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description Publicationkeyboard_double_arrow_right Article 2021Publisher:Cambridge University Press (CUP) Funded by:WT, ANR | ParaFrap, UKRI | Regulating the trans-regu... +2 projectsWT ,ANR| ParaFrap ,UKRI| Regulating the trans-regulators: Investigating the PRMT7 molecular pathway as an epigenetic regulator of Leishmania spp. virulence ,UKRI| A Global Network for Neglected Tropical Diseases ,ANR| FLAGEL-OMEAuthors: Pegine B. Walrad; Mark C. Field; Miguel Navarro; Derrick R. Robinson;Pegine B. Walrad; Mark C. Field; Miguel Navarro; Derrick R. Robinson;pmc: PMC8292159 , PMC8311962 , PMC8311954
Trypanothione is the primary thiol redox carrier in Trypanosomatids whose biosynthesis and utilization pathways contain unique enzymes that include suitable drug targets against the human parasites in this family. Overexpression of the rate-limiting enzyme, γ-glutamylcysteine synthetase (GSH1), can increase the intracellular concentration of trypanothione. Melarsoprol directly inhibits trypanothione and has predicted the effects on downstream redox biology, including ROS management and dNTP synthesis that require further investigation. Thus, we hypothesized that melarsoprol treatment would inhibit DNA synthesis, which was tested using BrdU incorporation assays and cell cycle analyses. In addition, we analysed the effects of eflornithine, which interfaces with the trypanothione pathway, fexinidazole, because of the predicted effects on DNA synthesis, and pentamidine as an experimental control. We found that melarsoprol treatment resulted in a cell cycle stall and a complete inhibition of DNA synthesis within 24 h, which were alleviated by GSH1 overexpression. In contrast, the other drugs analysed had more subtle effects on DNA synthesis that were not significantly altered by GSH1 expression. Together these findings implicate DNA synthesis as a therapeutic target that warrants further investigation in the development of antitrypanosomal drugs.
Parasitology arrow_drop_down ParasitologyArticle . 2021Full-Text: http://europepmc.org/articles/PMC8292159Data sources: PubMed CentralEurope PubMed CentralArticle . 2021Full-Text: http://europepmc.org/articles/PMC8311962Data sources: PubMed CentralEurope PubMed CentralArticle . 2021Full-Text: http://europepmc.org/articles/PMC8311954Data sources: PubMed Centraladd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1017/s0031182021000317&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 3 citations 3 popularity Top 10% influence Average impulse Average Powered by BIP!more_vert Parasitology arrow_drop_down ParasitologyArticle . 2021Full-Text: http://europepmc.org/articles/PMC8292159Data sources: PubMed CentralEurope PubMed CentralArticle . 2021Full-Text: http://europepmc.org/articles/PMC8311962Data sources: PubMed CentralEurope PubMed CentralArticle . 2021Full-Text: http://europepmc.org/articles/PMC8311954Data sources: PubMed Centraladd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type 2023 France EnglishPublisher:Free Neuropathology Funded by:ANR | NeurATRIS, WTANR| NeurATRIS ,WTBoluda, Susana; Mokhtari, Karima; Mégarbane, Bruno; Annane, Djillali; Mathon, Bertrand; Cao, Albert; Adam, Clovis; Androuin, Alexandre; Bielle, Franck; Brochier, Guy; Charlotte, Frédéric; Chougar, Lydia; Khalid, Hamid; Eloit, Marc; Haïk, Stéphane; Hervé, Dominique; Kasri, Amal; Leducq, Valentin; Lehéricy, Stéphane; Levavasseur, Etienne; Lobsiger, Christian; Lorin La Grandmaison, Geoffroy; Malet, Isabelle; Malissin, Isabelle; Marot, Stéphane; Marty, Serge; Pérot, Philippe; Plu, Isabelle; Prigent, Annick; Stimmer, Lev; Potier, Marie-Claude; Marcelin, Anne-Geneviève; Delatour, Benoît; Duyckaerts, Charles; Seilhean, Danielle;In a neuropathological series of 20 COVID-19 cases, we analyzed six cases (three biopsies and three autopsies) with multiple foci predominantly affecting the white matter as shown by MRI. The cases presented with microhemorrhages evocative of small artery diseases. This COVID-19 associated cerebral microangiopathy (CCM) was characterized by perivascular changes: arterioles were surrounded by vacuolized tissue, clustered macrophages, large axonal swellings and a crown arrangement of aquaporin-4 immunoreactivity. There was evidence of blood-brain-barrier leakage. Fibrinoid necrosis, vascular occlusion, perivascular cuffing and demyelination were absent. While no viral particle or viral RNA was found in the brain, the SARS-CoV-2 spike protein was detected in the Golgi apparatus of brain endothelial cells where it closely associated with furin, a host protease known to play a key role in virus replication. Endothelial cells in culture were not permissive to SARS-CoV-2 replication. The distribution of the spike protein in brain endothelial cells differed from that observed in pneumocytes. In the latter, the diffuse cytoplasmic labeling suggested a complete replication cycle with viral release, notably through the lysosomal pathway. In contrast, in cerebral endothelial cells the excretion cycle was blocked in the Golgi apparatus. Interruption of the excretion cycle could explain the difficulty of SARS-CoV-2 to infect endothelial cells in vitro and to produce viral RNA in the brain. Specific metabolism of the virus in brain endothelial cells could weaken the cell walls and eventually lead to the characteristic lesions of COVID-19 associated cerebral microangiopathy. Furin as a modulator of vascular permeability could provide some clues for the control of late effects of microangiopathy. Free Neuropathology, Vol. 4 (2023)
Europe PubMed Centra... arrow_drop_down HAL-Pasteur; Mémoires en Sciences de l'Information et de la Communication; HAL-CEAArticle . 2023License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess RoutesGreen 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert Europe PubMed Centra... arrow_drop_down HAL-Pasteur; Mémoires en Sciences de l'Information et de la Communication; HAL-CEAArticle . 