterranean fever gene mutations in colchicine-responsive enterocolitis: a retrospective cohort study.","authors":"Hiroshi Nakase, Kohei Wagatsuma, Taku Kobayashi, Takayuki Matsumoto, Motohiro Esaki, Kenji Watanabe, Reiko Kunisaki, Teruyuki Takeda, Katsuhiro Arai, Takashi Ibuka, Dai Ishikawa, Yuichi Matsuno, Hirotake Sakuraba, Nobuhiro Ueno, Kaoru Yokoyama, Masayuki Saruta, Ryota Hokari, Junji Yokoyama, Shu Tamano, Masanori Nojima, Tadakazu Hisamatsu","doi":"10.1016/j.ebiom.2024.105454","DOIUrl":"10.1016/j.ebiom.2024.105454","url":null,"abstract":"<p><strong>Background: </strong>The involvement of Mediterranean fever (MEFV) gene mutations in patients with inflammatory bowel disease unclassified (IBDU) remains unclear. This study aimed to determine the clinical characteristics and responsiveness to colchicine in Japanese patients with IBDU carrying MEFV mutations.</p><p><strong>Methods: </strong>In this retrospective cohort study, we examined MEFV mutations using gene analysis, clinical information, and colchicine responsiveness. Furthermore, we examined cytokine production in exon 2-mutated THP-1 cells (a monocytic cell line) and microbiome analysis.</p><p><strong>Findings: </strong>Of the 396 patients diagnosed with IBDU, 60.1% had MEFV mutations. Exon 2 mutations were the most common (83.7%). Among patients with available clinical information, 43.3% of patients with IBDU had typical Familial Mediterranean fever (FMF). The efficacy of colchicine in patients with IBDU carrying MEFV mutations was 84.6%. Significant differences were noted in the production of inflammatory; cytokines between THP-1 cells with and without MEFV mutations. Microbial compositions differed between patients with IBDU carrying MEFV mutations and patients with IBD and healthy controls.</p><p><strong>Interpretation: </strong>Patients with IBDU carrying MEFV mutations responded well to colchicine treatment. A notable subset of patients met the criteria for typical FMF. Alterations in intestinal microbiota may contribute to disease pathogenesis.</p><p><strong>Funding: </strong>This work was supported by the Japan Agency for Medical Research and Development (21ek0410057h0003), a grant from the Uehara Memorial Foundation, and the Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare (MHLW) of Japan (Investigation and Research for Intractable Inflammatory Bowel Disease; Grant Number 20316729).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105454"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681144","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":"Advancing respiratory virus diagnostics: integrating the nasal IFN-I score for improved viral detection.","authors":"Marine Mommert-Tripon, Delphine Parraud, Cloé Grosbois, Alexandre Gaymard, Valérie Cheynet, Bruno Lina, Guy Oriol, Frédéric Laurent, Caroline Dupré, Quentin Semanas, Antonin Bal, Laurence Generenaz, Sylvie Pons, Karen Brengel-Pesce, Audrey Guichard, William Mouton, Florence Morfin, Aurore Fleurie, Sophie Trouillet-Assant","doi":"10.1016/j.ebiom.2024.105450","DOIUrl":"10.1016/j.ebiom.2024.105450","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to demonstrate the utility of the nasal Type I interferon (IFN-I) response as a marker for respiratory viral infections (RVIs) and its potential to enhance diagnosis when combined with first-line PCR tests for Influenza A/B, RSV, and SARS-CoV-2.</p><p><strong>Methods: </strong>Nasopharyngeal swabs (NPS) from patients at Hospices Civils de Lyon (November 2022-April 2024) suspected of viral infections (n = 788) and from healthy controls (n = 53) were analysed. The IFN-I score was measured using the FILMARRAY® IFN-I pouch prototype, which detects four interferon-stimulated genes. The study evaluated the performance of the IFN-I score in detecting samples positive for viruses by first-line PCR and assessed its benefit in diagnosing RVIs in samples initially classified as negative by PCR.</p><p><strong>Findings: </strong>Out of 788 NPS included, 504 (64%) were positive with the first-line PCR tests, and IFN-I score was significantly higher in those samples (median [IQR]: 13.00 [2.76-45.40]) compared to ones collected from healthy controls (1.09 [0.67-1.30]; p < 0.0001), with an area under the curve (AUC; 95% CI) of 0.92 (0.90-0.92). Moreover, out of the 284 NPS negative with first-line PCR tests, suspicion of viral infection according to IFN-I score was found in 63% of cases (178/284). Second-line test (BioFire® Respiratory Panel 2.1 plus) and viral metagenomic confirmed the presence of viruses 94% of cases.