EBioMedicine最新文献

{"title":"An automated blood test for glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) to predict the absence of intracranial lesions on head CT in adult patients with mild traumatic brain injury: BRAINI, a multicentre observational study in Europe.","authors":"Alfonso Lagares, Javier de la Cruz, Hugo Terrisse, Odile Mejan, Vladislav Pavlov, Celine Vermorel, Jean-François Payen","doi":"10.1016/j.ebiom.2024.105477","DOIUrl":"10.1016/j.ebiom.2024.105477","url":null,"abstract":"<p><strong>Background: </strong>Following mild traumatic brain injury (mTBI), elevated concentrations of brain-specific blood proteins glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) may be indicative of intracranial lesions normally detected by head CT scans. We sought to validate the performance of this combination of biomarkers at predetermined cutoff values with an automated immunoassay to predict which patients did not have intracranial lesions.</p><p><strong>Methods: </strong>This prospective, observational study was conducted in France and Spain at 16 emergency departments. Adult patients with mTBI were eligible if they had a head CT scan and gave a 10-ml blood sample within 12 h of injury. GFAP and UCH-L1 serum concentrations were measured and analysed, in less than an hour time, according to predefined cutoff values of 22 pg/ml and 327 pg/ml, respectively. Serum concentrations of S100B protein were concomitantly determined in a subset of patients. The primary outcome measures were the sensitivity and negative predictive value (NPV) of the combined GFAP-UCH-L1 test to rule out intracranial lesions on head CT scans.</p><p><strong>Clinicaltrials: </strong>gov (NCT04032509).</p><p><strong>Findings: </strong>Between August 2019 and June 2021, 1508 patients were recruited, and 1438 were included in the main analysis. Median age was 69 years (IQR 44-83). Most patients (74%) presented 3 h after trauma. 179 (12.4%) patients were positive for intracranial lesions by CT. The sensitivity of the combined test was 98.3% (95% CI 95.0-99.7) and the specificity 24.9 (95% CI 22.6-27.4), with a NPV of 99.1% (95% CI 97.1-99.8). Three patients with a positive CT scan had negative biomarker test results. S100B had a sensitivity of 83.0% (95% CI 76.2-88.2) and a NPV of 94.2% (95% CI 91.6-96.0). Patients with higher biomarker values more frequently had poorer recovery at 3 months after injury.</p><p><strong>Interpretation: </strong>Testing for GFAP and UCH-L1, using validated cutoffs obtained with a new, fast automated immunoassay platform, accurately predicted the absence of intracranial lesions on head CT following mTBI.</p><p><strong>Funding: </strong>This study is co-funded by the European Institute of Innovation and Technology (EIT) Health, a body of the European Union (Grant nº19474). Biomarkers tests were funded by bioMérieux.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105477"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754791","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":"Assessing the direct and spillover protective effectiveness of Wolbachia-mediated introgression to combat dengue.","authors":"Jo Yi Chow, Somya Bansal, Borame S L Dickens, Pei Ma, Ary Hoffmann, Yoon Ling Cheong, Nazni Wasi Ahmad, Jue Tao Lim","doi":"10.1016/j.ebiom.2024.105456","DOIUrl":"10.1016/j.ebiom.2024.105456","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Dengue remains a global health challenge with limited treatment options, highlighting the need for effective vector control strategies. The introduction of Wolbachia pipientis into Aedes aegypti populations has shown success in reducing dengue transmission across global field trials. However, the spillover effectiveness of the technology on untreated areas is not well-known. This study estimates the spillover protective effectiveness (PE) of Wolbachia-mediated introgression on dengue.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used the synthetic control method (SCM) under assumption of partial interference to evaluate the direct and spillover PEs of Wolbachia-mediated introgression in a long-running operational trial of the intervention in Malaysia. Synthetic controls (SCs), which comprise of a weighted sum of non-spillover controls, were constructed for each directly-treated and spillover site in the pre-intervention period to account for historical imbalances in dengue risk and risk trajectories. SCs were compared to directly/spillover-treated sites to estimate the impact of Wolbachia-introgression on dengue incidence across each site, calendar year and intervention time. Robustness checks, including visual inspections, root-mean-square error (RMSE) calculations, in-space and in-time placebo checks, and permutation tests, were used to inspect the model's ability in attributing dengue incidence reductions to the Wolbachia interventions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;The direct and spillover