2023License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2023 United Kingdom, Germany, Finland, Netherlands, United States, United KingdomPublisher:Springer Science and Business Media LLC Funded by:NIH | Decoding the cellular mec..., NIH | Uterine signaling network..., UKRI | Delineating late foetal h... +31 projectsNIH| Decoding the cellular mechanisms of COVID-19 severe disease susceptibility in patients with chronic respiratory disease ,NIH| Uterine signaling networks in the pathogenesis of pulmonary lymphangioleiomyomatosis (LAM) ,UKRI| Delineating late foetal human lung development and maturation ,NIH| Lung transplant injury drives chronic lung allograft dysfunction via recruitment ofmonocyte-derived alveolar macrophages ,NIH| Comparative, single-cell analysis of COVID-19 and other respiratory diseases ,NIH| Extracellular matrix composition and crosslinking patterns determine resident cell function in lung fibrosis ,NIH| Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center ,WT| Wellcome Trust Sanger Institute - generic account for deposition of all core- funded research papers. ,NIH| Targeting abnormal alveolar immune activation and failed epithelial repair in COVID-19 ,NIH| Normal Aging Lung Cell Atlas (NALCA) ,NIH| Fibroblast heterogeneity in pulmonary fibrosis ,NIH| LungMap Phase II - Building a multidimensional map of developing human lung ,NIH| Combining genome, function, and phenotype to define the cell type specific gene regulatory architecture of idiopathic pulmonary fibrosis ,NIH| Genetic Control of Airway Epithelium Gene Expression in Childhood Asthmatics ,NIH| Monocyte-derived alveolar macrophage drives inflammatory response to lung ozone exposure ,NIH| NIAMS: CORT ,WT| An Extended Pilot for the Human Cell Atlas: Adult tissues, human development and inflammation-mediated pathologies ,NIH| The Airway Functional Genomics of Bronchodilator Drug Response in Minority Children with Asthma ,EC| discovAIR ,NIH| Single-cell analysis of the lung immune microenvironment and cell-cell interactions across healthy and diseased patients ,NIH| Biorepository for INvestigation of Diseases of the Lung (BRINDL) - Phase II ,EC| RESPIRE4 ,NIH| Epithelial Protective Effects of Thyroid Hormone Signaling in Fibrosis ,NIH| Genomic Analysis of Tissue and Cellular Heterogeneity in IPF ,NIH| Administrative Core ,NIH| Midwest Murine-Tissue Mapping Center (MM-TMC) ,NIH| Molecular control of a novel transitional cell state in alveolar regeneration ,NIH| TriState SenNET (Lung and Heart) Tissue Map and Atlas consortium ,NIH| Role of VEGF in Perinatal Pulmonary Hypertension ,NIH| Transcriptomic and Pharmacogenetic Asthma Endotypes in Minority Children ,NIH| KULMAP: Human Kidney, urinary tract and lung mapping center ,NIH| Genes, air pollution, and asthma severity in minority children ,NIH| Disordered Proteostasis as a Driver of Disease in the Aging Lung ,ANR| 3IA@cote d'azurLisa Sikkema; Ciro Ramírez-Suástegui; Daniel C. Strobl; Tessa E. Gillett; Luke Zappia; Elo Madissoon; Nikolay S. Markov; Laure-Emmanuelle Zaragosi; Yuge Ji; Meshal Ansari; Marie-Jeanne Arguel; Leonie Apperloo; Martin Banchero; Christophe Bécavin; Marijn Berg; Evgeny Chichelnitskiy; Mei-i Chung; Antoine Collin; Aurore C. A. Gay; Janine Gote-Schniering; Baharak Hooshiar Kashani; Kemal Inecik; Manu Jain; Theodore S. Kapellos; Tessa M. Kole; Sylvie Leroy; Christoph H. Mayr; Amanda J. Oliver; Michael von Papen; Lance Peter; Chase J. Taylor; Thomas Walzthoeni; Chuan Xu; Linh T. Bui; Carlo De Donno; Leander Dony; Alen Faiz; Minzhe Guo; Austin J. Gutierrez; Lukas Heumos; Ni Huang; Ignacio L. Ibarra; Nathan D. Jackson; Preetish Kadur Lakshminarasimha Murthy; Mohammad Lotfollahi; Tracy Tabib; Carlos Talavera-López; Kyle J. Travaglini; Anna Wilbrey-Clark; Kaylee B. Worlock; Masahiro Yoshida; Yuexin Chen; James S. Hagood; Ahmed Agami; Peter Horvath; Joakim Lundeberg; Charles-Hugo Marquette; Gloria Pryhuber; Chistos Samakovlis; Xin Sun; Lorraine B. Ware; Kun Zhang; Maarten van den Berge; Yohan Bossé; Tushar J. Desai; Oliver Eickelberg; Naftali Kaminski; Mark A. Krasnow; Robert Lafyatis; Marko Z. Nikolic; Joseph E. Powell; Jayaraj Rajagopal; Mauricio Rojas; Orit Rozenblatt-Rosen; Max A. Seibold; Dean Sheppard; Douglas P. Shepherd; Don D. Sin; Wim Timens; Alexander M. Tsankov; Jeffrey Whitsett; Yan Xu; Nicholas E. Banovich; Pascal Barbry; Thu Elizabeth Duong; Christine S. Falk; Kerstin B. Meyer; Jonathan A. Kropski; Dana Pe’er; Herbert B. Schiller; Purushothama Rao Tata; Joachim L. Schultze; Sara A. Teichmann; Alexander V. Misharin; Martijn C. Nawijn; Malte D. Luecken; Fabian J. Theis;pmid: 37291214
pmc: PMC10287567
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1(+) profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.A single-cell atlas of the human lungs, integrating data from 2.4 million cells from 486 individuals and including samples from healthy and diseased lungs, provides a roadmap for the generation of organ-scale cell atlases. Peer reviewed
DZNE Pub arrow_drop_down HELDA - Digital Repository of the University of HelsinkiArticle . 2023 . Peer-reviewedData sources: HELDA - Digital Repository of the University of HelsinkieScholarship - University of CaliforniaArticle . 2023Data sources: eScholarship - University of Californiaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41591-023-02327-2&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid more_vert DZNE Pub arrow_drop_down HELDA - Digital Repository of the University of HelsinkiArticle . 2023 . Peer-reviewedData sources: HELDA - Digital Repository of the University of HelsinkieScholarship - University of CaliforniaArticle . 2023Data sources: eScholarship - University of Californiaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Preprint 2022 United KingdomPublisher:Cold Spring Harbor Laboratory Funded by:WT | Expanding the capabilitie..., WT | Structure and Mechanism o..., WT | Unlocking the structure, ... +6 projectsWT| Expanding the capabilities and use of the South West Regional Facility for High-Resolution Electron Cryo-microscopy ,WT| Structure and Mechanism of Key Nonsense-Mediated mRNA Decay Factor Complexes ,WT| Unlocking the structure, mechanism and cellular assembly of key multiprotein complexes in human gene transcription. ,UKRI| BlueCryo Image Processing Computing Cluster ,WT| South West Regional Facility for High-Resolution Electron Cryo-Microscopy ,UKRI| Future Vaccine Manufacturing Hub: Advancing the manufacture and deployment of cost effective vaccines ,ANR| AirMN ,ANR| SIGNALIFE ,UKRI| The production and application of SARS-CoV-2 reverse genetic systems to facilitate vaccine development and biosafe drug discovery platforms.Christine Toelzer; Kapil Gupta; Sathish K. N. Yadav; Lorna Hodgson; Maia Kavanagh Williamson; Dora Buzas; Ufuk Borucu; Kyle Powers; Richard Stenner; Kate Vasileiou; Frederic Garzoni; Daniel Fitzgerald; Christine Payré; Gunjan Gautam; Gérard Lambeau; Andrew D. Davidson; Paul Verkade; Martin Frank; Imre Berger; Christiane Schaffitzel;pmid: 36417532
pmc: PMC9683698
AbstractAs COVID-19 persists, severe acquired respiratory syndrome coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor-binding domain (RBD) comprises a free fatty acid (FFA)-binding pocket. FFA-binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2 and VOCs bind the essential FFA linoleic acid (LA), while binding is abolished by one mutation in common cold-causing HCoV-HKU1. In the SARS-CoV S structure, LA stabilizes the locked conformation while the open, infectious conformation is LA-free. Electron tomography of SARS-CoV-2 infected cells reveals that LA-treatment inhibits viral replication, resulting in fewer, deformed virions. Our results establish FFA-binding as a hallmark of pathogenic β-CoV infection and replication, highlighting potential antiviral strategies.One-Sentence SummaryFree fatty acid-binding is conserved in pathogenic β-coronavirus S proteins and suppresses viral infection and replication.
