Institution
Sheba Medical Center
Healthcare•Ramat Gan, Israel•
About: Sheba Medical Center is a healthcare organization based out in Ramat Gan, Israel. It is known for research contribution in the topics: Population & Transplantation. The organization has 12449 authors who have published 21761 publications receiving 734412 citations. The organization is also known as: Chaim Sheba Medical Center at Tel HaShomer & Tel HaShomer Hospital.
Topics: Population, Transplantation, Cancer, Medicine, Pregnancy
Papers published on a yearly basis
Papers
More filters
••
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
6,809 citations
••
University of New South Wales1, Hospital for Special Surgery2, Hokkaido University3, University of Utah4, University of Texas Health Science Center at San Antonio5, Utrecht University6, University of Milan7, Geneva College8, Sheba Medical Center9, University of Brescia10, National and Kapodistrian University of Athens11
TL;DR: This document appraise the existing evidence on clinical and laboratory features of APS addressed during the forum and proposes amendments to the Sapporo criteria, including definitions on features ofAPS that were not included in the updated criteria.
5,699 citations
••
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
••
TL;DR: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma.
Abstract: Background The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. Methods In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks. Primary end points were progressionfree and overall survival. Results The estimated 6-month progression-free-survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (hazard ratio for disease progression, 0.58; P<0.001 for both pembrolizumab regimens versus ipilimumab; 95% confidence intervals [CIs], 0.46 to 0.72 and 0.47 to 0.72, respectively). Estimated 12-month survival rates were 74.1%, 68.4%, and 58.2%, respectively (hazard ratio for death for pembrolizumab every 2 weeks, 0.63; 95% CI, 0.47 to 0.83; P = 0.0005; hazard ratio for pembrolizumab every 3 weeks, 0.69; 95% CI, 0.52 to 0.90; P = 0.0036). The response rate was improved with pembrolizumab administered every 2 weeks (33.7%) and every 3 weeks (32.9%), as compared with ipilimumab (11.9%) (P<0.001 for both comparisons). Responses were ongoing in 89.4%, 96.7%, and 87.9% of patients, respectively, after a median follow-up of 7.9 months. Efficacy was similar in the two pembrolizumab groups. Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups (13.3% and 10.1%) than in the ipilimumab group (19.9%). Conclusions The anti–PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. (Funded by Merck Sharp & Dohme; KEYNOTE-006 ClinicalTrials .gov number, NCT01866319.)
4,612 citations
••
TL;DR: The findings suggest that RNA decoration by m6A has a fundamental role in regulation of gene expression, and a subset of stimulus-dependent, dynamically modulated sites is identified.
Abstract: An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N(6)-methyladenosine (m(6)A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m(6)A modification landscape in a transcriptome-wide manner, using a novel approach, m(6)A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m(6)A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks--around stop codons and within long internal exons--and are highly conserved between human and mouse. Although most sites are well preserved across normal and cancerous tissues and in response to various stimuli, a subset of stimulus-dependent, dynamically modulated sites is identified. Silencing the m(6)A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the p53 (also known as TP53) signalling pathway and apoptosis. Our findings therefore suggest that RNA decoration by m(6)A has a fundamental role in regulation of gene expression.
3,237 citations
Authors
Showing all 12509 results
Name | H-index | Papers | Citations |
---|---|---|---|
Scott D. Solomon | 137 | 1145 | 103041 |
Moshe Oren | 125 | 340 | 57669 |
Yehuda Shoenfeld | 125 | 1629 | 77195 |
Philip Greenland | 114 | 528 | 69254 |
Patricia Hartge | 107 | 390 | 42043 |
Dan Rujescu | 106 | 552 | 60406 |
Mario Mikulincer | 105 | 414 | 40125 |
Marc Lipsitch | 104 | 516 | 39897 |
Dean Sheppard | 101 | 352 | 35085 |
Alison M. Dunning | 99 | 437 | 39481 |
Arnon Nagler | 98 | 1316 | 44298 |
Stafford L. Lightman | 98 | 714 | 36735 |
David H. Sachs | 96 | 906 | 46904 |
Nir Friedman | 95 | 269 | 69893 |
John D. Boice | 94 | 385 | 30839 |