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1. Notch1 switches progenitor competence in inducing medulloblastoma

Author: Matteo Gianesello, Tingting Zhang, Giuseppe Aiello, Francesca Gianno, Luca Tiberi, Francesco Antonica, Bassem A. Hassan, Felice Giangaspero, Konstantin Okonechnikov, Claudio Ballabio, Chiara Lago, Stefan M. Pfister, Marica Anderle, University of Trento [Trento], Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Università degli studi di Napoli Federico II, Heidelberg University Hospital [Heidelberg], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, and HAL-SU, Gestionnaire
Subjects: Poor prognosis, Cell of origin, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, Developmental Neuroscience, [SDV.CAN] Life Sciences [q-bio]/Cancer, SOX2, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, neoplasms, Research Articles, Cancer, 030304 developmental biology, Progenitor, Medulloblastoma, 0303 health sciences, Mouse Cerebellum, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Multidisciplinary, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, SciAdv r-articles, medicine.disease, Molecular biology, nervous system diseases, 3. Good health, stomatognathic diseases, ASCL1, 030220 oncology & carcinogenesis, embryonic structures, cardiovascular system, Cancer research, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Pathway activity, Research Article, Proto-oncogene tyrosine-protein kinase Src
Abstract: Notch1 pathway activation is required for group 3 medulloblastoma initiation., The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b+ cells are competent to initiate group 3 MB, and we observed that S100b+ cells have higher levels of Notch1 pathway activity compared to Math1+ cells. We found that additional activation of Notch1 in Math1+ and Sox2+ cells was sufficient to induce group 3 MB upon MYC/Gfi1 expression. Together, our data suggest that the Notch1 pathway plays a critical role in group 3 MB initiation.
Published: 2021

2. Diffuse Glioneuronal tumour with Oligodendroglioma‐like features and Nuclear Clusters (DGONC) – a molecularly‐defined glioneuronal CNS tumour class displaying recurrent monosomy 14

Author: Martin U. Schuhmann, Till Milde, A. von Deimling, Matija Snuderl, Kathy Keyvani, Nada Jabado, Thorsten Pietsch, Eleonora Aronica, Olaf Witt, Christian Hartmann, David T.W. Jones, David Ellison, Felix Sahm, Martin Sill, Dominik Sturm, M Kool, M. Y. Deng, Damian Stichel, Matthias Preusser, Felice Giangaspero, K. von Hoff, M. Lauten, Christine Haberler, Ori Staszewski, Ulrich Schüller, Jonas Ecker, Pieter Wesseling, Christopher Dunham, Martin Ebinger, Jens Schittenhelm, Christel Herold-Mende, Hendrik Witt, Wolfgang Wick, Andrey Korshunov, Nicholas G. Gottardo, Dominique Figarella-Branger, Andrea Wittmann, M. Deckert, Stefan M. Pfister, Heidelberg University Hospital [Heidelberg], Tübingen University Hospital [Germany], Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Service d’Anatomie Pathologique et de Neuropathologie, APHM, Hôpital de la Timone, Hôpital de la Timone [CHU - APHM] (TIMONE), Genome Analysis, Department of Pediatrics and Adolescent Medicine, University Freiburg, Freiburg, Institut d'écologie et des sciences de l'environnement de Paris (IEES), Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology, Massachusetts General Hospital [Boston], Department of Human Genetics , Department of Experimental Medicine, Radboud University Medical Center [Nijmegen], VU University Medical Center [Amsterdam], RMIT Melbourne, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Department of Neuropathology, Institute of Pathology, Division of Paediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany, Institut d'écologie et des sciences de l'environnement de Paris (iEES), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Pathology, CCA - Cancer biology, Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Recherche Agronomique (INRA), ANS - Cellular & Molecular Mechanisms, APH - Aging & Later Life, and APH - Mental Health
Subjects: 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Histology, [SDV]Life Sciences [q-bio], Oligodendroglioma, Medizin, Biology, Pathology and Forensic Medicine, Central Nervous System Neoplasms, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Monosomy, Physiology (medical), medicine, Humans, Neurocytoma, ComputingMilieux_MISCELLANEOUS, Paediatric patients, Chromosomes, Human, Pair 14, Glioma, DNA Methylation, medicine.disease, 3. Good health, 030104 developmental biology, Neurology, chemistry, Homogeneous, DNA methylation, Female, Neurology (clinical), Who classification, Monosomy 14, 030217 neurology & neurosurgery, DNA, Clear cell
Abstract: Aims: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. Patients and methods: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the ‘conumee’ package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. Results: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. Conclusions: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters.
Published: 2019

3. The molecular landscape of ETMR at diagnosis and relapse

Author: Olaf Witt, Maria Łastowska, Anna Darabi, Ulrich Schüller, Andreas von Deimling, Nada Jabado, Susanne Gröbner, David Sumerauer, Annie Huang, Sebastian M. Waszak, Martin Sill, Xiao-Nan Li, Andrey Korshunov, Julien Masliah-Planchon, Pablo Landgraf, David Ellison, Maria J. Gil-da-Costa, Alexander J.R. Bishop, Christin Schmidt, Pieter Wesseling, Sebastian Brabetz, Marc Remke, July Carolina Romero, Dominique Figarella-Branger, Peter Hauser, Simon Papillon-Cavanagh, Jennifer A. Chan, Felix Sahm, Benjamin Schwalm, Peter Lichter, Ivo Buchhalter, Stephan Wolf, Norman Mack, Matthias A. Karajannis, Till Milde, Jan Koster, Valérie Rigau, Monika Mauermann, Matija Snuderl, Franck Bourdeaut, Christine Haberler, Torsten Pietsch, Volker Hovestadt, Wiesława Grajkowska, Katja von Hoff, Felice Giangaspero, Marcel Kool, Emmanuelle Uro-Coste, Jan O. Korbel, Michael D. Taylor, Martin Hasselblatt, Tobias Rausch, Danny A. Zwijnenburg, Jonas Ecker, Brent A. Orr, David T.W. Jones, Jens Schittenhelm, Aparna Gorthi, Sonja Krausert, Sanda Alexandrescu, Sander Lambo, Jens Martin Hübner, Ben Ho, Stefan M. Pfister, Marina Ryzhova, German Cancer Consortium [Heidelberg] (DKTK), Department of Oncogenomics [Amsterdam, Pays-Bas], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Heidelberg University Hospital [Heidelberg], Division of Medical Genetics [Seattle], University of Washington [Seattle], Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany, Department of Neuropathology, Institute of Pathology, RMIT Melbourne, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Service d'Anatomie Pathologique et de Neuropathologie [Hôpital de la Timone - CHU - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), VU University Medical Center [Amsterdam], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Pathology, Massachusetts General Hospital [Boston], Department of Human Genetics , Department of Experimental Medicine, Radboud University Medical Center [Nijmegen], European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany., Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Pathology, CCA - Imaging and biomarkers, Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier (INM), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS), and Oncogenomics
Subjects: Ribonuclease III, 0301 basic medicine, Genome instability, medicine.medical_specialty, Somatic cell, [SDV]Life Sciences [q-bio], Disease, Poly(ADP-ribose) Polymerase Inhibitors, Polymorphism, Single Nucleotide, Article, DEAD-box RNA Helicases, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Recurrence, Chromosome instability, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Cisplatin, Multidisciplinary, biology, embryonal tumours, Topoisomerase, brain tumours, genomic landscape, Neoplasms, Germ Cell and Embryonal, 3. Good health, MicroRNAs, 030104 developmental biology, DNA Topoisomerases, Type I, 030220 oncology & carcinogenesis, multilayered rosettes, Mutation, biology.protein, Cancer research, Medical genetics, RNA, Long Noncoding, Poly(ADP-ribose) Polymerases, medicine.drug
Abstract: Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis1. Here we collected 193 primary ETMRs and 23 matched relapse samples to investigate the genomic landscape of this distinct tumour type. We found that patients with tumours in which the proposed driver C19MC2–4 was not amplified frequently had germline mutations in DICER1 or other microRNA-related aberrations such as somatic amplification of miR-17-92 (also known as MIR17HG). Whole-genome sequencing revealed that tumours had an overall low recurrence of single-nucleotide variants (SNVs), but showed prevalent genomic instability caused by widespread occurrence of R-loop structures. We show that R-loop-associated chromosomal instability can be induced by the loss of DICER1 function. Comparison of primary tumours and matched relapse samples showed a strong conservation of structural variants, but low conservation of SNVs. Moreover, many newly acquired SNVs are associated with a mutational signature related to cisplatin treatment. Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be an effective treatment strategy for this deadly disease.
Published: 2019

4. SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue

Author: Frank Kirchhoff, Dominik Hotter, Daniel Sauter, Martine Peeters, Christine Goffinet, Oliver T. Fackler, Konstantin M. J. Sparrer, Zhong Yao, Birthe Trautz, Ahidjo Ayouba, Bengisu Akbil, Thomas Zillinger, Igor Stagljar, Christina M. Stürzel, Swetha Ananth, Vânia Passos, Dorota Kmiec, Institute of Molecular Virology [Ulm, Allemagne], Universitätsklinikum Ulm - University Hospital of Ulm, Department of Infectious Diseases, Integrative Virology [Heidelberg, Allemagne], Center for Integrative Infectious Diseases Research [Heidelberg, Allemagne] (CIID), Heidelberg University Hospital [Heidelberg]-Heidelberg University Hospital [Heidelberg], German Center for Infection Research, Partner Site Heidelberg [Allemagne] (DZIF), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Donnelly Centre [Toronto, ON, Canada], University of Toronto, Department of Biochemistry [University of Toronto], Department of Molecular Genetics [Toronto], Institute of Virology [Hannover], Hannover Medical School [Hannover] (MHH), Institute of Clinical Chemistry and Clinical Pharmacology [Bonn, Allemagne], University of Bonn, This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG, European Project: 323035,EC:FP7:ERC,ERC-2012-ADG_20120314,ANTI-VIROME(2013), Bodescot, Myriam, A combined evolutionary and proteomics approach to the discovery, induction and application of antiviral immunity factors - ANTI-VIROME - - EC:FP7:ERC2013-04-01 - 2018-03-31 - 323035 - VALID, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Universität Bonn = University of Bonn, and Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)
Subjects: 0301 basic medicine, RNA viruses, CD4-Positive T-Lymphocytes, viruses, Xenopus, Monkeys, Pathology and Laboratory Medicine, Virus Replication, Gene Products, nef, Virions, White Blood Cells, Database and Informatics Methods, Jurkat Cells, Immunodeficiency Viruses, Animal Cells, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, lcsh:QH301-705.5, Cells, Cultured, Infectivity, Mammals, T Cells, CD28, Eukaryota, virus diseases, Transfection, 3. Good health, Cell biology, medicine.anatomical_structure, Infectious Diseases, Medical Microbiology, Viral Pathogens, Viruses, Vertebrates, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Simian Immunodeficiency Virus, Pathogens, Cellular Types, Sequence Analysis, Research Article, Primates, lcsh:Immunologic diseases. Allergy, Proteasome Endopeptidase Complex, Infectious Disease Control, [SDV.IMM] Life Sciences [q-bio]/Immunology, Bioinformatics, Lymphoid Tissue, T cell, Immune Cells, Immunology, Biology, Viral Structure, Colobus, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Sequence Motif Analysis, Virology, Retroviruses, Old World monkeys, Genetics, medicine, Animals, Humans, Molecular Biology, Microbial Pathogens, Blood Cells, Lentivirus, Organisms, Actin remodeling, Biology and Life Sciences, HIV, Membrane Proteins, Cell Biology, biology.organism_classification, Viral Replication, 030104 developmental biology, HEK293 Cells, Viral replication, lcsh:Biology (General), Amniotes, Proteolysis, Tetherin, HIV-1, Parasitology, lcsh:RC581-607
Abstract: SERINC5 is a host restriction factor that impairs infectivity of HIV-1 and other primate lentiviruses and is counteracted by the viral accessory protein Nef. However, the importance of SERINC5 antagonism for viral replication and cytopathicity remained unclear. Here, we show that the Nef protein of the highly divergent SIVcol lineage infecting mantled guerezas (Colobus guereza) is a potent antagonist of SERINC5, although it lacks the CD4, CD3 and CD28 down-modulation activities exerted by other primate lentiviral Nefs. In addition, SIVcol Nefs decrease CXCR4 cell surface expression, suppress TCR-induced actin remodeling, and counteract Colobus but not human tetherin. Unlike HIV-1 Nef proteins, SIVcol Nef induces efficient proteasomal degradation of SERINC5 and counteracts orthologs from highly divergent vertebrate species, such as Xenopus frogs and zebrafish. A single Y86F mutation disrupts SERINC5 and tetherin antagonism but not CXCR4 down-modulation by SIVcol Nef, while mutation of a C-proximal di-leucine motif has the opposite effect. Unexpectedly, the Y86F change in SIVcol Nef had little if any effect on viral replication and CD4+ T cell depletion in preactivated human CD4+ T cells and in ex vivo infected lymphoid tissue. However, SIVcol Nef increased virion infectivity up to 10-fold and moderately increased viral replication in resting peripheral blood mononuclear cells (PBMCs) that were first infected with HIV-1 and activated three or six days later. In conclusion, SIVcol Nef lacks several activities that are conserved in other primate lentiviruses and utilizes a distinct proteasome-dependent mechanism to counteract SERINC5. Our finding that evolutionarily distinct SIVcol Nefs show potent anti-SERINC5 activity supports a relevant role of SERINC5 antagonism for viral fitness in vivo. Our results further suggest this Nef function is particularly important for virion infectivity under conditions of limited CD4+ T cell activation., Author summary The accessory protein Nef promotes primate lentiviral replication and enhances the pathogenicity of HIV-1 by mechanisms of immune evasion and enhancing viral infectivity and replication. Here, we show that the evolutionarily most isolated primate lentivirus SIVcol lacks several otherwise conserved Nef functions. Nevertheless, SIVcol Nef potently antagonizes SERINC5, a recently discovered inhibitor of viral infectivity, by down-modulating it from the cell surface and inducing its proteasomal degradation. We identified Y86 in SIVcol Nef as a key determinant of SERINC5 antagonism. Efficient counteraction of SERINC5 did not increase HIV-1 replication in preactivated CD4+ T cells and in ex vivo infected lymphoid tissue but had modest enhancing effects when resting PBMCs were first infected and activated six days later. Evolution of high anti-SERINC5 activity by SIVcol Nef supports a relevant role of this antagonism in vivo, for instance by enhancing virion infectivity under conditions of limited T cell activation.
Published: 2018

5. Zika virus epidemiology in Bolivia : A seroprevalence study in volunteer blood donors

Author: Xavier de Lamballerie, Thomas Jaenisch, Paola Mariela Saba Villarroel, Stéphane Priet, Laetitia Ninove, Boris Pastorino, Pierre Gallian, Elif Nurtop, Isabelle Leparc-Goffart, Jan Felix Drexler, Yelin Roca, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro Nacional de Enfermedades Tropicales [Santa Cruz de la Sierra, Bolivia] (CENETROP), Institute of Virology [Berlin, Germany] (Charité), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Centre for Infection Research [Berlin, Germany] (DZIF - Charité), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Section Clinical Tropical Medicine [Heidelberg], Department of Infectious Diseases [Heidelberg, Germany], Heidelberg University Hospital [Heidelberg]-Heidelberg University Hospital [Heidelberg], Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), European Project: 734548,ZIKAlliance(2016), European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), German Centre for Infection Research (DZIF), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), European Union’s Horizon 2020 research and innovation programmes ZIKAlliance and EVAg under grant agreements No 734548 and 653316, Dubois Frid, Caroline, A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID, and European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID
Subjects: RNA viruses, Male, Volunteers, 0301 basic medicine, [SDV]Life Sciences [q-bio], Disease Vectors, Dengue virus, Pathology and Laboratory Medicine, medicine.disease_cause, Mosquitoes, Geographical locations, Zika virus, Dengue fever, Dengue, 0302 clinical medicine, Aedes aegypti, Aedes, Seroepidemiologic Studies, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Epidemiology, Medicine and Health Sciences, Mass Screening, Enzyme-linked immunoassays, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Zika Virus Infection, lcsh:Public aspects of medicine, Eukaryota, Middle Aged, 3. Good health, Insects, [SDV] Life Sciences [q-bio], Infectious Diseases, Geography, Medical Microbiology, Viral Pathogens, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Pathogens, Chikungunya virus, Research Article, Adult, medicine.medical_specialty, Bolivia, lcsh:Arctic medicine. Tropical medicine, Arthropoda, Adolescent, lcsh:RC955-962, Alphaviruses, Immunology, 030231 tropical medicine, Mosquito Vectors, Research and Analysis Methods, Blood donors, Microbiology, Virus, Togaviruses, Young Adult, 03 medical and health sciences, Environmental health, parasitic diseases, medicine, Animals, Humans, Seroprevalence, Immunoassays, Microbial Pathogens, Biology and life sciences, Flaviviruses, Organisms, Public Health, Environmental and Occupational Health, Immunity, lcsh:RA1-1270, South America, biology.organism_classification, medicine.disease, Invertebrates, Insect Vectors, Health Care, Species Interactions, 030104 developmental biology, Immunologic Techniques, Chikungunya Fever, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, People and places
Abstract: Background Zika virus (ZIKV), was widely reported in Latin America and has been associated with neuropathologies, as microcephaly, but only few seroprevalence studies have been published to date. Our objective was to determine the seroprevalence amongst Bolivian blood donors and estimate the future potential circulation of the virus. Methodology A ZIKV seroprevalence study was conducted between December 2016 and April 2017 in 814 asymptomatic Bolivian volunteer blood donors residing in various eco-environments corresponding to contrasting entomological activities. It was based on detection of IgG to ZIKV using NS1 ELISA screening, followed by a seroneutralisation test in case of positive or equivocal ELISA result. Conclusions/Significance Analysis revealed that ZIKV circulation occurred in tropical areas (Beni: 39%; Santa Cruz de la Sierra: 21.5%) but not in highlands (~0% in Cochabamba, La Paz, Tarija). It was modulated by Aedes aegypti activity and the virus spread was not limited by previous immunity to dengue. Cases were geo-localised in a wide range of urban areas in Santa Cruz and Trinidad. No differences in seroprevalence related to gender or age-groups could be identified. It is concluded that ZIKV has been intensely circulating in the Beni region and has still a significant potential for propagating in the area of Santa Cruz., Author summary Zika virus (ZIKV) is a virus of African origin, transmitted by Aedes mosquitoes, and related to dengue and yellow fever virus. It was originally believed to be responsible for a mild febrile illness in Africa and South-east Asia. However, in recent years, ZIKV has been responsible for outbreaks in the Pacific Islands before massively spreading in Latin America and the Caribbean. On this occasion, ZIKV has unexpectedly been associated with non-vector transmission (i.e., sexual and mother-to-foetus transmission) and with severe complications such as foetal abnormalities (e.g. microcephaly) and Guillain-Barré syndromes. Little is known about the actual proportion of the populations infected by ZIKV in Latin America. Here, we report a seroprevalence data in this region, after studying 814 asymptomatic Bolivian volunteer blood donors residing in various eco-environments corresponding to contrasting entomological activities. We conclude that ZIKV has been circulating in Bolivian tropical areas but not in highlands, and that the epidemic has not been limited by previous immunity against dengue. Specific attention should be paid to the region of Santa Cruz, where the seroprevalence is still limited, but the density of Aedes aegypti populations makes plausible further spreading of the disease.
Published: 2018

6. Dengue expansion in Africa—Not recognized or not happening?

Author: Thomas, Jaenisch, Thomas, Junghanss, Bridget, Wills, Oliver J, Brady, Isabella, Eckerle, Andrew, Farlow, Simon I, Hay, Philip J, McCall, Jane P, Messina, Victor, Ofula, Amadou A, Sall, Anavaj, Sakuntabhai, Raman, Velayudhan, G R William, Wint, Herve, Zeller, Harold S, Margolis, Osman, Sankoh, Heidelberg University Hospital [Heidelberg], Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), University of Oxford [Oxford], Universitätsklinikum Bonn (UKB), Liverpool School of Tropical Medicine (LSTM), United States Army (U.S. Army), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), European Centre for Disease Prevention and Control (ECDC), Centers for Disease Control and Prevention [San Juan], Centers for Disease Control and Prevention, International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH Network), The expert conference on dengue in Africa in Accra, Ghana, was supported by European Union grant FP7-281803 IDAMS., Members of the Dengue in Africa Study Group: Thierry A. Ouedraogo (Nouna HDSS, Burkina Faso), Oliver J. Brady, Andrew Farlow, Simon I. Hay, Janey P. Messina, (Oxford University, Oxford, UK), Isabella Eckerle (University of Bonn Medical Centre, Bonn, Germany), Moses Gwamaka (Rufiji HDSS, Tanzania), Thomas Jaenisch, Thomas Junghanss (Heidelberg University Hospital, Heidelberg, Germany), Harold S. Margolis (Centers for Disease Control and Prevention, San Juan, Puerto Rico, USA), Philip J. McCall (Liverpool School of Tropical Medicine, Liverpool, UK), Abraham Oduro (Navrongo HDSS, Ghana), Victor Ofula (US Army Medical Research Unit–Kenya, Nairobi, Kenya), Osman Sankoh (INDEPTH Network, Accra, Ghana and University of the Witwatersrand, Johannesburg, South Africa), Anavaj Sakunthabhai (Institut Pasteur, Paris, France), Amadou A. Sall (Institut Pasteur, Dakar, Senegal), Herrmann Sorgho (Nanoro HDSS, Burkina Faso), Alfred Tiono (Sapone HDSS, Burkina Faso), Raman Velayudhan (World Health Organization, Geneva), Bridget Wills (Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam), G.R. William Wint (Environmental Research Group Limited, Oxford, UK), Hervé Zeller (European Centre for Disease Control and Prevention, Stockholm, Sweden)., European Project: 281803,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,IDAMS(2011), University of Oxford, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC)
Subjects: Economic growth, Mosquito Control, Endemic Diseases, Happening, lcsh:Medicine, MESH: Dengue, Dengue virus, MESH: Africa, medicine.disease_cause, Diagnostic tools, MESH: Dengue Virus, Dengue fever, Disease Outbreaks, disease burden, Health services, 0302 clinical medicine, expansion, Aedes, Health care, diagnostics, MESH: Animals, 030212 general & internal medicine, MESH: Incidence, MESH: Disease Outbreaks, MESH: Mosquito Control, Health Policy, Incidence, MESH: Aedes, Online Report, 3. Good health, Infectious Diseases, disease incidence, MESH: Endemic Diseases, MESH: Health Policy, epidemiology, policy, Microbiology (medical), Dengue Expansion in Africa—Not Recognized or Not Happening?, 030231 tropical medicine, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, parasitic diseases, medicine, Animals, Humans, lcsh:RC109-216, viruses, Health policy, MESH: Humans, dengue virus, business.industry, lcsh:R, medicine.disease, dengue, Africa, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Endemic diseases, business, vector
Abstract: Addressing this expansion is essential before control and prevention of dengue are implemented., An expert conference on Dengue in Africa was held in Accra, Ghana, in February 2013 to consider key questions regarding the possible expansion of dengue in Africa. Four key action points were highlighted to advance our understanding of the epidemiology of dengue in Africa. First, dengue diagnostic tools must be made more widely available in the healthcare setting in Africa. Second, representative data need to be collected across Africa to uncover the true burden of dengue. Third, established networks should collaborate to produce these types of data. Fourth, policy needs to be informed so the necessary steps can be taken to provide dengue vector control and health services.
Published: 2014

7. Plasmodium Gametocyte Inhibition Identified from a Natural-Product-Based Fragment Library

Author: Wesley C. Van Voorhis, Hoan Vu, Katherine T. Andrews, Marc Ronald Campitelli, Katharine R. Trenholme, Catherine Roullier, Ronald J. Quinn, Gregory J. Crowther, Tina S. Skinner-Adams, Donald L. Gardiner, Département Réseaux, Information, Multimédia (RIM-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre G2I, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Agriculture Flagship, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Zentrum für Infektiologie [Heidelberg, Germany], Universität Heidelberg [Heidelberg]-Heidelberg University Hospital [Heidelberg], Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Universität Heidelberg [Heidelberg] = Heidelberg University-Heidelberg University Hospital [Heidelberg]
Subjects: Spectrometry, Mass, Electrospray Ionization, Recombinant Fusion Proteins, Plasmodium falciparum, Protozoan Proteins, Biology, 01 natural sciences, Biochemistry, Small Molecule Libraries, 03 medical and health sciences, chemistry.chemical_compound, Antimalarials, Lactones, Structure-Activity Relationship, Alkaloids, Piperidines, Gametocyte, Structure–activity relationship, [CHIM]Chemical Sciences, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biological sciences, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Biological Products, Life Cycle Stages, Natural product, Dose-Response Relationship, Drug, 010405 organic chemistry, General Medicine, Azepines, biology.organism_classification, Plasmodium gametocyte, Enzyme assay, Heterocyclic Compounds, Bridged-Ring, 3. Good health, 0104 chemical sciences, Kinetics, chemistry, Immunology, biology.protein, Molecular Medicine, Deoxyuracil Nucleotides
Abstract: Fragment-based screening is commonly used to identify compounds with relatively weak but efficient localized binding to protein surfaces. We used mass spectrometry to study fragment-sized three-dimensional natural products. We identified seven securinine-related compounds binding to Plasmodium falciparum 2′-deoxyuridine 5′-triphosphate nucleotidohydrolase (PfdUTPase). Securinine bound allosterically to PfdUTPase, enhancing enzyme activity and inhibiting viability of both P. falciparum gametocyte (sexual) and blood (asexual) stage parasites. Our results provide a new insight into mechanisms that may be applicable to transmission-blocking agents.
Published: 2013

8. Dengue Research Funded by the European Commission-Scientific Strategies of Three European Dengue Research Consortia

Author: Axel Kroeger, Fernando Augusto Bozza, Gavin Screaton, Peter Byass, Joacim Rocklöv, Bernard Cazelles, Marco Vignuzzi, Simon Hay, Annelies Wilder-Smith, Bridget Wills, Kerstin Rosenberger, Jeremy Farrar, Gabriela Maron, Adriana Tami, Michael Schreiber, Ernesto T A Marques, Andrea Caprara, Eric Daudé, Section Clinical Tropical Medicine [Heidelberg], Department of Infectious Diseases [Heidelberg, Germany], Heidelberg University Hospital [Heidelberg]-Heidelberg University Hospital [Heidelberg], Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Department of Public Health and Clinical Medicine, Umeå University, This work was supported by the IDAMS project (European Union 7th FP, grant 281803), the DENFREE project (European Union 7th FP, grant 282378), and the DengueTools project (European Union 7th FP, grant 282589)., IDAMS - International Research Consortium on Dengue Risk Assessment, Management, and Surveillance : Thomas Jaenisch, Thomas Junghanss, Kerstin Rosenberger, Jaswinder Kaur (Section Clinical Tropical Medicine, Heidelberg Universty Hospital), Simon Hay, Janey Messina, Adrian Hill (Oxford University), Bridget Wills, Cameron Simmons, Marcel Wolbers, Jeremy Farrar (Oxford University Clinical Research Unit, Vietnam), Phil McCall (Liverpool School of Tropical Medicine), Antonio Lanzavecchia, Federica Sallusto (Institute for Research in Biomedicine, Bellinzona, Switzerland), Axel Kroeger, Silvia Runge-Ranzinger (TDR-WHO), Lucy Lum (University of Malaya Medical Center), Ida Safitri (Gadja Madah University, Indonesia), Varun Kumar (Angkor Hospital for Children, Cambodia), Maria Guzman (Instituto Pedro Kouri, Cuba), Gabriela Maron, Ernesto Pleitess (Hospital National de Ninos Benjamin Bloom, San Salvador), Andrea Caprara, Bruno Benevides (State University of Ceara, Brazil), Willy Wint (Environmental Research Group Oxford Ltd.), Osman Sankoh (INDEPTH-Network, Ghana), Fleur Monasso (Red Cross/Red Crescent Climate Centre, The Netherlands), Adriana Tami (University of Carabobo, Venezuela), Ernesto T. A. Marques, Fernando A. Bozza (FIOCRUZ, Brazil), DENFREE - Dengue Research Framework for Resisting Epidemics in Europe : Anavaj Sakuntabhai, Richard Paul, Félix Rey, Anna-Bella Failloux, Marco Vignuzzi, Louis Lambrechts (Institut Pasteur, France), Gavin Screaton, Juthathip Mongkolsapaya (Imperial College, United Kingdom), Michael Schreiber, Rolf Horstmann (Bernard Nocht Institute, Germany), Pattamaporn Kittayapong, Pratap Singhasivanon, Sutee Yoksan (Mahidol University, Thailand), Philippe Buchy, Vincent Deubel (Institut Pasteur Cambodia, Cambodia), Xavier Rodó (Fundacio Institut Catala De Ciencies Del Clima, Spain), Eric Daude, Alain Vaguet (University of Rouen, France), Bernard Cazelles (CNRS, France), Nico Stollenwerk (Cmaf, Fundacao Da Faculdade De Ciencias Da Universidade De Lisboa, Portugal), Luísa Pereira (Instituto De Patologia E Imunologia Molecular Da Universidade Do Porto, Portugal), Timo Kanninen (Biocomputing Platforms Ltd Oy, Finland), Guido Krupp (Amptec Gmbh, Germany), Mark Thursz (Riotech Pharmaceticals Ltd, United Kingdom), María G. Guzmán (Instituto Pedro Kouri, Cuba), DengueTools - Innovative Tools and Strategies for the Surveillance and Control of Dengue : Annelies Wilder-Smith, Joacim Rocklöv, Peter Byass (Umeå University, Sweden), Paba Palihawadana, Hasitha Tissera (Epidemiological Unit, Ministry of Health, Sri Lanka), David Brooks (TwistDx Ltd, UK), Sazaly Abu Bakar (University of Malaya), Luke Alphey (Oxitec Ltd, UK), Pattamaporn Kittayapong (Mahidol University, Thailand), Steve Lindsay, James Logan (London School of Hygiene and Tropical Medicine, UK), Christoph Hatz, Andreas Neumayr (Swiss Tropical and Public Health Institute), Paul Reiter (Institut Pasteur, France), Yesim Tozan, Valérie R. Louis (Heidelberg University Hospital), Duane Gubler (Duke-NUS Graduate Medical School Singapore), Eduardo Massad (University of Sao Paolo), Antonio Tenorio (Instituto de Salud Carlos III), Christophe Lagneau, Grégory L'Ambert (Entente Inter-Départementale pour la Démoustication du littoral Mediterranéen), European Project: 281803,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,IDAMS(2011), European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), European Project: 282589,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENGUETOOLS(2011), Microbes in Health and Disease (MHD), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Medical Research Council (MRC)
Subjects: Economic growth, Biomedical Research, Infektionsmedicin, MESH: Dengue/prevention & control, Dengue virus, medicine.disease_cause, Dengue fever, Capital Financing, Dengue, IDAMS, 0302 clinical medicine, DENFREE, 030212 general & internal medicine, Chikungunya, MESH: Capital Financing, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), media_common, Disease surveillance, education.field_of_study, lcsh:Public aspects of medicine, Health Policy, Public Health, Global Health, Social Medicine and Epidemiology, 11 Medical And Health Sciences, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, epidemiology, MESH: Health Policy, DengueTools, Infectious Medicine, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Population, MESH: Dengue/epidemiology, Biology, 03 medical and health sciences, Tropical Medicine, MESH: Biomedical Research/trends, MESH: European Union, medicine, media_common.cataloged_instance, Humans, European Union, European union, education, Health policy, MESH: Humans, business.industry, Policy Platform, Public Health, Environmental and Occupational Health, International health, lcsh:RA1-1270, 06 Biological Sciences, medicine.disease, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 13. Climate action, business
Abstract: Dengue is a major international public health concern and one of the most important arthropod-borne diseases [1]. Approximately 2.5 billion people—40% of the world's population, in over 100 countries—are at risk of dengue virus (DENV) infection [2]. In recent years the average annual incidence of dengue-related serious disease in many tropical counties has been rising dramatically, with the infection becoming endemic in areas where its occurrence was once sporadic [3]. The exponential increase over the last decade has been connected to societal changes, such as population growth and increasing urbanization [4]. In addition, it has been suggested that rising temperatures and global climate change may lead to the expansion of the range of major mosquito vectors into new areas, extension of the transmission season in current endemic areas, and increase in the mosquito species vectorial capacity [5]–[7]. Human migration (likely including infected hosts) and international travel are constantly introducing new vectors and pathogens into novel geographic areas [8]. For example, chikungunya virus was introduced into northeastern Italy in 2007, causing an outbreak with local transmission due to the presence of Aedes albopictus, a vector also capable of transmitting dengue virus [9]. In 2010, three authochthonous cases of dengue were reported in Europe, thereby highlighting the potential for global spread of this disease [10], [11]. The island of Madeira, where the mosquito vector Aedes aegypti is present, experienced a major dengue outbreak in the fall of 2012 [12], highlighting that the introduction of dengue to non-endemic areas is a real threat. Dengue has been neglected for many years. Major research gaps for dengue exist in the areas of epidemiology under changing climate conditions, clinical management, pathogenesis, vector control, surveillance and response, vaccines, drugs, and health policy research [13]. The European Commission (EC) launched a call under the Seventh Framework Programme with the title of “Comprehensive control of Dengue fever under changing climatic conditions” (http://ec.europa.eu/research/participants/portal/page/cooperation?callIdentifier=FP7-HEALTH-2011-single-stage). The focus of this call is summarized in Box 1. Within this framework, in 2011, the EC awarded a total of approximately €18 million to three consortia. The hosting institutions are Heidelberg University Hospital (Germany), the Institute Pasteur (Paris, France), and Umea University (Sweden). Each consortium has partners from countries with endemic and epidemic dengue. In total, the consortia comprise 38 partners from 21 countries, of which 11 are from Asia and Latin America, the current hotspots of dengue endemicity, and one from Africa (Figure 1). Figure 1 The world map of the three EU-funded dengue consortia. Box 1. European Commission Seventh Framework Programme FP7 Cooperation - Health HEALTH.2011.2.3.3-2: Comprehensive control of Dengue fever under changing climatic conditions. FP7-HEALTH-2011-single-stage Research should develop innovative tools for one or more of the following aspects: better diagnosis, surveillance, development of treatment, prevention and vaccination strategies, prevention, and/or prediction and prevention of the spread of dengue fever to previously uninfected regions (including Europe), in the context of climate change. Research may also include studies on the underlying pathogenesis with respect to viral and host factors that can predict disease severity and prepare for further development of new vaccines, antiviral compounds, and more targeted treatment schemes. Funding Scheme Specific International Cooperation Action (SICA) Collaborative Project (small- or medium-scale focused research project) target regions: Latin America and/or Asia. SICA aims to bring about the balanced participation of third countries in collaboration with European partners. Expected Impact Better tools, and the use thereof, for improved comprehensive control of dengue fever at a global level. Participation from both SICA target regions and Small and Medium Enterprises SMEs in the projects should help ensure innovation and exploitation of the results in this area/topic. The degree of such participation will be considered during the evaluation. Source: http://ec.europa.eu/research/health/infectious-diseases/emerging-epidemics/call-for-proposals_en.html The funding of such a large and complex research programme focusing on a single disease highlights the emphasis that the European Commission has put on dengue and its potential threat to Europe. In this paper, we present these three consortia and outline their scientific strategies and potential role within the international dengue research community.
Published: 2013