Explore Bristol Rese... arrow_drop_down Mémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYFull-Text: https://hal.science/hal-03870926/documentMémoires en Sciences de l'Information et de la CommunicationPreprint . 2022add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2022.04.22.489083&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 21 citations 21 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert Explore Bristol Rese... arrow_drop_down Mémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYFull-Text: https://hal.science/hal-03870926/documentMémoires en Sciences de l'Information et de la CommunicationPreprint . 2022add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2022.04.22.489083&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2022 Denmark, France, United KingdomPublisher:Springer Science and Business Media LLC Funded by:WT | Arts, Society and Public ..., INCa, WT | COVID-Minds: Mental Healt... +2 projectsWT| Arts, Society and Public Health: An Exploration of the Major UK Cohort Studies ,INCa ,WT| COVID-Minds: Mental Health during Covid-19 ,ANR| CONSTANCES ,UKRI| MARCH: Social, Cultural and Community Assets for Mental HealthAmélie Keller; Jonathan Groot; Joane Matta; Feifei Bu; Tarik El Aarbaoui; Maria Melchior; Daisy Fancourt; Marie Zins; Marcel Goldberg; Anne-Marie Nybo Andersen; Naja H. Rod; Katrine Strandberg-Larsen; Tibor V. Varga;AbstractMany studies have investigated the impact of the COVID-19 pandemic on mental health. Throughout the pandemic, time spent at home increased to a great extent due to restrictive measures. Here we set out to investigate the relationship between housing conditions and the mental health of populations across European countries. We analyzed survey data collected during spring 2020 from 69,136 individuals from four cohorts from Denmark, France, and the UK. The investigated housing conditions included household density, composition, and crowding, access to outdoor facilities, dwelling type, and urbanicity. The outcomes were loneliness, anxiety, and life satisfaction. Logistic regression models were used, and results were pooled using random-effects meta-analysis. In the meta-analysis, living alone was associated with higher levels of loneliness (OR = 3.08, 95% CI 1.87–5.07), and lower life satisfaction (OR = 1.27, 95% CI 1.05–0.55), compared to living with others. Not having access to an outdoor space and household crowding were suggestively associated with worse outcomes. Living in crowded households, living alone, or lacking access to outdoor facilities may be particularly important in contributing to poor mental health during a lockdown. Addressing the observed fundamental issues related to housing conditions within society will likely have positive effects in reducing social inequalities, as well as improving preparedness for future pandemics.
Scientific Reports arrow_drop_down Copenhagen University Research Information SystemArticle . 2022Data sources: Copenhagen University Research Information SystemMémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYFull-Text: https://hal.science/hal-03642586/documentadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess Routesgold 14 citations 14 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert Scientific Reports arrow_drop_down Copenhagen University Research Information SystemArticle . 2022Data sources: Copenhagen University Research Information SystemMémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYFull-Text: https://hal.science/hal-03642586/documentadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Preprint 2022 FrancePublisher:Research Square Platform LLC Publicly fundedFunded by:ANR | AABIFNCOV, EC | EASI-Genomics, SFI | How immunology can help t... +6 projectsANR| AABIFNCOV ,EC| EASI-Genomics ,SFI| How immunology can help to address the COVID-19 epidemic in Ireland ,ANR| GenMIS-C ,SFI| DIRECTS: Detecting Innate protection against SARS-CoV2 ,NIH| Monogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19 ,WT| Wellcome – Health Research Board Irish Clinical Academic Training Programme ,NIH| Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational Success ,NIH| Inborn errors of immunity in patients with life-threatening COVID-19Duffy, Darragh; SMITH, Nikaïa; Possémé, Céline; Bondet, Vincent; Sugrue, Jamie; Townsend, Liam; Charbit, Bruno; Rouilly, Vincent; Saint-André, Violaine; Dott, Tom; Pozo, Andre Rodriguez; Yatim, Nader; Schwartz, Olivier; Cervantes-Gonzales, Minerva; Ghosn, Jade; Bastard, Paul; Casanova, Jean-Laurent; Szwebel, Tali-Anne; Terrier, Benjamin; Conlon, Niall; O'Farrelly, Cliona; Cheallaigh, Cliona Ni; Bourke, Nollaig;Abstract Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported that reduced blood type I interferon (IFN-I) in severe COVID-19 patients preceded clinical worsening. These results were supported by studies which identified genetic mutations in loci of the TLR3- or TLR7-dependent IFN-I pathways, or autoantibodies neutralizing IFNα or IFNω, as major risk factors for development of severe and critical COVID-19 pneumonia. Here, we analyzed a range of IFN-I associated responses in patient cohorts with different severities of COVID-19, showing that baseline plasma IFNα measures differed significantly according to the immunoassay used, as well as timing of sampling, the IFNα subtype measured, and the presence of autoantibodies. We then compared immune responses induced by ex vivo stimulation between non-hospitalized moderate cases (n=27) and hospitalized (n=17) adult patients that required oxygen supplementation. This showed a consistently reduced induction of IFN-I proteins in hospitalized COVID-19 patients upon stimulation, that was not associated with detectable neutralizing autoantibodies against IFNα or IFNω. We confirmed the poor induction of IFN-I in an independent patient cohort (n=33), and showed it was more pronounced with severe disease. Intracellular proteomic analysis showed that while monocyte numbers were increased in hospitalized COVID-19 patients, they did not secrete IFN-I in response to stimulation. This was further confirmed by ex vivo whole blood stimulation with IFN-I which induced a transcriptomic response associated with inflammation in hospitalized COVID-19 patients, that was not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to IFN-I based treatments in late stage COVID-19, despite the critical importance of IFN-I in early acute infection. An improved understanding of such variable responses to treatment may help to identify potential alternative therapeutic strategies.
https://doi.org/10.2... arrow_drop_down HAL Descartes; HAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationPreprint . 2022License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess Routeshybrid 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert https://doi.org/10.2... arrow_drop_down HAL Descartes; HAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationPreprint . 2022License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Preprint 2023Publisher:Cold Spring Harbor Laboratory Funded by:WT | Putting genomic surveilla..., UKRI | East of Scotland Bioscien..., NIH | Statistical innovation to... +10 projectsWT| Putting genomic surveillance at the heart of viral epidemic response. ,UKRI| East of Scotland Bioscience Doctoral Training Partnership ,NIH| Statistical innovation to integrate sequences and phenotypes for scalable phylodynamic inference ,NIH| University of Washington Arboviral Research Network (UWARN) ,NIH| Fast and flexible Bayesian phylogenetics via modern machine learning ,EC| VEO ,NIH| Role of Data Streams In Informing Infection Dynamics in Africa- INFORM Africa ,EC| MOOD ,EC| ReservoirDOCs ,ANR| INCEPTION ,EC| RECoVER ,WT| The ISARIC data platform: Optimizing data-driven pandemic preparedness and response ,UKRI| Doctoral Training Partnership in Environmental ResearchJoseph L.-H. Tsui; Ben Lambert; Sumali Bajaj; John T. McCrone; Rhys P.D. Inward; Paolo Bosetti; Verity Hill; Rosario Evans Pena; Alexander E. Zarebski; Thomas P. Peacock; Luyang Liu; Neo Wu; Megan Davis; Isaac I. Bogoch; Kamran Khan; Rachel Colquhoun; Áine O’Toole; Ben Jackson; Abhishek Dasgupta; Eduan Wilkinson; Houriiyah Tegally; Tulio de Oliveira; Thomas R. Connor; Nicholas J. Loman; Vittoria Colizza; Christophe Fraser; Erik Volz; Xiang Ji; Marc A. Suchard; Bernardo Gutierrez; Meera Chand; Simon Dellicour; Simon Cauchemez; Jayna Raghwani; Philippe Lemey; Andrew Rambaut; Oliver G. Pybus; Moritz U.G. Kraemer;SummarySARS-CoV-2 variants of concern (VOCs) arise against the backdrop of increasingly heterogeneous human connectivity and population immunity. Through a large-scale phylodynamic analysis of 115,622 Omicron genomes, we identified >6,000 independent introductions of the antigenically distinct virus into England and reconstructed the dispersal history of resulting local transmission. Travel restrictions on southern Africa did not reduce BA.1 importation intensity as secondary hubs became major exporters. We explored potential drivers of BA.1 spread across England and discovered an early period during which viral lineage movements mainly occurred between larger cities, followed by a multi-focal spatial expansion shaped by shorter distance mobility patterns. We also found evidence that disease incidence impacted human commuting behaviours around major travel hubs. Our results offer a detailed characterisation of processes that drive the invasion of an emerging VOC across multiple spatial scales and provide unique insights on the interplay between disease spread and human mobility.HighlightsOver 6,000 introductions ignited the epidemic wave of Omicron BA.1 in EnglandImportations prior to international travel restrictions were responsible for majority of local BA.1 infections but importations continued from sources other than southern AfricaHuman mobility at regional and local spatial scales shaped dissemination and growth of BA.1Changes in human commuting patterns are associated with higher case incidence in travel hubs across England
