EBioMedicine最新文献

{"title":"PfSPZ Vaccine induces focused humoral immune response in HIV positive and negative Tanzanian adults.","authors":"Anneth Tumbo, Freia-Raphaella Lorenz, Annie S P Yang, Stephanie Sefried, Tobias Schindler, Maximilian Mpina, Jean-Pierre Dangy, Florence A Milando, Mohammed A Rashid, Gloria Nyaulingo, Kamaka Ramadhani, Said Jongo, Philip L Felgner, Yonas Abebe, B Kim Lee Sim, L W Preston Church, Thomas L Richie, Peter F Billingsley, Tooba Murshedkar, Stephen L Hoffman, Salim Abdulla, Peter G Kremsner, Benjamin Mordmüller, Claudia Daubenberger, Rolf Fendel","doi":"10.1016/j.ebiom.2024.105364","DOIUrl":"10.1016/j.ebiom.2024.105364","url":null,"abstract":"<p><strong>Background: </strong>PfSPZ Vaccine, a promising pre-erythrocytic stage malaria vaccine candidate based on whole, radiation-attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), has proven safe and effective in mediating sterile protection from malaria in malaria-naïve and exposed healthy adults. Vaccine-induced protection presumably depends on cellular responses to early parasite liver stages, but humoral immunity contributes.</p><p><strong>Methods: </strong>On custom-made Pf protein microarrays, we profiled IgG and IgM responses to PfSPZ Vaccine and subsequent homologous controlled human malaria infection (CHMI) in 21 Tanzanian adults with (n = 12) or without (n = 9) HIV infection. Expression of the main identified immunogens in the pre-erythrocytic parasite stage was verified by immunofluorescence detection using freshly purified PfSPZ and an in vitro model of primary human hepatocytes.</p><p><strong>Findings: </strong>Independent of HIV infection status, immunisation induced focused IgG and IgM responses to circumsporozoite surface protein (PfCSP) and merozoite surface protein 5 (PfMSP5). We show that PfMSP5 is detectable on the surface and in the apical complex of PfSPZ.</p><p><strong>Interpretation: </strong>Our data demonstrate that HIV infection does not affect the quantity of the total IgG and IgM antibody responses to PfCSP and PfMSP5 after immunization with PfSPZ Vaccine. PfMSP5 represents a highly immunogenic, so far underexplored, target for vaccine-induced antibodies in malaria pre-exposed volunteers.</p><p><strong>Funding: </strong>This work was supported by the Equatorial Guinea Malaria Vaccine Initiative (EGMVI), the Clinical Trial Platform of the German Center for Infection Research (TTU 03.702), the Swiss Government Excellence Scholarships for Foreign Scholars and Artists (grant 2016.0056) and the Interdisciplinary Center for Clinical Research doctoral program of the Tübingen University Hospital. The funders had no role in design, analysis, or reporting of this study.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105364"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364803","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":"Neural network-assisted humanisation of COVID-19 hamster transcriptomic data reveals matching severity states in human disease.","authors":"Vincent D Friedrich, Peter Pennitz, Emanuel Wyler, Julia M Adler, Dylan Postmus, Kristina Müller, Luiz Gustavo Teixeira Alves, Julia Prigann, Fabian Pott, Daria Vladimirova, Thomas Hoefler, Cengiz Goekeri, Markus Landthaler, Christine Goffinet, Antoine-Emmanuel Saliba, Markus Scholz, Martin Witzenrath, Jakob Trimpert, Holger Kirsten, Geraldine Nouailles","doi":"10.1016/j.ebiom.2024.105312","DOIUrl":"10.1016/j.ebiom.2024.105312","url":null,"abstract":"<p><strong>Background: </strong>Translating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for models showing disease severity-dependent immune responses.</p><p><strong>Methods: </strong>Single-cell transcriptomics (scRNAseq) is well poised to reveal similarities and differences between species at the molecular and cellular level with unprecedented resolution. However, computational methods enabling detailed matching are still scarce. Here, we provide a structured scRNAseq-based approach that we applied to scRNAseq from blood leukocytes originating from humans and hamsters affected with moderate or severe COVID-19.