Institution
University of Rochester
Education•Rochester, New York, United States•
About: University of Rochester is a education organization based out in Rochester, New York, United States. It is known for research contribution in the topics: Population & Laser. The organization has 63915 authors who have published 112762 publications receiving 5484122 citations. The organization is also known as: Rochester University.
Topics: Population, Laser, Poison control, Health care, Large Hadron Collider
Papers published on a yearly basis
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TL;DR: In this paper, the authors evaluate the standard-setting inferences that can be drawn from value relevance research studies that are motivated by standard setting, and they argue that the underlying theories are not descriptive and hence drawing standard setting inferences is difficult.
1,346 citations
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City of Hope National Medical Center1, National Institutes of Health2, University of Würzburg3, Bosch4, University of British Columbia5, University of Arizona6, University of Barcelona7, University of Oslo8, University of Rochester9, Oregon Health & Science University10, Cleveland Clinic11, University of Nebraska Medical Center12
TL;DR: The dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, is described and the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MyD88 mutations are supported.
Abstract: The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations.
1,346 citations
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Ohio State University1, Harvard University2, University of Texas MD Anderson Cancer Center3, Hofstra University4, Mayo Clinic5, Vanderbilt University6, Stanford University7, St. Vincent's Health System8, Royal North Shore Hospital9, Medical University of Vienna10, University of Cambridge11, University of Rochester12, NewYork–Presbyterian Hospital13, University of California, San Diego14, East Kent Hospitals University Nhs Foundation Trust15, Beaumont Hospital16, Vita-Salute San Raffaele University17, Medical University of Łódź18, University of Barcelona19, University of Pennsylvania20, University of California, Los Angeles21, Princess Alexandra Hospital22, The Royal Marsden NHS Foundation Trust23, Autonomous University of Barcelona24, Leeds Teaching Hospitals NHS Trust25
TL;DR: Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL.
Abstract: Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton’s tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progressionfree survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Conclusions Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.)
1,343 citations
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McMaster University1, University of Toronto2, Dalhousie University3, Pennsylvania State University4, Nationwide Children's Hospital5, University of Iowa6, University of Miami7, University of South Carolina8, University of Paris9, Pasteur Institute10, University of Gothenburg11, Icahn School of Medicine at Mount Sinai12, Stanford University13, Vanderbilt University14, Johns Hopkins University15, University of North Carolina at Chapel Hill16, University of California, Los Angeles17, University of Pennsylvania18, Washington University in St. Louis19, University of Chicago20, Harvard University21, Emory University22, George Washington University23, Yale University24, University of Utah25, University of Washington26, University of Pittsburgh27, University of California, Irvine28, Veterans Health Administration29, University of Rochester30, University of Toulouse31, German Cancer Research Center32, Goethe University Frankfurt33, National and Kapodistrian University of Athens34, University of Bologna35, Utrecht University36, Guy's Hospital37, King's College London38, University of Cambridge39, University of Manchester40, Newcastle University41, University of Oxford42, University of Illinois at Chicago43, University of Michigan44, Centre Hospitalier Universitaire de Toulouse45, McGill University46, Autism Speaks47
TL;DR: Linkage and copy number variation analyses implicate chromosome 11p12–p13 and neurexins, respectively, among other candidate loci, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
Abstract: Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
1,338 citations
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TL;DR: Five groups of surgeries were selected because the incidence of pain is known to be high, thus improving the probability of detecting predictive factors and the natural history of patients with and without persistent pain after surgery provides an opportunity to improve the understanding of the physiology and psychology of chronic pain.
Abstract: ONE potential adverse outcome from surgery is chronic pain. Analysis of predictive and pathologic factors is important to develop rational strategies to prevent this problem. Additionally, the natural history of patients with and without persistent pain after surgery provides an opportunity to improve the understanding of the physiology and psychology of chronic pain. Ideally, studies of chronic postoperative pain should include (1) sufficient preoperative data (assessment of pain, physiologic and psychologic risk factors for chronic pain); (2) detailed descriptions of the operative approaches used (location and length of incisions, handling of nerves and muscles); (3) the intensity and character of acute postoperative pain and its management; and (4) follow-up at intervals to 1 yr or more. In addition, there would be information about postoperative interventions that may influence pain, such as radiation therapy or chemotherapy. At long-term follow-up visits, patient function, physical signs, and symptoms would be evaluated using a standardized algorithm, including quantitative and descriptive pain assessments. We found no studies that contain all of these data. For this review, we specifically sought population data that reflect the incidence of chronic postoperative pain or predictors (medical, physiologic, and psychologic) of chronic pain. We selected five groups of surgeries (limb amputations, breast surgery, gallbladder surgery, lung surgery, and inguinal hernia surgery). These surgeries were selected because the incidence of pain is known to be high, thus improving the probability of detecting predictive factors. They also represent a range of major surgical procedures.
1,337 citations
Authors
Showing all 64186 results
Name | H-index | Papers | Citations |
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Eugene Braunwald | 230 | 1711 | 264576 |
Cyrus Cooper | 204 | 1869 | 206782 |
Eric J. Topol | 193 | 1373 | 151025 |
Dennis W. Dickson | 191 | 1243 | 148488 |
Scott M. Grundy | 187 | 841 | 231821 |
John C. Morris | 183 | 1441 | 168413 |
Ronald C. Petersen | 178 | 1091 | 153067 |
David R. Williams | 178 | 2034 | 138789 |
John Hardy | 177 | 1178 | 171694 |
Russel J. Reiter | 169 | 1646 | 121010 |
Michael Snyder | 169 | 840 | 130225 |
Jiawei Han | 168 | 1233 | 143427 |
Gang Chen | 167 | 3372 | 149819 |
Marc A. Pfeffer | 166 | 765 | 133043 |
Salvador Moncada | 164 | 495 | 138030 |