9. Le virus de la fièvre de la vallée du Rift et son étonnante protéine NSs

Author: Pierre-Yves Lozach, Psylvia Léger, Heidelberg University Hospital [Heidelberg], Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0303 health sciences, 03 medical and health sciences, Rift Valley fever virus, 030306 microbiology, viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, General Medicine, Biology, Humanities, General Biochemistry, Genetics and Molecular Biology, 030304 developmental biology, 3. Good health
Abstract: International audience; Rift Valley Fever Virus (RVFV) is an emerging zoonotic pathogen transmitted to humans and livestock through mosquito bites, which was first isolated in Kenya in 1930. The virus is classified by the WHO among the pathogens for which there is an urgent need to develop research, diagnostics, and therapies. However, the efforts developed to control the virus remain limited, and the virus is not well characterized. In this article, we will introduce RVFV and then focus on its virulence factor, the nonstructural protein NSs. We will mainly discuss the ability of this viral protein to form amyloid-like fibrils and its implication in the neurotoxicity associated with RVFV infection.; Le virus de la fièvre de la vallée du Rift (VFVR) est un agent pathogène transmis à l’homme et au bétail par la piqûre de moustiques. Ce virus, découvert au Kenya en 1930, est considéré par l’Organisation mondiale de la santé comme présentant un risque important de provoquer de vastes épidémies. Les moyens dédiés à la lutte contre le VFVR restent toutefois particulièrement limités et le virus est mal connu. Dans cette Synthèse, nous nous attacherons à présenter ce virus avant de nous intéresser plus spécifiquement à son facteur de virulence, la protéine NSs. Nous discuterons la capacité de cette protéine virale à former des fibrilles de type amyloïde et son implication dans la neurotoxicité du virus chez les animaux infectés.
Published: 2021

10. Dynamic risk assessment to improve quality of care in patients with atrial fibrillation

Author: Ursula Ravens, Bushra S. Ilyas, Ulrich Schotten, Isabelle C. Van Gelder, Christian G Meyer, Burcu Vardar, Elena Andreassi Marinelli, Moritz F. Sinner, Stephan Willems, Christophe Leclercq, Renate B. Schnabel, Doreen Haase, Larissa Fabritz, Dierk Thomas, Dobromir Dobrev, Mattias Wieloch, Jeff S. Healey, Emma Svennberg, Paul D. Ziegler, Christina Easter, Stefan H. Hohnloser, Gregory Y.H. Lip, Gerhard Hindricks, A. John Camm, Andreas Goette, Monika Stoll, Irina Savelieva, Tatjana S. Potpara, Guenter Breithardt, Stéphane N. Hatem, Karl Georg Häusler, Rüdiger Smolnik, Alice J Sitch, Reza Wakili, Jan Steffel, Helmut Pürerfellner, Winnie Chua, José L. Merino, Anthony W.S. Chan, Harry J.G.M. Crijns, Thomas Huebner, Paulus Kirchhof, Christina Dimopoulou, Thorsten Lewalter, Stef Zeemering, Kenneth M. Stein, Mirko De Melis, Eduard Guasch, Jordi Heijman, Dipak Kotecha, Lluís Mont, Jonas Oldgren, Michael Nabauer, Michiel Rienstra, Ingo Kutschka, Aaron Isaacs, Lars Eckardt, Hein Heidbuchel, Cardiovascular Centre (CVC), University of Birmingham [Birmingham], University Hospitals Birmingham [Birmingham, Royaume-Uni], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Barcelona, University Hospital of Würzburg, University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University of Belgrade [Belgrade], University Medical Center Groningen [Groningen] (UMCG), Asklepios Klinik St. Georg, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University of London [London], Pfizer, Medtronic Inc [Minneapolis, MI, USA], European Society of Cardiology (ESC), University Hospital [Essen, Germany], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Population Health Research Institute [Hamilton, ON, Canada], Goethe-Universität Frankfurt am Main, University Hospital Göttingen, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Liverpool, La Paz University Hospital, Universitat de Barcelona (UB), University-Hospital Munich-Großhadern [München], Uppsala University, Ordensklinikum Linz Elisabethinen, St George's, University of London, Universität Zürich [Zürich] = University of Zurich (UZH), Boston Scientific, Karolinska Institutet [Stockholm], Heidelberg University Hospital [Heidelberg], University of Groningen [Groningen], University Hospital Essen, SANOFI Recherche, University of Antwerp (UA), Leipzig University, EHRA, 633196, EU Horizon 2020, AFNet, AFNET, MUMC+: MA Cardiologie (9), Cardiologie, RS: Carim - H01 Clinical atrial fibrillation, Fysiologie, RS: FHML MaCSBio, RS: Carim - B01 Blood proteins & engineering, Biochemie, RS: Carim - H08 Experimental atrial fibrillation, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Technology, Quality management, Rate control, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medizin, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, Stroke, Research priorities, CATHETER ABLATION, ROADMAP, Integrated care, Atrial fibrillation, 3. Good health, OPPORTUNITIES, Treatment Outcome, Consensus statement, Screening, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Rhythm control, Cognitive function, Cardiology and Cardiovascular Medicine, Risk assessment, medicine.medical_specialty, Consensus, Catheter ablation, Heart failure, Outcomes, DIAGNOSIS, Risk Assessment, CLASSIFICATION, 03 medical and health sciences, Big data, Anticoagulation, FUTURE, Physiology (medical), medicine, MANAGEMENT, Humans, Intensive care medicine, Atrial cardiomyopathy, business.industry, Research, Bleeding, Quality of care, Anticoagulants, EHRA, medicine.disease, Lifestyle, AFNET, Comorbidity, PREVENTION, REDUCTION, Human medicine, business
Abstract: Aims The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. Methods and results This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. Conclusion The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
Published: 2021

11. Objective neurocognitive functioning and neurocognitive complaints in patients with high-grade glioma

Author: Martin J. van den Bent, Martin Klein, Andrew Bottomley, Wolfgang Wick, Jos W. R. Twisk, Jaap C. Reijneveld, A Josephine Drijver, Ahmed Idbaih, Madeline Pe, Ivan Caramanna, Neurology, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Vrije Universiteit Amsterdam [Amsterdam] (VU), European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), VU University Medical Center [Amsterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Heidelberg University Hospital [Heidelberg], Clinical Neuropsychology, Medical psychology, Epidemiology and Data Science, APH - Health Behaviors & Chronic Diseases, APH - Methodology, CCA - Cancer Treatment and quality of life, Gestionnaire, HAL Sorbonne Université 5, Unité de recherche de l'institut du thorax (ITX-lab), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Health Knowledge, Attitudes, Practice, Cancer Research, Cognition Disorders/etiology, Health-related quality of life, Neuropsychological Tests, Correlation, High-grade glioma, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Medicine, Practice, Brain Neoplasms, Health Knowledge, Cognition, Glioma, Middle Aged, Mental Status and Dementia Tests, Prognosis, humanities, 3. Good health, Europe, Oncology, 030220 oncology & carcinogenesis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Clinical psychology, Cognitive awareness, Concordance, [SDV.CAN]Life Sciences [q-bio]/Cancer, Glioma/complications, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cognitive skill, business.industry, Cancer, medicine.disease, Clinical trial, Neurocognitive functioning, 030104 developmental biology, Cross-Sectional Studies, Brain Neoplasms/complications, Attitudes, Quality of Life, PROs, Cognition Disorders, business, Neurocognitive, Follow-Up Studies
Abstract: BACKGROUND: Neurocognitively impaired patients with brain tumour are presumed to have reduced cognitive awareness preventing them from adequately valuing and reporting their own functioning, for instance, when providing patient-reported outcomes (PROs) such as health-related quality of life instruments. In this cross-sectional study, we aimed at assessing the concordance of neurocognitive complaints (NCCs) and objective neurocognitive functioning (NCF) as a measure of cognitive awareness.METHODS: NCF was assessed using an internationally accepted clinical trial battery. NCC was assessed using the cognitive functioning questionnaire from the Medical Outcome Study (MOS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire cognitive functioning subscale. Patients were divided in cognitively impaired and unimpaired groups, based on their NCF performance. Pearson's correlation coefficients between NCF and NCCs were calculated. The same procedure was used to evaluate the correlation of NCF and QLQ-C30 CF subscale.RESULTS: Data from EORTC trials 26091 and 26101 were pooled into a data set of 546 patients. Twenty percent of patients could be characterised as unimpaired (109) and 80% as impaired (437). Impaired patients reported more cognitive complaints on the MOS scale than unimpaired patients. Correlations between NCF and NCCs were weak but significant for impaired patients and non-significant for unimpaired ones. Similar results were found for the correlation between NCF test performance and the QLQ-C30 CF subscale.CONCLUSION: Correlations between NCF test scores and complaints were weak but suggesting that neurocognitive impairment in patients with HGG does not preclude cognitive awareness. However, considering the findings of this study, we would suggest not to use PROs as a surrogate of performance-based neurocognitive evaluation.
Published: 2021

12. NSs amyloid formation is associated with the virulence of Rift Valley fever virus in mice

Author: Susann Kummer, Hans-Georg Kräusslich, Psylvia Léger, Steeve Boulant, Jana Koch, Pierre-Yves Lozach, Megan L. Stanifer, Qilin Xin, Michèle Bouloy, Robin Burk, Carmen Nussbaum-Krammer, Carole Tamietti, Marie Flamand, Karsten Richter, Eliana Nachman, Xavier Montagutelli, Heidelberg University Hospital [Heidelberg], Center for Molecular Biology - Zentrum für Molekulare Biologie [Heidelberg, Germany] (ZMBH), Universität Heidelberg [Heidelberg] = Heidelberg University, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Moléculaire des Bunyavirus, Institut Pasteur [Paris] (IP), Génétique de la souris - Mouse Genetics, This work was supported by grants from CellNetworks Research Group funds, Heidelberg, and from the Deutsche Forschungsgemeinschaft (DFG, LO-2338/1-1 and LO-2338/3-1). It was also supported by a Chinese Scholarship Council fellowship to Q.X, Universität Heidelberg [Heidelberg], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Rift Valley Fever, General Physics and Astronomy, Protein aggregation, Viral Nonstructural Proteins, MESH: Virulence, Virulence factor, chemistry.chemical_compound, Mice, MESH: Chlorocebus aethiops, Chlorocebus aethiops, MESH: Rift Valley Fever, MESH: Microscopy, Confocal, MESH: Animals, lcsh:Science, Multidisciplinary, Microscopy, Confocal, MESH: Protein Aggregation, Pathological, Virulence, Virus structures, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Microscopy, Electron, Transmission, MESH: Rift Valley fever virus, Thioflavin, Encephalitis, MESH: Cell Nucleus, Amyloid, MESH: Cell Line, Tumor, Virulence Factors, Prions, Science, MESH: Vero Cells, Amyloidogenic Proteins, macromolecular substances, Biology, Fibril, Protein Aggregation, Pathological, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Microscopy, Electron, Transmission, Cell Line, Tumor, mental disorders, medicine, Animals, Humans, Vero Cells, MESH: Mice, MESH: Virulence Factors, Cell Nucleus, MESH: Amyloid, MESH: Amyloidogenic Proteins, MESH: Humans, 030102 biochemistry & molecular biology, General Chemistry, medicine.disease, Rift Valley fever virus, Virology, 030104 developmental biology, chemistry, MESH: HeLa Cells, Vero cell, MESH: Viral Nonstructural Proteins, lcsh:Q, HeLa Cells
Abstract: Amyloid fibrils result from the aggregation of host cell-encoded proteins, many giving rise to specific human illnesses such as Alzheimer’s disease. Here we show that the major virulence factor of Rift Valley fever virus, the protein NSs, forms filamentous structures in the brain of mice and affects mortality. NSs assembles into nuclear and cytosolic disulfide bond-dependent fibrillary aggregates in infected cells. NSs structural arrangements exhibit characteristics typical for amyloids, such as an ultrastructure of 12 nm-width fibrils, a strong detergent resistance, and interactions with the amyloid-binding dye Thioflavin-S. The assembly dynamics of viral amyloid-like fibrils can be visualized in real-time. They form spontaneously and grow in an amyloid fashion within 5 hours. Together, our results demonstrate that viruses can encode amyloid-like fibril-forming proteins and have strong implications for future research on amyloid aggregation and toxicity in general., Rift Valley fever virus (RVFV) can cause severe diseases in humans, including encephalitis. Here the authors show that NSs, the major virulence factor of RVFV, is an amyloidogenic protein forming fibrils in infected mouse brains and causing increased mortality in mice.
Published: 2020

13. Surgical data science – from concepts toward clinical translation

Author: Hubertus Feussner, Swaroop Vedula, Ozanan R. Meireles, Nicolas Padoy, Carla M. Pugh, Russell H. Taylor, Duygu Sarikaya, Bernard Gibaud, Jan Goedeke, Pietro Mascagni, Pierre Jannin, Hirenkumar Nakawala, Toby Collins, Beat P. Müller-Stich, Teodor P. Grantcharov, Stamatia Giannarou, Ines Gockel, Gregory D. Hager, Dogu Teber, Doreen Heckmann-Nötzel, Justin W. Collins, Matthias Eisenmann, Lena Maier-Hein, Sinan Onogur, Anand Malpani, Frank Ückert, Hani J. Marcus, Germain Forestier, Luc Joyeux, Daniel R. Leff, Keno März, Daniel A. Hashimoto, Johannes Fallert, Thomas Neumuth, Minu D. Tizabi, Tobias Roß, Makoto Hashizume, Lars Mündermann, Kevin Cleary, Raphael Sznitman, Kyle Lam, Nassir Navab, Alexander Seitel, Martin Wagner, Amin Madani, Stefanie Speidel, Ron Kikinis, Adrian Park, Danail Stoyanov, Gabor Fichtinger, Hannes Kenngott, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg University, Gazi University, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Contre les Cancers de l'Appareil Digestif-European Institute of Telesurgery (IRCAD/EITS), Johns Hopkins University (JHU), La société Karl STORZ, Technische Universität München = Technical University of Munich (TUM), Imperial College London, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Università degli studi di Verona = University of Verona (UNIVR), Johns Hopkins University School of Medicine [Baltimore], Stanford University School of Medicine [CA, USA], University College of London [London] (UCL), Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington DC, Queen's University [Kingston, Canada], Institut de Recherche en Informatique Mathématiques Automatique Signal - IRIMAS - UR 7499 (IRIMAS), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Monash university, University of Toronto, Kyushu University, Heidelberg University Hospital [Heidelberg], Harvard Medical School [Boston] (HMS), University of Bern, Universität Leipzig, University Hospital Leipzig, Ludwig-Maximilians-Universität München (LMU), Massachusetts General Hospital [Boston], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Baylor College of Medicine (BCM), Baylor University, University Health Network, UCL Institute of Neurology, Queen Square [London], Universität Karlsruhe (TH), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), National Center for Tumor Diseases [Dresden] (NCT), Technische Universität Dresden = Dresden University of Technology (TU Dresden)-German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Helmholtz-Zentrum Dresden-Rossendorf (HZDR), This work was supported by the European Research Council (ERC) starting grant COMBIOSCOPY under the New Horizon Framework Programme grant agreement [ERC-2015-StG-637960], the Helmholtz Imaging Platform (HIP), a platform of the Helmholtz Incubator on Information and Data Science, the NCT Heidelberg, BPI France (project CONDOR), the Johns Hopkins Science of Learning Institute Research Grant, the National Institutes of Health [NIDCR R01 DE025265, P41 EB015902, P41 EB015898, R01 CA235589], the Surgical Oncology Program of the National Center for Tumor Diseases (NCT) Heidelberg, KARL STORZ SE & Co. KG, the Royal Society (UF140290) and NIHR Imperial BRC (Biomedical Research Centre), the ERC - H2020 Autonomous Robotic Surgery (ARS) grant agreement [ERC-2016-ADG-742671], the Surgical Metrics Project - American College of Surgeons (National Society Contract), the Quantified Physician - 7-SIGMA Simulation Systems, Minnesota, MN (Industry Contract), the Tourniquet Master Training - DOD SBIR Phase IIb - Continuation Award [W81XWH-13-C-0021], the Ontology for Human Motion and Psychomotor Performance - Stanford University Media-X, Motion Analysis for Microvascular Anastomosis - University of Wisconsin (Academic Contract), the Precision Learning Initiative - American Medical Association (National Society Grant), Quantifying the Metrics of Surgical Mastery: An Exploration in Data Science (NIH) [R01DK123445], the Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS) [203145Z/16/Z], Engineering and Physical Sciences Research Council (EPSRC) [EP/P027938/1, EP/R004080/1, EP/P012841/1], the Royal Academy of Engineering Chair in Emerging Technologies, the St. Michael’s Hospital, the University of Toronto, the Grant-in-Aid for Scientific Research on Innovative Area from MEXT, Japan, the National Cancer Data Ecosystem, contract number 19X037Q under Task Order HHSN26100071 from NCI, the project ProteCT [BMBF 16SV8568], the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft) as part of Germany’s Excellence Strategy - EXC 2050/1 - Project ID 390696704 - Cluster of Excellence 'Centre for Tactile Internet with Human-in-the-Loop' (CeTI), the Canada Research Chair in Computer Integrated Surgery, Natural Sciences and Engineering Research Council of Canada, the ANR with grants ANR-16-CE33-0009 (project DeepSurg), ANR-10-IAHU-02 (IHU Strasbourg) and ANR-20-CHIA-0029-01 (Chair AI4ORSafety), and the Federal Ministry of Economics and Energy (BMWi) and the German Aerospace Center (DLR) within the OP 4.1 project [BMWI 01MT17001C]., ANR-16-CE33-0009,DeepSurg,Apprentissage Profond à partir de Vidéos Chirurgicales Multi-vues et Multimodales pour Faciliter la Gestion du Bloc Opératoire(2016), ANR-10-IAHU-0002,MIX-Surg,Institut de Chirurgie Mini-Invasive guidée par l'Image(2010), ANR-20-CHIA-0029,AI4ORSafety,Evaluation automatique des vues endoscopiques pour la validation des points de contrôle au bloc opératoire(2020), European Project: 637960,H2020,ERC-2014-STG,COMBIOSCOPY(2015), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Kyushu University [Fukuoka], Universität Leipzig [Leipzig], Institute of Neurology - UCL/Queen Square [London, UK] (IN-UCL-QS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Center for Tumor Diseases - Deutsches Krebsforschungszentrum [Heidelberg, Allemagne] (NCT / DKFZ), and Technische Universität Dresden = Dresden University of Technology (TU Dresden)
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Artificial intelligence, Surgical data science, Computer science, Computer Vision and Pattern Recognition (cs.CV), media_common.quotation_subject, Aucun, Delphi method, Computer Science - Computer Vision and Pattern Recognition, Health Informatics, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Field (computer science), Machine Learning (cs.LG), [SPI.AUTO]Engineering Sciences [physics]/Automatic, Machine Learning, 03 medical and health sciences, Computer Science - Computers and Society, 0302 clinical medicine, Computers and Society (cs.CY), Health care, FOS: Electrical engineering, electronic engineering, information engineering, Humans, Radiology, Nuclear Medicine and imaging, Quality (business), 030304 developmental biology, media_common, 0303 health sciences, Radiological and Ultrasound Technology, business.industry, Clinical translation, Image and Video Processing (eess.IV), Data Science, Deep learning, Electrical Engineering and Systems Science - Image and Video Processing, Computer aided surgery, Computer Graphics and Computer-Aided Design, Data science, 3. Good health, Current practice, 030220 oncology & carcinogenesis, Data analysis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Computer Vision and Pattern Recognition, business, Data Annotation
Abstract: Recent developments in data science in general and machine learning in particular have transformed the way experts envision the future of surgery. Surgical Data Science (SDS) is a new research field that aims to improve the quality of interventional healthcare through the capture, organization, analysis and modeling of data. While an increasing number of data-driven approaches and clinical applications have been studied in the fields of radiological and clinical data science, translational success stories are still lacking in surgery. In this publication, we shed light on the underlying reasons and provide a roadmap for future advances in the field. Based on an international workshop involving leading researchers in the field of SDS, we review current practice, key achievements and initiatives as well as available standards and tools for a number of topics relevant to the field, namely (1) infrastructure for data acquisition, storage and access in the presence of regulatory constraints, (2) data annotation and sharing and (3) data analytics. We further complement this technical perspective with (4) a review of currently available SDS products and the translational progress from academia and (5) a roadmap for faster clinical translation and exploitation of the full potential of SDS, based on an international multi-round Delphi process.
Published: 2022

14. SARS‐CoV‐2 variants as super cell fusers: cause or consequence of COVID‐19 severity?

Author: Jana Koch, Pierre-Yves Lozach, Zina M Uckeley, Heidelberg University Hospital [Heidelberg], Department of Infectious Diseases/Virology [Heidelberg, Germany] (Cluster of Excellence CellNetworks), Universität Heidelberg [Heidelberg], Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, Cell, Alpha (ethology), Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Beta (finance), Molecular Biology, 030304 developmental biology, 0303 health sciences, Syncytium, General Immunology and Microbiology, General Neuroscience, Spike Protein, virus diseases, respiratory system, biochemical phenomena, metabolism, and nutrition, Virology, 3. Good health, respiratory tract diseases, medicine.anatomical_structure, 030217 neurology & neurosurgery
Abstract: International audience; The most severe forms of coronavirus disease 2019 (COVID-19) are often associated with the presence of syncytia in the lungs resulting from cell-cell fusion mediated by the SARS-CoV-2 spike protein. In this issue, Rajah and colleagues show that the SARS-CoV-2 alpha, beta, and delta variants promote enhanced syncytia formation as compared to the original strain.
Published: 2021

15. Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage

Author: Martin Kaiser, Baldeep Wirk, Monika Engelhardt, Bruno Paiva, Laurent Garderet, S. Vincent Rajkumar, Maria-Victoria Mateos, Philippe Moreau, Carlos Fernández de Larrea, Robert A. Kyle, Jo Caers, Wilson I. Gonsalves, Hermann Einsele, Hartmut Goldschmidt, Giampaolo Merlini, Suzanne Lentzch, Ashraf Badros, Saad Z. Usmani, Joan Bladé, Pellegrino Musto, Fredrik Schjesvold, Pieter Sonneveld, Jesús F. San Miguel, Laura Rosiñol, Gösta Gahrton, Patrick Hayden, Enrique M. Ocio, Brian G.M. Durie, Sascha A. Tuchman, Universidad de Cantabria, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Mayo Clinic [Rochester], Clínica Universidad de Navarra [Pamplona], Freiburg University Medical Center, The Levine Cancer Institute, Université de Liège, University of Oslo (UiO), University of Pavia, Columbia University [New York], Hospital Universitario de Salamanca, Servicio de Haematologia, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Maryland [Baltimore], Karolinska Institutet [Stockholm], Heidelberg University Hospital [Heidelberg], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University Hospital of Würzburg, Samuel Oschin Comprehensive Cancer Institute, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, The institute of cancer research [London], Instituto de Salud Carlos III, Ministerio de Sanidad (España), European Commission, Generalitat de Catalunya, and Hematology
Subjects: Male, Cell biology, medicine.medical_specialty, Plasma Cells, Myeloma, macromolecular substances, Disease, Plasma cell, Gastroenterology, Article, Leukemia, Plasma Cell, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Effective treatment, In patient, Cancer genetics, RC254-282, Multiple myeloma, Aged, Retrospective Studies, Plasma cell leukemia, business.industry, technology, industry, and agriculture, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Hematology, Prognosis, equipment and supplies, musculoskeletal system, medicine.disease, Peripheral blood, 3. Good health, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. We could identify two retrospective series where the question about what number of circulating plasma cells in peripheral blood should be used for defining PCL. The presence of ≥5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL. Therefore, PCL should be defined by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma., This work has been supported in part by grants from the Instituto de Salud Carlos III, Spanish Ministry of Health (FIS PI19/00669), Fondo Europeo de Desarrollo Regional (FEDER) and 2017SGR00792 (AGAUR; Generalitat de Catalunya).
Published: 2021

16. Rift Valley fever virus: a new avenue of research on the biological functions of amyloids?

Author: Ke Peng, Pierre-Yves Lozach, Chinese Academy of Agricultural Sciences (CAAS), Heidelberg University Hospital [Heidelberg], Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CellNetworks (University Heidelberg)German Research Foundation (DFG)LO-2338/3-1INRAEIDEX-Impulsion 2020 (University of Lyon)
Subjects: emerging virus, 0303 health sciences, Rift Valley fever virus, NSs, fibril, viruses, 030302 biochemistry & molecular biology, amyloid, Biology, Rift Valley fever, Virology, 3. Good health, virulence, 03 medical and health sciences, arbovirus, parasitic diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030304 developmental biology
Abstract: International audience; Rift Valley fever is a mosquito-borne viral zoonosis that was first discovered in the Great Rift Valley, Kenya, in 1930. Rift Valley fever virus (RVFV) primarily infects domestic animals and humans, with clinical outcomes ranging from self-limiting febrile illness to acute hepatitis and encephalitis. The virus left Africa a few decades ago, and there is a risk of introduction into southern Europe and Asia. From this perspective, we introduce RVFV and focus on the capacity of its virulence factor, the nonstructural protein NSs, to form amyloid-like fibrils. Here, we discuss the implications for the NSs biological function, the ability of RVFV to evade innate immunity, and RVFV virulence and neurotoxicity.
Published: 2021

17. Chromatin accessibility combined with enhancer clusters activation mediates heterogeneous response to dexamethasone in myeloma cells

Author: Loïc Campion, Catherine Guérin-Charbonnel, Stephane Minvielle, Victor Gaborit, Jennifer Derrien, Jérémie Bourdon, P. Moreau, Carl Herrmann, Nathalie Roi, Jonathan Cruard, Elise Douillard, Florence Magrangeas, Magali Devic, Jean-Baptiste Alberge, Frank Westermann, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Heidelberg, Medical Faculty, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), and Bernardo, Elizabeth
Subjects: 0303 health sciences, Chemistry, Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, 3. Good health, Cell biology, Chromatin, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, [SDV.CAN] Life Sciences [q-bio]/Cancer, Regulatory sequence, medicine, Binding site, Enhancer, Receptor, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, Epigenomics
Abstract: Glucocorticoids (GC) effects occur through binding to the GC receptor (GR) which, once translocated to the nucleus, binds to GC response elements (GREs) to activate or repress target genes. Among GCs, dexamethasone (Dex) is widely used in treatment of multiple myeloma (MM), mainly in combination regimens. However, despite a definite benefit, all patients relapse. Moreover, while GC efficacy can be largely attributed to lymphocyte-specific apoptosis, its molecular basis remains elusive.To determine the functional role of GR binding in myeloma cells, we generated bulk and single cell multi-omic data and high-resolution contact maps of active enhancers and target genes. We show that a minority (6%) of GR binding sites are associated with enhancer activity gains and increased interaction loops. We find that enhancers contribute to regulate gene activity through combinatorial assembly of large stretches of enhancers and/or enhancer cliques. Furthermore, one enhancer, proximal to GR-responsive genes, is predominantly associated with increased chromatin accessibility and higher H3K27ac occupancy. Finally, we show that Dex exposure leads to co-accessibility changes between predominant enhancer and other regulatory regions of the interaction network. Notably, these epigenomic changes are associated with cell-to-cell transcriptional heterogeneity. As consequences, BIM critical for GR-induced apoptosis and CXCR4 protective from chemotherapy-induced apoptosis are rather upregulated in different cells.In summary, our work provides new insights into the molecular mechanisms involved in Dex escape.
Published: 2021

18. CLinical Assessment of WEB device in Ruptured aneurYSms (CLARYS): results of 1-month and 1-year assessment of rebleeding protection and clinical safety in a multicenter study

Author: Jildaz Caroff, Léon Ikka, S. Velasco, Georg Bohner, Xavier Barreau, Laurent Pierot, Werner Weber, Joachim Berkefeld, Hubert Desal, Sebastian Fischer, Ana Paula Narata, R. Bibi, Jean-Christophe Ferré, Denis Herbreteau, Jean-Yves Gauvrit, Anne-Christine Januel, Jan-Hendrik Buhk, Jens Fiehler, Vincent Costalat, Thomas Liebig, Markus A Möhlenbruch, Cristian Mihalea, Laurent Spelle, James V. Byrne, Romain Bourcier, Augustin Ozanne, Hélène Raoult, Vanessa Chalumeau, Richard du Mesnil de Rochemont, Lamiae Grimaldi, Jacques Moret, Christophe Cognard, Alessandra Biondi, Maxim Bester, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Saclay, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département de Radiologie [CHU de Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hôpital Pierre-Paul Riquet [Toulouse], CHU Toulouse [Toulouse], Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University-Hospital Munich-Großhadern [München], Centre hospitalier universitaire de Nantes (CHU Nantes), Heidelberg University Hospital [Heidelberg], Universitätsklinikum Frankfurt am Main [Germany], Goethe-Universität Frankfurt am Main, Ruhr University Bochum (RUB), Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Asklepios Klinikum Uckermark GmbH, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Hôpital JeanMinjoz, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, John Radcliffe Hospital [Oxford University Hospital], Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Ferré, Jean-Christophe, Université de Rennes (UR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Gui de Chauliac [CHU Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: medicine.medical_specialty, Intraoperative Complication, Ruptured aneurysms, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, subarachnoid, Aneurysm, Ruptured, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, Modified Rankin Scale, Clinical endpoint, Medicine, Fluoroscopy, Humans, Prospective Studies, Adverse effect, device, intervention, Retrospective Studies, medicine.diagnostic_test, business.industry, Endovascular Procedures, Intracranial Aneurysm, General Medicine, Prostheses and Implants, medicine.disease, Embolization, Therapeutic, 3. Good health, Surgery, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Treatment Outcome, Multicenter study, aneurysm, Neurology (clinical), hemorrhage, business, 030217 neurology & neurosurgery
Abstract: BackgroundThe primary goal of the CLARYS study is to assess the protection against rebleeding when treating ruptured bifurcation aneurysms with the Woven EndoBridge (WEB) device.MethodsThe CLARYS study is a prospective, multicenter study conducted in 13 European centers. Patients with ruptured bifurcation aneurysms were consecutively included between February 2016 and September 2017. The primary endpoint was defined as the rebleeding rate of the target aneurysm treated with the WEB within 30 days postprocedure. Secondary endpoints included periprocedural and postprocedural adverse events, total procedure and fluoroscopy times, and modified Rankin Scale score at 1 month and 1 year.ResultsSixty patients with 60 ruptured bifurcation aneurysms to be treated with the WEB were included. A WEB device was successfully implanted in 93.3%. The rebleeding rate at 1 month and 1 year was 0%. The mean fluoroscopy time was 27.0 min. Twenty-three periprocedural complications were observed in 18 patients and resolved without sequelae in 16 patients. Two of these complications were attributed to the procedure and/or the use of the WEB, leading to a procedure/device-related intraoperative complication rate of 3.3%. Overall mortality at 1 month and 1 year was 1.7% and 3.8%, respectively and overall morbidity at 1 month and 1 year was 15% and 9.6%, respectively. WEB-related 1-month and 1-year morbidity and mortality was 0%.ConclusionsThe interim results of CLARYS show that the endovascular treatment of ruptured bifurcation aneurysms with the WEB is safe and effective and, in particular, provides effective protection against rebleeding. It may induce profound change in the endovascular management of ruptured bifurcation aneurysms.
Published: 2021