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.01.02.23284109&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu3 citations 3 popularity Top 10% influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.01.02.23284109&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2022 United Kingdom, FrancePublisher:Elsevier BV Funded by:ANR | IDEXLYON, UKRI | Isaac Newton Institute fo..., WT | Improving scientific and ...ANR| IDEXLYON ,UKRI| Isaac Newton Institute for Mathematical Sciences ,WT| Improving scientific and public health decision making by developing technologies to increase use of robust methods to calibrate and analyse complex mathematical modelsMichael Dunne; Hossein Mohammadi; Peter Challenor; Rita Borgo; Thibaud Porphyre; Ian Vernon; Elif E. Firat; Cagatay Turkay; Thomas Torsney-Weir; Michael Goldstein; Richard Reeve; Hui Fang; Ben Swallow;Funding: This work was supported by EPSRC, United Kingdom grant no. EP/R014604/1. RR was funded by STFC, United Kingdom grant no ST/V006126/1. IV gratefully acknowledges Wellcome funding (218261/Z/19/Z) and EPSRC funding (EP W011956). TP gratefully acknowledges funding from the Scottish Government Rural and Environment Science and Analytical Services Division, United Kingdom, as part of the Centre of Expertise on Animal Disease Outbreaks (EPIC). TP would also like to thank the French National Research Agency and Boehringer Ingelheim Animal Health France for support through the IDEXLYON project (ANR-16-IDEX-0005) and the Industrial Chair in Veterinary Public Health, as part of the VPH Hub in Lyon. Uncertainty quantification is a formal paradigm of statistical estimation that aims to account for all uncertain-ties inherent in the modelling process of real-world complex systems. The methods are directly applicable to stochastic models in epidemiology, however they have thus far not been widely used in this context. In this paper, we provide a tutorial on uncertainty quantification of stochastic epidemic models, aiming to facilitate the use of the uncertainty quantification paradigm for practitioners with other complex stochastic simulators of applied systems. We provide a formal workflow including the important decisions and considerations that need to be taken, and illustrate the methods over a simple stochastic epidemic model of UK SARS-CoV-2 transmission and patient outcome. We also present new approaches to visualisation of outputs from sensitivity analyses and uncertainty quantification more generally in high input and/or output dimensions. Peer reviewed
Durham Research Onli... arrow_drop_down Durham Research Online; EpidemicsArticle . 2022 . Peer-reviewedLicense: CC BYFull-Text: http://dro.dur.ac.uk/35936/1/35936.pdfSt Andrews Research RepositoryArticle . 2022 . Peer-reviewedData sources: St Andrews Research Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.epidem.2022.100574&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 1 citations 1 popularity Average influence Average impulse Average Powered by BIP!visibility 4visibility views 4 download downloads 5 Powered bymore_vert Durham Research Onli... arrow_drop_down Durham Research Online; EpidemicsArticle . 2022 . Peer-reviewedLicense: CC BYFull-Text: http://dro.dur.ac.uk/35936/1/35936.pdfSt Andrews Research RepositoryArticle . 2022 . Peer-reviewedData sources: St Andrews Research Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.epidem.2022.100574&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2023 United Kingdom, United Kingdom, NetherlandsPublisher:Springer Science and Business Media LLC Funded by:ANR | 3IA@cote d'azur, UKRI | A systems based approach ..., WT | Developing a locally-appr... +9 projectsANR| 3IA@cote d'azur ,UKRI| A systems based approach to integrating genetic and longitudinal omics data to support diagnosis and prediction of common chronic disease ,WT| Developing a locally-appropriate socioeconomic support package for TB-affected households in Nepal: a seed project to inform the END-TB trial ,WT| Programme for High Dimensional Translation in Neurology ,UKRI| The Alan Turing Institute ,UKRI| Epidemic modelling and statistical support for policy: sub-populations, forecasting, and long-term planning ,WT| King's College London Medical Engineering Centre of Research Excellence ,UKRI| GEroscience and Multi-Morbidity: identifying targets for intervention (GEMM) ,UKRI| COVID-19 Modelling Consortium: quantitative epidemiological predictions in response to an evolving pandemic ,UKRI| London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare ,WT| TwinsUK (2019-2023) - An Epidemiological and Genomic Resource ,UKRI| Addressing the Social Determinants and Consequences of Tuberculosis (ASCOT): a pilot randomised controlled trial and process evaluation in NepalFyles, Martyn; Vihta, Karina-Doris; Sudre, Carole H; Long, Harry; Das, Rajenki; Jay, Caroline; Wingfield, Tom; Cumming, Fergus; Green, William; Hadjipantelis, Pantelis; Kirk, Joni; Steves, Claire J; Ourselin, Sebastien; Medley, Graham F; Fearon, Elizabeth; House, Thomas;Through the use of cutting-edge unsupervised classification techniques from statistics and machine learning, we characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases. We first analyse each dataset in isolation and across age bands, before using methods that allow us to compare multiple datasets. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. In this way, we are able to demonstrate the deep structure of symptoms of COVID-19 without usual biases due to study design. This is expected to have implications for the identification and management of community SARS-CoV-2 cases and could be further applied to symptom-based management of other diseases and syndromes. Comment: 60 pages; 29 figures
Scientific Reports arrow_drop_down Amsterdam UMC (VU Amsterdam) - Institutional RepositoryArticle . 2023Data sources: Amsterdam UMC (VU Amsterdam) - Institutional RepositoryarXiv.org e-Print ArchiveOther literature type . Preprint . 2021Data sources: arXiv.org e-Print ArchiveThe University of Manchester - Institutional RepositoryArticle . 2023Data sources: The University of Manchester - Institutional Repositoryhttps://doi.org/10.48550/arxiv...Article . 2021License: arXiv Non-Exclusive DistributionData sources: Dataciteadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41598-023-47488-9&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert Scientific Reports arrow_drop_down Amsterdam UMC (VU Amsterdam) - Institutional RepositoryArticle . 2023Data sources: Amsterdam UMC (VU Amsterdam) - Institutional RepositoryarXiv.org e-Print ArchiveOther literature type . Preprint . 2021Data sources: arXiv.org e-Print ArchiveThe University of Manchester - Institutional RepositoryArticle . 2023Data sources: The University of Manchester - Institutional Repositoryhttps://doi.org/10.48550/arxiv...Article . 2021License: arXiv Non-Exclusive DistributionData sources: Dataciteadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41598-023-47488-9&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2022 FrancePublisher:MDPI AG Funded by:SFI | DIRECTS: Detecting Innate..., WT | Wellcome – Health Researc..., ANR | INCEPTIONSFI| DIRECTS: Detecting Innate protection against SARS-CoV2 ,WT| Wellcome – Health Research Board Irish Clinical Academic Training Programme ,ANR| INCEPTIONLaura Garcia; Tom Woudenberg; Jason Rosado; Adam H. Dyer; Françoise Donnadieu; Delphine Planas; Timothée Bruel; Olivier Schwartz; Thierry Prazuck; Aurélie Velay; Samira Fafi-Kremer; Isabella Batten; Conor Reddy; Emma Connolly; Matt McElheron; Sean P. Kennelly; Nollaig M. Bourke; Michael T. White; Stéphane Pelleau;Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics. International audience
Viruses arrow_drop_down VirusesOther literature type . Article . 2022 . Peer-reviewedLicense: CC BYFull-Text: http://www.mdpi.com/1999-4915/14/7/1491/pdfHAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.3390/v14071491&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesgold 13 citations 13 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert Viruses arrow_drop_down VirusesOther literature type . Article . 2022 . Peer-reviewedLicense: CC BYFull-Text: http://www.mdpi.com/1999-4915/14/7/1491/pdfHAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.3390/v14071491&type=result"></script>'); --> </script>
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description Publicationkeyboard_double_arrow_right Article 2021Publisher:Cambridge University Press (CUP) Funded by:WT, ANR | ParaFrap, UKRI | Regulating the trans-regu... +2 projectsWT ,ANR| ParaFrap ,UKRI| Regulating the trans-regulators: Investigating the PRMT7 molecular pathway as an epigenetic regulator of Leishmania spp. virulence ,UKRI| A Global Network for Neglected Tropical Diseases ,ANR| FLAGEL-OMEAuthors: Pegine B. Walrad; Mark C. Field; Miguel Navarro; Derrick R. Robinson;Pegine B. Walrad; Mark C. Field; Miguel Navarro; Derrick R. Robinson;pmc: PMC8292159 , PMC8311962 , PMC8311954
Trypanothione is the primary thiol redox carrier in Trypanosomatids whose biosynthesis and utilization pathways contain unique enzymes that include suitable drug targets against the human parasites in this family. Overexpression of the rate-limiting enzyme, γ-glutamylcysteine synthetase (GSH1), can increase the intracellular concentration of trypanothione. Melarsoprol directly inhibits trypanothione and has predicted the effects on downstream redox biology, including ROS management and dNTP synthesis that require further investigation. Thus, we hypothesized that melarsoprol treatment would inhibit DNA synthesis, which was tested using BrdU incorporation assays and cell cycle analyses. In addition, we analysed the effects of eflornithine, which interfaces with the trypanothione pathway, fexinidazole, because of the predicted effects on DNA synthesis, and pentamidine as an experimental control. We found that melarsoprol treatment resulted in a cell cycle stall and a complete inhibition of DNA synthesis within 24 h, which were alleviated by GSH1 overexpression. In contrast, the other drugs analysed had more subtle effects on DNA synthesis that were not significantly altered by GSH1 expression. Together these findings implicate DNA synthesis as a therapeutic target that warrants further investigation in the development of antitrypanosomal drugs.
