Institution
University of Duisburg-Essen
Education•Essen, Nordrhein-Westfalen, Germany•
About: University of Duisburg-Essen is a education organization based out in Essen, Nordrhein-Westfalen, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 16072 authors who have published 39972 publications receiving 1109199 citations.
Papers published on a yearly basis
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TL;DR: Inhibition of Asm as a new treatment strategy for cystic fibrosis is suggested because it shows that ceramide age-dependently accumulates in the respiratory tract of uninfected Cftr-deficient mice and prevents all pathological findings, including susceptibility to infection.
Abstract: Microbial lung infections are the major cause of morbidity and mortality in the hereditary metabolic disorder cystic fibrosis, yet the molecular mechanisms leading from the mutation of cystic fibrosis transmembrane conductance regulator (CFTR) to lung infection are still unclear. Here, we show that ceramide age-dependently accumulates in the respiratory tract of uninfected Cftr-deficient mice owing to an alkalinization of intracellular vesicles in Cftr-deficient cells. This change in pH results in an imbalance between acid sphingomyelinase (Asm) cleavage of sphingomyelin to ceramide and acid ceramidase consumption of ceramide, resulting in the higher levels of ceramide. The accumulation of ceramide causes Cftr-deficient mice to suffer from constitutive age-dependent pulmonary inflammation, death of respiratory epithelial cells, deposits of DNA in bronchi and high susceptibility to severe Pseudomonas aeruginosa infections. Partial genetic deficiency of Asm in Cftr(-/-)Smpd1(+/-) mice or pharmacological treatment of Cftr-deficient mice with the Asm blocker amitriptyline normalizes pulmonary ceramide and prevents all pathological findings, including susceptibility to infection. These data suggest inhibition of Asm as a new treatment strategy for cystic fibrosis.
517 citations
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University of Erlangen-Nuremberg1, University of Tübingen2, University of Zurich3, University of Duisburg-Essen4, Hannover Medical School5, Heidelberg University6, Otto-von-Guericke University Magdeburg7, University Hospital Heidelberg8, Ludwig Maximilian University of Munich9, University of Münster10, RWTH Aachen University11, University of Würzburg12, Technische Universität München13
TL;DR: Anti-PD1 antibodies can induce a plethora of irAEs, and the knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity.
517 citations
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TL;DR: The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index.
Abstract: Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
517 citations
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TL;DR: Genetic profiling revealed that molecular subgroups of patients undergoing allogeneic hematopoietic stem‐cell transplantation for MDS may inform prognostic stratification and the selection of conditioning regimen.
Abstract: BackgroundGenetic mutations drive the pathogenesis of the myelodysplastic syndrome (MDS) and are closely associated with clinical phenotype. Therefore, genetic mutations may predict clinical outcomes after allogeneic hematopoietic stem-cell transplantation. MethodsWe performed targeted mutational analysis on samples obtained before transplantation from 1514 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research Repository between 2005 and 2014. We evaluated the association of mutations with transplantation outcomes, including overall survival, relapse, and death without relapse. ResultsTP53 mutations were present in 19% of the patients and were associated with shorter survival and a shorter time to relapse than was the absence of TP53 mutations, after adjustment for significant clinical variables (P<0.001 for both comparisons). Among patients 40 years of age or older who did not have TP53 mutations, the presence of RAS pathway mutations was associated with...
508 citations
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TL;DR: Clinically silent new foci of restricted diffusion on cerebral magnetic resonance imaging were detected in almost all patients undergoing TAVI, although typically multiple, these foci were not associated with apparent neurological events or measurable deterioration of neurocognitive function during 3-month follow-up.
Abstract: Background— The risk of stroke after transfemoral aortic valve implantation (TAVI) due to dislodgement and subsequent embolization of debris from aortic arch atheroma or from the calcified valve itself ranges between 2% and 10%. The rate of clinically silent cerebral ischemia is unknown but may be even higher. Methods and Results— Thirty-two patients who underwent TAVI with the use of a balloon-expandable (n=22) or self-expandable (n=10) stent valve prosthesis were included in this descriptive study and compared with a historical control group of 21 patients undergoing open surgical aortic valve replacement. Periprocedural apparent and silent cerebral ischemia was assessed by neurological testing and serial cerebral diffusion-weighted magnetic resonance imaging at baseline, at 3.4 (2.5 to 4.4) days after the procedure, and at 3 months. TAVI was successful in all patients. After the procedure, new foci of restricted diffusion on cerebral diffusion-weighted magnetic resonance imaging were found in 27 of 32 ...
507 citations
Authors
Showing all 16364 results
Name | H-index | Papers | Citations |
---|---|---|---|
Rui Zhang | 151 | 2625 | 107917 |
Olli T. Raitakari | 142 | 1232 | 103487 |
Anders Hamsten | 139 | 611 | 88144 |
Robert Huber | 139 | 671 | 73557 |
Christopher T. Walsh | 139 | 819 | 74314 |
Patrick D. McGorry | 137 | 1097 | 72092 |
Stanley Nattel | 132 | 778 | 65700 |
Luis M. Liz-Marzán | 132 | 616 | 61684 |
Dirk Schadendorf | 127 | 1017 | 105777 |
William Wijns | 127 | 752 | 95517 |
Raimund Erbel | 125 | 1364 | 74179 |
Khalil Amine | 118 | 652 | 50111 |
Hans-Christoph Diener | 118 | 1025 | 91710 |
Bruce A.J. Ponder | 116 | 403 | 54796 |
Andre Franke | 115 | 682 | 55481 |