19. Orthobunyaviruses: From Virus Binding to Penetration into Mammalian Host Cells

Author: Stefan Windhaber, Qilin Xin, Pierre-Yves Lozach, Heidelberg University Hospital [Heidelberg], Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and IDEX-Impulsion 2020 (University of Lyon)FINOVI (Fondation pour l'Universite de Lyon)CellNetworks Research Group fundsGerman Research Foundation (DFG)LO-2338/3-1Chinese Scholarship Council fellowship (CSC)201904910701
Subjects: 0301 basic medicine, emerging virus, fusion, Orthobunyavirus, receptor, 030106 microbiology, Virus Attachment, Genome, Viral, Review, Biology, Endocytosis, Bunyaviridae Infections, Arbovirus, Genome, Microbiology, 03 medical and health sciences, Species Specificity, Virology, medicine, Animals, Humans, endocytosis, Receptor, cell entry, Host (biology), Cell Membrane, Virion, RNA, Biological Transport, La Crosse, Virus Internalization, medicine.disease, biology.organism_classification, QR1-502, 3. Good health, Oropouche, Cytosol, Viral Tropism, 030104 developmental biology, Infectious Diseases, arbovirus, Bunyamwera, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Schmallenberg
Abstract: International audience; With over 80 members worldwide, Orthobunyavirus is the largest genus in the Peribunyaviridae family. Orthobunyaviruses (OBVs) are arthropod-borne viruses that are structurally simple, with a trisegmented, negative-sense RNA genome and only four structural proteins. OBVs are potential agents of emerging and re-emerging diseases and overall represent a global threat to both public and veterinary health. The focus of this review is on the very first steps of OBV infection in mammalian hosts, from virus binding to penetration and release of the viral genome into the cytosol. Here, we address the most current knowledge and advances regarding OBV receptors, endocytosis, and fusion.
Published: 2021

20. Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics

Author: Dominique Langin, Jeremie Boucher, Pauline Morigny, Peter Arner, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Helmholtz Zentrum München = German Research Center for Environmental Health, Heidelberg University Hospital [Heidelberg], German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), AstraZeneca, University of Gothenburg (GU), Karolinska Institutet [Stockholm], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mégard, Roxane, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Helmholtz-Zentrum München (HZM), and CHU Toulouse [Toulouse]
Subjects: 0301 basic medicine, Anabolism, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Adipocytes, White, Adipose tissue, 030209 endocrinology & metabolism, White adipose tissue, Carbohydrate metabolism, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, medicine, Animals, Homeostasis, Humans, Obesity, Glucose metabolism, Catabolism, business.industry, Disease Management, Lipid metabolism, medicine.disease, White adipocytes, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, Adipocyte hypertrophy, business
Abstract: International audience; In mammals, the white adipocyte is a cell type that is specialized for storage of energy (in the form of triacylglycerols) and for energy mobilization (as fatty acids). White adipocyte metabolism confers an essential role to adipose tissue in whole-body homeostasis. Dysfunction in white adipocyte metabolism is a cardinal event in the development of insulin resistance and associated disorders. This Review focuses on our current understanding of lipid and glucose metabolic pathways in the white adipocyte. We survey recent advances in humans on the importance of adipocyte hypertrophy and on the in vivo turnover of adipocytes and stored lipids. At the molecular level, the identification of novel regulators and of the interplay between metabolic pathways explains the fine-tuning between the anabolic and catabolic fates of fatty acids and glucose in different physiological states. We also examine the metabolic alterations involved in the genesis of obesity-associated metabolic disorders, lipodystrophic states, cancers and cancer-associated cachexia. New challenges include defining the heterogeneity of white adipocytes in different anatomical locations throughout the lifespan and investigating the importance of rhythmic processes. Targeting white fat metabolism offers opportunities for improved patient stratification and a wide, yet unexploited, range of therapeutic opportunities.
Published: 2021

21. NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Author: Stephan Spahn, Florian Müller, Revant Gupta, Dominik Pfister, Kornelius Schulze, Pierre Bedossa, Eleni Kotsiliti, Lars Zender, Mathias Heikenwalder, Nicolás Gonzalo Núñez, Peter Schirmacher, Axel Schulz, Jan Kosla, Adrian T. Billeter, Thomas Engleitner, Aleksandra Deczkowska, Danijela Heide, Donato Inverso, Susanne Roth, Olivier Govaere, Carla Montironi, Martha M. Kirstein, Dan G. Duda, Antonio D'Alessio, Jörn M. Schattenberg, Ekaterina Friebel, Tiziana Pressiani, F. Hucke, Jörg Trojan, Michael Bitzer, Suhail Yousuf, Bernhard Scheiner, Marina Ruiz de Galarreta, Markus Peck-Radosavljevic, Michael Allison, Nuh N. Rahbari, Simon Cockell, Brinda Emu, Ahmed Kaseb, David J. Pinato, Matthias P. Ebert, Joachim C. Mertens, Jean-François Dufour, Fabian Rössler, Achim Weber, Katharina Wolter, Thomas Decaens, Amaia Lujambio, Anja Moncsek, Daniela Lenggenhager, Katharina Pomej, Nisar P. Malek, Fabian Finkelmeier, Elisabetta Bugianesi, Valentina Leone, Ann K. Daly, Michael Dudek, Manfred Claassen, Zuzana Macek Jilkova, Henning Wege, Florian Castet, Marta Szydlowska, Beat P. Müller-Stich, Ramy Younes, Nicola Personeni, Philipp K. Haber, Marco Bueter, Manfred Jugold, Andrea Schietinger, Hiroto Kikuchi, Ido Amit, Sandra Koch, Dina Tiniakos, Ana Teijeiro, Jan-Philipp Mallm, Josep M. Llovet, Indrabahadur Singh, Percy A. Knolle, Sara De Dosso, Roland Rad, Arndt Vogel, Henrik E. Mei, Burkhard Becher, Nabil Djouder, Tom Luedde, Felix Meissner, Oliver Waidmann, Parice N. Marche, Viktor Umansky, Hellmut G. Augustin, Thomas U. Marron, Matthias Pinter, Mengjie Qiu, Arndt Weinmann, Ankit Sinha, Kristian Unger, Assaf Weiner, Vlad Ratziu, Quentin M. Anstee, Kristin Stirm, Yi Hsiang Huang, Alexander Siebenhüner, Fabian Kütting, Lorenza Rimassa, Dirk Waldschmidt, Masatoshi Kudo, Marc Ringelhan, Michele Vacca, Roser Pinyol, Fabio Marra, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Novo Nordisk A/S [Maløv, Denmark], Universität Zürich [Zürich] = University of Zurich (UZH), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Newcastle University [Newcastle], Medizinische Universität Wien = Medical University of Vienna, University of Tübingen, UniversitätsKlinikum Heidelberg, Weizmann Institute of Science [Rehovot, Israël], Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, Technical University of Munich (TUM), University hospital of Zurich [Zurich], Helmholtz-Zentrum München (HZM), Heidelberg University, Spanish National Cancer Research Center (CNIO), Icahn School of Medicine at Mount Sinai [New York] (MSSM), National and Kapodistrian University of Athens (NKUA), University of Turin, Addenbrooke's Hospital, Cambridge University NHS Trust, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University Medical Center [Mainz], Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Hannover Medical School [Hannover] (MHH), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Klinikum Klagenfurt am Wörthersee, Universitätsklinikum Frankfurt, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Oncology Institute of Southern Switzerland (IOSI), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Heidelberg University Hospital [Heidelberg], Medical Faculty [Mannheim], Massachusetts General Hospital [Boston], University of Cologne, Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, German Center for Infection Research, Partnersite Munich (DZIF), University Medical Center [Tubingen, Germany], Inselspital Bern, University of Bern, The University of Texas M.D. Anderson Cancer Center [Houston], Kindai University, National Yang Ming University (NYMU), Taipei Veterans General Hospital [Taiwan], Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Eberhard Karls University [Tübingen, Germany], Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Grenoble, Hammersmith Hospital NHS Imperial College Healthcare, Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Institució Catalana de Recerca i Estudis Avançats (ICREA), Pfister, Dominik [0000-0002-0542-2638], Núñez, Nicolás Gonzalo [0000-0003-3837-270X], Govaere, Olivier [0000-0002-4426-6930], Szydlowska, Marta [0000-0002-4660-899X], Gupta, Revant [0000-0002-0881-5074], Deczkowska, Aleksandra [0000-0003-0844-4346], Friebel, Ekaterina [0000-0003-1419-2376], Lenggenhager, Daniela [0000-0002-5382-9854], Moncsek, Anja [0000-0002-1191-5842], Inverso, Donato [0000-0003-0987-3345], Vacca, Michele [0000-0002-1973-224X], Marra, Fabio [0000-0001-8629-0878], Allison, Michael [0000-0003-3677-3294], D'Alessio, Antonio [0000-0002-9164-3671], Personeni, Nicola [0000-0002-7995-272X], Rimassa, Lorenza [0000-0001-9957-3615], Pomej, Katharina [0000-0002-2807-3565], Peck-Radosavljevic, Markus [0000-0002-0597-2728], Mallm, Jan-Philipp [0000-0002-7059-4030], Schietinger, Andrea [0000-0003-3644-1687], Augustin, Hellmut G [0000-0002-7173-4242], Kikuchi, Hiroto [0000-0002-3601-8435], Duda, Dan G [0000-0001-7065-8797], Mei, Henrik E [0000-0003-0697-7755], Schulz, Axel Ronald [0000-0002-5106-0148], Ringelhan, Marc [0000-0003-3131-5657], Lujambio, Amaia [0000-0002-2798-1481], Dufour, Jean-Francois [0000-0002-8062-1346], Kudo, Masatoshi [0000-0002-4102-3474], Djouder, Nabil [0000-0001-8423-1030], Zender, Lars [0000-0001-7626-2849], Pinato, David J [0000-0002-3529-0103], Rad, Roland [0000-0002-6849-9659], Mertens, Joachim C [0000-0003-2007-0308], Weber, Achim [0000-0003-0073-3637], Meissner, Felix [0000-0003-1000-7989], Amit, Ido [0000-0003-2968-877X], Knolle, Percy [0000-0003-2983-0414], Becher, Burkhard [0000-0002-1541-7867], Llovet, Josep M [0000-0003-0547-2667], Heikenwalder, Mathias [0000-0002-3135-2274], Apollo - University of Cambridge Repository, Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Helmholtz Zentrum München = German Research Center for Environmental Health, Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Firenze = University of Florence (UniFI), MARCHE, Patrice, D’Alessio, Antonio [0000-0002-9164-3671], Augustin, Hellmut G. [0000-0002-7173-4242], Duda, Dan G. [0000-0001-7065-8797], Mei, Henrik E. [0000-0003-0697-7755], Pinato, David J. [0000-0002-3529-0103], Mertens, Joachim C. [0000-0003-2007-0308], and Llovet, Josep M. [0000-0003-0547-2667]
Subjects: Male, Carcinogenesis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, CD8-Positive T-Lymphocytes, B7-H1 Antigen, 13/2, 13/1, Mice, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, LIVER-CANCER, R PACKAGE, RNA-SEQ, 14/19, Cancer, 0303 health sciences, Multidisciplinary, NONALCOHOLIC STEATOHEPATITIS, Liver Neoplasms, article, ddc, 3. Good health, 13/31, Multidisciplinary Sciences, medicine.anatomical_structure, Liver, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Disease Progression, Science & Technology - Other Topics, [SDV.IMM]Life Sciences [q-bio]/Immunology, 64/60, Tumor necrosis factor alpha, Immunotherapy, Adjuvant, 631/67, Carcinoma, Hepatocellular, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, 610 Medicine & health, [SDV.CAN]Life Sciences [q-bio]/Cancer, 14/32, 03 medical and health sciences, 14/34, 13/21, [SDV.CAN] Life Sciences [q-bio]/Cancer, ADVANCED HEPATOCELLULAR-CARCINOMA, NAFLD, medicine, Animals, Humans, 14/35, 030304 developmental biology, Science & Technology, Tumor Necrosis Factor-alpha, business.industry, 631/250/251, medicine.disease, PHASE-III, digestive system diseases, 13/51, 14/63, 59/57, T-CELLS, Cancer research, Steatohepatitis, business, CD8
Abstract: Hepatocellular carcinoma (HCC) can have viral or non-viral causes1–5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH–HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH–HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH–HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment., In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.
Published: 2021

22. Differences in infection control and diagnostic measures for multidrug-resistant organisms in the tristate area of France, Germany and Switzerland in 2019 – survey results from the RH(E)IN-CARE network

Author: Stéphanie Deboscker, Nico T. Mutters, Vanessa M. Eichel, Sarah Tschudin-Sutter, Hajo Grundmann, Benoît Jaulhac, Thierry Lavigne, Julia Rauch, University of Basel (Unibas), Les Hôpitaux Universitaires de Strasbourg (HUS), University of Freiburg [Freiburg], Heidelberg University Hospital [Heidelberg], Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), CHU Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), and univOAK, Archive ouverte
Subjects: Methicillin-Resistant Staphylococcus aureus, medicine.medical_specialty, Isolation (health care), Psychological intervention, Survey result, law.invention, 03 medical and health sciences, law, Drug Resistance, Multiple, Bacterial, Germany, Humans, Infection control, Medicine, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Cross Infection, Infection Control, 0303 health sciences, 030306 microbiology, Transmission (medicine), business.industry, Public health, General Medicine, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Intensive care unit, 3. Good health, Multiple drug resistance, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Family medicine, France, business, Switzerland
Abstract: BACKGROUND Multidrug-resistant organisms (MDROs) are a public health threat. Single-centre interventions, however, are likely to fail in the long term, as patients are commonly transferred between institutions given the economic integration across borders. A transnational approach targeting larger regions is needed to plan overarching sets of interventions. Here, we aim to describe differences in diagnostic and infection prevention and control (IPC) measures in the fight against MDROs. METHODS In 2019, we systematically assessed diagnostic algorithms and IPC measures implemented for detection and control of MDROs at three tertiary academic care centres (Freiburg; Strasbourg; Basel). Data were collected using a standardised data collection sheet to be filled in by every centre. Uncertainties were clarified by direct contact via telephone or email with the data supplier. Internal validity was checked by at least two researchers independently filling in the survey. RESULTS All centres have established a primarily culture-based, rather than a nucleic acid amplification-based approach for detection of MDROs (i.e., vancomycin-resistant Enterococci [VRE], methicillin-resistant Staphylococcus aureus [MRSA], extended-spectrum beta-lactamase-producing Enterobacteriaceae [ESBL], carbapenemase-producing and carbapenem-resistant Gram-negatives [CPGN/CRGN]). IPC measures differed greatly across all centres. High-risk patients are screened for most MDROs on intensive care unit (ICU) admission in all centres; only the French centre is screening all patients admitted to the ICU for VRE, MRSA and ESBL. Patients colonised/infected by MRSA, quinolone-resistant ESBL Klebsiella spp. and CPGN/CRGN are isolated everywhere, whereas patients colonised/infected by VRE and ESBL are usually not isolated in the German centre. CONCLUSIONS In contrast to the French and Swiss centres, the German centre no longer uses isolation measures to control VRE and quinolone-susceptible ESBL. Overall, the French centre is more focused on intercepting MDRO transmission from outside, whereas the German and Swiss centres are more focused on intercepting endemic MDRO transmission. These findings point to important challenges regarding future attempts to standardise IPC measures across borders.
Published: 2021

23. Entry of Phenuiviruses into Mammalian Host Cells

Author: Qilin Xin, Pierre-Yves Lozach, Jana Koch, Nicole D. Tischler, Heidelberg University Hospital [Heidelberg], Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidad San Sebastian, and INRAEIDEX-Impulsion 2020 (University of Lyon)FINOVI (Fondation pour l'Universite de Lyon)CellNetworks Research Group fundsGerman Research Foundation (DFG)LO-2338/1-1LO-2338/3-1China Scholarship Council
Subjects: emerging virus, 0301 basic medicine, Phlebovirus, fusion, RNA virus, receptor, 030106 microbiology, lcsh:QR1-502, Virus Attachment, Review, Heartland, Biology, Endocytosis, Bunyaviridae Infections, Arbovirus, lcsh:Microbiology, Virus, 03 medical and health sciences, Virology, arthropod, Rift, bandavirus, medicine, Animals, Humans, cell entry, Cell entry, Mammals, Host (biology), Uukuniemi, Toscana, Virus Internalization, biology.organism_classification, medicine.disease, 3. Good health, arbovirus, 030104 developmental biology, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, SFTSV, Arthropod Vector, uukuvirus
Abstract: International audience; Phenuiviridae is a large family of arthropod-borne viruses with over 100 species worldwide. Several cause severe diseases in both humans and livestock. Global warming and the apparent geographical expansion of arthropod vectors are good reasons to seriously consider these viruses potential agents of emerging diseases. With an increasing frequency and number of epidemics, some phenuiviruses represent a global threat to public and veterinary health. This review focuses on the early stage of phenuivirus infection in mammalian host cells. We address current knowledge on each step of the cell entry process, from virus binding to penetration into the cytosol. Virus receptors, endocytosis, and fusion mechanisms are discussed in light of the most recent progress on the entry of banda-, phlebo-, and uukuviruses, which together constitute the three prominent genera in the Phenuiviridae family.
Published: 2021

24. Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

Author: Ajit S. Puri, Allan Taylor, Huynh Le Vu, Tatemi Todaka, Teddy Y. Wu, Octavio M. Pontes-Neto, Eytan Raz, Pedro Lylyk, Jasmine Johann, Roberta Novakovic, Hormuzdiyar H. Dasenbrock, Francisco Mont’Alverne, Nobuyuki Sakai, Melanie Walker, Hugh Stephen Winters, Ossama Mansour, Yohei Takenobu, Gregory Walker, Miki Fujimura, Saif Bushnaq, Odysseas Kargiotis, Nabeel Herial, Markus A Möhlenbruch, Malveeka Sharma, Hiroshi Tokimura, Maxim Mokin, Jean Raymond, Michael D. Hill, Amal Abou-Hamden, Leonardo Renieri, Serdar Geyik, Yuri Sugiura, Luisa Fonseca, Roberto Crosa, Fabricio O Lima, Ameer E Hassan, Viet Quy Nguyen, Jane G. Morris, Steven W. Hetts, Jawad F. Kirmani, Matthew S. Tenser, Muhammad M. Qureshi, Gianmarco Bernava, Mahmoud H Mohammaden, Verónica V. Olavarría, Jun Deguchi, André Beer-Furlan, Steve M. Cordina, Hiroshi Yamagami, Mohamad Abdalkader, Toshiyuki Fujinaka, Clifford J. Eskey, Rotem Sivan-Hoffmann, Hao Zhang, Anirudh Kulkarni, Brendan Steinfort, Özlem Aykaç, Barbara Voetsch, Alex Brehm, Italo Linfante, Wenguo Huang, Omer Eker, M. Luis Silva, Pascal Jabbour, Lissa Peeling, Mollie McDermott, Pascale Lavoie, Kazutaka Sonoda, Thomas Devlin, Alicia C. Castonguay, Jin Soo Lee, Diogo C Haussen, Dileep R. Yavagal, Thanh N. Nguyen, Umair Rashid, Vasu Saini, Raghid Kikano, Hiroyuki Hashimoto, Masaaki Uno, Saima Ahmad, Artem Kaliaev, Eiji Hagashi, Ajay K. Wakhloo, Romain Bourcier, Ryoo Yamamoto, Jesse M. Thon, Georgios Tsivgoulis, Dorothea Altschul, Achmad Fidaus Sani, Satoshi Yamada, Varsha Singh, David S Liebeskind, Tatsuo Amano, Anchalee Churojana, Juan F. Arenillas, Junichi Iida, Charles C. Matouk, Nobuyuki Ohara, Osama O. Zaidat, Mario Martínez-Galdámez, Chandril Chugh, Don Frei, Vanessa Chalumeau, Brijesh P Mehta, Marios Psychogios, Anna Luisa Kühn, Leticia C Rebello, Xianjin Shang, Hosam Al-Jehani, Hiroki Fukuda, Hong Gee Roh, Gisele Sampaio Silva, Rakesh Khatri, Kenichi Todo, Amal Al Hashmi, Alex Bou Chebl, Sunil A Sheth, Zhongming Qiu, Oriana Cornett, Zhengzhou Yuan, Wazim Izzath, Hesham Masoud, Rodrigo Rivera, Michel Piotin, Vikram Huded, Mamoru Murakami, Mohamed Teleb, Viktor Szeder, Ruchir Shah, Dheeraj Gandhi, John Thornton, Michael Chen, Vitor Mendes Pereira, Nadia Hammami, Alice Ma, Anna M. Cervantes-Arslanian, James E. Siegler, Seby John, Carlos Ynigo Lopez, Mudassir Farooqui, David Ozretić, Takuya Kanamaru, Romain Guile, Daisuke Watanabe, Kosuke Miyake, Alejandro Rodriguez Vasquez, Patrick Nicholson, Yuki Yamamoto, William J. Mack, Naoto Kimura, Simon Mathew John, Robert Fahed, Yuji Matsumaru, David Y. Chung, Rishi Gupta, Ryuhei Kono, Michael Frankel, Victor S. Lopez Rivera, Johanna T. Fifi, Raul G Nogueira, Paolo Machi, Tudor G. Jovin, Jordi Blasco, Emma Griffin, Salvatore Mangiafico, Masafumi Morimoto, Jun Luo, Santiago Ortega-Gutierrez, Monika Killer-Oberpfalzer, Daniel Giansante Abud, Syed I. Hussain, Fawaz Al-Mufti, Yusuke Sugimura, Atilla Özcan Özdemir, Stephan A. Mayer, Sumeet Multani, Adel Alhazzani, Alhamza R Al-Bayati, Michael Kelly, Lee A Birnbaum, Shadi Yaghi, Jeyaraj D Pandian, Ji Man Hong, Junsuke Shimbo, Johnny Ho-Yin Wong, Elena A. Cora, Laura Mechtouff, Pedro S.C. Magalhães, Pablo M. Lavados, Yuichi Murayama, Dong Hun Shin, Simon Nagel, Ken Wong, Jose Antonio Fiorot, Jeremy Payne, Randall C. Edgell, Adrienne Weeks, CarMeN, laboratoire, Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Emory University School of Medicine, Emory University [Atlanta, GA], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), National Hospital Organization Osaka National Hospital [Japon] (NHO Osaka National Hospital), Alexandria University [Alexandrie], Boston Medical Center [Boston, MA, USA] (BMC), Xinqiao Hospital [Chongqing, China] (XH), University of Cape Town, La Sagrada Familia Clinic/Clínica La Sagrada Familia [Buenos Aires, Argentina] (LSFC), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Hospital General de Fortaleza [Fortaleza, Brazil] (HGF), Nottingham University Hospitals NHS Trust [UK], Kobe City Medical Center General Hospital [Kobe, Hyogo, Japan] (KCMCGH), Azienda Ospedaliero-Universitaria Careggi [Firenze, Toscana, Italy] (AOUC), University Hospital Centre Zagreb, Partenaires INRAE, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cleveland Clinic Abu Dhabi [Abou Dabi, Émirats arabes unis], Hôpital de Beaumont [Dublin, Ireland] (HB), Hospital-Estadual Central [Vitoria, Brazil] (HEC), Instituto de NeuroCirugía Asenjo, Institut national de neurologie Mongi-Ben Hamida [Tunis], Hue Central Hospital [Thua Thien Hue, Vietnam] (HCH), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre hospitalier universitaire de Nantes (CHU Nantes), Washington University School of Medicine (WUSM), University of Washington [Seattle], Englewood Hospital and Medical Center [Englewood], Jefferson (Philadelphia University + Thomas Jefferson University), Westchester Medical Center [Valhalla, New York, USA] (WMC), Eskisehir Osmangazi University, University of Maryland School of Medicine, University of Maryland System, MAX Superspecialty Hospital [Saket, New Delhi, India] (MSH), Yale School of Medicine [New Haven, Connecticut] (YSM), Université Laval [Québec] (ULaval), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Rush University Medical Center [Chicago], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Toronto, NH Mazumdar Shah Medical Center [Bangalore, India] (NHMSMC), IMS Tokyo-Katsushika General Hospital [Tokyo, Japan], Gachon University [Seongnam, Korea] (GU), Hospital Municipal Sao Jose [Joinville, Santa Catarina, Brazil] (HMSJ), Lau Medical Center [Beirut, Lebanon] (LMC), University of Iowa [Iowa City], Royal Adelaide Hospital [Adelaide Australia], Kyorin University [Tokyo, Japan], Yokohama Brain and Spine Center [Yokohama, Japan] (YBSC), Dalhousie University [Halifax], Rambam Health Care Campus [Haifa, Israel], Centro Endovascular Neurologico Medica Uruguaya [Montevideo, Uruguay] (CENMU), Heidelberg University Hospital [Heidelberg], Imam Abdulrahman bin Faisal University [Alkhobar, Saudi Arabia] (IAFU), McGovern Medical School [Houston, TX, USA] (McGMS), The University of Texas Health Science Center at Houston (UTHealth), Cooper Medical School of Rowan University [Camden] (CMSRU), Airlangga University [Jawa Timur, Indonesia] (AU), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Geneva University Hospitals and Geneva University, Universidade de São Paulo = University of São Paulo (USP), Beth Israel Lahey Health [Burlington, MA, USA] (BILH), New York University School of Medicine (NYU Grossman School of Medicine), Memorial Neuroscience Institute [Pembroke Pines, FL, USA] (MNI), Iwate Prefectural Central Hospital [Morioka, Iwate, Japan] (IPCH), Japanese Red Cross Musashino Hospital [Tokyo], Ajou University, University of Ottawa [Ottawa], Saga-ken Medical Centre Koseikan [Saga, Japan] (SMCK), University of South Alabama, Konkuk University [Seoul], Royal Free Hospital [London, UK], Hospital Clinico Universitario de Valladolid [Castilla y León, Spain] (HCUV), Universidad de Valladolid [Valladolid] (UVa), Instituto de Ciencia de Materiales de Aragón [Saragoza, España] (ICMA-CSIC), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Hospital Clínic de Barcelona [Catalonia, Spain], Centro Hospitalar Universitário de São João [Porto], Christchurch Hospital [Christchurch, New Zealand] (CH), University Hospital Basel [Basel], University of Southern California (USC), Kohnan Hospital - Sendai [Miyagi, Japan], University of Texas Southwestern Medical Center [Dallas], Nara City Hospital [Nara, Japan] (NCH), Toyonaka Municipal Hospital [Osaka, Japan] (TMH), Kagoshima City Hospita [Kagoshima, Japan] (KCH), Texas Tech University System [Lubbock, TX, USA] (TTUS), University of Saskatchewan [Saskatoon] (U of S), National Institute of Information and Communications Technology [Tokyo, Japan] (NICT), Royal Prince Alfred Hospital [Camperdown, Australia] (RPAH), Banner Desert Medical Center [Mesa, AZ, USA] (BDMC), Japanese Red Cross Matsue Hospital [Shimane, Japan] (JRCMH), Shiroyama Hospital [Osaka, Japan] (SH), Niigata City General Hospital [Niigata, Japan] (NCGH), Sugimura Hospital [Kumamoto, Japan] (SH), Kawasaki Medical School [Kurashiki, Japan] (KMS), Osaka Red Cross Hospital [Osaka, Japan] (ORCH), Université de Tsukuba = University of Tsukuba, Saiseikai Central Hospital [Tokyo, Japan] (SCH), Kinikyo Chuo Hospital - Sapporo [Hokkaido, Japan] (KCHS), NTT Medical Center Tokyo [Tokyo, Japan] (NTTMCT), Yokohama Shintoshi Neurosurgical Hospital [Yokohama, Japan]. (YSNH), Osaka General Medical Center [Osaka, Japan] (OGMC), University of Miami Leonard M. Miller School of Medicine (UMMSM), Bon Secours Mercy Health System [Toledo, OH, USA] (BSMHS), Maoming City Hospital [Guandong, China] (MCH), Miami Cardiac & Vascular Institute [Miami, FL, USA] (MC&VI), Hackensack University Medical Center [Hackensack], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of Tennessee [Chattanooga] (UTC), The University of Texas at San Antonio (UTSA), Mianyang 404 Hospital [Sichuan, China] (M404H), Siriraj Hosital - Mahidol University [Bangkok, Thailand] (SHMU), SUNY Upstate Medical University, State University of New York (SUNY), Royal North Shore Hospital (RNSH), The University of Texas Rio Grande Valley [Harlingen, TX, USA] (UTRGV), Khoula Hospital [Muscat, Oman] (Ministry of Health - KH), University of Michigan [Ann Arbor], University of Michigan System, University of South Florida [Tampa] (USF), Henry Ford Health System [Detroit, MI, USA] (HFHS), Metropolitan Hospital [Piraeus, Greece] (MH), National and Kapodistrian University of Athens (NKUA), Maine Medical Center, Dartmouth Hitchcock Medical Center [Lebanon, NH, USA] (DHMC), Centro Universitário Feevale (BRAZIL), The Valley Hospital [Ridgewood, NJ, USA] (TVH), St Joseph's University Medical Center [Paterson, NJ, USA] (StJUMC), Christian Medical College and Hospital Ludhiana [Punjab, India] (CMCHL), Universidad del Desarrollo, University Graduate School of Medicine [Osaka, Japan], Tokushima University, Universidade Federal de São Paulo, Istanbul Aydin University [İstanbul, Turkey] (IAU), Swedish Medical Center [Englewood, CO, USA] (SMC), Bayhealth Medical Center [Dover, DE, USA] (BMC), Saiseikai Fukuoka General Hospital [Fukuoka, Japan] (SFGH), Osaka Rosai Hospital - Sakai [Osaka, Japan] (ORHS), King Saud University [Riyadh] (KSU), Mount Sinai Health System, University of Calgary, Huzhou University [Zhejiang], The Affiliated Hospital of Southwest Medical University - Luzhou [Sichuan, China] (TAHSMUL), Yijishan Hospital of Wannan Medical College [Wuhu, Anhui, China] (YHWMC), University of Toledo, WellStar Health System [Marietta, GA, USA] (WHS), Institut National de la Recherche Scientifique [Québec] (INRS), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), SVIN COVID-19 Registry, the Middle East North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO), Japanese Society of Vascular and Interventional Neurology Society (JVIN), University of California [San Francisco] (UCSF), University of California, Yale University School of Medicine, University of São Paulo (USP), and University of California-University of California
Subjects: [SDV]Life Sciences [q-bio], COVID-19, Subarachnoid Hemorrhage* / diagnostic imaging, 030204 cardiovascular system & hematology, Intracranial Aneurysm* / therapy, lcsh:RC346-429, 0302 clinical medicine, Pandemic, Myocardial infarction, Prospective Studies, Stroke, Original Research, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Intracranial Aneurysm* / diagnostic imaging, Cardiology, Subarachnoid haemorrhage, haemorrhage, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Subgroup analysis, subarachnoid, Intracranial Aneurysm* / epidemiology, 03 medical and health sciences, Aneurysm, Internal medicine, medicine, Humans, coil, cardiovascular diseases, Pandemics, lcsh:Neurology. Diseases of the nervous system, Retrospective Studies, business.industry, SARS-CoV-2, Intracranial Aneurysm, Subarachnoid Hemorrhage, medicine.disease, infection, nervous system diseases, Mechanical thrombectomy, Cross-Sectional Studies, aneurysm, Neurology (clinical), Subarachnoid Hemorrhage* / epidemiology, business, 030217 neurology & neurosurgery
Abstract: BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study’s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March–31 May 2020. The prior 1-year control period (1 March–31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI −24.3% to −20.7%, pInterpretationThere was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
Published: 2021

25. Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium

Author: Pierre Laurent-Puig, Yan Ren, Frédérique Rachédi, Pascal Guénel, Sandya Liyanarachchi, Asta Försti, Albert de la Chapelle, Om Kulkarni, Claire Mulot, Huiling He, Federica Gemignani, Julie Guibon, Anne-Valérie Guizard, Fabienne Lesueur, Rossella Elisei, Ausrele Kesminiene, Anthony F. Herzig, Mojgan Karimi, Pierre-Emmanuel Sugier, Thérèse Truong, Delphine Bacq-Daian, Anne-Louise Leutenegger, Constance Xhaard, Daniel F. Comiskey, Celia M Pereda, Evgenia Ostroumova, Florent de Vathaire, Elisabeth Adjadj, Françoise Borson-Chazot, Jean-François Deleuze, Carole Rubino, Anne Boland-Auge, Hauke Thomsen, Elise A. Lucotte, Marie-Christine Boutron-Ruault, Juan J Lence-Anta, Rosa Ortiz, Claire Schvartz, Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université Paris-Saclay, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Épidémiologie des radiations, épidémiologie clinique des cancers et survie (U1018 (Équipe 3) ), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Institut Jean Godinot [Reims], UNICANCER, Registre Général des Tumeurs du Calvados, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Taaone, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institute of Oncology and Radiobiology, Ohio State University [Columbus] (OSU), University of Pisa - Università di Pisa, Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], German Cancer Consortium [Heidelberg] (DKTK), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, MESRI: 2102 918823 National Institute of Ecology, NIE Agence Nationale de la Recherche, ANR: ANR‐10‐COHO‐0006 Fondation ARC pour la Recherche sur le Cancer, ARC: PGA120150202302 Ligue Contre le Cancer Fondation de France Institut National Du Cancer, INCa: 9533 Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, ANSES Mutuelle Générale de l'Education Nationale, MGEN Electricité de France, EDF: EP 2019‐01, We thank Dr Yannick Rougier and Dr Dominique Baron-Dubourdieu for providing pathological reports for the NC study, as well as Dr Sylvie Laumond, Dr Jean-Paul Grangeon (Direction des affaires sanitaires et sociales de Nouvelle-Cal?donie) and the country's provincial health authorities (DPASS Sud, DPASS Nord, DPASS Iles Loyaut?) for support during data collection in the NC study. We thank Milagros Velasco, Mae Chappe and Idalmis Infante (Institute of Oncology and Radiobiology, La Havana, Cuba) and Silvia Turcios (National Institute of Endocrinology, La Havana, Cuba) for helping in the collection of the data in the Cuban Study. We thank John Paoaafaite and Joseph Teuri who contacted and interviewed cases and controls for the study. Finally, we also thank P. Morales, J. Iltis, P. Giraud, P. Didiergeorge, M. Brisard, G. Soubiran, B. Caillou, P. Dupire, J. Ienfa, G. de Clermont, N. Cerf, B. Oddo, M. Bambridge, C. Baron, A. Mouchard-Rachet, O. Simonet, D. Lamarque, J. Vabret, J. Delacre, M.P. Darquier and J. Leninger, for their help in the collection of the cases or in the organization of study in French Polynesia. We would like to thank the Association Centre de Regroupement Informatique et Statistique en Anatomie Pathologique en Provence-Alpes-C?te d'Azur (CRISAP PACA), as well as Dr Arlette Danzon, Dr Genevi?ve Sasolas, Dr Marc Christophe Sattonnet, Dr Marc Colonna, Dr Brigitte Lacour, Dr Michel Velten, Dr Enora Clero, Dr St?phane Maillard, Dr Laurent Bailly, Dr Eug?nia Marin? Barjoan, Dr Jean-Luc Lassalle, Dr Z Hafdi-Nejjari, Dr P Delafosse, Dr Elisabeth Adjadj, Kami-Marie Moreau, Cyrielle Orenes, Laurianne Sarrazin, St?phanie Bonnay, Fr?d?rique Chatelain, Maryse Barouh, Evelyne Rapp, Julie Festra?ts, Julie Valbousquet, Yusuf Atilgan, Jean Chappellet, Lallia Bedhouche, Florent Dayet and Ziyan Fami, for their help in the collection of cases, the organization and the management of the Young-Thyr study. We acknowledge Stefano Landi for the Italian GWAS data and Subhayan Chattopadhyay and Yasmeen Niazi (Division of Molecular Genetic Epidemiology, German Cancer Research Center?DKFZ) for technical assistance in these data analysis. We are grateful to Dr Herv? Perdry for his help in using the GASTON package. The EPITHYR GWAS was supported by Institut National du Cancer (grant number 9533) and Fondation ARC (grant number PGA120150202302). The E3N cohort received support from the MGEN, Gustave Roussy and Ligue contre le cancer for its setup and maintenance. The E3N cohort was also supported by a state grant from the Agence Nationale pour la Recherche (ANR) (grant number ANR-10-COHO-0006) within the Investissement d'Avenir program and from the French Ministry of Higher Education, Research and Innovation (MESRI, grant number 2102 918823). The other participating studies were funded by Ligue Nationale Contre le Cancer, ANR, the Direction G?n?rale de la Sante, the Agence Fran?aise de S?curit? Sanitaire de l'alimentation, de l'environnement et du travail (ANSES), CHILDTHYR EEC program, and the Fondation de France. JG was the recipient of a PhD fellowship from R?gion Ile-de-France, part of OK was the recipient of a post-doc fellowship from Electricit? de France (conseil scientifique de Radioprotection d'EDF, grant EP 2019-01)., The EPITHYR GWAS was supported by Institut National du Cancer (grant number 9533) and Fondation ARC (grant number PGA120150202302). The E3N cohort received support from the MGEN, Gustave Roussy and Ligue contre le cancer for its setup and maintenance. The E3N cohort was also supported by a state grant from the Agence Nationale pour la Recherche (ANR) (grant number ANR‐10‐COHO‐0006) within the Investissement d'Avenir program and from the French Ministry of Higher Education, Research and Innovation (MESRI, grant number 2102 918823). The other participating studies were funded by Ligue Nationale Contre le Cancer, the Direction Générale de la Sante, the Agence Française de Sécurité Sanitaire de l'alimentation, and the Fondation de France. JG was the recipient of a PhD fellowship from Région Ile‐de‐France, part of OK was the recipient of a post‐doc fellowship from Electricité de France (conseil scientifique de Radioprotection d'EDF, grant EP 2019‐01)., Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Male, Cancer Research, Native Hawaiian or Other Pacific Islander, [SDV]Life Sciences [q-bio], Ethnic group, Genome-wide association study, 0302 clinical medicine, Gene Frequency, Informed consent, Epidemiology, thyroid cancer, Chromosomes, Human, Medicine, Prospective cohort study, Thyroid cancer, Genetics, 0303 health sciences, education.field_of_study, Incidence (epidemiology), Middle Aged, Checklist, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Pacific islanders, Female, Adult, medicine.medical_specialty, case-control study, education, Population, Biology, Pacific Islands, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, Humans, Genetic Predisposition to Disease, Thyroid Neoplasms, Aged, 030304 developmental biology, genome-wide association study, business.industry, Case-control study, medicine.disease, Clinical trial, Case-Control Studies, Family medicine, business
Abstract: Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. Here, we conducted a genome-wide association study (GWAS) involving 1,554 cases/1,973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from the EPITHYR consortium. Our results confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 (rs334729) and 16q23.2 (rs16950982), which were associated with TSH levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. The frequency of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans and may explain part of the highest DTC incidence observed in Oceanians.Competing Interest StatementThe authors have declared no competing interest.Funding StatementINCA (grant number 9533) and ARC (grant number PGA120150202302), Ligue Nationale Contre le Cancer, Agence Nationale pour la Recherche (ANR), the Direction Generale de la Sante, the Agence Francaise de Securite Sanitaire de l alimentation, de lenvironnement et du travail (ANSES), CHILDTHYR EEC program, and the Fondation de France. JG and CX were the recipient of a PhD fellowship from Region Ile-de-France.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All participants provided informed consent and each study was approved by their governing ethics committee.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. (Less)
Published: 2021

26. Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3

Author: Holger Hengel, Judith van Gaalen, Gülin Öz, Thiago Junqueira Ribeiro de Rezende, Hector Garcia-Moreno, Sandro Romanzetti, L. Schoels, Kathrin Reetz, Richard Joules, Koyak Berkan, Bart P.C. van de Warrenburg, Jon Infante, Matthis Synofzik, James M. Joers, Robin Wolz, Marcondes C. França, Heike Jacobi, Jereon J. de Vries, Tamara Schaprian, Jiang Hong, Jun Suk Kang, Matthias Schmid, Paola Giunti, Jörn Diedrichsen, Fanny Mochel, Thomas Klockgether, Alexandra Durr, Dagmar Timmann-Braun, Benjamin Bender, Weihua Liao, Jennifer Faber, HAL-SU, Gestionnaire, University Hospital Bonn, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Jülich Aachen Research Alliance (JARA), Universidade Estadual de Campinas = University of Campinas (UNICAMP), Central South University [Changsha], Radboud University Medical Center [Nijmegen], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University College of London [London] (UCL), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, University of Minnesota Medical School, University of Minnesota System, University of Groningen [Groningen], Goethe-University Frankfurt am Main, University of Duisburg-Essen, Heidelberg University Hospital [Heidelberg], Universidad de Cantabria [Santander], University of Western Ontario (UWO), Universidad de Cantabria, RWTH Aachen University, University of Campinas [Campinas] (UNICAMP), Radboud University Medical Centre [Nijmegen, The Netherlands], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cerebellum, Pathology, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Movement disorders, Ataxia, diagnostic imaging [Spinocerebellar Ataxias], Medizin, 03 medical and health sciences, 0302 clinical medicine, spinocerebellar ataxia, medicine, Humans, Spinocerebellar Ataxias, Brain segmentation, Psychology, genetics [Spinocerebellar Ataxias], ddc:610, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], diagnostic imaging [Brain], volumetry, business.industry, Neurosciences, Brain, Machado-Joseph Disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Spinal cord, medicine.disease, Pons, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Neurology, nervous system, Medulla oblongata, Spinocerebellar ataxia, biomarker, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, MRI
Abstract: Background: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity. Objective: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease. Methods: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels. Results: The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume. Conclusion: Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society Funding agencies: This publication is an outcome of ESMI, an EU Joint Programme - Neurodegenerative Disease Research (JPND) Project (see www.jpnd.eu). The project is supported under the aegis of JPND through the following funding organizations: Germany, Federal Ministry of Education and Research (BMBF; funding codes 01ED1602A/B); Netherlands, The Netherlands Organisation for Health Research and Development; Portugal, Foundation for Science and Technology and Regional Fund for Science and Technology of the Azores; United Kingdom, Medical Research Council. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement 643417. At the US sites this work was in part supported y the National Ataxia Foundation and the National Institute of Neurological Disorders and Stroke (NINDS) grant R01 NS080816. The Center for Magnetic Resonance Research is supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) grant P41 EB027061, and the Institutional Center Cores for Advanced Neuroimaging award P30 NS076408 and S10 OD017974 grant.
Published: 2021

27. SARS-CoV-2 and Stroke Characteristics: A Report From the Multinational COVID-19 Stroke Study Group

Author: Saeideh Aghayari Sheikh Neshin, Guillaume Turc, Georgios Tsivgoulis, Fahimeh Vahabizad, Stefania Mondello, Oluwaseyi Olulana, Thomas Yasuda, Gelareh Banihashemi, Ali Reza Noorian, Mojdeh Ghabaee, Hany Mohamed Aref, Aristeidis H. Katsanos, Sahar Hojjat-Anasri Komachali, Alaleh Vaghefi Far, Saeed Ansari, Francisco Purroy, Leo H. Bonati, Sakineh Ranji-Burachaloo, Juan F. Arenillas, Afshin Borhani-Haghighi, Peyman Nowrouzi-Sohrabi, Ilaria Gandoglia, Zabihollah Babaeepour, Mohammad Hossein Harirchian, Alia Saberi, Vivek Sharma, Fabricio Buchadid Cardoso, Jusun Moon, Nitin Goyal, Arash Kia, Ronen R. Leker, Mercedeh Sepehrnia, João Sargento-Freitas, Apoorva Dev, Asadollah Mir Ghasemi, Mirna Sabra, Mohammad Ghorbani, Aicha Lyoubi, Bruce C.V. Campbell, Saeideh Salehizadeh, Christos Krogias, Shailesh Male, Mehrdad Roozbeh, Elahe Mohammadi-Vosough, Durgesh Chaudhary, Soheil Naderi, Nasrin Rahimian, Konark Malhotra, Mehmet Hanci, Mehdi Farhoudi, Arefeh Babazadeh, Ali Amini Harandi, Ghasem Farahmand, Massimo Del Sette, Martin Punter, Miljenko Crnjakovic, Faezeh Khodadadi, Gian Marco De Marchis, Ashkan Mowla, Nuno Reis Carreira, Fariborz Khorvash, Annemarei Ranta, Zeinab Mohseni Afshar, Orkhan Alizada, Shima Shahjouei, Ana Paula Aires, Diana Aguiar de Sousa, Christoph J. Griessenauer, Ava Hamidi, Seyed Amir Ebrahimzadeh, Farhad Assarzadegan, Jong Ho Park, Hamidreza Mirkarimi, Mostafa Almasi-Dooghaee, Achille Cernigliaro, Jeffrey C Mai, Lawrence Nolan, Mahmoud Reza Azarpazhooh, Leila Poorsaadat, Yasaman Ahmadzadeh, João Pedro Marto, Humain Baharvahdat, Kristi Tempro, Seyed Aidin Sajedi, Teresa Mesquita, Bruno Gonçalves, Venkatesh Avula, Manuel Requena, Jason J. Chang, Mika Niemelä, Zeynab Sadat Hasheminejad, Branko Malojčić, Elsa Azevedo, Abhi Pandhi, Debdipto Misra, Ramin Zand, Vida Abedi, Marta Rubiera, Thorsten Steiner, Alireza Vafaei Sadr, Sepideh Paybast, Rohan Arora, Behnam Rezai Jahromi, Firas Kobeissy, Jiang Li, Daniel Bock, Behnam Sabayan, Eric Koza, Joan Montaner, Lev Lotman, Mercedes de Lera Alfonso, Carlo W. Cereda, Mahtab Ramezani, Matthew S. Tenser, Duchange, Nathalie, Geisinger Health System [Danville, PA, USA], National and Kapodistrian University of Athens (NKUA), Attikon University Hospital, Tehran University of Medical Sciences (TUMS), Geisinger Commonwealth School of Medicine [Scranton, PA, USA], University of Southern California (USC), Université de Genève = University of Geneva (UNIGE), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Messina, Regional Health Authority of Sicily [Palermo], University of Otago [Dunedin, Nouvelle-Zélande], PES University [Bangalore], Lebanese University [Beirut] (LU), Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], University of Melbourne, Universidad de Valladolid [Valladolid] (UVa), Klinikum Frankfurt Höchst, University Hospital Virgen Macarena [Sevilla], Poursina Hospital, Universidade de Lisboa = University of Lisbon (ULISBOA), Centro Hospitalar Universitário de São João [Porto], Universidade do Porto = University of Porto, Cerrahpasa Faculty of Medicine, Istanbul University, University of Tennessee [Chattanooga] (UTC), Valiasr Hospital [Borujen], University Hospital Basel [Basel], Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, MedStar Washington Hospital Center, Clinical Hospital Dubrava [Zagreb, Croatia] (CHD), University of Basel (Unibas), Galliera Hospital [Genova, Italy], Yasrebi Hospital [Kashan, Iran] (YH), Tabriz University of Medical Sciences [Tabriz, Iran] (TUOMS), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), McMaster University [Hamilton, Ontario], Ruhr University Bochum (RUB), Hadassah Hebrew University Medical Center [Jerusalem], Albany Medical College, Georgetown University Medical Center, Vidant Medical Center [Greenville, NC, USA] (VMC), Allegheny Health Network [Pittsburgh, PA, USA] (AHN), University Hospital Centre Zagreb, Partenaires INRAE, University of Zagreb, Hospital De Egas Moniz [Lisbon], University of Ottawa [Ottawa], Ain Shams University (ASU), Kermanshah University of Medical Sciences, Asan Medical Center [Seoul], University of Ulsan, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Hospital, Hanyang University College of Medicine, Universitat de Lleida, Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Golestan University of Medical Sciences, Universidade de Coimbra [Coimbra], National University Health System [Singapore] (NUHS), Heidelberg University Hospital [Heidelberg], Hospital for Special Surgery, Iran University of Medical Sciences, Shahid Beheshti University, Babol University of Medical Sciences, Mashhad University of Medical Sciences, Centro Médico de Campinas [São Paulo], Gheshm Hospital, Gilan University of Medical Sciences [Lahijan], Isfahan University of Medical Sciences [Iran] (MUI), University of Florida [Gainesville] (UF), Modarres Hospital [Kashmar], Southern California Permanente Medical Group, Shiraz University of Medical Sciences [Iran] (SUMS), Qazvin University of Medical Sciences, Arak University of Medical Sciences, Harvard Medical School [Boston] (HMS), Salahadin Ayubi Hospital [Baneh], University of Western Ontario (UWO), Long Island Jewish Forest Hills [New York], Biocomplexity Institute of Virginia Tech [Blacksburg], Virginia Tech [Blacksburg], Department of Neurosciences, HUS Neurocenter, Neurokirurgian yksikkö, Clinicum, University of Geneva [Switzerland], Universidade de Lisboa (ULISBOA), Universidade do Porto, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hospital De Egas Moniz [Lisbon, Portugal] (Centro Hospitalar Lisboa Ocidental), and University of Helsinki
Subjects: Male, Cerebrovascular disorders, MESH: Geography, Epidemiology, International Cooperation, SUBTYPES, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Prospective Studies, Young adult, Cerebral Venous Thrombosis, MESH: Treatment Outcome, Subtypes, neuroimaging, MESH: Middle Aged, MESH: Risk, Geography, STATEMENT, cerebrovascular disorders, intracranial hemorrhages, stroke, venous thrombosis, virus diseases, Countries, 3. Good health, MESH: Young Adult, Cardiology and Cardiovascular Medicine, MESH: Intracranial Hemorrhages, COUNTRIES, medicine.medical_specialty, Registry, MESH: Health Expenditures, 03 medical and health sciences, 1ST-EVER ISCHEMIC-STROKE, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Aged, Ischemic Stroke, Advanced and Specialized Nursing, MESH: Humans, 3112 Neurosciences, MESH: Adult, medicine.disease, MESH: International Cooperation, nervous system, RISK-FACTORS, Observational study, Neurology (clinical), Statement, Health Expenditures, Young-Adults, MESH: Female, 030217 neurology & neurosurgery, viruses, 030204 cardiovascular system & hematology, Sinus Thrombosis, Intracranial, Venous thrombosis, YOUNG-ADULTS, Risk-Factors, EPIDEMIOLOGY, MESH: COVID-19, Prospective cohort study, Stroke, MESH: Aged, musculoskeletal, neural, and ocular physiology, CEREBRAL VENOUS THROMBOSIS, Middle Aged, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, MESH: Sinus Thrombosis, Intracranial, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.symptom, Interstroke, MESH: Ischemic Stroke, Adult, Risk, Subarachnoid hemorrhage, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Neuroimaging, macromolecular substances, Asymptomatic, Young Adult, INTERSTROKE, Aneurysm, Internal medicine, medicine, cardiovascular diseases, business.industry, COVID-19, Artery occlusions, MESH: Male, MESH: Prospective Studies, Intracranial hemorrhages, REGISTRY, MESH: Venous Thrombosis, 1st-Ever Ischemic-Stroke, business
Abstract: Background and Purpose: Stroke is reported as a consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in several reports. However, data are sparse regarding the details of these patients in a multinational and large scale. Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke, intracranial hemorrhage, and cerebral venous or sinus thrombosis among SARS-CoV-2–infected patients. We further investigated the risk of large vessel occlusion, stroke severity as measured by the National Institutes of Health Stroke Scale, and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with acute ischemic stroke. In addition, we explored the neuroimaging findings, features of patients who were asymptomatic for SARS-CoV-2 infection at stroke onset, and the impact of geographic regions and countries’ health expenditure on outcomes. Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least 1 eligible stroke patient. Of 432 patients included, 323 (74.8%) had acute ischemic stroke, 91 (21.1%) intracranial hemorrhage, and 18 (4.2%) cerebral venous or sinus thrombosis. A total of 183 (42.4%) patients were women, 104 (24.1%) patients were P =0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; P Conclusions: We observed a considerably higher rate of large vessel occlusions, a much lower rate of small vessel occlusion and lacunar infarction, and a considerable number of young stroke when compared with the population studies before the pandemic. The rate of mechanical thrombectomy was significantly lower in countries with lower health expenditures.
Published: 2021

28. Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1

Author: Luisa Ladel, Anna Rita Redavid, Erik Zwart, Leonid Bystrykh, Patrick Mehlen, Benjamin Gibert, Jasper Panten, Maik Brune, Mathias Heikenwalder, Bertien Dethmers-Ausema, Katharina Schönberger, Dachuan Zhang, Maria Maryanovich, Pia Sommerkamp, Simon Renders, Simón Méndez-Ferrer, Andreas Narr, Markus Sohn, Manon Tourbez, Claudia Korn, Petra Zeisberger, Seka Lazare, Andreas Trumpp, Agnes Hotz-Wagenblatt, Benjamin Ducarouge, Gerald de Haan, Paul S. Frenette, Adriana Przybylla, Arthur Flohr Svendsen, Nina Cabezas-Wallscheid, Nicolas Rama, Daniel Klimmeck, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Heidelberg University Hospital [Heidelberg], University of Groningen [Groningen], Heidelberg University, Développement Cancer et Thérapies Ciblées [Lyon] (LabEx DEVweCAN), Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Albert Einstein College of Medicine [New York], Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, University of Cambridge [UK] (CAM), NHS Blood and Transplant [London, UK], German Cancer Consortium [Heidelberg] (DKTK), Stem Cell Aging Leukemia and Lymphoma (SALL), Rama, Nicolas [0000-0003-1614-7755], Maryanovich, Maria [0000-0002-2015-0538], Gibert, Benjamin [0000-0002-5295-3124], Zwart, Erik [0000-0002-4552-003X], Zhang, Dachuan [0000-0002-1746-275X], Mendez-Ferrer, Simon [0000-0002-9805-9988], Heikenwälder, Mathias [0000-0002-3135-2274], Bystrykh, Leonid [0000-0001-6924-5602], Frenette, Paul S [0000-0003-0862-9922], de Haan, Gerald [0000-0001-9706-0138], Cabezas-Wallscheid, Nina [0000-0003-0870-0530], Trumpp, Andreas [0000-0002-6212-3466], Apollo - University of Cambridge Repository, and Frenette, Paul S. [0000-0003-0862-9922]
Subjects: 0301 basic medicine, Cellular differentiation, [SDV]Life Sciences [q-bio], General Physics and Astronomy, 631/532/2441, Transgenic, Mice, 0302 clinical medicine, Netrin, Hematopoietic Stem Cells/metabolism, 14/19, Stem Cell Niche, Cellular Senescence, Multidisciplinary, Haematopoietic stem cells, Arterioles/metabolism, Hematopoietic Stem Cell Transplantation, Hematopoietic stem cell, Cell Differentiation, Netrin-1, 3. Good health, Cell biology, 13/31, Mutant Strains, Haematopoiesis, Arterioles, medicine.anatomical_structure, Self-renewal, 64/60, Stem cell, Signal Transduction, Stromal cell, Science, 13/106, Mice, Transgenic, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 38/91, 631/532/2139, 03 medical and health sciences, 13/100, Downregulation and upregulation, medicine, Animals, Cell Proliferation, 631/443/7, Membrane Proteins, General Chemistry, Hematopoietic Stem Cells, 631/532/1542, Mice, Mutant Strains, Ageing, 030104 developmental biology, 13/51, Netrin-1/metabolism, Membrane Proteins/metabolism, Bone marrow, 030217 neurology & neurosurgery, Stem-cell niche, Gene Deletion
Abstract: Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential associated to dormancy. Here we identify the cell surface receptor neogenin-1 as specifically expressed in dormant HSCs. Loss of neogenin-1 initially leads to increased HSC expansion but subsequently to loss of self-renewal and premature exhaustion in vivo. Its ligand netrin-1 induces Egr1 expression and maintains quiescence and function of cultured HSCs in a Neo1 dependent manner. Produced by arteriolar endothelial and periarteriolar stromal cells, conditional netrin-1 deletion in the bone marrow niche reduces HSC numbers, quiescence and self-renewal, while overexpression increases quiescence in vivo. Ageing associated bone marrow remodelling leads to the decline of netrin-1 expression in niches and a compensatory but reversible upregulation of neogenin-1 on HSCs. Our study suggests that niche produced netrin-1 preserves HSC quiescence and self-renewal via neogenin-1 function. Decline of netrin-1 production during ageing leads to the gradual decrease of Neo1 mediated HSC self-renewal., Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential and associated dormancy. Here the authors show that niche produced netrin-1 preserves HSC quiescence and self-renewal via neogenin-1, and that decline of netrin-1 production during ageing leads to decreased Neo1 mediated HSC self-renewal.
Published: 2021

29. Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

Author: Mercè Brunet, Eberhard Wieland, Alexander A. Vinks, Pierre Wallemacq, Nils Tore Vethe, Nicolas Picard, Dirk Jan A.R. Moes, Mariadelfina Molinaro, Paweł K. Kunicki, Klemens Budde, Satohiro Masuda, Maja Theresa Dieterlen, Tomoyuki Mizuno, Stein Bergan, Laure Elens, Anders Åsberg, Olga Millán, Florian Lemaitre, Burkhard Tönshoff, Maria Shipkova, Jesse J. Swen, Teun van Gelder, Tomasz Pawinski, Vincent Haufroid, Ofelia Noceti, Tom C. Zwart, Pierre Marquet, Smita Pattanaik, Jean-Baptiste Woillard, Loralie J. Langman, Markus J. Barten, Dennis A. Hesselink, Ron H.N. van Schaik, Michael Oellerich, Christoph Seger, Linda Salzmann, Kamisha L. Johnson-Davis, Raman Venkataramanan, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, University of Oslo (UiO), University of Barcelona, Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Utah, Medical University of Warsaw - Poland, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Fondazione IRCCS Policlinico San Matteo [Pavia], Università di Pavia, Leiden University Medical Center (LUMC), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), University Heart Center [Hamburg], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University Hospital Leipzig, Louvain Drug Research Institute [Bruxelles, Belgique] (LDRI), Université Catholique de Louvain = Catholic University of Louvain (UCL), Cliniques Universitaires Saint-Luc [Bruxelles], International University of Health and Welfare (IUHW), University of Cincinnati (UC), University Medical Center Göttingen (UMG), Heidelberg University Hospital [Heidelberg], Cliniques universitaires St Luc [Bruxelles], Mayo Clinic [Jacksonville], Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Università degli Studi di Pavia = University of Pavia (UNIPV), Universiteit Leiden, and Chard-Hutchinson, Xavier
Subjects: Graft Rejection, medicine.medical_specialty, Consensus, [SDV]Life Sciences [q-bio], 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, limited sampling strategy, Medicine, Humans, Pharmacology (medical), Dosing, Adverse effect, Intensive care medicine, pharmacogenetics, Pharmacology, medicine.diagnostic_test, business.industry, Area under the curve, mycophenolate mofetil, personalized, biomarkers, Evidence-based medicine, Organ Transplantation, Bayesian estimation, Pharmacometrics, 3. Good health, Discontinuation, [SDV] Life Sciences [q-bio], population PK, Therapeutic drug monitoring, Area Under Curve, Drug Monitoring, business, pharmacokinetics, Pharmacogenetics, Immunosuppressive Agents, mycophenolic acid
Abstract: When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved
Published: 2021

30. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author: Samuel Kuperman, Leila Karhunen, Geòrgia Escaramís, Sébastien Guillaume, Kelly L. Klump, David C. Whiteman, Colin A. Hodgkinson, Stephanie H. Witt, Artemis Tsitsika, Hana Papezova, Renato Polimanti, P. Eline Slagboom, Peter Zill, Jakob Grove, Toni-Kim Clarke, Michael Soyka, Jennifer Jordan, Steven Gallinger, Philip Gorwood, Preben Bo Mortensen, Yuri Milaneschi, Ingrid Meulenbelt, Jen Chyong Wang, Markus M. Nöthen, Katrin Männik, Henry R. Kranzler, Michael M. Vanyukov, Anna Keski-Rahkonen, William G. Iacono, Raymond K. Walters, Stephanie Le Hellard, Bochao Danae Lin, Vesna Boraska Perica, Marion Roberts, Patrick F. Sullivan, Steven Crawford, Mark A. Frye, Melissa A. Munn-Chernoff, Hakon Hakonarson, Andreas Birgegård, Robert Culverhouse, Alexis C. Edwards, Jerome C. Foo, Alessandro Rotondo, Brenda W.J.H. Penninx, Laura M. Hack, Michael T. Lynskey, Mario Maj, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Julie K. O'Toole, Marta Tyszkiewicz-Nwafor, Matt McGue, Julien Bryois, Martina de Zwaan, Norbert Dahmen, Stefanie Heilmann-Heimbach, Deborah Kaminská, Benedetta Nacmias, Nicholas G. Martin, Anna R. Docherty, Christopher Hübel, Nancy L. Pedersen, Janet Treasure, William E. Copeland, Roger A.H. Adan, Jaakko Kaprio, Aarno Palotie, L. John Horwood, Maria La Via, Philippe Courtet, Virpi M. Leppä, Judy L. Silberg, Jason D. Boardman, Fazil Aliev, Wade H. Berrettini, Doo Sup Choi, Youl-Ri Kim, Konstantinos Hatzikotoulas, Harriet de Wit, Sandra A. Brown, Elisabeth Widen, Caroline Hayward, Nicholas J. Schork, Penelope A. Lind, Ralph E. Tarter, Jana Strohmaier, Allan S. Kaplan, Richard A. Grucza, Bradley T. Webb, Angela Favaro, Dalila Pinto, Helena Gaspar, Andrew W. Bergen, Beate Herpertz-Dahlmann, Robert Levitan, Wolfgang Gäbel, Xavier Estivill, Emma C. Johnson, Konstantinos Tziouvas, Lindsay A. Farrer, Lenka Foretova, Marc A. Schuckit, Joanna M. Biernacka, André Scherag, Robbee Wedow, Abraham A. Palmer, Amy E. Adkins, Franziska Degenhardt, Louisa Degenhardt, Jurjen J. Luykx, Marius Lahti-Pulkkinen, Brien P. Riley, Monika Ridinger, Matteo Cassina, Harry Brandt, Yiran Guo, Stephan Ripke, Palmiero Monteleone, Katri Räikkönen, Jonathan R. I. Coleman, Martin A. Kennedy, Stephen W. Scherer, Ioanna Tachmazidou, Catherine M. Olsen, Bernice Porjesz, Esther Walton, Yi-Ling Chou, Nicolas Ramoz, Tetsuya Ando, Andres Metspalu, Bertram Müller-Myhsok, Brion S. Maher, Sarah Bertelsen, Melanie L. Schwandt, Janiece E. DeSocio, Margaret Keyes, John F. Pearson, Dongbing Lai, Paul Lichtenstein, James MacKillop, George Dedoussis, Jari Lahti, Ulrike Schmidt, Stefan Ehrlich, Amanda G. Wills, Teemu Palviainen, David Goldman, Elena Tenconi, Dimitris Dikeos, Scott I. Vrieze, Sietske G. Helder, Katharina Buehren, Hongyu Zhao, Sara McDevitt, Jolanta Lissowska, Joseph M. Boden, Li-Shiun Chen, Susanne Lucae, Sara Marsal, Dan Rujescu, Claes Norring, Howard J. Edenberg, Victor M. Karpyak, Fragiskos Gonidakis, Per Hoffmann, Christopher S. Franklin, Karin Egberts, Johanna Giuranna, Stefan Herms, Leah Wetherill, Stephanie Zerwas, Anthony Batzler, Elliot C. Nelson, Jouke-Jan Hottenga, Marcella Rietschel, Ioanna Ntalla, Victor Hesselbrock, Sarah M. Hartz, Marie Navratilova, Falk Kiefer, Martien J H Kas, Richard J. Rose, Andrew C. Heath, Jin P. Szatkiewicz, Lenka Slachtova, Lisa Lilenfeld, Katherine A. Halmi, John P. Rice, Anjali K. Henders, Christian Dina, Norbert Wodarz, Satu Männistö, Hamdi Mbarek, Shuyang Yao, Vladimir Janout, Alison Goate, Bettina Konte, Alexandra Schosser, Danfeng Chen, Kirsty Kiezebrink, Euijung Ryu, Dana B. Hancock, James Mitchell, Sarah E. Medland, Ina Giegling, Valdo Ricca, Scott D. Gordon, Gabrielle Koller, Samuli Ripatti, Laura M. Thornton, Alison D. Murray, Morten Mattingsdal, Zeynep Yilmaz, Jens Treutlein, Kathleen K. Bucholz, Tim B. Bigdeli, Eric F. van Furth, Hermine H. Maes, Ken B. Hanscombe, Sandra Sanchez-Roige, Daniela Degortes, Monica Forzan, Manuel Mattheisen, Richard Sherva, Scott J. Crow, Mikael Landén, Wolfgang Herzog, Jeanette N. McClintick, Tõnu Esko, Louis Fox, Wolfgang Maier, Liselotte Petersen, Laura J. Bierut, Roseann E. Peterson, Gursharan Kalsi, Kathleen Mullan Harris, Margarita C T Slof-Op 't Landt, Tamara L. Wall, Patrik K. E. Magnusson, Unna N. Danner, Stephan Zipfel, Ulrich W. Preuss, Elisa Docampo, D. Blake Woodside, Alfonso Tortorella, Benjamin W. Domingue, Franziska Ritschel, Johan G. Eriksson, Anu Raevuori, Benjamin M. Neale, Marcus Ising, Annemarie A. van Elburg, Filip Rybakowski, Maureen Reynolds, Tracey D. Wade, Manfred M. Fichter, Monica Gratacos Mayora, Claudette Boni, Andreas J. Forstner, John Whitfield, Silviu Alin Bacanu, Matthew B. McQueen, Andrew M. McIntosh, Norbert Scherbaum, Tatiana Foroud, Gun Peggy Knudsen, Sven Cichon, Christian J. Hopfer, Josef Frank, Eleftheria Zeggini, Federica Tozzi, Nadia Micali, Danielle M. Dick, Pamela A. F. Madden, Christian R. Marshall, Johannes Hebebrand, Fernando Fernández-Aranda, Roel A. Ophoff, Roland Burghardt, Nathaniel Thomas, Leonid Padyukov, Nancy L. Saccone, Anu Loukola, Fabian Streit, James L. Kennedy, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Pei Hong Shen, Anne Farmer, Roger D. Cone, Ilka Boehm, Jacquelyn L. Meyers, Paolo Santonastaso, Maurizio Clementi, Susana Jiménez-Murcia, Gudrun Wagner, Anke Hinney, Richard Parker, James I. Hudson, Nathan A. Gillespie, Michael Strober, John I. Nurnberger, Sandro Sorbi, Dorret I. Boomsma, Beata Świątkowska, Janne Tidselbak Larsen, Kenneth S. Kendler, Hidetoshi Inoko, Jessica E. Salvatore, Hunna J. Watson, Jochen Seitz, Jacques Pantel, Karl Mann, Hang Zhou, Antonio Julià, Oliver S. P. Davis, Nancy Diazgranados, Krista Fischer, John K. Hewitt, Karen S. Mitchell, Joanna Hauser, Eric O. Johnson, Craig Johnson, E. Jane Costello, Agnieszka Słopień, Dong Li, Laramie E. Duncan, Arpana Agrawal, Grant W. Montgomery, Manuel Föcker, Thomas Werge, Lannie Ligthart, Andreas Karwautz, Raquel Rabionet, Kenneth Krauter, Joel Gelernter, James J. Crowley, Cynthia M. Bulik, Paola Giusti-Rodríguez, Laura M. Huckins, Gerome Breen, Michael C. Stallings, Daniel E. Adkins, Pierre J. Magistretti, John Kramer, Lars Alfredsson, Hartmut Imgart, Annette M. Hartmann, Ole A. Andreassen, Monika Dmitrzak-Weglarz, Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], QIMR Berghofer Medical Research Institute, Karolinska Institutet [Stockholm], University Children's Hospital of Essen [Essen, Germany], University of Duisburg-Essen, Aarhus University [Aarhus], Stockholm County Council, University of Würzburg, Guy's Hospital [London], University Medical Center [Utrecht], University of Gothenburg (GU), Altrecht Center for Eating Disorders Rintveld [Zeist, The Netherlands] (Mental Health Institute), National Institute of Mental Health [Tokyo, Japan] (NIMH), National Center of Neurology and Psychiatry [Tokyo, Japan], University of Oslo (UiO), Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Perelman School of Medicine, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Split, The Wellcome Trust Sanger Institute [Cambridge], RWTH Aachen University, Universitätsklinikum Frankfurt, Universita degli Studi di Padova, University Hospital Basel [Basel], Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota System, University of Bristol [Bristol], Hannover Medical School [Hannover] (MHH), Harokopio University of Athens, Seattle University [Seattle], Virginia Commonwealth University (VCU), University of Athens Medical School [Athens], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Poznan University of Medical Sciences [Poland] (PUMS), Institute of Environmental Science and Technology [Barcelona] (ICTA), Universitat Autònoma de Barcelona (UAB), Massachusetts General Hospital [Boston], Stanford University, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Estonian Genome and Medicine, University of Tartu, Universitat Pompeu Fabra [Barcelona] (UPF), MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Ludwig-Maximilians-Universität München (LMU), Infectious diseases division, Department of internal medicine, University of Münster, Masaryk Memorial Cancer Institute, Masaryk Memorial Cancer Institute (RECAMO), Universitätsklinikum Bonn (UKB), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Medstar Research Institute, Universität Duisburg-Essen [Essen], National and Kapodistrian University of Athens (NKUA), Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Psychiatric Genetic Unit, Poznan University of Medical Sciences, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Heidelberg University Hospital [Heidelberg], Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Parkland-Klinik [Bad Wildungen-Reinhardshausen, Germany], Tokai University, Department of Epidemiology and Public Health [university of Ostrava], Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava-Ostravská univerzita / University of Ostrava, Vall d'Hebron University Hospital [Barcelona], Charles University [Prague] (CU), University of Eastern Finland, Medizinische Universität Wien = Medical University of Vienna, Centre de toxicomanie et de santé mentale [Toronto, ON, Canada], University of Helsinki, University of Aberdeen, Faculty of Science, J.E. Purkinje University, J. E. Purkinje University, Michigan State University System, Norwegian Institute of Public Health [Oslo] (NIPH), Haukeland University Hospital, University of Bergen (UiB), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Chicago School of Professional Psychology [Washington, District of Columbia, USA] (Washington DC Campus), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Psychiatry, University of Napoli, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University College Cork (UCC), Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, VA Boston Healthcare System, Università degli studi della Campania 'Luigi Vanvitelli', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kartini Clinic [Portland, Oregon, USA], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Vanderbilt University School of Medicine [Nashville], The Hospital for sick children [Toronto] (SickKids), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Epidemiology and Biostatistics (MEB), University of Pisa - Università di Pisa, Division of Psychiatric Genomics, Institute of Medical Informatics, Biometry and Epidemiology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Leiden University Medical Center (LUMC), Center for Eating Disorders Ursula [Leiden, The Netherlands] (Rivierduinen), Medical University of Łódź (MUL), The Jackson Laboratory [Bar Harbor] (JAX), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Human Genetics, Internal Medicine [Tuebingen, Germany], Tuebingen University [Germany], Oregon Research Institute (ORI), University of Otago [Dunedin, Nouvelle-Zélande], The Center for Eating Disorders at Sheppard Pratt [Baltimore, MD, USA], Weill Medical College of Cornell University [New York], Eating Recovery Center [Denver, CO, USA], Centre for Addiction and Mental Health [Toronto, ON, Canada], University of California [San Diego] (UC San Diego), University of California, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Institute of Medical Science [Toronto], University of Toronto, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Genomics, Yale University School of Medicine, Indiana University School of Medicine, Indiana University System, Mayo Clinic [Rochester], Mayo Clinic, SUNY Downstate Medical Center, State University of New York (SUNY), University of Edinburgh, Department of Genomics, Life and Brain Center, University of Bonn, University of Utah School of Medicine [Salt Lake City], University of Heidelberg, Medical Faculty, Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], National Institutes of Health [Bethesda] (NIH), National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA] (NIAAA), Martin-Luther-University Halle-Wittenberg, Helsinki Institute of Life Science (HiLIFE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Vrije Universiteit Amsterdam [Amsterdam] (VU), Mathematical Sciences Institute (MSI), Australian National University (ANU), University of Colorado [Boulder], VU University Medical Center [Amsterdam], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Universität Heidelberg [Heidelberg], Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Harvard University [Cambridge], University of Colorado Anschutz [Aurora], University of Vermont [Burlington], University of New South Wales [Sydney] (UNSW), University of Dusseldorf, Genetics and Pathology, Center for Human Genetic Research, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Heidelberg University, University of Iowa [Iowa City], Vienna University of Technology (TU Wien), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Indiana University System-Indiana University System, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Regensburg, Rush University Medical Center [Chicago], University of Utah, Duke University Medical Center, University of Illinois [Chicago] (UIC), University of Illinois System, Department of Medical and Molecular Genetics, Dpt of Neuroscience [New York], Laboratory of Neurogenetics, National Institutes of Health [Bethesda] (NIH)-National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, University of Connecticut (UCONN), University of Colorado [Denver], Research Triangle Institute International (RTI International), McMaster University [Hamilton, Ontario], CLinical Psychology, Department of Electrical and Computer Engineering [Montréal], McGill University = Université McGill [Montréal, Canada], Yale School of Public Health (YSPH), Analytic and Translational Genetics Unit, Flinders University [Adelaide, Australia], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Department of Public Health, Indiana University - Purdue University Indianapolis (IUPUI), National Institute of Mental Health (NIMH), University of Pennsylvania, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Università degli Studi di Padova = University of Padua (Unipd), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), King‘s College London-The Institute of Psychiatry, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Masaryk Memorial Cancer Institute (MMCI), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Medical Research Council-Cardiff University, Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California (UC), University of California (UC)-University of California (UC), Yale School of Medicine [New Haven, Connecticut] (YSM), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Martinez Rico, Clara, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Kas lab, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Munn-Chernoff, M. A., Johnson, E. C., Chou, Y. -L., Coleman, J. R. I., Thornton, L. M., Walters, R. K., Yilmaz, Z., Baker, J. H., Hubel, C., Gordon, S., Medland, S. E., Watson, H. J., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodriguez, P., Hanscombe, K. B., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Berrettini, W. H., Boehm, I., Boni, C., Boraska Perica, V., Buehren, K., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Cone, R. D., Courtet, P., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L. E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Fischer, K., Focker, M., Foretova, L., Forstner, A. J., Forzan, M., Franklin, C. S., Gallinger, S., Giegling, I., Giuranna, J., Gonidakis, F., Gorwood, P., Gratacos Mayora, M., Guillaume, S., Guo, Y., Hakonarson, H., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S. G., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Julia, A., Kalsi, G., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K. L., Knudsen, G. P. S., La Via, M. C., Le Hellard, S., Levitan, R. D., Li, D., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P. J., Maj, M., Mannik, K., Marsal, S., Marshall, C. R., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, K., Monteleone, A. M., Monteleone, P., Nacmias, B., Navratilova, M., Ntalla, I., O'Toole, J. K., Ophoff, R. A., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Swiatkowska, B., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Walton, E., Widen, E., Zeggini, E., Zerwas, S., Zipfel, S., Bergen, A. W., Boden, J. M., Brandt, H., Crawford, S., Halmi, K. A., Horwood, L. J., Johnson, C., Kaplan, A. S., Kaye, W. H., Mitchell, J., Olsen, C. M., Pearson, J. F., Pedersen, N. L., Strober, M., Werge, T., Whiteman, D. C., Woodside, D. B., Grove, J., Henders, A. K., Larsen, J. T., Parker, R., Petersen, L. V., Jordan, J., Kennedy, M. A., Birgegard, A., Lichtenstein, P., Norring, C., Landen, M., Mortensen, P. B., Polimanti, R., Mcclintick, J. N., Adkins, A. E., Aliev, F., Bacanu, S. -A., Batzler, A., Bertelsen, S., Biernacka, J. M., Bigdeli, T. B., Chen, L. -S., Clarke, T. -K., Degenhardt, F., Docherty, A. R., Edwards, A. C., Foo, J. C., Fox, L., Frank, J., Hack, L. M., Hartmann, A. M., Hartz, S. M., Heilmann-Heimbach, S., Hodgkinson, C., Hoffmann, P., Hottenga, J. -J., Konte, B., Lahti, J., Lahti-Pulkkinen, M., Lai, D., Ligthart, L., Loukola, A., Maher, B. S., Mbarek, H., Mcintosh, A. M., Mcqueen, M. B., Meyers, J. L., Milaneschi, Y., Palviainen, T., Peterson, R. E., Ryu, E., Saccone, N. L., Salvatore, J. E., Sanchez-Roige, S., Schwandt, M., Sherva, R., Streit, F., Strohmaier, J., Thomas, N., Wang, J. -C., Webb, B. T., Wedow, R., Wetherill, L., Wills, A. G., Zhou, H., Boardman, J. D., Chen, D., Choi, D. -S., Copeland, W. E., Culverhouse, R. C., Dahmen, N., Degenhardt, L., Domingue, B. W., Frye, M. A., Gaebel, W., Hayward, C., Ising, M., Keyes, M., Kiefer, F., Koller, G., Kramer, J., Kuperman, S., Lucae, S., Lynskey, M. T., Maier, W., Mann, K., Mannisto, S., Muller-Myhsok, B., Murray, A. D., Nurnberger, J. I., Preuss, U., Raikkonen, K., Reynolds, M. D., Ridinger, M., Scherbaum, N., Schuckit, M. A., Soyka, M., Treutlein, J., Witt, S. H., Wodarz, N., Zill, P., Adkins, D. E., Boomsma, D. I., Bierut, L. J., Brown, S. A., Bucholz, K. K., Costello, E. J., de Wit, H., Diazgranados, N., Eriksson, J. G., Farrer, L. A., Foroud, T. M., Gillespie, N. A., Goate, A. M., Goldman, D., Grucza, R. A., Hancock, D. B., Harris, K. M., Hesselbrock, V., Hewitt, J. K., Hopfer, C. J., Iacono, W. G., Johnson, E. O., Karpyak, V. M., Kendler, K. S., Kranzler, H. R., Krauter, K., Lind, P. A., Mcgue, M., Mackillop, J., Madden, P. A. F., Maes, H. H., Magnusson, P. K. E., Nelson, E. C., Nothen, M. M., Palmer, A. A., Penninx, B. W. J. H., Porjesz, B., Rice, J. P., Rietschel, M., Riley, B. P., Rose, R. J., Shen, P. -H., Silberg, J., Stallings, M. C., Tarter, R. E., Vanyukov, M. M., Vrieze, S., Wall, T. L., Whitfield, J. B., Zhao, H., Neale, B. M., Wade, T. D., Heath, A. C., Montgomery, G. W., Martin, N. G., Sullivan, P. F., Kaprio, J., Breen, G., Gelernter, J., Edenberg, H. J., Bulik, C. M., and Agrawal, A.
Subjects: Netherlands Twin Register (NTR), Alcoholism/genetics, Schizophrenia/genetics, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Medicine (miscellaneous), Genome-wide association study, Alcohol use disorder, Anorexia nervosa, Linkage Disequilibrium, ddc:616.89, [SCCO]Cognitive science, 0302 clinical medicine, Risk Factors, Tobacco Use Disorder/genetics, Substance-Related Disorders/genetics, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Factors de risc en les malalties, Bulimia nervosa, Feeding and Eating Disorders/genetics, eating disorders, genetic correlation, substance use, Tobacco Use Disorder, 3. Good health, Fenotip, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Alcoholism, Eating disorders, Phenotype, Schizophrenia, Drinking of alcoholic beverages, eating disorder, Consum d'alcohol, Major depressive disorder, medicine.symptom, Depressive Disorder, Major/genetics, eating disorders, genetic correlation, substance use, Clinical psychology, Substance abuse, Risk factors in diseases, Substance-Related Disorders, Polymorphism, Single Nucleotide, Article, Feeding and Eating Disorders, 03 medical and health sciences, SDG 3 - Good Health and Well-being, mental disorders, Genetics, medicine, Humans, Trastorns de la conducta alimentària, 030304 developmental biology, Genetic association, Pharmacology, Depressive Disorder, Major, Binge eating, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, [SCCO] Cognitive science, medicine.disease, Comorbidity, Twin study, 030227 psychiatry, Abús de substàncies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, Genètica, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract: Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs
Published: 2021

31. Cervical Artery Dissection and Sports

Author: Stefan T. Engelter, Christopher Traenka, Caspar Grond-Ginsbach, Tobias Brandt, Maani Hakimi, Bradford B. Worrall, Stephanie Debette, Alessandro Pezzini, Didier Leys, Turgut Tatlisumak, Christian H. Nolte, Philippe Lyrer, University of Basel (Unibas), Felix Splatter Hospital [Bâle], Heidelberg University Hospital [Heidelberg], Schweizerische Unfallversicherungsanstalt, Luzerner Kantonsspital [Lucerne, Switzerland], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Virginia, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Gothenburg (GU), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Admin, Oskar, and University of Virginia [Charlottesville]
Subjects: medicine.medical_specialty, Cervical Artery, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Vertebral artery dissection, Context (language use), 030204 cardiovascular system & hematology, Cervical artery dissection, Carotid artery dissection, 03 medical and health sciences, 0302 clinical medicine, medicine, Neurological sequela, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Intensive care medicine, RC346-429, Sport, Aortic dissection, business.industry, physical acitivity, Physical activity, medicine.disease, 3. Good health, Clinical Practice, Dissection, Neurology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Perspective, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Neurology. Diseases of the nervous system, business, human activities, 030217 neurology & neurosurgery
Abstract: International audience; Cervical artery dissection (CeAD) occurring in the context of sports is a matter of concern for CeAD patients. They seek advice on the role of sports in CeAD and on the safety of resuming sports after CeAD. The scarcity of studies and guidelines addressing these issues poses a challenge. We aimed at summarizing the current knowledge about CeAD and sports in order to provide an informed, comprehensive opinion for counseling CeAD patients. We took into account pathophysiological considerations, observations of cases reports, series, and registries, and conclusions by analogy from aortic dissection or inherited connective tissue syndromes. In summary, practicing active sports as the cause of CeAD seems uncommon. It seems recommendable to refrain from any kind of sports activities for at least 1 month, which can be extended in case of an unfavorable clinical or neurovascular course. We recommend starting with sport activities at low intensity-preferably with types of endurance sports-and to gradually increase the pace in an individually tailored manner, taking into circumstances of the occurrences of the CeAD in the individual patient (particularly in relation to sports), the meaning of sports activities for the individual well-being, the presence or absence of comorbidities and of neurological sequela, neurovascular findings, and whether there are signs of an underlying connective tissue alteration. Major limitations and several forms of bias are acknowledged. Still, in the absence of any better data, the summarized observations and considerations might help clinicians in advising and counseling patients with CeAD in clinical practice.
Published: 2021

32. Bayesian Inference Associates Rare KDR Variants with Specific Phenotypes in Pulmonary Arterial Hypertension

Author: Emilia M. Swietlik, Daniel Greene, Na Zhu, Karyn Megy, Marcella Cogliano, Smitha Rajaram, Divya Pandya, Tobias Tilly, Katie A. Lutz, Carrie C.L. Welch, Michael W. Pauciulo, Laura Southgate, Jennifer M. Martin, Carmen M. Treacy, Christopher J. Penkett, Jonathan C. Stephens, Harm J. Bogaard, Colin Church, Gerry Coghlan, Anna W. Coleman, Robin Condliffe, Christina A. Eichstaedt, Mélanie Eyries, Henning Gall, Stefano Ghio, Barbara Girerd, Ekkehard Grünig, Simon Holden, Luke Howard, Marc Humbert, David G. Kiely, Gabor Kovacs, Jim Lordan, Rajiv D. Machado, Robert V. MacKenzie Ross, Colm McCabe, Shahin Moledina, David Montani, Horst Olschewski, Joanna Pepke-Zaba, Laura Price, Christopher J. Rhodes, Werner Seeger, Florent Soubrier, Jay Suntharalingam, Mark R. Toshner, Anton Vonk Noordegraaf, John Wharton, James M. Wild, Stephen John Wort, Allan Lawrie, Martin R. Wilkins, Richard C. Trembath, Yufeng Shen, Wendy K. Chung, Andrew J. Swift, William C. Nichols, Nicholas W. Morrell, Stefan Gräf, Stephen Abbs, Lara Abulhoul, Julian Adlard, Munaza Ahmed, Timothy J. Aitman, Hana Alachkar, David J. Allsup, Philip Ancliff, Richard Antrobus, Ruth Armstrong, Gavin Arno, Sofie Ashford, William J. Astle, Anthony Attwood, Paul Aurora, Christian Babbs, Chiara Bacchelli, Tamam Bakchoul, Siddharth Banka, Tadbir Bariana, Julian Barwell, Joana Batista, Helen E. Baxendale, Phil L. Beales, David L. Bennett, Agnieszka Bierzynska, Tina Biss, Maria A.K. Bitner-Glindzicz, Graeme C. Black, Marta Bleda, Iulia Blesneac, Detlef Bockenhauer, Sara Boyce, John R. Bradley, Gerome Breen, Paul Brennan, Carole Brewer, Matthew Brown, Andrew C. Browning, Michael J. Browning, Rachel J. Buchan, Matthew S. Buckland, Teofila Bueser, Carmen Bugarin Diz, John Burn, Siobhan O. Burns, Oliver S. Burren, Nigel Burrows, Carolyn Campbell, Gerald Carr-White, Keren Carss, Ruth Casey, Mark J. Caulfield, Jenny Chambers, John Chambers, Melanie M.Y. Chan, Floria Cheng, Patrick F. Chinnery, Manali Chitre, Martin T. Christian, Jill Clayton-Smith, Maureen Cleary, Naomi Clements Brod, Elizabeth Colby, Trevor R.P. Cole, Janine Collins, Peter W. Collins, Cecilia J. Compton, H. Terence Cook, Stuart Cook, Nichola Cooper, Paul A. Corris, Nicola S. Curry, Matthew J. Daniels, Mehul Dattani, Louise C. Daugherty, John Davis, Anthony De Soyza, Sri V.V. Deevi, Timothy Dent, Charu Deshpande, Eleanor F. Dewhurst, Peter H. Dixon, Sofia Douzgou, Kate Downes, Anna M. Drazyk, Elizabeth Drewe, Daniel Duarte, Tina Dutt, J. David M. Edgar, Karen Edwards, William Egner, Melanie N. Ekani, Perry Elliott, Wendy N. Erber, Marie Erwood, Maria C. Estiu, Dafydd Gareth Evans, Gillian Evans, Tamara Everington, Hiva Fassihi, Remi Favier, Debra Fletcher, Frances A. Flinter, R. Andres Floto, Tom Fowler, James Fox, Amy J. Frary, Courtney E. French, Kathleen Freson, Mattia Frontini, Abigail Furnell, Daniel P. Gale, Vijeya Ganesan, Michael Gattens, Hossein-Ardeschir Ghofrani, J. Simon R. Gibbs, Kate Gibson, Kimberly C. Gilmour, Nicholas S. Gleadall, Sarah Goddard, Keith Gomez, Pavels Gordins, David Gosal, Jodie Graham, Luigi Grassi, Lynn Greenhalgh, Andreas Greinacher, Paolo Gresele, Philip Griffiths, Sofia Grigoriadou, Detelina Grozeva, Mark Gurnell, Scott Hackett, Charaka Hadinnapola, Rosie Hague, William M. Hague, Matthias Haimel, Matthew Hall, Helen L. Hanson, Eshika Haque, Kirsty Harkness, Andrew R. Harper, Claire L. Harris, Daniel Hart, Ahamad Hassan, Grant Hayman, Alex Henderson, Archana Herwadkar, Jonathan Hoffman, Rita Horvath, Henry Houlden, Arjan C. Houweling, Fengyuan Hu, Gavin Hudson, Aarnoud P. Huissoon, Matthew Hurles, Melita Irving, Louise Izatt, Roger James, Sally A. Johnson, Stephen Jolles, Jennifer Jolley, Dragana Josifova, Neringa Jurkute, Mary A. Kasanicki, Hanadi Kazkaz, Rashid Kazmi, Peter Kelleher, Anne M Kelly, Wilf Kelsall, Carly Kempster, Nathalie Kingston, Nils Koelling, Myrto Kostadima, Ania Koziell, Roman Kreuzhuber, Taco W. Kuijpers, Ajith Kumar, Dinakantha Kumararatne, Manju A. Kurian, Michael A. Laffan, Fiona Lalloo, Michele Lambert, Hana Lango Allen, D. Mark Layton, Claire Lentaigne, Tracy Lester, Adam P. Levine, Rachel Linger, Hilary Longhurst, Lorena E. Lorenzo, Eleni Louka, Paul A. Lyons, Bella Madan, Eamonn R. Maher, Jesmeen Maimaris, Samantha Malka, Sarah Mangles, Rutendo Mapeta, Kevin J. Marchbank, Stephen Marks, Hugh S. Markus, Hanns-Ulrich Marschall, Andrew Marshall, Mary Mathias, Emma Matthews, Heather Maxwell, Paul McAlinden, Mark I. McCarthy, Harriet McKinney, Stuart Meacham, Adam J. Mead, Sarju G. Mehta, Michel Michaelides, Carolyn Millar, Shehla N. Mohammed, Anthony T. Moore, Monika Mozere, Keith W. Muir, Andrew D. Mumford, Andrea H. Nemeth, William G. Newman, Michael Newnham, Sadia Noorani, Paquita Nurden, Jennifer O’Sullivan, Samya Obaji, Chris Odhams, Steven Okoli, Andrea Olschewski, Kai Ren Ong, S. Helen Oram, Elizabeth Ormondroyd, Willem H. Ouwehand, Claire Palles, Sofia Papadia, Soo-Mi Park, David Parry, Smita Patel, Joan Paterson, Andrew Peacock, Simon H. Pearce, Kathelijne Peerlinck, Romina Petersen, Clarissa Pilkington, Kenneth E.S. Poole, Bethan Psaila, Angela Pyle, Richard Quinton, Shamima Rahman, Anupama Rao, F. Lucy Raymond, Paula J. Rayner-Matthews, Augusto Rendon, Tara Renton, Andrew S.C. Rice, Alex Richter, Leema Robert, Irene Roberts, Sarah J. Rose, Robert Ross-Russell, Catherine Roughley, Noemi B.A. Roy, Deborah M. Ruddy, Omid Sadeghi-Alavijeh, Moin A. Saleem, Nilesh Samani, Crina Samarghitean, Alba Sanchis-Juan, Ravishankar B. Sargur, Robert N. Sarkany, Simon Satchell, Sinisa Savic, Genevieve Sayer, John A. Sayer, Laura Scelsi, Andrew M. Schaefer, Sol Schulman, Richard Scott, Marie Scully, Claire Searle, Arjune Sen, W.A. Carrock Sewell, Denis Seyres, Neil Shah, Olga Shamardina, Susan E. Shapiro, Adam C. Shaw, Keith Sibson, Lucy Side, Ilenia Simeoni, Michael A. Simpson, Matthew C. Sims, Suthesh Sivapalaratnam, Damian Smedley, Katherine R. Smith, Kenneth G.C. Smith, Katie Snape, Nicole Soranzo, Olivera Spasic-Boskovic, Simon Staines, Emily Staples, Hannah Stark, Kathleen E. Stirrups, Alex Stuckey, Petros Syrris, R. Campbell Tait, Kate Talks, Rhea Y.Y. Tan, Jenny C. Taylor, John M. Taylor, James E. Thaventhiran, Andreas C. Themistocleous, David Thomas, Ellen Thomas, Moira J. Thomas, Patrick Thomas, Kate Thomson, Adrian J. Thrasher, Chantal Thys, Marc Tischkowitz, Catherine Titterton, Cheng-Hock Toh, Ian P. Tomlinson, Matthew Traylor, Paul Treadaway, Salih Tuna, Ernest Turro, Philip Twiss, Tom Vale, Chris Van Geet, Natalie van Zuydam, Anthony M Vandersteen, Marta Vazquez-Lopez, Julie von Ziegenweidt, Annette Wagner, Quinten Waisfisz, Neil Walker, Suellen M. Walker, James S. Ware, Hugh Watkins, Christopher Watt, Andrew R. Webster, Lucy Wedderburn, Wei Wei, Steven B. Welch, Julie Wessels, Sarah K. Westbury, John-Paul Westwood, Deborah Whitehorn, James Whitworth, Andrew O.M. Wilkie, Catherine Williamson, Brian T. Wilson, Edwin K.S. Wong, Nicholas Wood, Yvette Wood, Christopher Geoffrey Woods, Emma R. Woodward, Austen Worth, Michael Wright, Katherine Yates, Patrick F.K. Yong, Timothy Young, Ping Yu, Patrick Yu-Wai-Man, Eliska Zlamalova, Russel Hirsch, R. James White, Marc Simon, David Badesch, Erika Rosenzweig, Charles Burger, Murali Chakinala, Thenappan Thenappan, Greg Elliott, Robert Simms, Harrison Farber, Robert Frantz, Jean Elwing, Nicholas Hill, Dunbar Ivy, James Klinger, Steven Nathan, Ronald Oudiz, Ivan Robbins, Robert Schilz, Terry Fortin, Jeffrey Wilt, Delphine Yung, Eric Austin, Ferhaan Ahmad, Nitin Bhatt, Tim Lahm, Adaani Frost, Zeenat Safdar, Zia Rehman, Robert Walter, Fernando Torres, Sahil Bakshi, Stephen Archer, Rahul Argula, Christopher Barnett, Raymond Benza, Ankit Desai, Veeranna Maddipati, University of Cambridge [UK] (CAM), Columbia University [New York], University of Sheffield [Sheffield], University of Cincinnati (UC), St George's, University of London, Vrije Universiteit Amsterdam [Amsterdam] (VU), Golden Jubilee National Hospital, Glasgow, Royal Free Hospital [London, UK], Heidelberg University Hospital [Heidelberg], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Technische Hochschule Mittelhessen - University of Applied Sciences [Giessen] (THM), Fondazione IRCCS Policlinico San Matteo, Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Universität Heidelberg [Heidelberg], Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Imperial College London, Royal Hallamshire Hospital, University of Graz, Freeman Hospital, Royal United Hospitals Bath (RUH), Great Ormond Street Hospital for Children [London] (GOSH), Royal Papworth Hospital, Cambridge Biomedical Campus, Cambridge, United Kingdom., King‘s College London, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Karl-Franzens-Universität [Graz, Autriche], Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Swietlik, Emilia [0000-0002-4095-8489], Megy, Karyn [0000-0002-2826-3879], Tilly, Tobias [0000-0002-6762-5342], Stephens, Jonathan [0000-0003-2020-9330], Toshner, Mark [0000-0002-3969-6143], Morrell, Nicholas [0000-0001-5700-9792], Graf, Stefan [0000-0002-1315-8873], Apollo - University of Cambridge Repository, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Karl-Franzens-Universität Graz, HAL-SU, Gestionnaire, British Heart Foundation, and The Academy of Medical Sciences
Subjects: 0301 basic medicine, Candidate gene, Cardiac & Cardiovascular Systems, genetic association studies, 030204 cardiovascular system & hematology, Biology, Bayesian inference, 03 medical and health sciences, 0302 clinical medicine, Missing heritability problem, pulmonary hypertension, medicine, Family history, Gene, Genetics & Heredity, Genetics, family history, Science & Technology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Kinase insert domain receptor, computed tomography, General Medicine, Original Articles, medicine.disease, Pulmonary hypertension, Phenotype, 3. Good health, 030104 developmental biology, Cardiovascular System & Cardiology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Life Sciences & Biomedicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, vascular endothelial growth factor receptor
Abstract: Supplemental Digital Content is available in the text., Background: Approximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH, we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics. Methods: We analyzed 13 037 participants enrolled in the NBR study (NIHR BioResource—Rare Diseases), of which 1148 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension, we used the Bayesian rare variant association method BeviMed. Results: Heterozygous, high impact, likely loss-of-function variants in the kinase insert domain receptor (KDR) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (posterior probability=0.989) and older age at diagnosis (posterior probability=0.912). We also provide evidence for familial segregation of a rare nonsense KDR variant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the 5 patients harboring these predicted deleterious variants in KDR. Four additional PAH cases with rare likely loss-of-function variants in KDR were independently identified in the US PAH Biobank cohort with similar phenotypic characteristics. Conclusions: The Bayesian inference approach allowed us to independently validate KDR, which encodes for the VEGFR2 (vascular endothelial growth factor receptor 2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence for KDR being a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.
Published: 2020

33. Trends in prevalence of blindness and distance and nearvision impairment over 30 years: an analysis for the GlobalBurden of Disease Study