Parasitology arrow_drop_down ParasitologyArticle . 2021Full-Text: http://europepmc.org/articles/PMC8292159Data sources: PubMed CentralEurope PubMed CentralArticle . 2021Full-Text: http://europepmc.org/articles/PMC8311962Data sources: PubMed CentralEurope PubMed CentralArticle . 2021Full-Text: http://europepmc.org/articles/PMC8311954Data sources: PubMed Centraladd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1017/s0031182021000317&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 3 citations 3 popularity Top 10% influence Average impulse Average Powered by BIP!more_vert Parasitology arrow_drop_down ParasitologyArticle . 2021Full-Text: http://europepmc.org/articles/PMC8292159Data sources: PubMed CentralEurope PubMed CentralArticle . 2021Full-Text: http://europepmc.org/articles/PMC8311962Data sources: PubMed CentralEurope PubMed CentralArticle . 2021Full-Text: http://europepmc.org/articles/PMC8311954Data sources: PubMed Centraladd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1017/s0031182021000317&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type 2023 France EnglishPublisher:Free Neuropathology Funded by:ANR | NeurATRIS, WTANR| NeurATRIS ,WTBoluda, Susana; Mokhtari, Karima; Mégarbane, Bruno; Annane, Djillali; Mathon, Bertrand; Cao, Albert; Adam, Clovis; Androuin, Alexandre; Bielle, Franck; Brochier, Guy; Charlotte, Frédéric; Chougar, Lydia; Khalid, Hamid; Eloit, Marc; Haïk, Stéphane; Hervé, Dominique; Kasri, Amal; Leducq, Valentin; Lehéricy, Stéphane; Levavasseur, Etienne; Lobsiger, Christian; Lorin La Grandmaison, Geoffroy; Malet, Isabelle; Malissin, Isabelle; Marot, Stéphane; Marty, Serge; Pérot, Philippe; Plu, Isabelle; Prigent, Annick; Stimmer, Lev; Potier, Marie-Claude; Marcelin, Anne-Geneviève; Delatour, Benoît; Duyckaerts, Charles; Seilhean, Danielle;In a neuropathological series of 20 COVID-19 cases, we analyzed six cases (three biopsies and three autopsies) with multiple foci predominantly affecting the white matter as shown by MRI. The cases presented with microhemorrhages evocative of small artery diseases. This COVID-19 associated cerebral microangiopathy (CCM) was characterized by perivascular changes: arterioles were surrounded by vacuolized tissue, clustered macrophages, large axonal swellings and a crown arrangement of aquaporin-4 immunoreactivity. There was evidence of blood-brain-barrier leakage. Fibrinoid necrosis, vascular occlusion, perivascular cuffing and demyelination were absent. While no viral particle or viral RNA was found in the brain, the SARS-CoV-2 spike protein was detected in the Golgi apparatus of brain endothelial cells where it closely associated with furin, a host protease known to play a key role in virus replication. Endothelial cells in culture were not permissive to SARS-CoV-2 replication. The distribution of the spike protein in brain endothelial cells differed from that observed in pneumocytes. In the latter, the diffuse cytoplasmic labeling suggested a complete replication cycle with viral release, notably through the lysosomal pathway. In contrast, in cerebral endothelial cells the excretion cycle was blocked in the Golgi apparatus. Interruption of the excretion cycle could explain the difficulty of SARS-CoV-2 to infect endothelial cells in vitro and to produce viral RNA in the brain. Specific metabolism of the virus in brain endothelial cells could weaken the cell walls and eventually lead to the characteristic lesions of COVID-19 associated cerebral microangiopathy. Furin as a modulator of vascular permeability could provide some clues for the control of late effects of microangiopathy. Free Neuropathology, Vol. 4 (2023)
Europe PubMed Centra... arrow_drop_down HAL-Pasteur; Mémoires en Sciences de l'Information et de la Communication; HAL-CEAArticle . 2023License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.17879/freeneuropathology-2023-4584&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert Europe PubMed Centra... arrow_drop_down HAL-Pasteur; Mémoires en Sciences de l'Information et de la Communication; HAL-CEAArticle . 2023License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2023 United Kingdom, Germany, Finland, Netherlands, United States, United KingdomPublisher:Springer Science and Business Media LLC Funded by:NIH | Decoding the cellular mec..., NIH | Uterine signaling network..., UKRI | Delineating late foetal h... +31 projectsNIH| Decoding the cellular mechanisms of COVID-19 severe disease susceptibility in patients with chronic respiratory disease ,NIH| Uterine signaling networks in the pathogenesis of pulmonary lymphangioleiomyomatosis (LAM) ,UKRI| Delineating late foetal human lung development and maturation ,NIH| Lung transplant injury drives chronic lung allograft dysfunction via recruitment ofmonocyte-derived alveolar macrophages ,NIH| Comparative, single-cell analysis of COVID-19 and other respiratory diseases ,NIH| Extracellular matrix composition and crosslinking patterns determine resident cell function in lung fibrosis ,NIH| Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center ,WT| Wellcome Trust Sanger Institute - generic account for deposition of all core- funded research papers. ,NIH| Targeting abnormal alveolar immune activation and failed epithelial repair in COVID-19 ,NIH| Normal Aging Lung Cell Atlas (NALCA) ,NIH| Fibroblast heterogeneity in pulmonary fibrosis ,NIH| LungMap Phase II - Building a multidimensional map of developing human lung ,NIH| Combining genome, function, and phenotype to define the cell type specific gene regulatory architecture of idiopathic pulmonary fibrosis ,NIH| Genetic Control of Airway Epithelium Gene Expression in Childhood Asthmatics ,NIH| Monocyte-derived alveolar macrophage drives inflammatory response to lung ozone exposure ,NIH| NIAMS: CORT ,WT| An Extended Pilot for the Human Cell Atlas: Adult tissues, human development and inflammation-mediated pathologies ,NIH| The Airway Functional Genomics of Bronchodilator Drug Response in Minority Children