</p><p><strong>Interpretation: </strong>The study highlights the potential of integrating nasal IFN-I score into clinical workflows to improve RVI diagnosis and enhance preparedness for emerging viruses.</p><p><strong>Funding: </strong>Public grant overseen by the French National Research Agency (ANR21-RHUS-08/ANR-23-CHIN-0001).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105450"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692720","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":"FGF21 and its underlying adipose tissue-liver axis inform cardiometabolic burden and improvement in obesity after metabolic surgery.","authors":"Marie Patt, Isabel Karkossa, Laura Krieg, Lucas Massier, Kassem Makki, Shirin Tabei, Thomas Karlas, Arne Dietrich, Martin Gericke, Michael Stumvoll, Matthias Blüher, Martin von Bergen, Kristin Schubert, Peter Kovacs, Rima M Chakaroun","doi":"10.1016/j.ebiom.2024.105458","DOIUrl":"10.1016/j.ebiom.2024.105458","url":null,"abstract":"<p><strong>Background: </strong>This research investigates the determinants of circulating FGF21 levels in a cohort reflecting metabolic disease progression, examining the associations of circulating FGF21 with morphology and function of adipose tissue (AT), and with metabolic adjustments following metabolic surgery.</p><p><strong>Methods: </strong>We measured serum FGF21 in 678 individuals cross-sectionally and in 189 undergoing metabolic surgery longitudinally. Relationships between FGF21 levels, AT histology, transcriptomes and proteomes, cardiometabolic risk factors, and post-surgery metabolic adjustments were assessed using univariate and multivariate analyses, causal mediation analysis, and network integration of AT transcriptomes and proteomes.</p><p><strong>Findings: </strong>FGF21 levels were linked to central adiposity, subclinical inflammation, insulin resistance, and cardiometabolic risk, and were driven by circulating leptin and liver enzymes. Higher FGF21 were linked with AT dysfunction reflected in fibro-inflammatory and lipid dysmetabolism pathways. Specifically, visceral AT inflammation was tied to both FGF21 elevation and liver dysfunction. Post-surgery, FGF21 peaked transitorily at three months. Mediation analysis highlighted an underlying increased AT catabolic state with elevated free fatty acids (FFA), contributing to higher liver stress and FGF21 levels (total effect of free fatty acids on FGF21 levels: 0.38, p < 0.01; proportion mediation via liver 32%, p < 0.01). In line with this, histological AT fibrosis linked with less pronounced FGF21 responses and reduced fat loss post-surgery (FFA and visceral AT fibrosis: rho = -0.31, p = 0.030; FFA and fat-mass loss: rho = 0.17, p = 0.020).</p><p><strong>Interpretation: </strong>FGF21 reflects the liver's disproportionate metabolic stress response in both central adiposity and after metabolic surgery, with its dynamics reflecting an AT-liver crosstalk.</p><p><strong>Funding: </strong>This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through CRC 1052, project number 209933838, CRC1382 and a Walther-Benjamin Fellowship and by a junior research grant by the Medical Faculty, University of Leipzig, and by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1501. Part of this work was supported by the European Union's Seventh Framework Program for research, technological development and demonstration under grant agreement HEALTH-F4-2012-305312 and by the CRC1382 and the Novo Nordisk Foundation and by the Deutsche Forschungsgemeinschaft (DFG, German Research foundation) project number 530364326.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105458"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750432","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":"Identifying WHO global priority endemic pathogens for vaccine research and development (R&D) using multi-criteria decision analysis (MCDA): an objective of the Immunization Agenda 2030.","authors":"Mateusz Hasso-Agopsowicz, Angela Hwang, Maria-Graciela Hollm-Delgado, Isis Umbelino-Walker, Ruth A Karron, Raman Rao, Kwaku Poku Asante, Meru Sheel, Erin Sparrow, Birgitte Giersing","doi":"10.1016/j.ebiom.2024.105424","DOIUrl":"10.1016/j.ebiom.2024.105424","url":null,"abstract":"<p><strong>Background: </strong>To date, global priorities for new vaccine R&D have not been systematically identified for endemic pathogens. As part of Immunisation Agenda 2030 (IA2030), we have systematically identified priority endemic pathogens for new vaccine R&D based on country and regional stakeholder values to address this need.