Author: Bourne, Rupert, Steinmetz, Jaimie, Flaxman, Seth, Briant, Paul Svitil, Taylor, Hugh, Resnikoff, Serge, Casson, Robert James, Abdoli, Amir, Abu-Gharbieh, Eman, Afshin, Ashkan, Ahmadieh, Hamid, Akalu, Yonas, Alamneh, Alehegn Aderaw, Alemayehu, Wondu, Alfaar, Ahmed Samir, Alipour, Vahid, Anbesu, Etsay Woldu, Androudi, Sofia, Arabloo, Jalal, Arditi, Aries, Asaad, Malke, Bagli, Eleni, Baig, Atif Amin, Bärnighausen, Till Winfried, Battaglia Parodi, Maurizio, Bhagavathula, Akshaya Srikanth, Bhardwaj, Nikha, Bhardwaj, Pankaj, Bhattacharyya, Krittika, Bijani, Ali, Bikbov, Mukharram, Bottone, Michele, Braithwaite, Tasanee, Bron, Alain, Butt, Zahid, Cheng, Ching-Yu, Chu, Dinh-Toi, Cicinelli, Maria Vittoria, Coelho, João, Dagnew, Baye, Dai, Xiaochen, Dana, Reza, Dandona, Lalit, Dandona, Rakhi, Del Monte, Monte, Deva, Jenny, Diaz, Daniel, Djalalinia, Shirin, Dreer, Laura, Ehrlich, Joshua, Ellwein, Leon, Emamian, Mohammad Hassan, Fernandes, Arthur, Fischer, Florian, Friedman, David, Furtado, João, Gaidhane, Abhay Motiramji, Gaidhane, Shilpa, Gazzard, Gus, Gebremichael, Berhe, George, Ronnie, Ghashghaee, Ahmad, Golechha, Mahaveer, Hamidi, Samer, Hammond, Billy Randall, Hartnett, Mary Elizabeth R, Hartono, Risky Kusuma, Hay, Simon, Heidari, Golnaz, Ho, Hung Chak, Hoang, Chi Linh, Househ, Mowafa, Ibitoye, Segun Emmanuel, Ilic, Irena, Ilic, Milena, Ingram, April, Irvani, Seyed Sina Naghibi, Jha, Ravi Prakash, Kahloun, Rim, Kandel, Himal, Kasa, Ayele Semachew, Kempen, John, Keramati, Maryam, Khairallah, Moncef, Khan, Ejaz Ahmad, Khanna, Rohit, Khatib, Mahalaqua Nazli, Kim, Judy, Kim, Yun Jin, Kisa, Sezer, Kisa, Adnan, Koyanagi, Ai, Kurmi, Om, Lansingh, Van Charles, Leasher, Janet, Leveziel, Nicolas, Limburg, Hans, Majdan, Marek, Manafi, Navid, Mansouri, Kaweh, McAlinden, Colm, Mohammadi, Seyed Farzad, Mohammadian-Hafshejani, Abdollah, Mohammadpourhodki, Reza, Mokdad, Ali, Moosavi, Delaram, Morse, Alan, Naderi, Mehdi, Naidoo, Kovin, Nangia, Vinay, Nguyen, Cuong Tat, Nguyen, Huong Lan Thi, Ogundimu, Kolawole, Olagunju, Andrew, Ostroff, Samuel, Panda-Jonas, Songhomitra, Pesudovs, Konrad, Peto, Tunde, Quazi Syed, Zahiruddin, Rahman, Mohammad Hifz Ur, Ramulu, Pradeep, Rawaf, Salman, Rawaf, David Laith, Reinig, Nickolas, Robin, Alan, Rossetti, Luca, Safi, Sare, Sahebkar, Amirhossein, Samy, Abdallah, Saxena, Deepak, Serle, Janet, Shaikh, Masood Ali, Shen, Tueng, Shibuya, Kenji, Shin, Jae Il, Silva, Juan Carlos, Silvester, Alexander, Singh, Jasvinder, Singhal, Deepika, Sitorus, Rita, Skiadaresi, Eirini, Skirbekk, Vegard, Soheili, Amin, Sousa, Raúl, Spurlock, Emma Elizabeth, Stambolian, Dwight, Taddele, Biruk Wogayehu, Tadesse, Eyayou Girma, Tahhan, Nina, Tareque, Md Ismail, Topouzis, Fotis, Tran, Bach Xuan, Travillian, Ravensara, Tsilimbaris, Miltiadis, Varma, Rohit, Virgili, Gianni, Wang, Ya Xing, Wang, Ningli, West, Sheila, Wong, Tien, Zaidi, Zoubida, Zewdie, Kaleab Alemayehu, Jonas, Jost, Vos, Theo, Holden, Funding, Anglia Ruskin University (ARU), University of Washington [Seattle], Imperial College London, University of Melbourne, School of Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia, University of Adelaide, Jahrom University of Medical Sciences, University of Sharjah (UoS), Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University, University of Gondar, Debre Markos University, The Fred Hollows Foundation, University of Leipzig Medical Center, Iran University of Medical Sciences, Samara University, University of Thessaly [Volos] (UTH), Visibility Metrics LLC, University of Texas, University Hospital of Ioannina, Sultan Zainal Abidin University, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Charles University [Prague] (CU), Government Medical College Pali, All India Institute of Medical Sciences [New Delhi], National Institute of Biomedical Genomics, Babol University of Medical Sciences, Ufa Eye Research Institute, London School of Hygiene and Tropical Medicine (LSHTM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), University of Waterloo [Waterloo], Singapore Eye Research Institute [Singapore] (SERI), Hanoi National University of Education (HNUE), IRCCS San Raffaele Scientific Institute [Milan, Italie], University of Porto - Departamento de Geociências, Ambiente e Ordenamento do Territórioo (UP - DGAOT), Harvard University [Cambridge], University of Michigan [Ann Arbor], University of Michigan System, Universiti Tunku Abdul Rahman (UTAR), National Autonomous University of Mexico (UNAM), Ministry of Health and Medical Education [Iran] (MOHME), University of Alabama at Birmingham [ Birmingham] (UAB), National Institutes of Health [Bethesda] (NIH), Shahroud University of Medical Sciences, Federal University of Sao Paulo (Unifesp), University of Applied Sciences Ravensburg-Weingarten, University of São Paulo (USP), Datta Meghe Institute of Medical Sciences, University College of London [London] (UCL), Haramaya University (HU), Sankara Nethralaya Medical Research Foundation, Indian Institute of Public Health Gandhinagar, Hamdan Bin Mohammed Smart University, University of Georgia [USA], University of Utah, Institution of Public Health Sciences, Independent Consultant, The Chinese University of Hong Kong [Hong Kong], Hamad Bin Khalifa University (HBKU), University of Ibadan, University of Belgrade [Belgrade], Faculty of Science of the University of Kragujevac, University of Kragujevac, Banaras Hindu University [Varanasi] (BHU), Ophtalmologistes Associe Monastir, The University of Sydney, Bahir Dar University (BDU), Harvard University, Mashhad University of Medical Sciences, Fattouma Bourguiba University Hospital, Health Services Academy, L V Prasad Eye Institute, Medical College of Wisconsin [Milwaukee] (MCW), Xiamen University, Oslo Metropolitan University (OsloMet), Kristiania University College = Høyskolen Kristiania, San Juan de Dios Sanitary Park, McMaster University [Hamilton, Ontario], HelpMeSee, Nova Southeastern University (NSU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Health Information Services, Trnava University, University of Manitoba [Winnipeg], Glaucoma Research Center, Singleton Hospital, Tehran University of Medical Sciences (TUMS), Shahrekord University of Medical Sciences, Institute for Health Metrics and Evaluation [University of Washington], Iran University of Medical Sciences [Tehran, Iran] (IUMS), Lighthouse Guild, Kermanshah University of Medical Sciences, University of KwaZulu-Natal (UKZN), Suraj Eye Institute, Duy Tan University, Sightsavers, Heidelberg University Hospital [Heidelberg], University of New South Wales [Sydney] (UNSW), Queen's University [Belfast] (QUB), Maharishi Markandeshwar University [Mullana] (MM(DU)), Johns Hopkins University (JHU), Public Health England [London], Brien Holden Vision Institute, Fondation Thea, Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg., Bourne, R. R. A., Steinmetz, J. D., Flaxman, S., Briant, P. S., Taylor, H. R., Resnikoff, S., Casson, R. J., Abdoli, A., Abu-Gharbieh, E., Afshin, A., Ahmadieh, H., Akalu, Y., Alamneh, A. A., Alemayehu, W., Alfaar, A. S., Alipour, V., Anbesu, E. W., Androudi, S., Arabloo, J., Arditi, A., Asaad, M., Bagli, E., Baig, A. A., Barnighausen, T. W., Battaglia Parodi, M., Bhagavathula, A. S., Bhardwaj, N., Bhardwaj, P., Bhattacharyya, K., Bijani, A., Bikbov, M., Bottone, M., Braithwaite, T., Bron, A. M., Butt, Z. A., Cheng, C. -Y., Chu, D. -T., Cicinelli, M. V., Coelho, J. M., Dagnew, B., Dai, X., Dana, R., Dandona, L., Dandona, R., Del Monte, M. A., Deva, J. P., Diaz, D., Djalalinia, S., Dreer, L. E., Ehrlich, J. R., Ellwein, L. B., Emamian, M. H., Fernandes, A. G., Fischer, F., Friedman, D. S., Furtado, J. M., Gaidhane, A. M., Gaidhane, S., Gazzard, G., Gebremichael, B., George, R., Ghashghaee, A., Golechha, M., Hamidi, S., Hammond, B. R., Hartnett, M. E. R., Hartono, R. K., Hay, S. I., Heidari, G., Ho, H. C., Hoang, C. L., Househ, M., Ibitoye, S. E., Ilic, I. M., Ilic, M. D., Ingram, A. D., Irvani, S. S. N., Jha, R. P., Kahloun, R., Kandel, H., Kasa, A. S., Kempen, J. H., Keramati, M., Khairallah, M., Khan, E. A., Khanna, R. C., Khatib, M. N., Kim, J. E., Kim, Y. J., Kisa, A., Kisa, S., Koyanagi, A., Kurmi, O. P., Lansingh, V. C., Leasher, J. L., Leveziel, N., Limburg, H., Majdan, M., Manafi, N., Mansouri, K., Mcalinden, C., Mohammadi, S. F., Mohammadian-Hafshejani, A., Mohammadpourhodki, R., Mokdad, A. H., Moosavi, D., Morse, A. R., Naderi, M., Naidoo, K. S., Nangia, V., Nguyen, C. T., Nguyen, H. L. T., Ogundimu, K., Olagunju, A. T., Ostroff, S. M., Panda-Jones, S., Pesudovs, K., Peto, T., Syed, Z. Q., Ur Rahman, M. H., Ramulu, P. Y., Rawaf, D. L., Rawaf, S., Reinig, N., Robin, A. L., Rossetti, L., Safi, S., Sahebkar, A., Samy, A. M., Saxena, D., Serle, J. B., Shaikh, M. A., Shen, T. T., Shibuya, K., Shin, J. I., Silva, J. C., Silvester, A., Singh, J. A., Singhal, D., Sitorus, R. S., Skiadaresi, E., Skirbekk, V., Soheili, A., Sousa, R. A. R. C., Spurlock, E. E., Stambolian, D., Taddele, B. W., Tadesse, E. G., Tahhan, N., Tareque, Md. I., Topouzis, F., Tran, B. X., Travillian, R. S., Tsilimbaris, M. K., Varma, R., Virgili, G., Wang, N., Wang, Y. X., West, S. K., Wong, T. Y., Zaidi, Z., Zewdie, K. A., Jonas, J. B., and Vos, T.
Subjects: Visual acuity, genetic structures, 030231 tropical medicine, Population, Visual impairment, Glaucoma, Blindness, 03 medical and health sciences, 0302 clinical medicine, medicine, Global health, 030212 general & internal medicine, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, education, Eye diseases, Medicine(all), Near vision impairments, education.field_of_study, business.industry, General Medicine, Presbyopia, Systematic reviews, Macular degeneration, medicine.disease, eye diseases, 3. Good health, medicine.symptom, business, Demography
Abstract: Background: To contribute to the WHO initiative, VISION 2020: The Right to Sight, an assessment of global vision impairment in 2020 and temporal change is needed. We aimed to extensively update estimates of global vision loss burden, presenting estimates for 2020, temporal change over three decades between 1990–2020, and forecasts for 2050. Methods: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. Only studies with samples representative of the population and with clearly defined visual acuity testing protocols were included. We fitted hierarchical models to estimate 2020 prevalence (with 95% uncertainty intervals [UIs]) of mild vision impairment (presenting visual acuity ≥6/18 and
Published: 2020

34. A genetic mouse model recapitulates immune checkpoint inhibitor-associated myocarditis and supports a mechanism-based therapeutic intervention

Author: Margaret L Axelrod, Bjorn C. Knollmann, Lauren I.R. Ehrlich, Justin M. Balko, Joe-Elie Salem, James P. Allison, Javid Moslehi, Jing Wang, Padmanee Sharma, Nana Ama A.S. Anang, Jayashree Srinivasan, James J. Mancuso, Oluwatomisin T. Atolagbe, Elles M. Screever, Wouter C. Meijers, Elizabeth M. Whitley, Lorenz H. Lehmann, Lauren E. Himmel, Matthew Wleklinski, Pierre-Yves Courand, Elizabeth Wescott, Bénédicte Lebrun-Vignes, Douglas B. Johnson, Xiayu Rao, Yu Li, Spencer C. Wei, Yang Zhao, The University of Texas M.D. Anderson Cancer Center [Houston], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Heidelberg University Hospital [Heidelberg], Hospices Civils de Lyon (HCL), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Texas at Austin [Austin], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, cardio-oncology, Fulminant, Immune checkpoint inhibitors, [SDV]Life Sciences [q-bio], Mechanism based, Electrocardiography, Mice, 0302 clinical medicine, Neoplasms, Medicine, Molecular Targeted Therapy, Clinical syndrome, Immune Checkpoint Inhibitors, ComputingMilieux_MISCELLANEOUS, immune- related adverse events, autoimmunity, Disease Management, 3. Good health, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Disease Susceptibility, medicine.drug, Myocarditis, Cancer therapy, chemical and pharmacologic phenomena, Article, 03 medical and health sciences, Ctla4, PD -1, Biomarkers, Tumor, Animals, Humans, Adverse effect, negative costimulation, business.industry, Abatacept, T cell, medicine.disease, Cardiotoxicity, haploinsufficiency, Disease Models, Animal, 030104 developmental biology, Immunology, Pdcd1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, CTLA-4, myocarditis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Immune checkpoint inhibitors (ICI) targeting CTLA4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events, including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which monoallelic loss of Ctla4 in the context of complete genetic absence of Pdcd1 leads to premature death in approximately half of mice. Premature death results from myocardial infiltration by T cells and macrophages and severe ECG abnormalities, closely recapitulating the clinical and pathologic hallmarks of ICI-associated myocarditis observed in patients. Using this model, we show that Ctla4 and Pdcd1 functionally interact in a gene dosage–dependent manner, providing a mechanism by which myocarditis arises with increased frequency in the setting of combination ICI therapy. We demonstrate that intervention with CTLA4–Ig (abatacept) is sufficient to ameliorate disease progression and additionally provide a case series of patients in which abatacept mitigates the fulminant course of ICI myocarditis. Significance: We provide a preclinical model of ICI-associated myocarditis which recapitulates this clinical syndrome. Using this model, we demonstrate that CTLA4 and PD-1 (ICI targets) functionally interact for myocarditis development and that intervention with CTLA4–Ig (abatacept) attenuates myocarditis, providing mechanistic rationale and preclinical support for therapeutic clinical studies. See related commentary by Young and Bluestone, p. 537. This article is highlighted in the In This Issue feature, p. 521
Published: 2020

35. Cell Biology of Viral Infections

Author: Pierre-Yves Lozach, Center for Integrative Infectious Diseases Research [Heidelberg, Allemagne] (CIID), and Heidelberg University Hospital [Heidelberg]
Subjects: 0301 basic medicine, intracellular trafficking, viruses, organoid, inclusion bodies, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, virus, Biology, medicine.disease_cause, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Viral envelope, Viral entry, medicine, Animals, Humans, lcsh:QH301-705.5, host-virus interactions, Host factor, Coronavirus, 3D cell culture, cell stress responses, Ebola virus, SARS-CoV-2, Intracellular parasite, General Medicine, Zika Virus, Actin cytoskeleton, signaling pathways, 3. Good health, Cell biology, 030104 developmental biology, Editorial, cell death, Viral replication, lcsh:Biology (General), Virus Diseases, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Host-Pathogen Interactions, pluripotent stem cells, Signal Transduction
Abstract: International audience; Viruses exhibit an elegant simplicity, as they are so basic, but so frightening. Although only a few are life threatening, they have substantial implications for human health and the economy, as exemplified by the ongoing coronavirus pandemic. Viruses are rather small infectious agents found in all types of life forms, from animals and plants to prokaryotes and archaebacteria. They are obligate intracellular parasites, and as such, subvert many molecular and cellular processes of the host cell to ensure their own replication, amplification, and subsequent spread. This special issue addresses the cell biology of viral infections based on a collection of original research articles, communications, opinions, and reviews on various aspects of virus-host cell interactions. Together, these articles not only provide a glance into the latest research on the cell biology of viral infections, but also include novel technological developments.
Published: 2020

36. Haematopoietic stem cell transplantation in adult soft-tissue sarcoma: an analysis from the European Society for Blood and Marrow Transplantation

Author: Stefan Fröhling, Christian Chabannon, Peter Dreger, Jürgen Heinz, William Krüger, José Rifón, Didier Blaise, Salvatore Siena, Simona Secondino, Mareike Verbeek, Ulrike Koehl, Armando Santoro, Paolo Pedrazzoli, Emmanuelle Nicolas-Virelizier, Massimo Di Nicola, Manuela Badoglio, Clément Korenbaum, Myriam Labopin, Christoph E. Heilig, Jakob Passweg, Publica, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Cancer Consortium [Heidelberg] (DKTK), Heidelberg University Hospital [Heidelberg], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International des greffes [CHU Saint-Antoine] (EBMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Freiburg University Medical Center, Centre Léon Bérard [Lyon], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Oncologie médicale [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Greifswald University Hospital, Università degli Studi di Milano [Milano] (UNIMI), University Hospital Basel [Basel], Clínica Universidad de Navarra [Pamplona], Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Fraunhofer (Fraunhofer-Gesellschaft), Hannover Medical School [Hannover] (MHH), and Università degli Studi di Pavia
Subjects: Adult, Melphalan, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Transplantation, Autologous, stem cell transplantation, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Bone Marrow, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Original Research, Preparative Regimen, Chemotherapy, business.industry, Soft tissue sarcoma, Hematopoietic Stem Cell Transplantation, Sarcoma, soft-tissue sarcoma, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Clinical trial, Transplantation, 030220 oncology & carcinogenesis, business, Stammzelltransplantation, high-dose chemotherapy, medicine.drug
Abstract: Background The role of high-dose chemotherapy with autologous stem cell transplantation (ASCT) in the treatment of soft-tissue sarcoma (STS) remains an unsettled issue. Prospective clinical trials failed to prove a benefit of the procedure but were limited by small and heterogeneous patient cohorts. Thus, it is unknown if ASCT may be a valuable treatment option in specific patient subgroups. Methods The purpose of this study was to investigate the value of ASCT according to histological subtype in STS patients who were registered in the European Society for Blood and Marrow Transplantation database between 1996 and 2016. Results Median progression-free (PFS) and overall survival (OS) in the entire cohort of 338 patients were 8.3 and 19.8 months, respectively, and PFS and OS at 5 years were 13% and 25%, respectively. Analysis of outcomes in different subgroups showed that younger age, better remission status before transplantation and melphalan-based preparative regimen were predictive of benefit from ASCT, whereas histology and grading had no statistically significant impact. Conclusions Outcomes after ASCT compared favorably to those of recent trials on conventional chemotherapies and targeted therapies in STS, including histology-tailored approaches. ASCT, thus, should be reinvestigated in clinical trials focusing on defined patient subgroups.
Published: 2020

37. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Author: Daniel R. Barnes, Matti A. Rookus, Lesley McGuffog, Goska Leslie, Thea M. Mooij, Joe Dennis, Nasim Mavaddat, Julian Adlard, Munaza Ahmed, Kristiina Aittomäki, Nadine Andrieu, Irene L. Andrulis, Norbert Arnold, Banu K. Arun, Jacopo Azzollini, Judith Balmaña, Rosa B. Barkardottir, Daniel Barrowdale, Javier Benitez, Pascaline Berthet, Katarzyna Białkowska, Amie M. Blanco, Marinus J. Blok, Bernardo Bonanni, Susanne E. Boonen, Åke Borg, Aniko Bozsik, Angela R. Bradbury, Paul Brennan, Carole Brewer, Joan Brunet, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Lise Lotte Christensen, Wendy K. Chung, Kathleen B.M. Claes, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Antonis Antoniou, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D. Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-ren Ong, Lucy Side, Aoife O’Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Mary B. Daly, Miguel de la Hoya, Robin de Putter, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Cecilia M. Dorfling, Martine Dumont, Bent Ejlertsen, Christoph Engel, Lenka Foretova, Florentia Fostira, Michael Friedlander, Eitan Friedman, Patricia A. Ganz, Judy Garber, Andrea Gehrig, Anne-Marie Gerdes, Paul Gesta, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Anna González-Neira, Mark H. Greene, Daphne Gschwantler-Kaulich, Eric Hahnen, Ute Hamann, Julia Hentschel, Frans B.L. Hogervorst, Maartje J. Hooning, Judit Horvath, Chunling Hu, Peter J. Hulick, Evgeny N. Imyanitov, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Catherine Noguès, Claudine Isaacs, Angel Izquierdo, Anna Jakubowska, Paul A. James, Ramunas Janavicius, Esther M. John, Vijai Joseph, Beth Y. Karlan, Karin Kast, Torben A. Kruse, Ava Kwong, Yael Laitman, Conxi Lazaro, Jenny Lester, Fabienne Lesueur, Annelie Liljegren, Jennifer T. Loud, Jan Lubiński, Phuong L. Mai, Siranoush Manoukian, Hanne E.J. Meijers-Heijboer, Alfons Meindl, Arjen R. Mensenkamp, Austin Miller, Marco Montagna, Semanti Mukherjee, Anna Marie Mulligan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Dieter Niederacher, Finn Cilius Nielsen, Liene Nikitina-Zake, Edith Olah, Olufunmilayo I. Olopade, Ana Osorio, Claus-Eric Ott, Laura Papi, Sue K. Park, Michael T. Parsons, Inge Sokilde Pedersen, Bernard Peissel, Ana Peixoto, Paolo Peterlongo, Georg Pfeiler, Karolina Prajzendanc, Miquel Angel Pujana, Paolo Radice, Juliane Ramser, Susan J. Ramus, Johanna Rantala, Gad Rennert, Harvey A. Risch, Mark Robson, Karina Rønlund, Ritu Salani, Leigha Senter, Payal D. Shah, Priyanka Sharma, Lucy E. Side, Christian F. Singer, Thomas P. Slavin, Penny Soucy, Melissa C. Southey, Amanda B. Spurdle, Doris Steinemann, Zoe Steinsnyder, Christian Sutter, Yen Yen Tan, Manuel R. Teixeira, Soo Hwang Teo, Darcy L. Thull, Silvia Tognazzo, Amanda E. Toland, Alison H. Trainer, Nadine Tung, Elizabeth J. van Rensburg, Ana Vega, Jeroen Vierstraete, Gabriel Wagner, Shan Wang-Gohrke, Barbara Wappenschmidt, Jeffrey N. Weitzel, Siddhartha Yadav, Xin Yang, Drakoulis Yannoukakos, Dario Zimbalatti, Kenneth Offit, Mads Thomassen, Fergus J. Couch, Rita K. Schmutzler, Jacques Simard, Douglas F. Easton, Antonis C. Antoniou, Pediatric surgery, Human genetics, CCA - Cancer biology and immunology, CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Chapel Allerton Hospital, Great Ormond Street Hospital for Children [London] (GOSH), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Mount Sinai Hospital [Toronto, Canada] (MSH), University of Toronto (University of Toronto), Christian-Albrechts University of Kiel, The University of Texas M.D. Anderson Cancer Center [Houston], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], CIBER de Enfermedades Raras (CIBERER), Spanish National Cancer Research Center (CNIO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Pomeranian Medical University [Szczecin] (PUM), University of California (UC), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], European Institute of Oncology IRCCS [Milan, Italy] (EIO), Zealand University Hospital [Roskilde, Denmark], Lund University [Lund], National Institute of Oncology [Budapest, Hungary], Abramson Cancer Center [philadelphia], University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, Institute of Genetic Medicine [Newcastle], Newcastle University [Newcastle], Royal Devon & Exeter Hospital, Exeter, UK, Catalan Institute of Oncology [Barcelone, Espagne], Huntsman Cancer Institute [Salt Lake City], University of Utah, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Pisa University Hospital, Peter MacCallum Cancer Centre [Melbourne, Australie], University of Melbourne, Aarhus University Hospital, Columbia University [New York], Ghent University Hospital, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Sheffield Children's NHS Foundation Trust, Fox Chase Cancer Center, Queen Elizabeth University Hospital (Glasgow), Centre hospitalier universitaire de Nantes (CHU Nantes), Leiden University Medical Center (LUMC), Beckman Research Institute of the City of Hope, Abramson Cancer Center, University of Pretoria [South Africa], Centre Hospitalier Universitaire de Québec Research Center [Canada], Royal Marsden NHS Foundation Trust, Copenhagen University Hospital, Leipzig University, University of Manchester [Manchester], Manchester Academic Health Science Centre (MAHSC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Masaryk Memorial Cancer Institute (MMCI), Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research 'Demokritos' (NCSR), NHMRC Clinical Trials Centre [Camperdown NSW 2050, Australie], Chaim Sheba Medical Center, Tel Aviv University (TAU), Jonsson Comprehensive Cancer Center, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Dana-Farber Cancer Institute [Boston], University of Würzburg, Rigshospitalet [Copenhagen], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Hospices Civils de Lyon (HCL), University of Kansas [Kansas City], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Medizinische Universität Wien = Medical University of Vienna, University of Cologne, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Lancashire NHS Foundation Trust, University Hospital Leipzig, Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Mayo Clinic, NorthShore University HealthSystem [Evanston, IL, USA], The University of Chicago Medicine [Chicago], N. N. Petrov Institute of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Guy's and St Thomas' NHS Foundation Trust [London, UK], Peter MacCallum Cancer Center, East Melbourne, Peter MacCallum Cancer Center, Vilnius University [Vilnius], The State Scientific Research Institute Nature Research Centre, Vilnius, Lithuania, Stanford University School of Medicine [CA, USA], Memorial Sloane Kettering Cancer Center [New York], Cedars-Sinai Medical Center, Technische Universität Dresden = Dresden University of Technology (TU Dresden), University Medical Center [Utrecht], Odense University Hospital [Odense, Denmark], The Hong Kong Hereditary Breast Cancer Family Registry, The University of Hong Kong (HKU), Hong Kong Sanatorium and Hospital [Hong Kong] (HKSH), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), David Geffen School of Medicine [Los Angeles], Fondation MINES ParisTech, Karolinska Institutet [Stockholm], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Amsterdam UMC - Amsterdam University Medical Center, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Radboud University Medical Center [Nijmegen], Roswell Park Cancer Institute [Buffalo], Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], University of Toronto, University Health Network, University Hospital Düsseldorf, Latvian Biomedical Research and Study Centre [Rīga], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), University of Chicago, Birmingham Women's and Children's NHS Foundation Trust, Cambridge University Hospitals - NHS (CUH), Charité Campus Virchow-Klinikum (CVK), Università degli Studi di Firenze = University of Florence (UniFI), Seoul National University College of Medicine [Séoul, Corée du Sud] (SNUCM), Seoul National University [Seoul] (SNU), QIMR Berghofer Medical Research Institute, Aalborg University [Denmark] (AAU), IRCCS Istituto Nazionale dei Tumori [Milano], Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Klinikum rechts der Isar [Munich, Germany], University of New South Wales [Sydney] (UNSW), Garvan Institute of medical research, Technion Faculty of Medicine [Haifa, Israel], Yale School of Medicine [New Haven, Connecticut] (YSM), Vejle Hospital [Danemark], Ohio State University [Columbus] (OSU), Centre de lutte contre le cancer Paul-Strauss, Institut de Cancérologie de Strasbourg Europe (ICANS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Kansas Medical Center [Kansas City, KS, USA], Princess Anne Hospital, City of Hope Comprehensive Cancer Center [Duarte], Monash University [Clayton], Cancer Council Victoria [Melbourne, VIC, Australia], Hannover Medical School [Hannover] (MHH), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Heidelberg University Hospital [Heidelberg], Institute of Biomedical Sciences Abel Salazar - ICBAS [Porto, Portugal], Malaysia and University Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya [Kuala Lumpur, Malaisie], University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), McGill University = Université McGill [Montréal, Canada], Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Fundación Pública Galega Medicina Xenómica - SERGAS [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), CIBER de Enfermedades Raras (CIBERER)-Universidade de Santiago de Compostela [Spain] (USC ), Instituto de Investigaciones Sanitarias, Universidade de Santiago de Compostela [Spain] (USC ), Universiteit Gent = Ghent University (UGENT), Oxford University Hospitals NHS Trust, University of Oxford, Universitätsklinikum Ulm - University Hospital of Ulm, University Hospital of Cologne [Cologne], Mayo Clinic [Rochester], Collaborators : Pascaline Berthet, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Julian Adlard, Munaza Ahmed, Antonis Antoniou, Daniel Barrowdale, Paul Brennan, Carole Brewer, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-Ren Ong, Lucy Side, Aoife O'Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Peter Devilee, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Nadine Andrieu, Catherine Noguès, Dupuis, Christine, Institut Català de la Salut, [Barnes DR, McGuffog L, Leslie G, Dennis J] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Rookus MA, Mooij TM] The Netherlands Cancer Institute, Department of Epidemiology (PSOE), Amsterdam, The Netherlands. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Barnes, Daniel [0000-0002-3781-7570], Leslie, Goska [0000-0001-5756-6222], Dennis, Joe [0000-0003-4591-1214], Mavaddat, Nasim [0000-0003-0307-055X], RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), Universiteit Leiden, Roswell Park Cancer Institute [Buffalo] (RPCI), Medical Oncology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, Helsinki University Hospital Area, Department of Obstetrics and Gynecology, Biosciences, HUS Gynecology and Obstetrics, University of Helsinki, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Pomeranian Medical University, University of California, University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Pennsylvania [Philadelphia], University of Leipzig [Leipzig, Allemagne], Masaryk Memorial Cancer Institute (RECAMO), Tel Aviv University [Tel Aviv], University of California-University of California, University of Münster, Amsterdam UMC, Technical University of Munich (TUM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Garvan Institute of Medical Research [Sydney, Australia], Yale University School of Medicine, Vejle Hospital, University of Kansas Medical Center [Lawrence], Université Paris Descartes (Paris 5), University of Malaya [Kuala Lumpur, Malaisie], Universiteit Gent = Ghent University [Belgium] (UGENT), and University of Oxford [Oxford]
Subjects: 0301 basic medicine, Oncology, endocrine system diseases, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], [SDV]Life Sciences [q-bio], Càncer d'ovari, Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES], MODIFIERS, Diàtesi, SUSCEPTIBILITY, Carcinoma, Ovarian Epithelial, PRS, 0302 clinical medicine, Breast cancer, 3123 Gynaecology and paediatrics, Risk Factors, Medicine and Health Sciences, Medicine, Genetics(clinical), genetics, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, Genetics (clinical), Ovarian Neoplasms, education.field_of_study, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], BRCA1 Protein, Hazard ratio, Absolute risk reduction, 1184 Genetics, developmental biology, physiology, article, ASSOCIATION, neoplasias::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas::carcinoma epitelial de ovario [ENFERMEDADES], ddc, 3. Good health, [SDV] Life Sciences [q-bio], ovarian cancer, 030220 oncology & carcinogenesis, Female, Cohort study, medicine.medical_specialty, Heterozygote, Population, 3122 Cancers, Single-nucleotide polymorphism, Breast Neoplasms, MUTATION CARRIERS, Ovaris - Càncer - Aspectes genètics, Càncer de mama, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, Ovarian cancer, BRCA1/2, Internal medicine, Humans, Genetic Predisposition to Disease, education, Retrospective Studies, fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS], BRCA2 Protein, IDENTIFICATION, business.industry, Neoplasms::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms::Carcinoma, Ovarian Epithelial [DISEASES], Retrospective cohort study, ALLELES, medicine.disease, BRCA1, BRCA2, MODEL, PATHOLOGY, 030104 developmental biology, Mutation, Mama - Càncer - Aspectes genètics, 3111 Biomedicine, business
Abstract: Contains fulltext : 229292.pdf (Publisher’s version ) (Open Access) PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10(-72)). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10(-22)) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10(-12)) carriers. The associations in the prospective cohort were similar. CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
Published: 2020