</p><p><strong>Findings: </strong>Integration of data from patients with COVID-19 with two hamster models that develop moderate (Syrian hamster, Mesocricetus auratus) or severe (Roborovski hamster, Phodopus roborovskii) disease revealed that most cellular states are shared across species. A neural network-based analysis using variational autoencoders quantified the overall transcriptomic similarity across species and severity levels, showing highest similarity between neutrophils of Roborovski hamsters and patients with severe COVID-19, while Syrian hamsters better matched patients with moderate disease, particularly in classical monocytes. We further used transcriptome-wide differential expression analysis to identify which disease stages and cell types display strongest transcriptional changes.</p><p><strong>Interpretation: </strong>Consistently, hamsters' response to COVID-19 was most similar to humans in monocytes and neutrophils. Disease-linked pathways found in all species specifically related to interferon response or inhibition of viral replication. Analysis of candidate genes and signatures supported the results. Our structured neural network-supported workflow could be applied to other diseases, allowing better identification of suitable animal models with similar pathomechanisms across species.</p><p><strong>Funding: </strong>This work was supported by German Federal Ministry of Education and Research, (BMBF) grant IDs: 01ZX1304B, 01ZX1604B, 01ZX1906A, 01ZX1906B, 01KI2124, 01IS18026B and German Research Foundation (DFG) grant IDs: 14933180, 431232613.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105312"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343768","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":"Bifidobacterium longum and microbiome maturation modify a nutrient intervention for stunting in Zimbabwean infants.","authors":"Ethan K Gough, Thaddeus J Edens, Lynnea Carr, Ruairi C Robertson, Kuda Mutasa, Robert Ntozini, Bernard Chasekwa, Hyun Min Geum, Iman Baharmand, Sandeep K Gill, Batsirai Mutasa, Mduduzi N N Mbuya, Florence D Majo, Naume Tavengwa, Freddy Francis, Joice Tome, Ceri Evans, Margaret Kosek, Andrew J Prendergast, Amee R Manges","doi":"10.1016/j.ebiom.2024.105362","DOIUrl":"10.1016/j.ebiom.2024.105362","url":null,"abstract":"<p><strong>Background: </strong>Small-quantity lipid-based nutrient supplements (SQ-LNS), which has been widely tested to reduce child stunting, has largely modest effects to date, but the mechanisms underlying these modest effects are unclear. Child stunting is a longstanding indicator of chronic undernutrition and it remains a prevalent public health problem. The infant gut microbiome may be a key contributor to stunting; and mother and infant fucosyltransferase (FUT) phenotypes are important determinants of infant microbiome composition.</p><p><strong>Methods: </strong>We investigated whether mother-infant FUT status (n = 792) and infant gut microbiome composition (n = 354 fecal specimens from 172 infants) modified the impact of an infant and young child feeding (IYCF) intervention, that included SQ-LNS, on stunting at age 18 months in secondary analysis of a randomized trial in rural Zimbabwe.</p><p><strong>Findings: </strong>We found that the impact of the IYCF intervention on stunting was modified by: (i) mother-infant FUT2+/FUT3- phenotype (difference-in-differences -32.6% [95% CI: -55.3%, -9.9%]); (ii) changes in species composition that reflected microbiome maturation (difference-in-differences -68.1% [95% CI: -99.0%, -28.5%); and (iii) greater relative abundance of B. longum (differences-in-differences 49.1% [95% CI: 26.6%, 73.6%]). The dominant strains of B. longum when the intervention started were most similar to the proficient milk oligosaccharide utilizer subspecies infantis, which decreased with infant age and differed by mother-infant FUT2+/FUT3- phenotypes.</p><p><strong>Interpretation: </strong>These findings indicate that a persistently \"younger\" microbiome at initiation of the intervention reduced its benefits on stunting in areas with a high prevalence of growth restriction.