Institution
Hospital Sant Joan de Déu Barcelona
Healthcare•Barcelona, Spain•
About: Hospital Sant Joan de Déu Barcelona is a healthcare organization based out in Barcelona, Spain. It is known for research contribution in the topics: Population & Mutation. The organization has 1739 authors who have published 1789 publications receiving 35504 citations. The organization is also known as: Sant Joan de Déu-Barcelona Children’s Hospital.
Topics: Population, Mutation, Missense mutation, Sarcoma, Intensive care
Papers published on a yearly basis
Papers
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TL;DR: A fundamental problem with cancer genome studies is described: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds and the list includes many implausible genes, suggesting extensive false-positive findings that overshadow true driver events.
Abstract: Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.
4,411 citations
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Hospital General Universitario Gregorio Marañón1, Hospital Sant Joan de Déu Barcelona2, Boston Children's Hospital3, Sofia Medical University4, Ljubljana University Medical Centre5, University of Naples Federico II6, Great Ormond Street Hospital7, UCL Institute of Child Health8, Geneva College9, Royal Children's Hospital10, Ruhr University Bochum11, Guy's and St Thomas' NHS Foundation Trust12, Agostino Gemelli University Polyclinic13, Catholic University of the Sacred Heart14, University of Oslo15, University of Fribourg16
TL;DR: Key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic are captured to reflect the current uncertainties regarding specific treatment options.
918 citations
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St. Jude Children's Research Hospital1, German Cancer Research Center2, Heidelberg University3, University of Copenhagen4, Massachusetts Institute of Technology5, European Bioinformatics Institute6, Max Planck Society7, Broad Institute8, University Hospital Heidelberg9, Oregon Health & Science University10, Boston Children's Hospital11, University of Tübingen12, University of California, Los Angeles13, Hospital Sant Joan de Déu Barcelona14, Duke University15, McGill University16, Kitasato University17, BC Cancer Agency18, University of Toronto19
TL;DR: The application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
Abstract: Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
706 citations
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TL;DR: These findings support a model whereby the NLRP3 inflammasome, acting as an extracellular oligomeric complex, amplifies the inflammatory response.
Abstract: Assembly of the NLRP3 inflammasome activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1β and thereby serves a central role in the inflammatory response and in diverse human diseases. Here we found that upon activation of caspase-1, oligomeric NLRP3 inflammasome particles were released from macrophages. Recombinant oligomeric protein particles composed of the adaptor ASC or the p.D303N mutant form of NLRP3 associated with cryopyrin-associated periodic syndromes (CAPS) stimulated further activation of caspase-1 extracellularly, as well as intracellularly after phagocytosis by surrounding macrophages. We found oligomeric ASC particles in the serum of patients with active CAPS but not in that of patients with other inherited autoinflammatory diseases. Our findings support a model whereby the NLRP3 inflammasome, acting as an extracellular oligomeric complex, amplifies the inflammatory response.
655 citations
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University of Barcelona1, Leiden University Medical Center2, Uppsala University3, Johns Hopkins University4, National and Kapodistrian University of Athens5, Eskişehir Osmangazi University6, University of Cambridge7, St George's, University of London8, Hospital Sant Joan de Déu Barcelona9, University of Milano-Bicocca10
TL;DR: The ESC Guidelines for the management of patients with supraventricular tachycardia as discussed by the authors were developed in collaboration with the Association for European Paediatric and Congenital Cardiology (AEPC).
Abstract: 2019 ESC Guidelines for the management of patients with supraventricular tachycardia : The Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC): Developed in collaboration with the Association for European Paediatric and Congenital Cardiology (AEPC)
490 citations
Authors
Showing all 1756 results
Name | H-index | Papers | Citations |
---|---|---|---|
Georg F. Hoffmann | 87 | 707 | 24831 |
Ilona J. Frieden | 80 | 305 | 21327 |
Eduard Gratacós | 75 | 531 | 20178 |
Gertjan J.L. Kaspers | 67 | 469 | 17518 |
Lourdes Ibáñez | 63 | 289 | 13034 |
Francesc Villarroya | 63 | 282 | 13426 |
Albert Costa | 62 | 236 | 14258 |
Joost Schalkwijk | 57 | 223 | 12417 |
Francesc Figueras | 52 | 206 | 9055 |
Marta Giralt | 52 | 161 | 8885 |
Salvador Soto-Faraco | 48 | 153 | 7586 |
Rafael Artuch | 48 | 308 | 8046 |
Fatima Crispi | 47 | 240 | 6728 |
Sakari Reitamo | 46 | 148 | 7381 |
Nicole I. Wolf | 45 | 186 | 6810 |