38. Treatment of MOG-IgG-associated disorder with rituximab

Author: Jonathan Ciron, Kimihiko Kaneko, Ilijas Jelcic, Bruno Brochet, Mikael Cohen, Elisabeth Maillart, Sven Jarius, David M. Hunt, Dagoberto Callegaro, Sean J. Pittock, Daniel Whittam, Tanuja Chitnis, Stewart Webb, Rob Forsyth, Silvia Tenembaum, Thomas Berger, Alvaro Cobo-Calvo, Anu Jacob, Brian G. Weinshenker, Rinze F. Neuteboom, Alexander U. Brandt, Luana Micheli Oliveira, Venkatraman Karthikeayan, Ichiro Nakashima, David Laplaud, Douglas Kazutoshi Sato, Ayman Tourbah, Emily Gibbons, Lekha Pandit, Romain Deschamps, Grace Y. Gombolay, Su Hyun Kim, A. Sebastian Lopez-Chiriboga, Tom Solomon, Santiago Pardo, Andreas Lutterotti, Ming K. Lim, Saif Huda, M. Isabel Leite, Michael J. Levy, Klaus Berek, Damien Biotti, Romain Marignier, Eric Thouvenot, Markus Reindl, Katy Murray, Ho Jin Kim, Jeffrey Bennett, Kevin Rostasy, Guillaume Mathey, Jacqueline Palace, Matthew Gornall, Yael Hacohen, Marco Capobianco, Silvia Cicconi, Cheryl Hemingway, Kazuo Fujihara, Marcelo Matiello, Bertrand Audoin, Tatsuro Misu, Brigitte Wildemann, Friedemann Paul, The Walton Centre NHS Foundation Trust, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mayo Clinic [Rochester], Massachusetts General Hospital [Boston], University of Liverpool, Max Delbrueck Center for Molecular Medicine, Helmholtz-Gemeinschaft = Helmholtz Association, Innsbruck Medical University [Austria] (IMU), Medizinische Universität Wien = Medical University of Vienna, Universitätsspital Zürich (USZ), Emory Global Health Institute [Atlanta] (EGHI), Emory University [Atlanta, GA], Hospital das Clinicas, University of Sao Paulo School of Medicine, Tohoku University [Sendai], Azienda Ospedaliera Universitaria San Luigi di Orbassano, Institute of Infection and Global Health [University of Liverpool, UK], Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire de Psychopathologie et Neuropsychologie (LPN), Université Paris 8 Vincennes-Saint-Denis (UP8), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Universität Witten Herdecke, Children's Hospital of Datteln, Erasmus MC-Sophia Hospital [Rotterdam, Netherlands], Great Ormond Street Hospital for Children [London] (GOSH), Newcastle University [Newcastle], Queen Elizabeth University Hospital (Glasgow), Anne Rowling Clinic [Edinburgh, UK], University of Edinburgh, Institute of Neurology, Queen Square, London, Tourettes Clinic-Evelina Childrens Hospital at Guys and St. Thomas', Kings Health Partners AHSC, Nuffield Department of Clinical Neurosciences [Oxford], University of Oxford [Oxford], University of Colorado Anschutz [Aurora], Department of Pharmaceutics, NGSM Institute of Pharmaceutical Science, NITTE Deemed to be University, Mangalore 575018, India, Heidelberg University Hospital [Heidelberg], Pontifícia Universidade Católica do Rio Grande do Sul [Porto Alegre] (PUCRS), Hospital of National Cancer Center [Goyang], Hospital Nacional de Pediatría Prof. Dr Juan P. Garrahan [Buenos Aires], Cleveland Clinic Abu Dhabi [Abou Dabi, Émirats arabes unis], Salvy-Córdoba, Nathalie, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Oxford, Pontifical Catholic University of Rio Grande do Sul (PUC-RS), and Neurology
Subjects: medicine.medical_specialty, Optic neuritis, Controlled studies, Gastroenterology, Article, Myelin oligodendrocyte glycoprotein, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Internal medicine, medicine, Humans, MOG, 030212 general & internal medicine, Poisson regression, Prospective Studies, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Child, Autoantibodies, Retrospective Studies, Retrospective review, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Neuromyelitis optica, biology, business.industry, Multiple sclerosis, General Medicine, medicine.disease, 3. Good health, Neurology, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Immunoglobulin G, biology.protein, symbols, Rituximab, Myelin-Oligodendrocyte Glycoprotein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Objective: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Methods: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). Results: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3–14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3–24.9) months. In this ‘relapsing group’, relapse rate declined by 37% (95%CI=19–52%, p Conclusion: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.
Published: 2020

39. Are Autologous Stem Cell Transplants Still Required to Treat Myeloma in the Era of Novel Therapies? A Review from the Chronic Malignancies Working Party of the EBMT

Author: Stefan Schönland, Patrick Hayden, Curly Morris, Meral Beksac, Gösta Gahrton, Ibrahim Yakoub-Agha, Laurent Garderet, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Queen's University [Belfast] (QUB), Ankara University School of Medicine [Turkey], Karolinska Institutet [Stockholm], Heidelberg University Hospital [Heidelberg], Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Trinity College Dublin, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Melphalan, Oncology, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Myeloma, Autologous stem cell transplantation, Monoclonal antibody, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Internal medicine, medicine, Humans, Transplantation, CAR T cells, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, Immunotherapy, Chimeric antigen receptor, 3. Good health, First relapse, Pharmaceutical Preparations, Novel agents, 030220 oncology & carcinogenesis, Stem cell, business, Multiple Myeloma, 030215 immunology, medicine.drug, Stem Cell Transplantation
Abstract: International audience; Melphalan at a myeloablative dose followed by autologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible patients with myeloma. However, therapies such as new immunomodulatory drugs and proteasome inhibitors and, more recently, monoclonal antibodies and chimeric antigen receptor T cells are challenging the traditional role of ASCT. Which patients benefit from ASCT? Can its use be delayed until first relapse? The field is moving rapidly as novel agents lead to new patient care strategies. The place of ASCT in this changing landscape will be reviewed and reassessed.
Published: 2020

40. SUMOylation of Enzymes and Ion Channels in Sensory Neurons Protects against Metabolic Dysfunction, Neuropathy, and Sensory Loss in Diabetes

Author: Christian Njoo, Stefan G. Lechner, Mirko Moroni, Francisco J. Taberner, Faramarz Faghihi, Daniel Rangel Rojas, Thomas Fleming, Alexandra Andrieux, Nitin Agarwal, Gary R. Lewin, Pooja Gupta, Kiran Kumar Bali, Anne Dejean, Esther Herpel, Rohini Kuner, Peter P. Nawroth, Damir Omberbasic, Heidelberg University, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Heidelberg University Hospital [Heidelberg], This work was supported by Deutsche Forschungsgemeinschaft grants SFB1118 (project B06) (to N.A. and R.K.), SFB1118 (projects A04, S02, and S01) (to P.P.N., E.H., and T.F.), SFB1158 (project A01) (to S.G.L.), and SFB1158 (project A03) (to P.P.N.). R.K. is a member of the Molecular Medicine Partnership Unit, Heidelberg and a principal investigator in the Excellence Cluster 'CellNetworks' of Heidelberg University., The authors are grateful to D. Baumgartl-Ahlert for technical assistance. We acknowledge support from the Interdisciplinary Neurobehavioral Core (INBC), the Proteomics facility, and the Metabolomics facility at Heidelberg University. We acknowledge support from the tissue bank of the National Centre for Tumour Diseases (NCT, Heidelberg, Germany) in accordance with the regulations of the tissue bank and approval from the ethics committee of Heidelberg University (Ethic Votes 206/2005 and 207/2005)., and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Male, Nociception, Diabetic neuropathy, MESH: Nociception, [SDV]Life Sciences [q-bio], SUMO protein, Mice, 0302 clinical medicine, Diabetic Neuropathies, MESH: Sensory Receptor Cells, Ganglia, Spinal, MESH: Animals, Cells, Cultured, General Neuroscience, MESH: Sumoylation, 3. Good health, MESH: HEK293 Cells, MESH: Glycolysis, Female, MESH: Ganglia, Spinal, Glycolysis, MESH: Cells, Cultured, Sensory Receptor Cells, Citric Acid Cycle, TRPV1, TRPV Cation Channels, Sensory system, Neuropathology, 03 medical and health sciences, MESH: Citric Acid Cycle, MESH: Mice, Inbred C57BL, Diabetes mellitus, medicine, Animals, Humans, MESH: Mice, MESH: Humans, business.industry, MESH: Diabetic Neuropathies, Sumoylation, medicine.disease, MESH: Male, Mice, Inbred C57BL, Metabolic pathway, 030104 developmental biology, Peripheral neuropathy, HEK293 Cells, MESH: TRPV Cation Channels, MESH: Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), business, Neuroscience, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Diabetic peripheral neuropathy (DPN) is a highly frequent and debilitating clinical complication of diabetes that lacks therapies. Cellular oxidative stress regulates post-translational modifications, including SUMOylation. Here, using unbiased screens, we identified key enzymes in metabolic pathways and ion channels as novel molecular targets of SUMOylation that critically regulated their activity. Sensory neurons of diabetic patients and diabetic mice demonstrated changes in the SUMOylation status of metabolic enzymes and ion channels. In support of this, profound metabolic dysfunction, accelerated neuropathology, and sensory loss were observed in diabetic gene-targeted mice selectively lacking the ability to SUMOylate proteins in peripheral sensory neurons. TRPV1 function was impaired by diabetes-induced de-SUMOylation as well as by metabolic imbalance elicited by de-SUMOylation of metabolic enzymes, facilitating diabetic sensory loss. Our results unexpectedly uncover an endogenous post-translational mechanism regulating diabetic neuropathy in patients and mouse models that protects against metabolic dysfunction, nerve damage, and altered sensory perception.
Published: 2020

41. Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis

Author: Torsten Grehl, Bertold Schrank, Johannes Dorst, Matthias Boentert, Jens Dreyhaupt, Daniel Zeller, Susanne Petri, Markus Otto, Franceso Roselli, Julian Grosskreutz, Thomas Meyer, Joachim Schuster, Andreas Hermann, Luc Dupuis, Simon Witzel, Andrea Sylvia Winkler, Johannes Prudlo, Stanislav Gorbulev, Ulrike Weiland, Jochen H. Weishaupt, Berit Jordan, Albert C. Ludolph, Jan Kassubek, University of Ulm (UUlm), Hannover Medical School [Hannover] (MHH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ruhr-Universität Bochum [Bochum], Technische Universität Dresden = Dresden University of Technology (TU Dresden), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Rostock, Martin-Luther-University Halle-Wittenberg, Heidelberg University Hospital [Heidelberg], Jena University Hospital [Jena], University of Würzburg = Universität Würzburg, University of Münster, DKD Helios Klinik Wiesbaden [Wiesbaden, Germany] (DKD HELIOS Medical Center), University Medical Center Rostock, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University Medical Center [Mainz], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), and Dieterle, Stéphane
Subjects: Male, medicine.medical_specialty, Neurofilament, [SDV]Life Sciences [q-bio], blood [Neurofilament Proteins], Placebo, Diet, High-Fat, Gastroenterology, 03 medical and health sciences, blood [Amyotrophic Lateral Sclerosis], 0302 clinical medicine, Neurofilament Proteins, Internal medicine, Post-hoc analysis, medicine, Humans, ddc:610, Amyotrophic lateral sclerosis, MESH: Neurofilament Proteins, ComputingMilieux_MISCELLANEOUS, MESH: Amyotrophic Lateral Sclerosis, Randomized Controlled Trials as Topic, MESH: Humans, MESH: Middle Aged, business.industry, Therapeutic effect, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, MESH: Male, 3. Good health, Riluzole, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, MESH: Diet, High-Fat, MESH: Randomized Controlled Trials as Topic, Tolerability, statistics & numerical data [Randomized Controlled Trials as Topic], motor neuron disease, Population study, Surgery, Female, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery, medicine.drug
Abstract: Recent publications showed that circulating neurofilaments (Nfs) may be used as a diagnostic biomarker distinguishing amyotrophic lateral sclerosis (ALS) from ALS mimics with high sensitivity and specificity.1–3 Furthermore, it has been shown that patients with higher Nf levels show faster disease progression1 and shorter survival.2 3 Nf levels remain rather stable during the course of disease.2 Current literature suggests that the diagnostic value of neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains in cerebrospinal fluid is about equal, whereas in blood NfL seems to be superior.4 In this study, we investigated the effect of a high-caloric fatty diet (HCFD) on NfL serum levels, using blood samples collected during the LIPCAL-ALS (efficacy, safety and tolerability of high lipid and caloriesupplementation in amyotrophic lateral sclerosis) study, a randomised, double-blind, parallel-group, placebo-controlled, multicentre trial, which investigated the therapeutic effect of HCFD in ALS.5 In LIPCAL-ALS, 201 patients (80 women, 121 men, age 62.4±10.8) were randomly assigned (1:1) to receive either HCFD (405 kcal/day, 100% fat) or placebo in addition to riluzole (100 mg/day) for 18 months. Although the primary outcome overall survival was negative in the whole study population (p=0.44), the post hoc analysis revealed a significantly longer survival for fast-progressing patients (ie, patients with an Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope >median between disease onset and baseline) in the HCFD group compared with placebo.5 To further corroborate our hypothesis of a disease-modifying effect of HCFD, we analysed NfL serum levels from LIPCAL-ALS participants. At each on-site visit during LIPCAL-ALS (6-month intervals), patients were asked if they were willing to provide an additional serum sample for NfL analysis on a voluntary basis. Serum NfL concentrations were measured with the single molecule array (Simoa) platform provided by Quanterix (Lexington, Massachusetts, USA) with single measurements …
Published: 2020

42. Impaired autophagy increases susceptibility to endotoxin-induced chronic pancreatitis

Author: Franco Fortunato, Guido Kroemer, Z. Xu, M.W. Büchler, Frank Bergmann, L. Xia, Niels Grabe, John P. Neoptolemos, Thilo Hackert, X. Zhou, Heidelberg University Hospital [Heidelberg], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Gustave Roussy (IGR), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Lipopolysaccharides, Cancer Research, medicine.medical_specialty, Programmed cell death, Necroptosis, Immunology, Inflammation, Mice, Transgenic, Acinar Cells, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Internal medicine, Pancreatitis, Chronic, medicine, Acinar cell, Autophagy, Animals, Humans, lcsh:QH573-671, 030304 developmental biology, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Chemistry, lcsh:Cytology, Cell Biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Acute pancreatitis, Endotoxins, medicine.anatomical_structure, Endocrinology, 030220 oncology & carcinogenesis, TLR4, Pancreatitis, medicine.symptom, Pancreas, Chronic pancreatitis, Ceruletide
Abstract: Chronic pancreatitis (CP) is associated with elevated plasma levels of bacterial lipopolysaccharide (LPS) and we have demonstrated reduced acinar cell autophagy in human CP tissue. Therefore, we investigated the role of autophagy in experimental endotoxin-induced pancreatic injury and aimed to identify LPS in human CP tissue. Pancreatic Atg7-deficient mice were injected with a single sub-lethal dose of LPS. Expression of autophagy, apoptosis, necroptosis, and inflammatory markers was determined 3 and 24 h later utilizing immunoblotting and immunofluorescence. The presence of LPS in pancreatic tissue from mice and from patients and healthy controls was determined using immunohistochemistry, immunoblots, and chromogenic assay. Mice lacking pancreatic autophagy exhibited local signs of inflammation and were particularly sensitive to the toxic effect of LPS injection as compared to control mice. In response to LPS, Atg7Δpan mice exhibited enhanced vacuolization of pancreatic acinar cells, increase in TLR4 expression coupled to enhanced expression of NF-κΒ, JNK, and pro-inflammatory cytokines by acinar cells and enhanced infiltration by myeloid cells (but not Atg7F/F controls). Cell death was enhanced in Atg7Δpan pancreata, but only necroptosis and trypsin activation was further amplified following LPS injection along with elevated pancreatic LPS. The presence of LPS was identified in the pancreata from all 14 CP patients examined but was absent in the pancreata from all 10 normal controls. Altogether, these results support a potential role for metabolic endotoxemia in the pathogenesis of CP. Moreover, the evidence also supports the notion that autophagy plays a major cytoprotective and anti-inflammatory role in the pancreas, and blunting metabolic endotoxemia-induced CP.
Published: 2020

43. The Global Phosphorylation Landscape of SARS-CoV-2 Infection

Author: Yiming Cai, Maya Modak, Sebastian Weigang, Emmie de Wit, Jean K. Lim, Alistair Dunham, Benjamin J. Polacco, Qiongyu Li, Svenja Ulferts, Gwendolyn M. Jang, Aurelien Dugourd, David E. Gordon, Jeffrey Z. Guo, Kirsten Obernier, Sophia Bouhaddou, Elizabeth R. Fischer, Anna Gaulton, Jason C.J. Chang, Bjoern Meyer, Diego Quintero, Julian Knerr, Trupti Patil, Emma J. Manners, Michael C. O’Neal, Monita Muralidharan, Joseph Hiatt, Ajda Rojc, James E. Melnyk, Tanja Kortemme, Benjamin R. tenOever, Thomas Vallet, Rémy Robinot, Cassandra Koh, Benjamin E. Nilsson-Payant, Ruth Hüttenhain, Saker Klippsten, Alicia L. Richards, Eloy Felix, Brian K. Shoichet, Beril Tutuncuoglu, Danielle L. Swaney, Veronica V. Rezelj, Jeffery R. Johnson, Margaret Soucheray, Marisa Goff, R. Dyche Mullins, Kris M. White, Erica Stevenson, Jyoti Batra, Christopher J.P. Mathy, Yuan Zhou, Minkyu Kim, Marco Vignuzzi, Claudia Hernandez-Armenta, Kevan M. Shokat, Julio Saez-Rodriguez, Jacqueline M. Fabius, Timothy McBride, Adolfo García-Sastre, Quang Dinh Tran, Alexandra Hardy, Elena Moreno, Alberto Valdeolivas, Mehdi Bouhaddou, Andrew R. Leach, Melanie Ott, Georg Kochs, Pedro Beltrao, Jiewei Xu, Robyn M. Kaake, Merve Cakir, Ying Shi, Nevan J. Krogan, Lisa Miorin, Danish Memon, David J. Broadhurst, Miguel Correa Marrero, Robert Grosse, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Quantitative Biosciences Institute [UC San Francisco, USA] (QBI), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Gladstone Institutes [San Francisco], European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Howard Hughes Medical Institute (HHMI), University of Freiburg [Freiburg], Virus et Immunité - Virus and immunity (CNRS-UMR3569), Universität Heidelberg [Heidelberg] = Heidelberg University, Heidelberg University Hospital [Heidelberg], Zoic Labs [Culver City, CA], Rocky Mountain Laboratories, Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre for Integrative Biological Signalling Studies [Freiburg] (CIBSS), This research was funded by grants from the National Institutes of Health ( P50AI150476 , U19AI135990 , U19AI135972 , R01AI143292 , R01AI120694 , P01A1063302 , and R01AI122747 to N.J.K., 1R01CA221969 and 1R01CA244550 to K.M.S., R01GM133981 to D.L.S., 1F32CA236347-01 to J.E.M., U19AI118610 to J.R.J., and F32CA239333 to M.B.), Defense Advance Research Projects Agency HR0011-19-2-0020 (to N.J.K., A.G.S., and K.M.S.), by the Laboratory for Genomics Research (LGR) Excellence in Research Award (ERA) from the Innovative Genomics Institute at UC Berkeley (grant number 133122P ), by CRIP (Center for Research for Influenza Pathogenesis), a NIAID-supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400008C ) (to A.G.S.), by supplements to NIAID grant U19AI135972 and DoD grant W81XWH-19-PRMRP-FPA (to A.G.S.), and by the generous support of the JPB Foundation , the Open Philanthropy Project (research grant 2020-215611 [5384] ), and other philanthropic donations (to A.G.S.), by the Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' grant ANR-10-LABX-62-IBEID (to M.V.), by the DFG under Germany's Excellence Strategy ( EXC-2189 , project ID 390939984 to R.G.), by a Starting Grant Award from the European Research Council ( ERC-2014-STG 638884 PhosFunc to P.B.), by the Federal Ministry of Education and Research (BMBF, Computational Life Sciences grant 031L0181B to J.S.R.), by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (to E.R.F. and E.D.W.), and by funding from F. Hoffmann-La Roche and Vir Biotechnology and gifts from The Ron Conway Family . K.M.S. is an investigator of the Howard Hughes Medical Institute., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 638884,H2020,ERC-2014-STG,PhosFunc(2015), Universität Heidelberg [Heidelberg], and Vaccine Research Institute (VRI)
Subjects: Proteomics, MAPK/ERK pathway, MESH: Angiotensin-Converting Enzyme 2, MESH: Casein Kinase II, PIKFYVE, 0302 clinical medicine, MESH: Chlorocebus aethiops, MESH: Protein Kinase Inhibitors, MESH: Animals, Casein Kinase II, Lung, 0303 health sciences, Kinase, MESH: Proteomics, Phosphoproteomics, antiviral, Spike Glycoprotein, Cyclin-Dependent Kinases, 3. Good health, MESH: HEK293 Cells, Spike Glycoprotein, Coronavirus, Phosphorylation, Infection, MESH: Pandemics, p38 mitogen-activated protein kinases, Pneumonia, Viral, MESH: Vero Cells, p38, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Article, Betacoronavirus, 03 medical and health sciences, Biodefense, Humans, MESH: SARS-CoV-2, MESH: Humans, MESH: Phosphorylation, Prevention, MESH: Host-Pathogen Interactions, fungi, Receptor Protein-Tyrosine Kinases, AXL, Pneumonia, Virology, MAPK, Coronavirus, MESH: Peptidyl-Dipeptidase A, MESH: Pneumonia, Viral, MESH: Phosphatidylinositol 3-Kinases, A549 Cells, Vero cell, Drug Evaluation, 030217 neurology & neurosurgery, Developmental Biology, MESH: Coronavirus Infections, [SDV]Life Sciences [q-bio], viruses, CDK, Drug Evaluation, Preclinical, MESH: Spike Glycoprotein, Coronavirus, Medical and Health Sciences, p38 Mitogen-Activated Protein Kinases, Phosphatidylinositol 3-Kinases, Chlorocebus aethiops, MESH: COVID-19, Viral, Phosphoinositide-3 Kinase Inhibitors, mass spectrometry, biology, phosphoproteomics, Biological Sciences, Preclinical, MESH: Cyclin-Dependent Kinases, Infectious Diseases, Host-Pathogen Interactions, MESH: Betacoronavirus, MESH: Drug Evaluation, Preclinical, MESH: Receptor Protein-Tyrosine Kinases, MESH: Caco-2 Cells, Angiotensin-Converting Enzyme 2, Coronavirus Infections, MESH: Antiviral Agents, casein kinase II, Peptidyl-Dipeptidase A, Vaccine Related, Cyclin-dependent kinase, Proto-Oncogene Proteins, Animals, Pandemics, Protein Kinase Inhibitors, Vero Cells, MESH: Phosphoinositide-3 Kinase Inhibitors, 030304 developmental biology, SARS-CoV-2, COVID-19, Axl Receptor Tyrosine Kinase, MESH: p38 Mitogen-Activated Protein Kinases, MESH: Proto-Oncogene Proteins, Emerging Infectious Diseases, Good Health and Well Being, HEK293 Cells, biology.protein, MESH: A549 Cells, Caco-2 Cells
Abstract: Summary The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies., Graphical Abstract, Highlights • Phosphoproteomics analysis of SARS-CoV-2-infected cells uncovers signaling rewiring • Infection promotes host p38 MAPK cascade activity and shutdown of mitotic kinases • Infection stimulates CK2-containing filopodial protrusions with budding virus • Kinase activity analysis identifies potent antiviral drugs and compounds, Phosphoproteomics analysis of SARS-CoV-2-infected Vero E6 cells reveals host cellular pathways hijacked by viral infection, leading to the identification of small molecules that target dysregulated pathways and elicit potent antiviral efficacy.
Published: 2020

44. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions

Author: Patrick Roth, Jill S. Barnholtz-Sloan, Marc Sanson, Jonathan Tsang, Tracy T. Batchelor, Ingo K. Mellinghoff, Minesh P. Mehta, Kenneth Aldape, Martin J B Taphoorn, Floris P. Barthel, Ranjit S. Bindra, Emilie Le Rhun, David Nathanson, Matthias Preusser, David A. Reardon, Michael Platten, Susan M. Chang, Brian M. Alexander, Andreas von Deimling, Martin J. van den Bent, Andrew B. Lassman, Craig Horbinski, Gelareh Zadeh, Roel G.W. Verhaak, E. Antonio Chiocca, Evanthia Galanis, Susan C Short, Eudocia Q. Lee, Patrick Y. Wen, John DeGroot, Raymond Y. Huang, Michael Weller, Mark R. Gilbert, Joerg C. Tonn, Wolfgang Wick, Monika E. Hegi, David Schiff, Michael Lim, Giuseppe Minniti, Timothy F. Cloughesy, INSERM, Université de Lille, Harvard Medical School [Boston] [HMS], University hospital of Zurich [Zurich], Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM], Dana-Farber Cancer Institute [Boston], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Universität Zürich [Zürich] = University of Zurich (UZH), Case Western Reserve University [Cleveland], The Jackson Laboratory [Bar Harbor] (JAX), Yale University School of Medicine, University of California [San Francisco] (UCSF), University of California, University of California [Los Angeles] (UCLA), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Mayo Clinic [Rochester], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Northwestern University Feinberg School of Medicine, New York Presbyterian Hospital, Columbia University Irving Medical Center (CUIMC), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Johns Hopkins University School of Medicine [Baltimore], Miami Cancer Institute [Florida], Memorial Sloane Kettering Cancer Center [New York], Università degli Studi di Siena = University of Siena (UNISI), Heidelberg University, Medizinische Universität Wien = Medical University of Vienna, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Virginia [Charlottesville], University of Leeds, Leiden University Medical Center (LUMC), Ludwig Maximilian University [Munich] (LMU), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg University Hospital [Heidelberg], Princess Margaret Cancer Centre [Toronto, Canada], Erasmus University Medical Center [Rotterdam] (Erasmus MC), SALZET, Michel, Yale School of Medicine [New Haven, Connecticut] (YSM), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille-UNICANCER, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Virginia, Universiteit Leiden, and Neurology
Subjects: Oncology, clinical trials, diagnosis, glioblastoma, therapy, Cancer Research, medicine.medical_specialty, Consensus, Neuro oncology, [SDV]Life Sciences [q-bio], Oncology and Carcinogenesis, Brain tumor, Review, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, Internal medicine, medicine, Humans, Oncology & Carcinogenesis, Randomized Controlled Trials as Topic, Cancer, Brain Neoplasms, Molecular pathogenesis, Neurosciences, Chemoradiotherapy, medicine.disease, Isocitrate Dehydrogenase, 3. Good health, Brain Disorders, [SDV] Life Sciences [q-bio], Clinical trial, Phase III as Topic, Brain Cancer, Good Health and Well Being, Current management, 030220 oncology & carcinogenesis, Neurology (clinical), Glioblastoma, Societies, 030217 neurology & neurosurgery
Abstract: Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.
Published: 2020

45. Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension:A Double-Blind Placebo-controlled Clinical Trial

Author: R. James White, Carlos Jerjes-Sanchez, Gisela Martina Bohns Meyer, Tomas Pulido, Pablo Sepulveda, Kuo Yang Wang, Ekkehard Grünig, Shirish Hiremath, Zaixin Yu, Zhang Gangcheng, Wei Luen James Yip, Shuyang Zhang, Akram Khan, C. Q. Deng, Rob Grover, Victor F. Tapson, Graciela Noemi Svetliza, Adrian Jose Lescano, Guillermo Roberto Bortman, Fabian Antonio Diez, Christian Edgardo Botta, John Fitzgerald, Eelke Feenstra, Fiona Dawn Kermeen, Anne Margaret Keogh, Trevor John Williams, Peter Paul Yousseff, Benjamin Joh-Han Ng, David McNaughton Smallwood, Nathan Brent Dwyer, Martin Russell Brown, Irene M Lang, Regina Steringer-Mascherbauer, Jaquelina Sonoe Ota Arakaki, Frederico Thadeu Assis Figueiredo Campos, Ricardo de Amorim Correa, Rogerio de Souza, Gisela M. Bohns Meyer, Maria Auxiliadora Carmo Moreira, Hugo Hyung Bok Yoo, Monica Silveira Lapa, John Swiston, Naushad Hirani, Sanjay Mehta, Evangelos Michelakis, Pablo Andres Sepulveda, Monica Maria Zagolin Blancaire, Jimming Liu, Zhang Shuyang, Lei Pan, Bao Chunde, Yi Qun, Cheng Xiaoshu, Yu Zaixin, Xinli Li, Yao Hua, Xianyang Zhu, Yundai Chen, Cheng Zhaozhong, Yuanhua Yang, Zhou Daxin, Shen Jieyan, Jens Erik Nielsen-Kudsk, Jorn Carlsen, Arnaud Bourdin, Eric Hachulla, Claire Dromer, Ari Chaouat, Martine Reynaud-Gauber, Marie-France Seronde, Hans Klose, Michael Halank, Gert Hoffken, Ralf Ewert, Stephan Rosenkranz, Ekkehard Grunig, Ulrich Kruger, Juliane Kronsbein, Barbara Monika Hauptmeier, Andrea Koch, Matthias Held, Tobias Johannes Lange, Claus Neurohr, Heinrike Wilkens, Hubert Rolf Wilhelm Wirtz, Stavros Konstantinides, Paraskevi Argyropoulou-Pataka, Stylianos Orfanos, Prafulla Gopinath Kerkar, Pujar Venkateshacharya Suresh, Hemang Ashwinkumar Baxi, Abraham Oomman, Rajpal Kanaklal Abhaichand, Padma Kumar Edla Arjun, Vijay Chopra, Rahul Mehrotra, Rajeev Kumar Rajput, Jitendra Pal Singh Sawhney, Subir Bimalendu, Kamal Harishchandra Sharma, Bhagavathula Kutumba Srinivasa Sastry, Mordechai Reuben Kramer, Michael Jonathan Segel, Issahar Ben-Dov, Neville Berkman, Mordechai Yigla, Yochai Adir, Michael D’Alto, Carmine Dario Vizza, Laura Scelsi, Patrizio Vitulo, Tomas Rene Pulido, Anko Boonstra, Madelon Clementina Vonk, Bozena Sobkowicz, Tatiana Mularek-Kubzdela, Adam Torbicki, Piotr Podolec, Lim Soo Teik, Hyuk-Jae Chang, Hyung-Kwan Kim, Jun-Bean Park, Sung-A Chang, Duk-Kyung Kim, Wook-Jin Chung, Jong-Min Song, Magnus Nissell, Clara Hjalmarsson, Bengt Rundqvist, Wei-Chun Huang, Chin-Chang Cheng, Chih-Hsin Hsu, Hsao-Hsun Hsu, Kuo-Yang Wang, John Gerard Coghlan, David Gerard Kiely, Joanna Wanda Pepke-Zaba, James Lawrence Lordan, Paul Anthony Corris, Linda Cadaret, Sif Hansdottir, Ronald Jack Oudiz, David B. Badesch, Michael Mathier, Robert Schilz, Nicholas Hill, Aaron Waxman, Catherine J. Markin, Diane Lynn Zwicke, Micah Fisher, Veronica Franco, Namita Sood, Myung H. Park, Roblee Allen, Jeremy P. Feldman, Vijay Balasubramanian, Vandana Kavita Seeram, Abubakr Bajwa, Austin B. Thompson, Christina Migliore, Jean Elwing, John W. McConnell, Jinesh P. Mehta, Franck Farzad Rahaghi, J. Eduardo Rame, Bela Patel, Ron M. Oren, James R. Klinger, Hassan Alnuaimat, Samuel Allen, William Harvey, Michael S. Eggert, Antoine Hage, Chad E. Miller, Rana Lee Adawi Awdish, Hector Cajigas, Daniel Grinnan, Benjamin Howard Trichon, Clark McDonough, Franz Rischard, ACS - Pulmonary hypertension & thrombosis, Pulmonary medicine, University of Rochester Medical Center (URMC), Unidad de Investigación Clínica En Medicina, Complexo Hospitalar da Santa Casa de Misericórdia de Porto Alegre, Instituto Nacional de Cardiologia Ignacio Chavez, Pontificia Universidad Católica de Chile (UC), Taichung Veterans General Hospital, Heidelberg University Hospital [Heidelberg], Ruby Hall Clinic, The Second Xiangya Hospital of Central South University [Hunan, China], Wuhan Asia Heart Hospital, National Heart Centre Singapore & Duke-National University of Singapore, Peking Union Medical College Hospital [Beijing] (PUMCH), Oregon Health and Science University [Portland] (OHSU), United Therapeutics Corporation, and Cedars-Sinai Medical Center
Subjects: Male, Administration, Oral, Oral treprostinil, Critical Care and Intensive Care Medicine, Pulmonary arterial hypertension, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, combination therapy, oral, epoprostenol, 0302 clinical medicine, pulmonary arterial hypertension, middle aged, Clinical endpoint, double-blind method, MESH: Double-Blind Method, Familial Primary Pulmonary Hypertension, 030212 general & internal medicine, humans, MESH: Aged, MESH: Middle Aged, Epoprostenol/analogs & derivatives, adult, Hazard ratio, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, antihypertensive agents, 3. Good health, aged, female, MESH: Young Adult, oral treprostinil, MESH: Administration, Oral, young adult, Female, Pulmonary Arterial Hypertension/drug therapy, medicine.drug, Adult, Pulmonary and Respiratory Medicine, MESH: Pulmonary Arterial Hypertension, medicine.medical_specialty, Randomization, Adolescent, clinical study, sequential therapy, administration, oral, adolescent, male, placebos, Sequential therapy, MESH: Placebos, MESH: Epoprostenol, Lower risk, Placebo, administration, Clinical study, Young Adult, 03 medical and health sciences, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Combination therapy, Adverse effect, Placebos/therapeutic use, Aged, MESH: Adolescent, Pulmonary Vascular Disease, MESH: Antihypertensive Agents, MESH: Humans, business.industry, MESH: Adult, Original Articles, MESH: Male, Clinical trial, 030228 respiratory system, Antihypertensive Agents/administration & dosage, business, MESH: Female, Treprostinil
Abstract: Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.\ud \ud Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.\ud \ud Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.\ud \ud Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.\ud \ud Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.\ud \ud Clinical trial registered with www.clinicaltrials.gov (NCT01560624).
Published: 2020