</p><p><strong>Funding: </strong>Bill and Melinda Gates Foundation, UK DFID/Aid, Wellcome Trust, Swiss Agency for Development and Cooperation, US National Institutes of Health, UNICEF, and Nutricia Research Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105362"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343770","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":"Hypervirulent Klebsiella pneumoniae: an old enemy with a more powerful weapon.","authors":"eBioMedicine","doi":"10.1016/j.ebiom.2024.105402","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105402","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105402"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406235","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":"Clinical value of plasma pTau181 to predict Alzheimer's disease pathology in a large real-world cohort of a memory clinic.","authors":"Amanda Cano, María Capdevila, Raquel Puerta, Javier Arranz, Laura Montrreal, Itziar de Rojas, Pablo García-González, Claudia Olivé, Fernando García-Gutiérrez, Oscar Sotolongo-Grau, Adelina Orellana, Nuria Aguilera, Maribel Ramis, Maitee Rosende-Roca, Alberto Lleó, Juan Fortea, Juan Pablo Tartari, Asunción Lafuente, Liliana Vargas, Alba Pérez-Cordón, Nathalia Muñoz, Ángela Sanabria, Montserrat Alegret, Xavier Morató, Lluís Tárraga, Victoria Fernández, Marta Marquié, Sergi Valero, Daniel Alcolea, Mercè Boada, Agustín Ruiz","doi":"10.1016/j.ebiom.2024.105345","DOIUrl":"10.1016/j.ebiom.2024.105345","url":null,"abstract":"<p><strong>Background: </strong>The identification of patients with an elevated risk of developing Alzheimer's disease (AD) dementia and eligible for the disease-modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed to translate them to clinical practice. Here we evaluated the clinical applicability of plasma pTau181 as a predictive marker of AD pathology in a large real-world cohort of a memory clinic.</p><p><strong>Methods: </strong>Three independent cohorts (modelling [n = 991, 59.7% female], testing [n = 642, 56.2% female] and validation [n = 441, 55.1% female]) of real-world patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD dementia, and other dementias were included. Paired cerebrospinal fluid (CSF) and plasma samples were used to measure AT(N) CSF biomarkers and plasma pTau181.</p><p><strong>Findings: </strong>CSF and plasma pTau181 showed correlation in all phenotypes except in SCD and other dementias. Age significantly influenced the biomarker's performance. The general Aβ(+) vs Aβ(-) ROC curve showed an AUC = 0.77 [0.74-0.80], whereas the specific ROC curve of MCI due to AD vs non-AD MCI showed an AUC = 0.89 [0.85-0.93]. A cut-off value of 1.30 pg/ml of plasma pTau181 exhibited a sensitivity of 93.57% [88.72-96.52], specificity of 72.38% [62.51-79.01], VPP of 77.85% [70.61-83.54], and 8.30% false negatives in the subjects with MCI of the testing cohort. The HR of cox regression showed that patients with MCI up to this cut-off value exhibited a HR = 1.84 [1.05-3.22] higher risk to convert to AD dementia than patients with MCI below the cut-off value.</p><p><strong>Interpretation: </strong>Plasma pTau181 has the potential to be used in the memory clinics as a screening biomarker of AD pathology in subjects with MCI, presenting a valuable prognostic utility in predicting the MCI conversion to AD dementia. In the context of a real-world population, a confirmatory test employing gold-standard procedures is still advisable.</p><p><strong>Funding: </strong>This study has been mainly funded by Ace Alzheimer Center Barcelona, Instituto de Salud Carlos III (ISCIII), Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Spanish Ministry of Science and Innovation, Fundación ADEY, Fundación Echevarne and Grífols S.A.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105345"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282132","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":"Crowd-sourced machine learning prediction of long COVID using data from the National COVID Cohort Collaborative.","authors":"Timothy Bergquist, Johanna Loomba, Emily Pfaff, Fangfang Xia, Zixuan Zhao, Yitan Zhu, Elliot Mitchell, Biplab Bhattacharya, Gaurav Shetty, Tamanna Munia, Grant Delong, Adbul Tariq, Zachary Butzin-Dozier, Yunwen Ji, Haodong Li, Jeremy Coyle, Seraphina Shi, Rachael V Philips, Andrew Mertens, Romain Pirracchio, Mark van der Laan, John M Colford, Alan Hubbard, Jifan Gao, Guanhua Chen, Neelay Velingker, Ziyang Li, Yinjun Wu, Adam Stein, Jiani Huang, Zongyu Dai, Qi Long, Mayur Naik, John Holmes, Danielle Mowery, Eric Wong, Ravi Parekh, Emily Getzen, Jake Hightower, Jennifer Blase","doi":"10.1016/j.ebiom.2024.105333","DOIUrl":"10.1016/j.ebiom.2024.105333","url":null,"abstract":"<p><strong>Background: </strong>While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID.</p><p><strong>Methods: </strong>A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.).</p><p><strong>Findings: </strong>Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events.</p><p><strong>Interpretation: </strong>As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions.</p><p><strong>Funding: </strong>Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105333"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343695","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":"Empirical application of a multidimensional approach to capture a broader assessment of clinical benefits in a heterogenous spine population - author's reply.","authors":"Karlo M Pedro, Mohammed Ali Alvi, Michael G Fehlings","doi":"10.1016/j.ebiom.2024.105365","DOIUrl":"10.1016/j.ebiom.2024.105365","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105365"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343696","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":"Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model.","authors":"Ole Vidhammer Bjørnstad, Manuel Carrasco, Kenneth Finne, Vandana Ardawatia, Ingeborg Winge, Cecilie Askeland, Jarle B Arnes, Gøril Knutsvik, Dimitrios Kleftogiannis, Joao A Paulo, Lars A Akslen, Heidrun Vethe","doi":"10.1016/j.ebiom.2024.105325","DOIUrl":"10.1016/j.ebiom.2024.105325","url":null,"abstract":"<p><strong>Background: </strong>Presence of nerves in tumours, by axonogenesis and neurogenesis, is gaining increased attention for its impact on cancer initiation and development, and the new field of cancer neuroscience is emerging. A recent study in prostate cancer suggested that the tumour microenvironment may influence cancer progression by recruitment of Doublecortin (DCX)-expressing neural progenitor cells (NPCs). However, the presence of such cells in human breast tumours has not been comprehensively explored.</p><p><strong>Methods: </strong>Here, we investigate the presence of DCX-expressing cells in breast cancer stromal tissue from patients using Imaging Mass Cytometry. Single-cell analysis of 372,468 cells across histopathological images of 107 breast cancers enabled spatial resolution of neural elements in the stromal compartment in correlation with clinicopathological features of these tumours. In parallel, we established a 3D in vitro model mimicking breast cancer neural progenitor-innervation and examined the two cell types as they co-evolved in co-culture by using mass spectrometry-based global proteomics.</p><p><strong>Findings: </strong>Stromal presence of DCX + cells is associated with tumours of higher histological grade, a basal-like phenotype, and shorter patient survival in tumour tissue from patients with breast cancer. Global proteomics analysis revealed significant changes in the proteomic landscape of both breast cancer cells and neural progenitors in co-culture.</p><p><strong>Interpretation: </strong>These results support that neural involvement plays an active role in breast cancer and warrants further studies on the relevance of nerve elements for tumour progression.</p><p><strong>Funding: </strong>This work was supported by the Research Council of Norway through its Centre of Excellence funding scheme, project number 223250 (to L.A.A), the Norwegian Cancer Society (to L.A.A. and H.V.), the Regional Health Trust Western Norway (Helse Vest) (to L.A.A.), the Meltzer Research Fund (to H.V.) and the National Institutes of Health (NIH)/NIGMS grant R01 GM132129 (to J.A.P.).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105325"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132156","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":"Transcriptomic signatures during normothermic liver machine perfusion correspond with graft quality and predict the early graft function.","authors":"Theresa Hautz, Hubert Hackl, Hendrik Gottschling, Raphael Gronauer, Julia Hofmann, Stefan Salcher, Bettina Zelger, Rupert Oberhuber, Benno Cardini, Annemarie Weissenbacher, Thomas Resch, Jakob Troppmair, Stefan Schneeberger","doi":"10.1016/j.ebiom.2024.105330","DOIUrl":"10.1016/j.ebiom.2024.105330","url":null,"abstract":"<p><strong>Background: </strong>A better understanding of the molecular events during liver normothermic machine perfusion (NMP) is warranted to develop a data-based approach for the identification of biomarkers representative of graft quality and posttransplant outcome. We analysed the dynamic transcriptional changes during NMP and linked them to clinical and biochemical parameters.