</p><p><strong>Methods: </strong>MCDA surveys targeting policy makers and immunisation stakeholders in each World Health Organization (WHO) region were used to weight eight criteria for prioritisation. Applying those weights to regional pathogen data yielded regional top ten pathogen lists, which are intended to inform regional deliberations on R&D priorities. The regional top ten lists were combined into an IA2030 global priority list. To inform R&D, use cases for new vaccines and monoclonal antibodies were identified, then categorized in terms of the activities needed to accelerate progress.</p><p><strong>Findings: </strong>In five out of six WHO regions, Annual deaths in children under five and Contribution to antimicrobial resistance were the most heavily weighted criteria. How participants weighted the criteria was not associated with their region, biographical characteristics, or areas of expertise. Five pathogens were common priorities across all regions: M tuberculosis, HIV-1, K pneumoniae, S aureus, and Extra-intestinal pathogenic E coli. Six pathogens were priorities in single regions. Combining regional top ten lists provided a global list of 17 priority pathogens for new vaccine R&D. Thirty-four distinct use cases were identified for new products targeting these pathogens. While most are in the \"Advance product development\" category, ten are in the \"Research\" category and seven are in the \"Prepare to implement\" category.</p><p><strong>Interpretation: </strong>These priorities for new vaccine R&D will help stakeholders better respond to regional and country needs. The use cases will inform R&D and enable monitoring of R&D under IA2030.</p><p><strong>Funding: </strong>The work was funded by a Bill and Melinda Gates Foundation grant to WHO (INV-005318).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105424"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582338","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":"Association of early life cardiovascular risk factors with grey matter structure in young adults in the United Kingdom: the ALSPAC study.","authors":"Holly T Haines, Sana Suri, Raihaan Patel, Scott T Chiesa","doi":"10.1016/j.ebiom.2024.105490","DOIUrl":"10.1016/j.ebiom.2024.105490","url":null,"abstract":"<p><strong>Background: </strong>Cumulative exposures to obesity, hypertension, and physical inactivity from midlife (40-65 years) onwards are three known cardiovascular risk factors for dementia and associated cerebral structural damage. Exactly how early in the lifespan sensitive periods for exposure to these risk factors begin is yet to be established, specifically with respect to onset of cerebral structural changes. We aimed to investigate whether cardiovascular risk across childhood and adolescence is already associated with cerebral structure in regions previously linked with dementia, during young adulthood.</p><p><strong>Methods: </strong>Participants were selected from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK-based prospective cohort of young people, if they had participated in a neuroimaging sub-study (N = 862). We entered data from repeated clinical assessments into mixed-effects models to estimate baseline and rate of change in body mass index (BMI) and mean arterial pressure (MAP) between ages 7-17 years, and physical activity (PA) between 11-15 years. Linear models assessed whether cardiovascular risk factors were associated with grey matter macrostructural indices (cortical thickness, surface area, volume) in young adulthood (∼20 years).</p><p><strong>Findings: </strong>BMI was found to be associated with grey matter macrostructure in nodes of Default Mode Network previously found to show atrophy in dementia. Baseline BMI was associated with thickness of precuneus cortex and entorhinal surface area, whilst rate of change in BMI across childhood and adolescence was associated with thickness of parahippocampal and middle temporal gyri and inferior parietal cortex in addition to entorhinal and parahippocampal surface area. Further, we identified associations between baseline MAP and PA and entorhinal surface area. Exploratory whole-brain analyses revealed associations between baseline and rate of change in these cardiovascular risk factors and the cortical thickness, surface area, and volume of broader groups of cortical and subcortical regions.