46. Kinome expression profiling to target new therapeutic avenues in multiple myeloma

Author: Jérôme Moreaux, Claire Gourzones, Nicolas Robert, Anke Maes, Michel Jourdan, Philippe Pasero, Elke De Bruyne, Guillaume Cartron, Angelique Bruyer, Anja Seckinger, Alboukadel Kassambara, Laure Vincent, Dirk Hose, Hugues de Boussac, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Vrije Universiteit Brussel (VUB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Interactions moléculaires et cancer (IMC (UMR 8126)), Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Heidelberg University Hospital [Heidelberg], Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE15-0024,TIE-Skip,Impact des immunoglobulines tronquées produites par saut d'exon dans les plasmocytes : vers des approches thérapeutiques utilisant des oligonucléotides antisens(2017), Vrije Universiteit Brussel, Clinical sciences, Faculty of Medicine and Pharmacy, Basic (bio-) Medical Sciences, and Hematology
Subjects: Melphalan, CHK1, SRPK1, Cell Cycle Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Protein Serine-Threonine Kinases, Article, Plasma Cell Disorders, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, MELK, medicine, Humans, Immunologic Factors, Kinome, CHEK1, Multiple myeloma (MM), Lenalidomide, Multiple myeloma, 030304 developmental biology, 0303 health sciences, Kinase, business.industry, MPS1/TTK), [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, 3. Good health, Gene expression profiling, 030220 oncology & carcinogenesis, Cancer research, CDC7-DBF4, PLK4, Neoplasm Recurrence, Local, Multiple Myeloma, business, medicine.drug, Protein kinas-es (PBK
Abstract: International audience; Multiple myeloma (MM) account for approximately 10% of hematological malignancies and is the second most common hematological disorder. Kinases inhibitors are widely used and their efficiency for the treatment of cancers has been demonstrated. Here, in order to identify kinases of potential therapeutic interest for the treatment of MM, we investigated the prognostic impact of the kinome expression profile in large cohorts of patients. We identified 36 kinome-related genes significantly linked with a prognostic value to MM, and built a kinome index based on their expression. The Kinome Index (KI) is linked to prognosis, proliferation, differentiation, and relapse in MM. We then tested inhibitors targeting seven of the identified protein kinas-es (PBK, SRPK1, CDC7-DBF4, MELK, CHK1, PLK4, MPS1/TTK) in human myeloma cell lines. All tested inhibitors significantly reduced the viability of myeloma cell lines, and we confirmed the potential clinical interest of three of them on primary myeloma cells from patients. In addition, we demonstrated their ability to potentialize the toxicity of conventional treatments, including Melphalan and Lenalidomide. This highlights their potential beneficial effect in myeloma therapy. Three kinases inhibitors (CHK1i, MELKi and PBKi) overcome resistance to Lenalidomide, while CHK1, PBK and DBF4 inhibitors re-sensitize Melphalan resistant cell line to this conventional therapeutic agent. Altogether, we demonstrate that kinase inhibitors could be of therapeutic interest especially in high-risk myeloma patients defined by the KI. CHEK1, MELK, PLK4, SRPK1, CDC7-DBF4, MPS1/TTK and PBK inhibitors could represent new treatment options either alone or in combination with Melphalan or IMiD for refractory/relapsing myeloma patients.
Published: 2020

47. 2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations

Author: Catherine Leroy, Séverine Amand, Anthony Mouray, David Tulasne, Andreas E. Kulozik, Christine Bailly, Thierry Chassat, Carole Trzaska, David Hannebique, Eric Adriaenssens, Jean-Michel Saliou, Elisabeth Werkmeister, Pierre-Arthur Moreau, Eric Westhof, Evelyne Duvernois-Berthet, Yuri Motorin, Romain Guilbert, Marie-Christine Copin, Virginie Marchand, Sylvie Rebuffat, Fabrice Lejeune, Hana Benhabiles, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Ingénierie, Biologie et Santé en Lorraine (IBSLor), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie moléculaire et adaptation (PhyMA), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Réseau International des Instituts Pasteur (RIIP), Laboratoire de Génie civil et Géo-environnement (LGCgE), Ecole nationale supérieure Mines-Télécom Lille Douai (IMT Lille Douai), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Lille-Université d'Artois (UA)-Université catholique de Lille (UCL)-École polytechnique universitaire de Lille (Polytech Lille), Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), F.L. is an Inserm researcher supported by fundings from Vaincre la mucoviscidose, the Association française contre les myopathies, the GIP Cancéropôle Nord Ouest, the Fondation Maladies Rares and the SATT Lutech, Authors would like to thank Dr. Jens Lykke-Andersen, Pr. P.A. Jänne and Pr. Lynne Maquat for reagents, Dr. Clément Carré, Dr. Bruno Lapeyre, Dr. Gabriele Neu-Yilik, Dr. Matthias Hentze, and Dr. Jean-Paul Renaud for helpful discussions. Authors also thank the Bicel facility for technical help, the PLEHTA for technical help on mouse managing and in vivo experiments, Valérie IGEL-BOURGUIGNON and Dr. Lilia AYADI from the Next-Generation Sequencing Core Facility of UMS2008 IBSLor (Université de Lorraine-CNRS-INSERM) for their help in RiboMethSeq library preparation and sequencing., Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers [Lille] (CANTHER), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université Lille Nord (France)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Pediatric Oncology, Alder Hey Children's Hospital, Alder Hey Children's Hospital, Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Médecine cellulaire et molécualire, PRES Université Lille Nord de France-Institut de Biologie de Lille-IFR 142, Université d'Artois (UA)-École polytechnique universitaire de Lille (Polytech Lille)-Université de Lille-Ecole nationale supérieure Mines-Télécom Lille Douai (IMT Lille Douai), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Yncréa Hauts-de-France, and Université catholique de Lille (UCL)-Université catholique de Lille (UCL)
Subjects: 0301 basic medicine, Molecular biology, General Physics and Astronomy, chemistry.chemical_compound, Mice, RNA, Transfer, lcsh:Science, 2-Aminopurine, ComputingMilieux_MISCELLANEOUS, Genetics, Regulation of gene expression, tRNA Methyltransferases, Multidisciplinary, Molecular medicine, Drug discovery, Lepisma, 3. Good health, Gene Expression Regulation, Neoplastic, Drug screening, Codon, Nonsense, Cytosine, Science, Nonsense mutation, Mice, Nude, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, Gene, RNA metabolism, 030102 biochemistry & molecular biology, 2,6-Diaminopurine, HEK 293 cells, fungi, RNA, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Chemistry, Genes, p53, Disease Models, Animal, 030104 developmental biology, HEK293 Cells, chemistry, Cancer cell, Mutation, lcsh:Q, Drug Screening Assays, Antitumor, HeLa Cells
Abstract: Nonsense mutations cause about 10% of genetic disease cases, and no treatments are available. Nonsense mutations can be corrected by molecules with nonsense mutation readthrough activity. An extract of the mushroom Lepista inversa has recently shown high-efficiency correction of UGA and UAA nonsense mutations. One active constituent of this extract is 2,6-diaminopurine (DAP). In Calu-6 cancer cells, in which TP53 gene has a UGA nonsense mutation, DAP treatment increases p53 level. It also decreases the growth of tumors arising from Calu-6 cells injected into immunodeficient nude mice. DAP acts by interfering with the activity of a tRNA-specific 2′-O-methyltransferase (FTSJ1) responsible for cytosine 34 modification in tRNATrp. Low-toxicity and high-efficiency UGA nonsense mutation correction make DAP a good candidate for the development of treatments for genetic diseases caused by nonsense mutations., Nonsense mutations can be corrected by several molecules that activate readthrough of premature termination codon. Here, the authors report that 2,6-diaminopurine efficiently corrects UGA nonsense mutations with no significant toxicity.
Published: 2020

48. The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

Author: Buffin-Meyer, Bénédicte, Klein, Julie, van der Zanden, Loes F M, Levtchenko, Elena, Moulos, Panogiotis, Lounis, Nadia, Conte-Auriol, Françoise, Hindryckx, An, Wühl, Elke, Persico, Nicola, Oepkes, Dick, Schreuder, Michiel F, Tkaczyk, Marcin, Ariceta, Gema, Fossum, Magdalena, Parvex, Paloma, Feitz, Wout, Olsen, Henning, Montini, Giovanni, Decramer, Stéphane, Schanstra, Joost P, De Catte, Luc, Vayssieres, Christophe, Sartor, Agnès, Groussolles, Marion, Plard, Christelle, Guerby, Paul, Connan, Laure, Morin, Mathieu, Simon, Elizabeth, Breaud, Jean, Saliou, Anne-Hélène, De Parscau, Loic, Jay, Nadine, Germouty, Isabelle, Le Bouar, Gwenaelle, Ryckewaert, Amelie, Manca-Pellissier, Marie-Christine, Merrot, Thierry, Laurichesse, Helene, Gallot, Denis, Bessenay, Lucie, Bidat, Laurent, Boize, Philippe, Winer, Norbert, Allain-Launey, Emma, Le Vaillant, Claudine, Prieur, Fabienne, Lavocat, Marie-Pierre, Coatleven, Frederic, Debromez, Eric, Harembat, Jérôme, Llanas, Brigitte, Favre, Romain, Moog, Raphael, Zaloszyc, Ariane, Massardier, Jérôme, Demede, Delphine, Perrotin, Franck, Cloarec, Sylvie, Vequeau-Goua, Valérie, Descombes, Emmanuelle, Boulot, Pierre, Morin, Denis, Fuchs, Florent, Tenenbaum, Julie, Ville, Yves, Blanc, Thomas, Heidet, Laurence, Paris, Anne, Dobremez, Eric, Froute, Marie-Françoise, Gondry, Jean, Muszynski, Charles, Haraux, Elodie, Lobelle, Fabienne, Chevreau, Julien, Rosenblatt, Jonathan, Baudoin, Véronique, Deschenes, Georges, Guigue, Virginie, Amblard, Florence, Bourdat-Michel, Guylhène, Schaefer, Franz, Elsässer, Michael, Rossi, Federica, Manzoni, Gianantonio, De Marco, Erika A, Capone, Valentina, Caforio, Leonardo, Zaccara, Antonio, Innocenzi, Michele, Bagolan, Pietro, Capozza, Nicola, Castagnetti, Marco, Mancini, Mariangela, van Scheltema, Phebe Adama, Kortmann, Barbara, Schreuder, Michiel, Stańczyk, Małgorzata, Szaflik, Krzysztof, Wojtera, Justyna, Krzeszowski, Waldemar, Talar, Tomasz, Pawłowska, Barbara, Fortecka-Piestrzeniewicz, Katarzyna, Olejniczak, Dariusz, Arevalo, Silvia, Rodo, Carlota, Lindgren, Peter, Chehade, Hassib, ANTENATAL Consortium, Hindryckx, A., De Catte, L., Vayssieres, C., Sartor, A., Groussolles, M., Plard, C., Guerby, P., Connan, L., Morin, M., Simon, E., Breaud, J., Saliou, A.H., De Parscau, L., Jay, N., Germouty, I., Le Bouar, G., Ryckewaert, A., Manca-Pellissier, M.C., Merrot, T., Laurichesse, H., Gallot, D., Bessenay, L., Bidat, L., Boize, P., Winer, N., Allain-Launey, E., Le Vaillant, C., Prieur, F., Lavocat, M.P., Coatleven, F., Debromez, E., Harembat, J., Llanas, B., Favre, R., Moog, R., Zaloszyc, A., Massardier, J., Demede, D., Perrotin, F., Cloarec, S., Vequeau-Goua, V., Descombes, E., Boulot, P., Morin, D., Fuchs, F., Tenenbaum, J., Ville, Y., Blanc, T., Heidet, L., Paris, A., Dobremez, E., Froute, M.F., Gondry, J., Muszynski, C., Haraux, E., Lobelle, F., Chevreau, J., Rosenblatt, J., Baudoin, V., Deschenes, G., Guigue, V., Amblard, F., Bourdat-Michel, G., Wühl, E., Schaefer, F., Elsässer, M., Persico, N., Rossi, F., Manzoni, G., De Marco, E.A., Montini, G., Capone, V., Caforio, L., Zaccara, A., Innocenzi, M., Bagolan, P., Capozza, N., Castagnetti, M., Mancini, M., Oepkes, D., van Scheltema, P.A., Feitz, W., Kortmann, B., Schreuder, M., Tkaczyk, M., Stańczyk, M., Szaflik, K., Wojtera, J., Krzeszowski, W., Talar, T., Pawłowska, B., Fortecka-Piestrzeniewicz, K., Olejniczak, D., Ariceta, G., Arevalo, S., Rodo, C., Fossum, M., Lindgren, P., Parvex, P., Chehade, H., Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Radboud University Medical Center [Nijmegen], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), HybridStat Predictive Analytics [Athens, Greece], Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospitals Leuven [Leuven], Heidelberg University Hospital [Heidelberg], University of Milan, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico [Milan, Italy], Leiden University Medical Center (LUMC), Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Polish Mother’s Memorial Hospital Research Institute [Lodz] (ICZMP), Pediatric Nephrology [Barcelona, Spain] (Vall d’Hebron Hospital), Universitat Autònoma de Barcelona (UAB)-Vall d'Hebron University Hospital [Barcelona], Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Geneva University Hospital (HUG), Aarhus University Hospital, Aarhus University [Aarhus], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, ANTENATAL Consortium: An Hindryckx, Luc De Catte, Christophe Vayssieres, Agnès Sartor, Marion Groussolles, Christelle Plard, Paul Guerby, Laure Connan, Mathieu Morin, Elizabeth Simon, Jean Breaud, Anne-Hélène Saliou, Loic De Parscau, Nadine Jay, Isabelle Germouty, Gwenaelle Le Bouar, Amelie Ryckewaert, Marie-Christine Manca-Pellissier, Thierry Merrot, Helene Laurichesse, Denis Gallot, Lucie Bessenay, Laurent Bidat, Philippe Boize, Norbert Winer, Emma Allain-Launey, Claudine Le Vaillant, Fabienne Prieur, Marie-Pierre Lavocat, Frederic Coatleven, Eric Debromez, Jérôme Harembat, Brigitte Llanas, Romain Favre, Raphael Moog, Ariane Zaloszyc, Jérôme Massardier, Delphine Demede, Franck Perrotin, Sylvie Cloarec, Valérie Vequeau-Goua, Emmanuelle Descombes, Pierre Boulot, Denis Morin, Florent Fuchs, Julie Tenenbaum, Yves Ville, Thomas Blanc, Laurence Heidet, Anne Paris, Eric Dobremez, Marie-Françoise Froute, Jean Gondry, Charles Muszynski, Elodie Haraux, Fabienne Lobelle, Julien Chevreau, Jonathan Rosenblatt, Véronique Baudoin, Georges Deschenes, Virginie Guigue, Florence Amblard, Guylhène Bourdat-Michel, Elke Wühl, Franz Schaefer, Michael Elsässer, Nicola Persico, Federica Rossi, Gianantonio Manzoni, Erika A De Marco, Giovanni Montini, Valentina Capone, Leonardo Caforio, Antonio Zaccara, Michele Innocenzi, Pietro Bagolan, Nicola Capozza, Marco Castagnetti, Mariangela Mancini, Dick Oepkes, Phebe Adama van Scheltema, Wout Feitz, Barbara Kortmann, Michiel Schreuder, Marcin Tkaczyk, Małgorzata Stańczyk, Krzysztof Szaflik, Justyna Wojtera, Waldemar Krzeszowski, Tomasz Talar, Barbara Pawłowska, Katarzyna Fortecka-Piestrzeniewicz, Dariusz Olejniczak, Gema Ariceta, Silvia Arevalo, Carlota Rodo, Magdalena Fossum, Peter Lindgren, Paloma Parvex, Hassib Chehade., Schanstra, Joost, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: Posterior urethral valve, medicine.medical_specialty, Urinary system, [SDV]Life Sciences [q-bio], kidney disease, prenatal biomarkers, Renal function, Prenatal care, 030204 cardiovascular system & hematology, DIAGNOSIS, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Medicine, obstructive uropathy, Obstructive uropathy, development, 030304 developmental biology, RISK, 0303 health sciences, Transplantation, Kidney, ddc:618, Science & Technology, business.industry, Obstetrics, Original Articles, prediction, Urology & Nephrology, Omics, medicine.disease, 6. Clean water, 3. Good health, [SDV] Life Sciences [q-bio], Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], medicine.anatomical_structure, Nephrology, embryonic structures, Settore MED/20, URINARY-TRACT OBSTRUCTION, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, Life Sciences & Biomedicine, Kidney disease
Abstract: Altres ajuts: The study is partially made possible by support of the 'Programme Hospitalier de Recherche Clinique and 'La Foundation de la Recherche Médicale (grant number DEQ20170336759, France). M.T. was supported by the Polish Mothers Memorial Hospital Research Institute (internal grant number 2016/IV/54-GW. LvdZ is supported by a Kolff grant from the Dutch Kidney Foundation (13OKJ36) and a ZonMW-VENI grant from the Netherlands Organisation for Scientific Research (91618036). This project has been supported by ERN ERKNet and ERN eUROGEN, which are partly co-funded by the European Union within the framework of the Third Health Programme 'ERN-2016-Framework Partnership Agreement 2017-2021'. Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1-β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV.
Published: 2020

49. Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Author: Edoardo Bertero, Linda W. van Laake, Petar M. Seferovic, Ewa A. Jankowska, Javid Moslehi, Frank Ruschitzka, Richard N. Kitsis, Johann Bauersachs, Jean-Sébastien Hulot, Ovidiu Chioncel, Patrycja Nowak-Sliwinska, Joseph Pierre Aboumsallem, Dirk Jäger, Rudolf A. de Boer, Peter van der Meer, Douglas B. Sawyer, Dimitrios Farmakis, Lorenz H. Lehmann, Johannes Backs, Christoph Maack, Carlo G. Tocchetti, Suma H Konety, Massimo F Piepoli, Thomas Thum, Radek Pudil, Oliver J. Müller, Daniel J. Lenihan, James Larkin, Alexander R. Lyon, Pierre Dodion, Thomas M. Suter, Pietro Ameri, Thomas Eschenhagen, Antoni Bayes-Genis, Jelena Čelutkienė, Stephan von Haehling, Peter P. Rainer, Andrew J.S. Coats, Piotr Ponikowski, Stefan D. Anker, Stephane Heymans, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), University Medical Center Groningen [Groningen] (UMCG), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University of Naples Federico II, Universita degli studi di Genova, IRCCS Ospedale Policlinico San Martino [Genoa, Italy], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Hannover Medical School [Hannover] (MHH), University Hospital of Würzburg, San Raffaele Pisana Scientific Institute for Resaearch, Hospitalisation, and Health Care, San Raffaele Institute Pisana, Vilnius University [Vilnius], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Innate Pharma, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Cyprus (UCY), National and Kapodistrian University of Athens (NKUA), Hospital Universitari Germans Trias I Pujol [Badalona], Universitat Autònoma de Barcelona (UAB), Instituto de Salud Carlos III [Madrid] (ISC), Heidelberg University Hospital [Heidelberg], Wroclaw Medical University [Wrocław, Pologne], Albert Einstein College of Medicine [New York], University of Minnesota Medical School, University of Minnesota System, Royal Marsden NHS Foundation Trust, Universität Heidelberg [Heidelberg], Washington University in Saint Louis (WUSTL), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Kiel University, University of Geneva [Switzerland], University of Parma = Università degli studi di Parma [Parme, Italie], University Hospital Hradec Kralove, Medical University of Graz, University hospital of Zurich [Zurich], Maine Medical Center Research Institute (MMCRI), University of Belgrade [Belgrade], University of Bern, Utrecht University [Utrecht], University of Göttingen - Georg-August-Universität Göttingen, Maastricht University [Maastricht], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Imperial College London, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: Carim - H02 Cardiomyopathy
Subjects: Cardiac & Cardiovascular Systems, SYMPATHETIC-NERVOUS-SYSTEM, [SDV]Life Sciences [q-bio], angiogenesis, cancer, cardio-oncology, cardiotoxicity, clonal haematopoiesis, extracellular matrix, heart failure, inflammation, metabolism, Disease, Comorbidity, 030204 cardiovascular system & hematology, Bioinformatics, DISEASE, 0302 clinical medicine, Risk Factors, Neoplasms, CACHEXIA, INCREASED RISK, Cancer, ddc:615, TUMOR-GROWTH, CLONAL HEMATOPOIESIS, Extracellular matrix, 3. Good health, Cardio‐oncology, Cardio-oncology, oncology, Position Paper, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, CARDIAC DYSFUNCTION, DOXORUBICIN, Translational research, Context (language use), Heart failure, Clonal haematopoiesis, RADIATION-EXPOSURE, ANTHRACYCLINE CARDIOTOXICITY, 03 medical and health sciences, Genetic predisposition, medicine, Humans, Clinical significance, Inflammation, Science & Technology, business.industry, Cardio&#8208, medicine.disease, Cardiotoxicity, Metabolism, Cardiovascular System & Cardiology, Personalized medicine, Angiogenesis, business
Abstract: The co‐occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre‐clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time., We describe the co‐occurrence of cancer and heart failure (HF), their potential shared risk factors, and their pathophysiological mechanisms. We advocate intense interaction between cardiologists and oncologists to achieve unifying hypotheses and collaborative pre‐clinical and clinical studies.
Published: 2020

50. SBML Level 3: an extensible format for the exchange and reuse of biological models

Author: Edda Klipp, Marco Antoniotti, Frank Bergmann, James C. Schaff, Peter D. Karp, Daniel Lucio, Kedar Nath Natarajan, Thomas M. Hamm, Leandro Watanabe, Henning Hermjakob, David Tolnay, John Wagner, Joerg Stelling, Alida Palmisano, Falk Schreiber, Yukiko Matsuoka, Harold F. Gómez, Huaiyu Mi, Carole J. Proctor, Ulrike Wittig, Neil Swainston, Jan Červený, Denis Thieffry, Piero Dalle Pezze, Julio Saez-Rodriguez, Maciej J. Swat, Bin Hu, Martina Kutmon, Thomas Pfau, Bas Teusink, Sarah M. Keating, Fedor A. Kolpakov, Andreas Dräger, Pedro Mendes, Martin Scharm, Emek Demir, Ioannis Xenarios, Christoph Flamm, Axel von Kamp, Darren J. Wilkinson, Nick Juty, Fengkai Zhang, Leonard A. Harris, Michael Schubert, Dagmar Waltemath, Lucian P. Smith, Steffen Klamt, Herbert M. Sauro, Ali Ebrahim, Wolfram Liebermeister, Christian Knüpfer, Nicolas Rodriguez, Tramy Nguyen, Naoki Tanimura, Christopher Cox, Stuart C. Sealfon, Nicholas Alexander Allen, Clemens Wrzodek, Bastian R. Angermann, Martin Meier-Schellersheim, Anna Zhukova, Jean-Baptiste Pettit, Hovakim Grabski, Devin P. Sullivan, Claudine Chaouiya, Michael L. Blinov, John Doyle, Ilya Kiselev, Roman Schulte, Alex Gutteridge, Mélanie Courtot, Eric Mjolsness, Finja Wrzodek, Rahuman S Malik-Sheriff, Ronan M. T. Fleming, Bruce E. Shapiro, Kimberly Begley, Leslie M. Loew, Colin S. Gillespie, Ibrahim Vazirabad, Michael Hucka, Akira Funahashi, Bernhard O. Palsson, Hamid Bolouri, Tomáš Helikar, Camille Laibe, William S. Denney, Chris T. Evelo, Florian Mittag, William S. Hlavacek, Ron Henkel, Harish Dharuri, Julien Dorier, Karthik Raman, Martina Fröhlich, Conor Lawless, Rainer Machné, Falko Krause, Damon Hachmeister, Matthias König, Clifford A. Shaffer, Benjamin D. Heavner, Douglas B. Kell, Jonathan R. Karr, Mihai Glont, Lukas Endler, Melanie I. Stefan, Robert Phair, Lu Li, Henning Schmidt, Dirk Drasdo, Johan Elf, Allyson L. Lister, Hiroaki Kitano, Richard R. Adams, Oliver A. Ruebenacker, Roland Keller, Sven Sahle, Ion I. Moraru, Gary D. Bader, Poul M. F. Nielsen, Johann M. Rohwer, Johannes Eichner, Daniel R. Hyduke, James R. Faeder, Stefan Hoops, Emanuel Gonçalves, Yuichiro Inagaki, Aurélien Naldi, Koichi Takahashi, Sylvain Soliman, Brett G. Olivier, Kieran Smallbone, Stuart L. Moodie, Pedro T. Monteiro, Chris J. Myers, Martin Golebiewski, Tomas Radivoyevitch, Jeremy Zucker, Hidde de Jong, Andrew Finney, Keating, S, Waltemath, D, König, M, Zhang, F, Dräger, A, Chaouiya, C, Bergmann, F, Finney, A, Gillespie, C, Helikar, T, Hoops, S, Malik-Sheriff, R, Moodie, S, Moraru, I, Myers, C, Naldi, A, Olivier, B, Sahle, S, Schaff, J, Smith, L, Swat, M, Thieffry, D, Watanabe, L, Wilkinson, D, Blinov, M, Begley, K, Faeder, J, Gómez, H, Hamm, T, Inagaki, Y, Liebermeister, W, Lister, A, Lucio, D, Mjolsness, E, Proctor, C, Raman, K, Rodriguez, N, Shaffer, C, Shapiro, B, Stelling, J, Swainston, N, Tanimura, N, Wagner, J, Meier-Schellersheim, M, Sauro, H, Palsson, B, Bolouri, H, Kitano, H, Funahashi, A, Hermjakob, H, Doyle, J, Hucka, M, Adams, R, Allen, N, Angermann, B, Antoniotti, M, Bader, G, Červený, J, Courtot, M, Cox, C, Dalle Pezze, P, Demir, E, Denney, W, Dharuri, H, Dorier, J, Drasdo, D, Ebrahim, A, Eichner, J, Elf, J, Endler, L, Evelo, C, Flamm, C, Fleming, R, Fröhlich, M, Glont, M, Gonçalves, E, Golebiewski, M, Grabski, H, Gutteridge, A, Hachmeister, D, Harris, L, Heavner, B, Henkel, R, Hlavacek, W, Hu, B, Hyduke, D, Jong, H, Juty, N, Karp, P, Karr, J, Kell, D, Keller, R, Kiselev, I, Klamt, S, Klipp, E, Knüpfer, C, Kolpakov, F, Krause, F, Kutmon, M, Laibe, C, Lawless, C, Li, L, Loew, L, Machne, R, Matsuoka, Y, Mendes, P, Mi, H, Mittag, F, Monteiro, P, Natarajan, K, Nielsen, P, Nguyen, T, Palmisano, A, Jean-Baptiste, P, Pfau, T, Phair, R, Radivoyevitch, T, Rohwer, J, Ruebenacker, O, Saez-Rodriguez, J, Scharm, M, Schmidt, H, Schreiber, F, Schubert, M, Schulte, R, Sealfon, S, Smallbone, K, Soliman, S, Stefan, M, Sullivan, D, Takahashi, K, Teusink, B, Tolnay, D, Vazirabad, I, Kamp, A, Wittig, U, Wrzodek, C, Wrzodek, F, Xenarios, I, Zhukova, A, Zucker, J, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Heidelberg University Hospital [Heidelberg], Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), European Molecular Biology Laboratory (EMBL), University of Connecticut (UCONN), National Institutes of Health [Bethesda] (NIH), Chercheur indépendant, Amazon Web Services [Seattle] (AWS), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), University of Toronto, Masaryk University [Brno] (MUNI), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, The University of Tennessee [Knoxville], The Babraham Institute [Cambridge, UK], Oregon Health and Science University [Portland] (OHSU), Human Predictions LLC, Illumina, Swiss-Prot Group, Swiss Institute of Bioinformatics [Genève] (SIB), Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California [San Diego] (UC San Diego), University of California (UC), Center for Bioinformatics (ZBIT), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Uppsala University, Institut für Populationsgenetik [Vienna], Veterinärmedizinische Universität Wien, Maastricht University [Maastricht], Alpen-Adria-Universität Klagenfurt [Klagenfurt, Austria], Medizinische Universität Wien = Medical University of Vienna, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg Institute for Theoretical Studies (HITS ), Russian-Armenian University (RAU), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Microsoft Technology Licensing (MTL), Microsoft Corporation [Redmond, Wash.], Vanderbilt University School of Medicine [Nashville], University of Washington [Seattle], University of Rostock, Los Alamos National Laboratory (LANL), Lorentz Institute, Universiteit Leiden, Tegmine Therapeutics, Modeling, simulation, measurement, and control of bacterial regulatory networks (IBIS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Jean Roget, SRI International [Menlo Park] (SRI), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Liverpool, Universitätsklinikum Tübingen - University Hospital of Tübingen, Institute of Information and Computational Technologies (IICT), Max Planck Institute for Dynamics of Complex Technical Systems, Max-Planck-Gesellschaft, Max-Planck-Institut für Molekulare Genetik (MPIMG), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Humboldt University Of Berlin, Newcastle University [Newcastle], École polytechnique (X), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], The Systems Biology Institute [Tokyo] (SBI), Centro de Quimica Estrutural (CQE), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST), University of Southern California (USC), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, University of Southern Denmark (SDU), University of Auckland [Auckland], University of Utah, Virginia Tech [Blacksburg], University of Luxembourg [Luxembourg], Integrative Bioinformatics Inc [Mountain View], Cleveland Clinic, Stellenbosch University, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Universität Heidelberg [Heidelberg] = Heidelberg University, Leibniz Institute of Plant Genetics and Crop Plant Research [Gatersleben] (IPK-Gatersleben), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Manchester [Manchester], Computational systems biology and optimization (Lifeware), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), California Institute of Technology (CALTECH), Encodia Inc [San Diego], Shinshu University [Nagano], University of Amsterdam [Amsterdam] (UvA), Versiti Blood Center of Wisconsin, Greifswald University Hospital, Bioinformatique évolutive - Evolutionary Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Pacific Northwest National Laboratory (PNNL), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), Department of Bioengineering, University of California (UC)-University of California (UC), ANSYS, Virginia Polytechnic Institute and State University [Blacksburg], Eight Pillars Ltd, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Universität Heidelberg, Bioquant, Applied Biomathematics [New York], SimCYP Ltd, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Utah School of Medicine [Salt Lake City], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Mizuho Information and Research Institute, Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Oxford, Computer Science (North Carolina State University), North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of California [Irvine] (UC Irvine), Indian Institute of Technology Madras (IIT Madras), California State University [Northridge] (CSUN), Biotechnology and Biological Sciences Research Council (BBSRC), IBM Research [Melbourne], Benaroya Research Institute [Seattle] (BRI), Okinawa Institute of Science and Technology Graduate University, Keio University, Department of Computing and Mathematical sciences, members, SBML Level 3 Community, Université de Lausanne (UNIL), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of California, Universiteit Leiden [Leiden], Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Inria Grenoble - Rhône-Alpes, Humboldt University of Berlin, Universität Heidelberg [Heidelberg], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Humboldt-Universität zu Berlin, University of California-University of California, Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], University of California [Irvine] (UCI), Biotechnology and Biological Sciences Research Council, Computer Science, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)
Subjects: computational modeling, Medicine (General), Markup language, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, INFORMATION, Interoperability, interoperability, Review, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], ANNOTATION, 0302 clinical medicine, Software, file forma, Models, Biology (General), 0303 health sciences, Computational model, Applied Mathematics, Systems Biology, systems biology, File format, 3. Good health, Networking and Information Technology R&D, Networking and Information Technology R&D (NITRD), Computational Theory and Mathematics, SIMULATION, General Agricultural and Biological Sciences, STANDARDS, REPOSITORY, Information Systems, QH301-705.5, Bioinformatics, Systems biology, Software ecosystem, Reviews, Bioengineering, Methods & Resources, Biology, MARKUP LANGUAGE, Models, Biological, SBML Level 3 Community members, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, R5-920, Animals, Humans, SBML, reproducibility, 030304 developmental biology, ENVIRONMENT, General Immunology and Microbiology, file format, business.industry, Computational Biology, Biological, ONTOLOGY, Metabolism, Logistic Models, Biochemistry and Cell Biology, Other Biological Sciences, Software engineering, business, 030217 neurology & neurosurgery
Abstract: Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution., Over the past two decades, scientists from different fields have been developing SBML, a standard format for encoding computational models in biology and medicine. This article summarizes recent progress and gives perspectives on emerging challenges.
Published: 2020

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