</p><p><strong>Methods: </strong>50 livers subjected to NMP for up to 24 h were enrolled. Bulk RNA sequencing was performed in serial biopsies collected pre and during NMP, and after reperfusion. Perfusate was sampled to monitor liver function. qPCR and immunohistochemistry were performed to validate findings. Molecular profiles were compared between transplanted and non-transplanted livers, and livers with and without early allograft dysfunction.</p><p><strong>Findings: </strong>Pathways related to immune and cell stress responses, cell trafficking and cell regulation were activated during NMP, while cellular metabolism was downregulated over time. Anti-inflammatory responses and genes involved in tissue remodelling were induced at later time-points, suggesting a counter-response to the immediate damage. NMP strongly induced a gene signature associated with ischemia-reperfusion injury. A 7-gene signature corresponds with the benchmarking criteria for transplantation or discard at 6 h NMP (area under curve 0.99). CD274 gene expression (encoding programmed cell-death ligand-1) showed the highest predictive value. LEAP2 gene expression at 6 h NMP correlated with impaired graft function.</p><p><strong>Interpretation: </strong>Assessment of gene expression markers could serve as a reliable tool to evaluate liver quality during NMP and predicts early graft function after transplantation.</p><p><strong>Funding: </strong>The research was supported by \"In Memoriam Dr. Gabriel Salzner Stiftung\", Tiroler Wissenschaftsfond, Jubiläumsfonds-Österreichische Nationalbank and MUI Start grant.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105330"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282147","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":"Higher small pulmonary artery and vein volume on computed tomography is associated with mortality in current and former smokers.","authors":"Anastasia K A L Kwee, Eleni-Rosalina Andrinopoulou, Tjeerd van der Veer, Leticia Gallardo-Estrella, Jean-Paul Charbonnier, Stephen M Humphries, David A Lynch, Harm A W M Tiddens, Pim A de Jong, Esther Pompe","doi":"10.1016/j.ebiom.2024.105366","DOIUrl":"10.1016/j.ebiom.2024.105366","url":null,"abstract":"<p><strong>Background: </strong>In chronic obstructive pulmonary disease (COPD), vascular alterations have been shown to contribute to hypoxia and pulmonary hypertension, but the independent contribution of small vessel abnormalities to mortality remains unclear.</p><p><strong>Methods: </strong>We quantified artery and vein dimensions on computed tomography (CT) down to 0.2 mm. Small vessel volumes (<1 mmᴓ) were normalized by body surface area. In 7903 current and former smokers of the COPDGene study (53.2% male) the independent contribution of small artery and small vein volume to all-cause mortality was tested in multivariable Cox models. Additionally, we calculated the 95^th percentile of small arteries and veins in 374 never smokers to create two groups: normal and high small artery or vein volume. We describe clinical, physiological and imaging characteristics of subjects with a high small artery and high small vein volume.</p><p><strong>Findings: </strong>Both high small artery and high small vein volumes were independently associated with mortality with an adjusted hazard ratio of 1.07 [1.01, 1.14] and 1.34 [1.21, 1.49] per mL/m² increase, respectively. In COPDGene, 447 (5.7%) had high small artery volume and 519 (9.1%) subjects had high small vein volume and both had more emphysema, more air trapping and more severe coronary calcium.</p><p><strong>Interpretation: </strong>In smokers, abnormally high volumes in small arteries and veins are both relevant for mortality, which urges investigations into the aetiology of small pulmonary vessels and cardiac function in smokers.</p><p><strong>Funding: </strong>Award Number U01-HL089897 and U01-HL089856 from the NHLBI. COPD Foundation with contributions from AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105366"},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364801","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}