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Pracoviště: Department of Neurology University of Ulm

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Genome-wide Association Study Identifies 2 New Loci Associated With Anti-NMDAR Encephalitis

Tietz, Anja K
Autor Tietz, Anja K From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany
Angstwurm, Klemens
Autor Angstwurm, Klemens ORCID From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany
Baumgartner, Tobias
Autor Baumgartner, Tobias From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany
Doppler, Kathrin
Autor Doppler, Kathrin ORCID From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany
Eisenhut, Katharina
Autor Eisenhut, Katharina ORCID From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany
Elisak, Martin
Autor Elisak, Martin From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany
Franke, Andre
Autor Franke, Andre ORCID From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany
Golombeck, Kristin S
Autor Golombeck, Kristin S From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany
Handreka, Robert
Autor Handreka, Robert From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany
Kaufmann, Max
Autor Kaufmann, Max ORCID From the Department of Neurology (A.K.T., F.L., G.K.), Kiel University Department of Neurology (K.A.), University Hospital Regensburg Department of Epileptiology (T.B.), University Hospital Bonn Department of Neurology (K.D.), University Hospital Würzburg Institute of Clinical Neuroimmunology (K.E.), Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany Department of Neurology (M.E., H.M.), Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Institute of Clinical Molecular Biology (A.F.), Kiel University Department of Neurology (K.S.G.), University Hospital Münster Department of Neurology (R.H.), Carl-Thiem-Klinikum Cottbus Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (Max Kaufmann), University Medical Center Hamburg-Eppendorf Department of Neurology (Markus Kraemer), Alfried Krupp Hospital, Essen Department of Neurology (Markus Kraemer, N.M.), Medical Faculty, Heinrich-Heine University Düsseldorf Department of Neurology (A.K.), Martha-Maria Hospital Halle Department of Neurology (J.L.), University of Ulm Institute of Epidemiology (W.L.), Kiel University Department of Neurology (M.M.), University Hospital Cologne Department of Neurology and Clinical Neurophysiology (P.M.), Klinikum Weimar Department of Neurology (T.P.), Klinikum Ingolstadt Department of Neurology and Experimental Neurology (H.P.), Charité - Universitätsmedizin Berlin and German Center for Neurodegenerative Diseases (DZNE) Berlin Department of Pediatric Neurology (K.R.), Children's Hospital Datteln, Witten/Herdecke University Department of Neurology (M.S.), Asklepios Hospitals Schildautal, Seesen Neuroimmunology (I.S., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck Epilepsy Center Frankfurt Rhine-Main and Department of Neurology (K.S.), Unversity Hospital and Goethe Universiy Frankfurt Department of Neurology (K.-W.S.), Hannover Medical School and Section Translational Neuroimmunology (J.W.), Department of Neurology, University Hospital Jena, Germany

Neurology® neuroimmunology & neuroinflammation. 2021 ; 8 (6) : . [pub] 20210928

Neurol Neuroimmunol Neuroinflamm
ISSN 2332-7812
Medvik
Zdroj

BACKGROUND AND OBJECTIVES: To investigate the genetic determinants of the most common type of antibody-mediated autoimmune encephalitis, anti-NMDA receptor (anti-NMDAR) encephalitis. METHODS: We performed a genome-wide association study in 178 patients with anti-NMDAR encephalitis and 590 healthy controls, followed by a colocalization analysis to identify putatively causal genes. RESULTS: We identified 2 independent risk loci harboring genome-wide significant variants (p < 5 × 10-8, OR ≥ 2.2), 1 on chromosome 15, harboring only the LRRK1 gene, and 1 on chromosome 11 centered on the ACP2 and NR1H3 genes in a larger region of high linkage disequilibrium. Colocalization signals with expression quantitative trait loci for different brain regions and immune cell types suggested ACP2, NR1H3, MADD, DDB2, and C11orf49 as putatively causal genes. The best candidate genes in each region are LRRK1, encoding leucine-rich repeat kinase 1, a protein involved in B-cell development, and NR1H3 liver X receptor alpha, a transcription factor whose activation inhibits inflammatory processes. DISCUSSION: This study provides evidence for relevant genetic determinants of antibody-mediated autoimmune encephalitides outside the human leukocyte antigen (HLA) region. The results suggest that future studies with larger sample sizes will successfully identify additional genetic determinants and contribute to the elucidation of the pathomechanism.

MeSH
celogenomová asociační studie * MeSH
dospělí MeSH
encefalitida s protilátkami proti NMDA receptorům genetika MeSH
genetické lokusy MeSH
lidé MeSH
studie případů a kontrol MeSH
Check Tag
dospělí MeSH
lidé MeSH
mužské pohlaví MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Research Support, N.I.H., Extramural MeSH

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