with Asthma ,EC| discovAIR ,NIH| Single-cell analysis of the lung immune microenvironment and cell-cell interactions across healthy and diseased patients ,NIH| Biorepository for INvestigation of Diseases of the Lung (BRINDL) - Phase II ,EC| RESPIRE4 ,NIH| Epithelial Protective Effects of Thyroid Hormone Signaling in Fibrosis ,NIH| Genomic Analysis of Tissue and Cellular Heterogeneity in IPF ,NIH| Administrative Core ,NIH| Midwest Murine-Tissue Mapping Center (MM-TMC) ,NIH| Molecular control of a novel transitional cell state in alveolar regeneration ,NIH| TriState SenNET (Lung and Heart) Tissue Map and Atlas consortium ,NIH| Role of VEGF in Perinatal Pulmonary Hypertension ,NIH| Transcriptomic and Pharmacogenetic Asthma Endotypes in Minority Children ,NIH| KULMAP: Human Kidney, urinary tract and lung mapping center ,NIH| Genes, air pollution, and asthma severity in minority children ,NIH| Disordered Proteostasis as a Driver of Disease in the Aging Lung ,ANR| 3IA@cote d'azurLisa Sikkema; Ciro Ramírez-Suástegui; Daniel C. Strobl; Tessa E. Gillett; Luke Zappia; Elo Madissoon; Nikolay S. Markov; Laure-Emmanuelle Zaragosi; Yuge Ji; Meshal Ansari; Marie-Jeanne Arguel; Leonie Apperloo; Martin Banchero; Christophe Bécavin; Marijn Berg; Evgeny Chichelnitskiy; Mei-i Chung; Antoine Collin; Aurore C. A. Gay; Janine Gote-Schniering; Baharak Hooshiar Kashani; Kemal Inecik; Manu Jain; Theodore S. Kapellos; Tessa M. Kole; Sylvie Leroy; Christoph H. Mayr; Amanda J. Oliver; Michael von Papen; Lance Peter; Chase J. Taylor; Thomas Walzthoeni; Chuan Xu; Linh T. Bui; Carlo De Donno; Leander Dony; Alen Faiz; Minzhe Guo; Austin J. Gutierrez; Lukas Heumos; Ni Huang; Ignacio L. Ibarra; Nathan D. Jackson; Preetish Kadur Lakshminarasimha Murthy; Mohammad Lotfollahi; Tracy Tabib; Carlos Talavera-López; Kyle J. Travaglini; Anna Wilbrey-Clark; Kaylee B. Worlock; Masahiro Yoshida; Yuexin Chen; James S. Hagood; Ahmed Agami; Peter Horvath; Joakim Lundeberg; Charles-Hugo Marquette; Gloria Pryhuber; Chistos Samakovlis; Xin Sun; Lorraine B. Ware; Kun Zhang; Maarten van den Berge; Yohan Bossé; Tushar J. Desai; Oliver Eickelberg; Naftali Kaminski; Mark A. Krasnow; Robert Lafyatis; Marko Z. Nikolic; Joseph E. Powell; Jayaraj Rajagopal; Mauricio Rojas; Orit Rozenblatt-Rosen; Max A. Seibold; Dean Sheppard; Douglas P. Shepherd; Don D. Sin; Wim Timens; Alexander M. Tsankov; Jeffrey Whitsett; Yan Xu; Nicholas E. Banovich; Pascal Barbry; Thu Elizabeth Duong; Christine S. Falk; Kerstin B. Meyer; Jonathan A. Kropski; Dana Pe’er; Herbert B. Schiller; Purushothama Rao Tata; Joachim L. Schultze; Sara A. Teichmann; Alexander V. Misharin; Martijn C. Nawijn; Malte D. Luecken; Fabian J. Theis;pmid: 37291214
pmc: PMC10287567
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1(+) profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.A single-cell atlas of the human lungs, integrating data from 2.4 million cells from 486 individuals and including samples from healthy and diseased lungs, provides a roadmap for the generation of organ-scale cell atlases. Peer reviewed
DZNE Pub arrow_drop_down HELDA - Digital Repository of the University of HelsinkiArticle . 2023 . Peer-reviewedData sources: HELDA - Digital Repository of the University of HelsinkieScholarship - University of CaliforniaArticle . 2023Data sources: eScholarship - University of Californiaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess Routeshybrid more_vert DZNE Pub arrow_drop_down HELDA - Digital Repository of the University of HelsinkiArticle . 2023 . Peer-reviewedData sources: HELDA - Digital Repository of the University of HelsinkieScholarship - University of CaliforniaArticle . 2023Data sources: eScholarship - University of Californiaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Preprint 2022 United KingdomPublisher:Cold Spring Harbor Laboratory Funded by:WT | Expanding the capabilitie..., WT | Structure and Mechanism o..., WT | Unlocking the structure, ... +6 projectsWT| Expanding the capabilities and use of the South West Regional Facility for High-Resolution Electron Cryo-microscopy ,WT| Structure and Mechanism of Key Nonsense-Mediated mRNA Decay Factor Complexes ,WT| Unlocking the structure, mechanism and cellular assembly of key multiprotein complexes in human gene transcription. ,UKRI| BlueCryo Image Processing Computing Cluster ,WT| South West Regional Facility for High-Resolution Electron Cryo-Microscopy ,UKRI| Future Vaccine Manufacturing Hub: Advancing the manufacture and deployment of cost effective vaccines ,ANR| AirMN ,ANR| SIGNALIFE ,UKRI| The production and application of SARS-CoV-2 reverse genetic systems to facilitate vaccine development and biosafe drug discovery platforms.Christine Toelzer; Kapil Gupta; Sathish K. N. Yadav; Lorna Hodgson; Maia Kavanagh Williamson; Dora Buzas; Ufuk Borucu; Kyle Powers; Richard Stenner; Kate Vasileiou; Frederic Garzoni; Daniel Fitzgerald; Christine Payré; Gunjan Gautam; Gérard Lambeau; Andrew D. Davidson; Paul Verkade; Martin Frank; Imre Berger; Christiane Schaffitzel;pmid: 36417532
pmc: PMC9683698
AbstractAs COVID-19 persists, severe acquired respiratory syndrome coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor-binding domain (RBD) comprises a free fatty acid (FFA)-binding pocket. FFA-binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2 and VOCs bind the essential FFA linoleic acid (LA), while binding is abolished by one mutation in common cold-causing HCoV-HKU1. In the SARS-CoV S structure, LA stabilizes the locked conformation while the open, infectious conformation is LA-free. Electron tomography of SARS-CoV-2 infected cells reveals that LA-treatment inhibits viral replication, resulting in fewer, deformed virions. Our results establish FFA-binding as a hallmark of pathogenic β-CoV infection and replication, highlighting potential antiviral strategies.One-Sentence SummaryFree fatty acid-binding is conserved in pathogenic β-coronavirus S proteins and suppresses viral infection and replication.