PEs of Wolbachia on dengue incidence were expressed as a percentage reduction of dengue incidence, or the absolute case reductions, by comparing SCs to actual intervention/spillover sites. Findings indicate a direct reduction in dengue incidence by 64.35% (95% CI: 63.50-66.71, p &lt; 0.05 using permutation tests) in directly treated areas, corresponding to 1802 (95% CI: 1768-1932) cases averted. Meanwhile, spillover effects contributed to a 37.69% (95% CI: 36.45-38.49, p &lt; 0.05) reduction in adjacent non-intervention areas, accounting for 115 (95% CI: 104-132) absolute cases averted. Tracking PEs by intervention time revealed a dose-response relationship, where PEs increased concomitantly with Wolbachia frequency. Model checks confirmed the robustness of these results, and ascertained that these PEs were not an artefact of poor control selection, pre-trends in dengue incidence or poor predictive ability of the fitted SCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Wolbachia-introgression effectively diminished dengue incidence in directly-treated and surrounding spillover regions. This dual effectiveness highlights the potential of Wolbachia-infected mosquitoes as a sustainable, cost-effective strategy against dengue.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;This research is hosted by CNRS@CREATE and supported by the National Research Foundation, Prime Minister's Office, Singapore, under its Campus for Research Excellence and Technological Enterpri","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105456"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767432","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":"Deep learning-based body composition analysis from whole-body magnetic resonance imaging to predict all-cause mortality in a large western population.","authors":"Matthias Jung, Vineet K Raghu, Marco Reisert, Hanna Rieder, Susanne Rospleszcz, Tobias Pischon, Thoralf Niendorf, Hans-Ulrich Kauczor, Henry Völzke, Robin Bülow, Maximilian F Russe, Christopher L Schlett, Michael T Lu, Fabian Bamberg, Jakob Weiss","doi":"10.1016/j.ebiom.2024.105467","DOIUrl":"10.1016/j.ebiom.2024.105467","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Manually extracted imaging-based body composition measures from a single-slice area (A) have shown associations with clinical outcomes in patients with cardiometabolic disease and cancer. With advances in artificial intelligence, fully automated volumetric (V) segmentation approaches are now possible, but it is unknown whether these measures carry prognostic value to predict mortality in the general population. Here, we developed and tested a deep learning framework to automatically quantify volumetric body composition measures from whole-body magnetic resonance imaging (MRI) and investigated their prognostic value to predict mortality in a large Western population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The framework was developed using data from two large Western European population-based cohort studies, the UK Biobank (UKBB) and the German National Cohort (NAKO). Body composition was defined as (i) subcutaneous adipose tissue (SAT), (ii) visceral adipose tissue (VAT), (iii) skeletal muscle (SM), SM fat fraction (SMFF), and (iv) intramuscular adipose tissue (IMAT). The prognostic value of the body composition measures was assessed in the UKBB using Cox regression analysis. Additionally, we extracted body composition areas for every level of the thoracic and lumbar spine (i) to compare the proposed volumetric whole-body approach to the currently established single-slice area approach on the height of the L3 vertebra and (ii) to investigate the correlation between volumetric and single slice area body composition measures on the level of each vertebral body.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;In 36,317 UKBB participants (mean age 65.1 ± 7.8 years, age range 45-84 years; 51.7% female; 1.7% [634/36,471] all-cause deaths; median follow-up 4.8 years), Cox regression revealed an independent association between V&lt;sub&gt;SM&lt;/sub&gt; (adjusted hazard ratio [aHR]: 0.88, 95% confidence interval [CI] [0.81-0.91], p = 0.00023), V&lt;sub&gt;SMFF&lt;/sub&gt; (aHR: 1.06, 95% CI [1.02-1.10], p = 0.0043), and V&lt;sub&gt;IMAT&lt;/sub&gt; (aHR: 1.19, 95% CI [1.05-1.35], p = 0.0056) and mortality after adjustment for demographics (age, sex, BMI, race) and cardiometabolic risk factors (alcohol consumption, smoking status, hypertension, diabetes, history of cancer, blood serum markers). This association was attenuated when using traditional single-slice area measures. Highest correlation coefficients (R) between volumetric and single-slice area body composition measures were located at vertebra L5 for SAT (R = 0.820) and SMFF (R = 0.947), at L3 for VAT (R = 0.892), SM (R = 0.944), and at L4 for IMAT (R = 0.546) (all p &lt; 0.0001). A similar pattern was found in 23,725 NAKO participants (mean age 53.9 ± 8.3 years, age range 40-75; 44.9% female).