</p><p><strong>Interpretation: </strong>Findings provide preliminary evidence that cerebral structural differences in regions linked to dementia in old age may be legacy of developmental differences associated with cardiovascular risk exposure during early life. This has relevance for lifespan models of dementia risk and timing of preventative interventions. Further work is required to generalise findings beyond this predominantly white, male, and middle-class sample to more diverse cohorts.</p><p><strong>Funding: </strong>NIHR Oxford Health BRC (NIHR203316), Wellcome Trust (203139/Z/16/Z).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105490"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779656","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":"Liver SMN restoration rescues the Smn^2B/- mouse model of spinal muscular atrophy.","authors":"Emma R Sutton, Ariane Beauvais, Rebecca Yaworski, Yves De Repentigny, Aoife Reilly, Monique Marylin Alves de Almeida, Marc-Olivier Deguise, Kathy L Poulin, Robin J Parks, Bernard L Schneider, Rashmi Kothary","doi":"10.1016/j.ebiom.2024.105444","DOIUrl":"10.1016/j.ebiom.2024.105444","url":null,"abstract":"<p><strong>Background: </strong>The liver is a key metabolic organ, acting as a hub to metabolically connect various tissues. Spinal muscular atrophy (SMA) is a neuromuscular disorder whereby patients have an increased susceptibility to developing dyslipidaemia and liver steatosis. It remains unknown whether fatty liver is due to an intrinsic or extrinsic impact of survival motor neuron (SMN) protein depletion.</p><p><strong>Methods: </strong>Using an adeno-associated viral vector with a liver specific promoter (albumin), we restored SMN protein levels in the liver alone in Smn^2B/- mice, a model of SMA. Experiments assessed central and peripheral impacts using immunoblot, immunohistochemistry, and electron microscopy techniques.</p><p><strong>Findings: </strong>We demonstrate that AAV9-albumin-SMN successfully expresses SMN protein in the liver with no detectable expression in the spinal cord or muscle in Smn^2B/- mice. Liver intrinsic rescue of SMN protein was sufficient to increase survival of Smn^2B/- mice. Fatty liver was ameliorated while key markers of liver function were also restored to normal levels. Certain peripheral pathologies were rescued including muscle size and pancreatic cell imbalance. Only a partial CNS recovery was seen using a liver therapeutic strategy alone.</p><p><strong>Interpretation: </strong>The fatty liver phenotype is a direct impact of liver intrinsic SMN protein loss. Correction of SMN protein levels in liver is enough to restore some aspects of disease in SMA. We conclude that the liver is an important contributor to whole-body pathology in Smn^2B/- mice.</p><p><strong>Funding: </strong>This work was funded by Muscular Dystrophy Association (USA) [grant number 963652 to R.K.]; the Canadian Institutes of Health Research [grant number PJT-186300 to R.K.].</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105444"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603845","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":"Multi-omic characteristics of longitudinal immune profiling after breakthrough infections caused by Omicron BA.5 sublineages.","authors":"Yanhua Li, Shijie Qin, Lei Dong, Yunfeng Xiao, Yanan Zhang, Yali Hou, Shitong Qiao, Rong Zhang, Ying Li, Yanmin Bao, Xin Zhao, Yueyun Ma, George Fu Gao","doi":"10.1016/j.ebiom.2024.105428","DOIUrl":"10.1016/j.ebiom.2024.105428","url":null,"abstract":"<p><strong>Background: </strong>Omicron sub-variants breakthrough infections (BTIs) have led to millions of coronavirus disease 2019 (COVID-19) cases worldwide. The acute-phase immune status is critical for prognosis, however, the dynamic immune profiling of COVID-19 during the first month after BTIs remains unclear.</p><p><strong>Methods: </strong>In this study, we monitored the immune dynamics at various timepoints in a longitudinal cohort during the first month post-BTIs through clinical evaluation, single-cell RNA sequencing (scRNA-seq), T cell receptor (TCR)/B cell receptor (BCR) sequencing, and antibody mass spectrometry.