Explore Bristol Rese... arrow_drop_down Mémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYFull-Text: https://hal.science/hal-03870926/documentMémoires en Sciences de l'Information et de la CommunicationPreprint . 2022add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2022.04.22.489083&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 21 citations 21 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert Explore Bristol Rese... arrow_drop_down Mémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYFull-Text: https://hal.science/hal-03870926/documentMémoires en Sciences de l'Information et de la CommunicationPreprint . 2022add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2022.04.22.489083&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2022 Denmark, France, United KingdomPublisher:Springer Science and Business Media LLC Funded by:WT | Arts, Society and Public ..., INCa, WT | COVID-Minds: Mental Healt... +2 projectsWT| Arts, Society and Public Health: An Exploration of the Major UK Cohort Studies ,INCa ,WT| COVID-Minds: Mental Health during Covid-19 ,ANR| CONSTANCES ,UKRI| MARCH: Social, Cultural and Community Assets for Mental HealthAmélie Keller; Jonathan Groot; Joane Matta; Feifei Bu; Tarik El Aarbaoui; Maria Melchior; Daisy Fancourt; Marie Zins; Marcel Goldberg; Anne-Marie Nybo Andersen; Naja H. Rod; Katrine Strandberg-Larsen; Tibor V. Varga;AbstractMany studies have investigated the impact of the COVID-19 pandemic on mental health. Throughout the pandemic, time spent at home increased to a great extent due to restrictive measures. Here we set out to investigate the relationship between housing conditions and the mental health of populations across European countries. We analyzed survey data collected during spring 2020 from 69,136 individuals from four cohorts from Denmark, France, and the UK. The investigated housing conditions included household density, composition, and crowding, access to outdoor facilities, dwelling type, and urbanicity. The outcomes were loneliness, anxiety, and life satisfaction. Logistic regression models were used, and results were pooled using random-effects meta-analysis. In the meta-analysis, living alone was associated with higher levels of loneliness (OR = 3.08, 95% CI 1.87–5.07), and lower life satisfaction (OR = 1.27, 95% CI 1.05–0.55), compared to living with others. Not having access to an outdoor space and household crowding were suggestively associated with worse outcomes. Living in crowded households, living alone, or lacking access to outdoor facilities may be particularly important in contributing to poor mental health during a lockdown. Addressing the observed fundamental issues related to housing conditions within society will likely have positive effects in reducing social inequalities, as well as improving preparedness for future pandemics.
Scientific Reports arrow_drop_down Copenhagen University Research Information SystemArticle . 2022Data sources: Copenhagen University Research Information SystemMémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYFull-Text: https://hal.science/hal-03642586/documentadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess Routesgold 14 citations 14 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert Scientific Reports arrow_drop_down Copenhagen University Research Information SystemArticle . 2022Data sources: Copenhagen University Research Information SystemMémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYFull-Text: https://hal.science/hal-03642586/documentadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41598-022-09316-4&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Preprint 2022 FrancePublisher:Research Square Platform LLC Publicly fundedFunded by:ANR | AABIFNCOV, EC | EASI-Genomics, SFI | How immunology can help t... +6 projectsANR| AABIFNCOV ,EC| EASI-Genomics ,SFI| How immunology can help to address the COVID-19 epidemic in Ireland ,ANR| GenMIS-C ,SFI| DIRECTS: Detecting Innate protection against SARS-CoV2 ,NIH| Monogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19 ,WT| Wellcome – Health Research Board Irish Clinical Academic Training Programme ,NIH| Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational Success ,NIH| Inborn errors of immunity in patients with life-threatening COVID-19Duffy, Darragh; SMITH, Nikaïa; Possémé, Céline; Bondet, Vincent; Sugrue, Jamie; Townsend, Liam; Charbit, Bruno; Rouilly, Vincent; Saint-André, Violaine; Dott, Tom; Pozo, Andre Rodriguez; Yatim, Nader; Schwartz, Olivier; Cervantes-Gonzales, Minerva; Ghosn, Jade; Bastard, Paul; Casanova, Jean-Laurent; Szwebel, Tali-Anne; Terrier, Benjamin; Conlon, Niall; O'Farrelly, Cliona; Cheallaigh, Cliona Ni; Bourke, Nollaig;Abstract Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported that reduced blood type I interferon (IFN-I) in severe COVID-19 patients preceded clinical worsening. These results were supported by studies which identified genetic mutations in loci of the TLR3- or TLR7-dependent IFN-I pathways, or autoantibodies neutralizing IFNα or IFNω, as major risk factors for development of severe and critical COVID-19 pneumonia. Here, we analyzed a range of IFN-I associated responses in patient cohorts with different severities of COVID-19, showing that baseline plasma IFNα measures differed significantly according to the immunoassay used, as well as timing of sampling, the IFNα subtype measured, and the presence of autoantibodies. We then compared immune responses induced by ex vivo stimulation between non-hospitalized moderate cases (n=27) and hospitalized (n=17) adult patients that required oxygen supplementation. This showed a consistently reduced induction of IFN-I proteins in hospitalized COVID-19 patients upon stimulation, that was not associated with detectable neutralizing autoantibodies against IFNα or IFNω. We confirmed the poor induction of IFN-I in an independent patient cohort (n=33), and showed it was more pronounced with severe disease. Intracellular proteomic analysis showed that while monocyte numbers were increased in hospitalized COVID-19 patients, they did not secrete IFN-I in response to stimulation. This was further confirmed by ex vivo whole blood stimulation with IFN-I which induced a transcriptomic response associated with inflammation in hospitalized COVID-19 patients, that was not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to IFN-I based treatments in late stage COVID-19, despite the critical importance of IFN-I in early acute infection. An improved understanding of such variable responses to treatment may help to identify potential alternative therapeutic strategies.
https://doi.org/10.2... arrow_drop_down HAL Descartes; HAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationPreprint . 2022License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.21203/rs.3.rs-1685544/v1&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert https://doi.org/10.2... arrow_drop_down HAL Descartes; HAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationPreprint . 2022License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.21203/rs.3.rs-1685544/v1&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Preprint 2023Publisher:Cold Spring Harbor Laboratory Funded by:WT | Putting genomic surveilla..., UKRI | East of Scotland Bioscien..., NIH | Statistical innovation to... +10 projectsWT| Putting genomic surveillance at the heart of viral epidemic response. ,UKRI| East of Scotland Bioscience Doctoral Training Partnership ,NIH| Statistical innovation to integrate sequences and phenotypes for scalable phylodynamic inference ,NIH| University of Washington Arboviral Research Network (UWARN) ,NIH| Fast and flexible Bayesian phylogenetics via modern machine learning ,EC| VEO ,NIH| Role of Data Streams In Informing Infection Dynamics in Africa- INFORM Africa ,EC| MOOD ,EC| ReservoirDOCs ,ANR| INCEPTION ,EC| RECoVER ,WT| The ISARIC data platform: Optimizing data-driven pandemic preparedness and response ,UKRI| Doctoral Training Partnership in Environmental ResearchJoseph L.-H. Tsui; Ben Lambert; Sumali Bajaj; John T. McCrone; Rhys P.D. Inward; Paolo Bosetti; Verity Hill; Rosario Evans Pena; Alexander E. Zarebski; Thomas P. Peacock; Luyang Liu; Neo Wu; Megan Davis; Isaac I. Bogoch; Kamran Khan; Rachel Colquhoun; Áine O’Toole; Ben Jackson; Abhishek Dasgupta; Eduan Wilkinson; Houriiyah Tegally; Tulio de Oliveira; Thomas R. Connor; Nicholas J. Loman; Vittoria Colizza; Christophe Fraser; Erik Volz; Xiang Ji; Marc A. Suchard; Bernardo Gutierrez; Meera Chand; Simon Dellicour; Simon Cauchemez; Jayna Raghwani; Philippe Lemey; Andrew Rambaut; Oliver G. Pybus; Moritz U.G. Kraemer;SummarySARS-CoV-2 variants of concern (VOCs) arise against the backdrop of increasingly heterogeneous human connectivity and population immunity. Through a large-scale phylodynamic analysis of 115,622 Omicron genomes, we identified >6,000 independent introductions of the antigenically distinct virus into England and reconstructed the dispersal history of resulting local transmission. Travel restrictions on southern Africa did not reduce BA.1 importation intensity as secondary hubs became major exporters. We explored potential drivers of BA.1 spread across England and discovered an early period during which viral lineage movements mainly occurred between larger cities, followed by a multi-focal spatial expansion shaped by shorter distance mobility patterns. We also found evidence that disease incidence impacted human commuting behaviours around major travel hubs. Our results offer a detailed characterisation of processes that drive the invasion of an emerging VOC across multiple spatial scales and provide unique insights on the interplay between disease spread and human mobility.HighlightsOver 6,000 introductions ignited the epidemic wave of Omicron BA.1 in EnglandImportations prior to international travel restrictions were responsible for majority of local BA.1 infections but importations continued from sources other than southern AfricaHuman mobility at regional and local spatial scales shaped dissemination and growth of BA.1Changes in human commuting patterns are associated with higher case incidence in travel hubs across England