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Automated volumetric body composition assessment from whole-body MRI predicted mortality in a large Western population beyond traditional clinical risk factors. Single slice areas were highly corr","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105467"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of neuroinflammation in cerebral amyloid angiopathy.","authors":"Hilde van den Brink, Sabine Voigt, Mariel Kozberg, Ellis S van Etten","doi":"10.1016/j.ebiom.2024.105466","DOIUrl":"10.1016/j.ebiom.2024.105466","url":null,"abstract":"<p><p>Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease characterized by vascular amyloid-β (Aβ) deposition. CAA is often seen in the brains of elderly individuals and in a majority of patients with Alzheimer's disease. The molecular pathways triggered by vascular Aβ, causing vessel wall breakdown and ultimately leading to intracerebral haemorrhage and cognitive decline, remain poorly understood. The occurrence of CAA-related inflammation (CAA-ri) and Amyloid-Related Imaging Abnormalities (ARIA) have sparked interest for a role of neuroinflammation in CAA pathogenesis. This review discusses prior studies of neuroinflammation in CAA and outlines potential future research directions targeting candidates such as matrix metalloproteinases, complement activation, microglial activation, reactive astrocytes and parenchymal border macrophages. Understanding the role of neuroinflammation in CAA pathogenesis could help identify new therapeutic strategies.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105466"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750439","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":"Composition of the neutralising antibody response predicts risk of BK virus DNAaemia in recipients of kidney transplants.","authors":"Stephanie M Y Chong, Rachel K Y Hung, Fernando Yuen Chang, Claire Atkinson, Raymond Fernando, Mark Harber, Ciara N Magee, Alan D Salama, Matthew Reeves","doi":"10.1016/j.ebiom.2024.105430","DOIUrl":"10.1016/j.ebiom.2024.105430","url":null,"abstract":"<p><strong>Background: </strong>BK polyomavirus (BKV) DNAaemia occurs in 10% of recipients of kidney transplants, contributing to premature allograft failure. Evidence suggests disease is donor derived. Hypothetically, recipient infection with a different BKV serotype increases risk due to poorer immunological control. Thus, understanding the composition and activity of the humoral anti-BKV responses in donor/recipient (D/R) pairs is critical.</p><p><strong>Methods: </strong>Using 224 paired pre-transplant D/R samples, BKV VP1 genotype-specific pseudoviruses were employed to define the breadth of the antibody response against different serotypes (ELISA) and, to characterise specific neutralising activity (nAb) using the 50% inhibitory concentration (LogIC50). Mismatch (MM) ratios were calculated using the ratio of recipient ELISA or nAb reactive BKV serotypes relative to the number of donor reactive serotypes.</p><p><strong>Findings: </strong>BKV DNAaemia was observed in 28/224 recipients of kidney transplants. These recipients had lower nAb titres against all the serotypes, with median logIC50 values of 1.19-2.91, compared to non-viraemic recipients' median logIC50 values of 2.13-3.30. nAb D/R MM ratios >0.67 associated with significantly higher risk of BKV viraemia, with an adjusted odds ratio of 5.12 (95% CI 2.07 to 13.04; p < 0.001). Notably, a mismatch against donor serotype Ic and II associated with adjusted odds ratios of 8.12 (95% CI 2.10 to 35.61; p = 0.002) and 4.52 (95% CI 1.19 to 19.23; p = 0.03) respectively. 21 recipients demonstrated broadly neutralising responses against all the serotypes, none of whom developed BKV DNAaemia post-transplant. In contrast, there was poor concordance with PsV-specific ELISA data that quantified the total antibody response against different serotypes.</p><p><strong>Interpretation: </strong>BKV nAb mismatch predicts post-transplant BKV DNAaemia. Specific mismatches in nAb, rather than total seroreactivity, are key indicators of BKV risk post-transplant. This has the potential to risk-stratify individuals and improve clinical outcomes by influencing the frequency of monitoring and individualised tailoring of immunosuppression. Furthermore, detailed examination of individuals with broadly neutralising responses may provide future therapeutic strategies.</p><p><strong>Funding: </strong>The research was funded by St. Peters Trust, Royal Free Hospital Charity and Wellcome Trust (grant numbers RFCG1718/05, SPT97 and 204870/Z/WT_/Wellcome Trust/United Kingdom).