</p><p><strong>Findings: </strong>Serological analysis revealed limited impairment to functions of major organs, active cellular and humoral immunity at 2 weeks post-BTI, with significant increases in cytokines (CKs) and neutralizing antibody levels. However, 1 month post-BTI, organ function parameters and CK levels reverted to pre-infection levels, whereas neutralizing antibody levels remained high. Notably, scRNA-seq showed that lymphocytes maintained strong antiviral activity and cell depletion at 2 weeks and 1 month post-BTI, with genes CD81, ABHD17A, CXCR4, DUSP1, etc. upregulated, and genes PFDN5, DYNLRB1, CD52, etc. downregulated, indicating that lymphocytes status take longer to recover to normal levels than that routine blood tests revealed. Additionally, T cell-exhaustion associated genes, including LAG3, TIGIT, PDCD1, CTLA4, HAVCR2, and TOX, were upregulated after BTI. TCRs and BCRs exhibited higher clonotypes, mainly in CD8Tem or plasmablast cells, at 2 weeks post-BTI comparing 1 month. More IgG and IgA-type BCRs were found in the groups of 1 month post-BTI, with higher somatic hypermutation, indicating greater maturity. Verification of monoclonal antibodies corresponding to amplified BCRs highlighted the antigen-specific and broad-spectrum characteristics.</p><p><strong>Interpretation: </strong>Our study elucidated the dynamic immune profiling of individuals after Omicron BA.5 sublineages BTI. Strong immune activation, antiviral response, antibody maturation and class transition at 2 weeks and 1 month after BTI may provide essential insights into pathogenicity, sequential immune status, recovery mechanisms of Omicron sublineage BTI.</p><p><strong>Funding: </strong>This study was supported by the National Key R&D Program of China, the China Postdoctoral Science Foundation, Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, CAS Project for Young Scientists in Basic Research, and the Air Force Special Medical Center Science and Technology Booster Program.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105428"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616649","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":"Translocation of black carbon particles to human intestinal tissue.","authors":"Thessa Van Pee, Kenneth Vanbrabant, Leen Rasking, Peter Van Eyken, Janneke Hogervorst, Philip Caenepeel, Marcel Ameloot, Michelle Plusquin, Tim S Nawrot","doi":"10.1016/j.ebiom.2024.105464","DOIUrl":"10.1016/j.ebiom.2024.105464","url":null,"abstract":"<p><strong>Background: </strong>Evidence is accumulating that elevated levels of particulate air pollution, including black carbon, have been linked to gastrointestinal disorders and a lower intestinal bacterial richness and diversity. One of the hypothesized underlying mechanisms is the absorption of air pollution-related particles from the gastrointestinal tract.</p><p><strong>Methods: </strong>We visualized and quantified black carbon particles via white light generation under femtosecond-pulsed laser illumination in ileum and colon biopsies of five human patients. The biodistribution was assessed in three different layers (i.e., mucosa, submucosa, and muscularis propria).</p><p><strong>Findings: </strong>Black carbon particles could be identified in all three tissue layers of the ileum and colon biopsies of five participants (two men and three women; mean ± standard deviation age, 76.40 ± 7.37 years), and their carbonaceous nature was confirmed via emission fingerprinting. The median (±SD) black carbon load was borderline statistically significantly higher in the ileum compared to the colon (1.21 × 10⁵ ± 1.68 × 10⁴ particles/mm³ versus 9.34 × 10⁴ ± 1.33 × 10⁴ particles/mm³; p = 0.07) and was driven by a difference in black carbon load in the submucosa layer (p = 0.01). Regarding the three tissue layers, loads were higher in the submucosa, compared with the mucosa (ileum: +76%, p < 0.0001; colon: +70%, p = 0.0001) and muscularis propria (ileum: +88%, p < 0.0001; colon: +88%, p < 0.0001). In ileum, loads were borderline higher in the mucosa versus muscularis propria (p = 0.09).</p><p><strong>Interpretation: </strong>This explorative study provides real-life evidence that black carbon particles can reach the intestinal tissue and accumulate in different intestinal tissue layers. These findings support further research into how particulate air pollution directly affects gastrointestinal health.</p><p><strong>Funding: </strong>Thessa Van Pee holds a doctoral fellowship from the Research Foundation Flanders (FWO), grant number: 11C7421N. Tim Nawrot is a Methusalem grant holder.