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.01.02.23284109&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu3 citations 3 popularity Top 10% influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.01.02.23284109&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2022 United Kingdom, FrancePublisher:Elsevier BV Funded by:ANR | IDEXLYON, UKRI | Isaac Newton Institute fo..., WT | Improving scientific and ...ANR| IDEXLYON ,UKRI| Isaac Newton Institute for Mathematical Sciences ,WT| Improving scientific and public health decision making by developing technologies to increase use of robust methods to calibrate and analyse complex mathematical modelsMichael Dunne; Hossein Mohammadi; Peter Challenor; Rita Borgo; Thibaud Porphyre; Ian Vernon; Elif E. Firat; Cagatay Turkay; Thomas Torsney-Weir; Michael Goldstein; Richard Reeve; Hui Fang; Ben Swallow;Funding: This work was supported by EPSRC, United Kingdom grant no. EP/R014604/1. RR was funded by STFC, United Kingdom grant no ST/V006126/1. IV gratefully acknowledges Wellcome funding (218261/Z/19/Z) and EPSRC funding (EP W011956). TP gratefully acknowledges funding from the Scottish Government Rural and Environment Science and Analytical Services Division, United Kingdom, as part of the Centre of Expertise on Animal Disease Outbreaks (EPIC). TP would also like to thank the French National Research Agency and Boehringer Ingelheim Animal Health France for support through the IDEXLYON project (ANR-16-IDEX-0005) and the Industrial Chair in Veterinary Public Health, as part of the VPH Hub in Lyon. Uncertainty quantification is a formal paradigm of statistical estimation that aims to account for all uncertain-ties inherent in the modelling process of real-world complex systems. The methods are directly applicable to stochastic models in epidemiology, however they have thus far not been widely used in this context. In this paper, we provide a tutorial on uncertainty quantification of stochastic epidemic models, aiming to facilitate the use of the uncertainty quantification paradigm for practitioners with other complex stochastic simulators of applied systems. We provide a formal workflow including the important decisions and considerations that need to be taken, and illustrate the methods over a simple stochastic epidemic model of UK SARS-CoV-2 transmission and patient outcome. We also present new approaches to visualisation of outputs from sensitivity analyses and uncertainty quantification more generally in high input and/or output dimensions. Peer reviewed
Durham Research Onli... arrow_drop_down Durham Research Online; EpidemicsArticle . 2022 . Peer-reviewedLicense: CC BYFull-Text: http://dro.dur.ac.uk/35936/1/35936.pdfSt Andrews Research RepositoryArticle . 2022 . Peer-reviewedData sources: St Andrews Research Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.epidem.2022.100574&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 1 citations 1 popularity Average influence Average impulse Average Powered by BIP!visibility 4visibility views 4 download downloads 5 Powered bymore_vert Durham Research Onli... arrow_drop_down Durham Research Online; EpidemicsArticle . 2022 . Peer-reviewedLicense: CC BYFull-Text: http://dro.dur.ac.uk/35936/1/35936.pdfSt Andrews Research RepositoryArticle . 2022 . Peer-reviewedData sources: St Andrews Research Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.epidem.2022.100574&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2023 United Kingdom, United Kingdom, NetherlandsPublisher:Springer Science and Business Media LLC Funded by:ANR | 3IA@cote d'azur, UKRI | A systems based approach ..., WT | Developing a locally-appr... +9 projectsANR| 3IA@cote d'azur ,UKRI| A systems based approach to integrating genetic and longitudinal omics data to support diagnosis and prediction of common chronic disease ,WT| Developing a locally-appropriate socioeconomic support package for TB-affected households in Nepal: a seed project to inform the END-TB trial ,WT| Programme for High Dimensional Translation in Neurology ,UKRI| The Alan Turing Institute ,UKRI| Epidemic modelling and statistical support for policy: sub-populations, forecasting, and long-term planning ,WT| King's College London Medical Engineering Centre of Research Excellence ,UKRI| GEroscience and Multi-Morbidity: identifying targets for intervention (GEMM) ,UKRI| COVID-19 Modelling Consortium: quantitative epidemiological predictions in response to an evolving pandemic ,UKRI| London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare ,WT| TwinsUK (2019-2023) - An Epidemiological and Genomic Resource ,UKRI| Addressing the Social Determinants and Consequences of Tuberculosis (ASCOT): a pilot randomised controlled trial and process evaluation in NepalFyles, Martyn; Vihta, Karina-Doris; Sudre, Carole H; Long, Harry; Das, Rajenki; Jay, Caroline; Wingfield, Tom; Cumming, Fergus; Green, William; Hadjipantelis, Pantelis; Kirk, Joni; Steves, Claire J; Ourselin, Sebastien; Medley, Graham F; Fearon, Elizabeth; House, Thomas;Through the use of cutting-edge unsupervised classification techniques from statistics and machine learning, we characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases. We first analyse each dataset in isolation and across age bands, before using methods that allow us to compare multiple datasets. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. In this way, we are able to demonstrate the deep structure of symptoms of COVID-19 without usual biases due to study design. This is expected to have implications for the identification and management of community SARS-CoV-2 cases and could be further applied to symptom-based management of other diseases and syndromes. Comment: 60 pages; 29 figures
Scientific Reports arrow_drop_down Amsterdam UMC (VU Amsterdam) - Institutional RepositoryArticle . 2023Data sources: Amsterdam UMC (VU Amsterdam) - Institutional RepositoryarXiv.org e-Print ArchiveOther literature type . Preprint . 2021Data sources: arXiv.org e-Print ArchiveThe University of Manchester - Institutional RepositoryArticle . 2023Data sources: The University of Manchester - Institutional Repositoryhttps://doi.org/10.48550/arxiv...Article . 2021License: arXiv Non-Exclusive DistributionData sources: Dataciteadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41598-023-47488-9&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert Scientific Reports arrow_drop_down Amsterdam UMC (VU Amsterdam) - Institutional RepositoryArticle . 2023Data sources: Amsterdam UMC (VU Amsterdam) - Institutional RepositoryarXiv.org e-Print ArchiveOther literature type . Preprint . 2021Data sources: arXiv.org e-Print ArchiveThe University of Manchester - Institutional RepositoryArticle . 2023Data sources: The University of Manchester - Institutional Repositoryhttps://doi.org/10.48550/arxiv...Article . 2021License: arXiv Non-Exclusive DistributionData sources: Dataciteadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41598-023-47488-9&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2022 FrancePublisher:MDPI AG Funded by:SFI | DIRECTS: Detecting Innate..., WT | Wellcome – Health Researc..., ANR | INCEPTIONSFI| DIRECTS: Detecting Innate protection against SARS-CoV2 ,WT| Wellcome – Health Research Board Irish Clinical Academic Training Programme ,ANR| INCEPTIONLaura Garcia; Tom Woudenberg; Jason Rosado; Adam H. Dyer; Françoise Donnadieu; Delphine Planas; Timothée Bruel; Olivier Schwartz; Thierry Prazuck; Aurélie Velay; Samira Fafi-Kremer; Isabella Batten; Conor Reddy; Emma Connolly; Matt McElheron; Sean P. Kennelly; Nollaig M. Bourke; Michael T. White; Stéphane Pelleau;Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics. International audience
Viruses arrow_drop_down VirusesOther literature type . Article . 2022 . Peer-reviewedLicense: CC BYFull-Text: http://www.mdpi.com/1999-4915/14/7/1491/pdfHAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.3390/v14071491&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesgold 13 citations 13 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert Viruses arrow_drop_down VirusesOther literature type . Article . 2022 . Peer-reviewedLicense: CC BYFull-Text: http://www.mdpi.com/1999-4915/14/7/1491/pdfHAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationArticle . 2022License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.3390/v14071491&type=result"></script>'); --> </script>
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