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105430"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638437","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 short-term exposure to ambient air pollution and temperature with bronchiectasis mortality: a nationwide time-stratified case-crossover study.","authors":"Shunlian Hu, Xiaowei Xue, Jiayan Xu, Peng Yin, Xia Meng, Haidong Kan, Renjie Chen, Maigeng Zhou, Jin-Fu Xu","doi":"10.1016/j.ebiom.2024.105465","DOIUrl":"10.1016/j.ebiom.2024.105465","url":null,"abstract":"<p><strong>Background: </strong>Ambient pollution and non-optimal temperature are major risk factors for respiratory health. However, the relationships between short-term exposure to these factors and bronchiectasis mortality remain unknown.</p><p><strong>Methods: </strong>A nationwide, time-stratified case-crossover study across Mainland China was conducted from 2013 to 2019. Records of bronchiectasis deaths were extracted from the National Death Registration Reporting Information System. Daily concentrations of fine particulate matter (PM_2.5), coarse particulate matter (PM_2.5-10), nitrogen dioxide (NO₂), ozone (O₃), and daily temperature were obtained from high-resolution prediction models. We utilized conditional logistic regression model and distributed lag nonlinear model to explore the associations of these exposures with bronchiectasis mortality.</p><p><strong>Findings: </strong>We included a total of 19,320 bronchiectasis deaths. Air pollutant was associated with bronchiectasis mortality within the first 3 days after exposure and the exposure-response relationships were almost linear. An interquartile range increase in PM_2.5, PM_2.5-10, and O₃ was associated with increments of 3.18%, 4.14%, and 4.36% in bronchiectasis mortality at lag 02 d, respectively. Additionally, lower temperature was associated with higher odds of bronchiectasis mortality. Compared to referent temperature (23.6 °C), the odds ratio for bronchiectasis mortality associated with extremely low temperature (P₁: -13.4 °C) was 1.54 (95% CI: 1.05, 2.25).</p><p><strong>Interpretation: </strong>This national study provides compelling evidence, and highlights the necessity and importance of reducing air pollution exposures and keeping warm for susceptible populations.</p><p><strong>Funding: </strong>National Natural Science Foundation of China (81925001; 82330070); Innovation Program of Shanghai Municipal Education Commission (202101070007-E00097); Program of Shanghai Municipal Science and Technology Commission (21DZ2201800); Program of Shanghai Shenkang Development Center (SHDC12023110); and Major Project of National Health Commission of China.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105465"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692734","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":"Response to the Letter regarding the EBIOM-D-23-04056: \"CPAP may promote an endothelial inflammatory milieu in sleep apnoea after coronary revascularization\".","authors":"Yuksel Peker, Yeliz Celik, Afrouz Behboudi, Susan Redline, Daniel J Gottlieb, Sanja Jelic","doi":"10.1016/j.ebiom.2024.105348","DOIUrl":"10.1016/j.ebiom.2024.105348","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105348"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563975","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":"Adjuvant rituximab and elevated intratumoural CD8 expression are associated with sustained disease control after radiotherapy in a randomised trial of systemic therapy in early-stage follicular lymphoma.","authors":"Michael P MacManus, John F Seymour, Hennes Tsang, Richard Fisher, Colm Keane, Muhammed B Sabdia, Soi C Law, Jay Gunawardana, Karthik Nath, Stephen H Kazakoff, Mario L Marques-Piubelli, Daniela E Duenas, Michael R Green, Daniel Roos, Peter O'Brien, Andrew McCann, Richard Tsang, Sidney Davis, David Christie, Chan Cheah, Benhur Amanuel, Tara Cochrane, Jason Butler, Anna Johnston, Mohamed Shanavas, Li Li, Claire Vajdic, Robert Kridel, Victoria Shelton, Samantha Hershenfield, Tara Baetz, David Lebrun, Nathalie Johnson, Marianne Brodtkorb, Maja Ludvigsen, Francesco d'Amore, Ella R Thompson, Piers Blombery, Maher K Gandhi, Joshua W D Tobin","doi":"10.1016/j.ebiom.2024.105468","DOIUrl":"10.1016/j.ebiom.2024.105468","url":null,"abstract":"<p><strong>Background: </strong>We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies.</p><p><strong>Methods: </strong>Patients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT + CVP). From 2006 rituximab was added to IFRT + CVP (IFRT + R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively).</p><p><strong>Findings: </strong>Between 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR] = 0.60, 95% CI = 0.37-0.98, p = 0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR = 0.44, 95% CI = 0.16-1.18, p = 0.11, 10-year OS 95% vs. 