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105464"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709567","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":"Continuous characterisation of exacerbation pathophysiology using wearable technologies in free-living outpatients with COPD: a prospective observational cohort study.","authors":"Felix-Antoine Coutu, Olivia C Iorio, Seyedfakhreddin Nabavi, Amir Hadid, Dennis Jensen, Sushmita Pamidi, Jianguo Xia, Bryan A Ross","doi":"10.1016/j.ebiom.2024.105472","DOIUrl":"10.1016/j.ebiom.2024.105472","url":null,"abstract":"<p><strong>Background: </strong>The most recent exacerbation of COPD (ECOPD) classification criteria relies in part on changes in respiratory rate (RR), heart rate (HR) and oxygen saturation (SpO₂). Despite this paradigm shift, a thorough understanding of exacerbation patterns is still lacking, as is the identification of physiological exacerbation biomarkers.</p><p><strong>Methods: </strong>Using a convenience sampling approach, this prospective observational cohort study was conducted between February 2023 and January 2024. Continuous measurements of daytime/overnight respiratory (primary outcome), cardiovascular, autonomic, activity and sleep-related parameters were collected by a wearable biometric wristband and ring over 21 consecutive days in free-living outpatients experiencing and receiving treatment (≤3 days) for a current exacerbation from the home environment. The EXACT-PRO questionnaire served as the validated reference for daily symptom burden and to identify 'recovered' versus 'persistent worsening' participants. Unadjusted and adjusted (for age, sex, FEV₁) linear mixed-effects models were fitted to estimate associations between each physiological parameter with daily EXACT-PRO score (points, pts), in all, 'recovered', and 'persistent worsening' participants. Results are presented as point estimates with 95% CIs.</p><p><strong>Findings: </strong>In 21 participants with COPD (43% female, mean age 66.8, BMI 27.7 kg/m², FEV₁ 36.3% predicted; 85.7% with GOLD 3-4 disease), significant associations in unadjusted models with daily EXACT-PRO score included RR variability (-1.45 [-2.84, -0.073] pts/breath/min) but not RR, daily step count (-0.56 [-0.82, -0.31] pts/1000 steps), and sleep efficiency (-0.12 [-0.20, -0.037] pts/%asleep). In 'recovered' participants (n = 10), significant associations included nighttime HR, movement intensity and nightly SpO₂. In 'persistent worsening' participants (n = 11), significant associations included HR variability, nightly RR variability, nightly SpO₂, sleep efficiency, and skin temperature. Similar results were found in adjusted models.</p><p><strong>Interpretation: </strong>This study provides a prospective continuous characterisation of exacerbations of COPD using remotely collected, ambulatory/free-living data. The physiological patterns presented may contribute to the understanding of exacerbations and may enhance the development of effective remote monitoring solutions.</p><p><strong>Funding: </strong>University hospital (MUHC-CAS) grant.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105472"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695276","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":"Circadian rhythms in haematological malignancies: therapeutic potential and personalised interventions.","authors":"Marjan Motiei, Raed Abu-Dawud, Angela Relógio, Chalid Assaf","doi":"10.1016/j.ebiom.2024.105451","DOIUrl":"10.1016/j.ebiom.2024.105451","url":null,"abstract":"<p><p>The circadian clock, a fundamental cellular mechanism, regulates the rhythmic expression of numerous genes and biological processes across various organs. Disruptions in this system, driven by genetic or environmental factors, have been reported to be involved in cancer progression. This review explores the role of the circadian clock in cancer hallmarks and its impact on cellular homeostasis within haematological malignancies. Drawing on findings from in vitro, in vivo, and clinical trials, this review highlights the potential of clock genes as diagnostic and prognostic biomarkers, and as therapeutic targets for optimising treatment timing. It discusses how circadian rhythms can enhance treatment efficacy through both pharmacological and non-pharmacological interventions, outlining strategies for optimising dosing schedules and implementing personalised chronobiological interventions, with a particular focus on haematological malignancies, including cutaneous lymphoma. Ongoing research holds promise for advancing personalised therapeutic approaches and ultimately improving cancer care standards.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105451"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681133","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}