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p = 0.045). PFS of IFRT + R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT + CVP) was superior (HR = 0.36, 95% CI = 0.13-0.82, p = 0.013). Amongst PET-staged patients, PFS differences between IFRT + R-CVP vs. IFRT were maintained (HR = 0.38, 95% CI = 0.16-0.89, p = 0.027) indicating benefit distinct from stage migration. FL-related mutations and BCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR = 0.45, 95% CI = 0.26-0.79, p = 0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p = 0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p = 0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease.</p><p><strong>Interpretation: </strong>Adjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL.</p><p><strong>Funding: </strong>Cancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105468"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779653","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":"A retrospective genomic characterisation of the 2022 mpox outbreak in Belgium, and in vitro assessment of three antiviral compounds.","authors":"Tony Wawina-Bokalanga, Bert Vanmechelen, Anne-Sophie Logist, Mandy Bloemen, Lies Laenen, Sébastien Bontems, Marie-Pierre Hayette, Cécile Meex, Christelle Meuris, Catherine Orban, Emmanuel André, Robert Snoeck, Guy Baele, Samuel L Hong, Graciela Andrei, Piet Maes","doi":"10.1016/j.ebiom.2024.105488","DOIUrl":"10.1016/j.ebiom.2024.105488","url":null,"abstract":"<p><strong>Background: </strong>Since the beginning of May 2022, cases of mpox have been reported in several European and American countries where the disease is nonendemic. We performed a retrospective genomic characterisation of the 2022 mpox outbreak in Belgium, and assessed the in vitro sensitivity of three antiviral compounds to a monkeypox virus (MPXV) strain from the 2022 outbreak.</p><p><strong>Methods: </strong>We sequenced the complete genomes of MPXV isolated from skin-, throat-, anorectal- and genital swab samples using the Oxford Nanopore Technologies (ONT) GridION. We subsequently analysed high-quality complete MPXV genomes and conducted a genomic analysis of MPXV complete genomes from this study with all other complete MPXV genomes available on GISAID up to October 28th, 2022. The in vitro activity of tecovirimat, brincidofovir, and cidofovir was also tested in human and monkey cell lines.</p><p><strong>Findings: </strong>We produced 248 complete MPXV genomes. Phylogenetic analysis of the complete MPXV genomes revealed that they all belong to MPXV Clade IIb B.1. Surprisingly, through phylogeographic analysis we identified a minimum number of 79 introduction events into Belgium, along with sustained local transmission. We also demonstrated the superior in vitro efficacy and selectivity of tecovirimat to the 2022 MPXV clinical strain.</p><p><strong>Interpretation: </strong>The number of sequences provides sufficient information about the MPXV lineages that were circulating in Belgium. The 2022 mpox outbreak, in Belgium, was mainly characterised by many introduction events that were promptly contained and resulted in limited human-to-human transmission of MPXV. The in vitro efficacy of antivirals against a 2022 MPXV Belgian strain highlights the potent activity and specificity of tecovirimat and its ability to prevent the formation of the extracellular enveloped viruses.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105488"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767428","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":"Force-sensing protein expression in response to cardiovascular mechanotransduction.","authors":"Yongtao Wang, Emeli Chatterjee, Guoping Li, Jiahong Xu, Junjie Xiao","doi":"10.1016/j.ebiom.2024.105412","DOIUrl":"10.1016/j.ebiom.2024.105412","url":null,"abstract":"<p><p>Force-sensing biophysical cues in microenvironment, including extracellular matrix performances, stretch-mediated mechanics, shear stress and flow-induced hemodynamics, have a significant influence in regulating vascular morphogenesis and cardiac remodeling by mechanotransduction. Once cells perceive these extracellular mechanical stimuli, Piezo activation promotes calcium influx by forming integrin-adhesion-coupling receptors. This induces robust contractility of cytoskeleton structures to further transmit biomechanical alternations into nuclei by regulating Hippo-Yes associated protein (YAP) signaling pathway between cytoplasmic and nuclear translocation. Although biomechanical stimuli are widely studied in cardiovascular diseases, the expression of force-sensing proteins in response to cardiovascular mechanotransduction has not been systematically concluded. Therefore, this review will summarize the force-sensing Piezo, cytoskeleton and YAP proteins to mediate extracellular mechanics, and also give the prominent emphasis on intrinsic connection of these mechanical proteins and cardiovascular mechanotransduction. Extensive insights into cardiovascular mechanics may provide some new strategies for cardiovascular clinical therapy.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105412"},"PeriodicalIF":9.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557423","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}