Institution
University of Cambridge
Education•Cambridge, United Kingdom•
About: University of Cambridge is a education organization based out in Cambridge, United Kingdom. It is known for research contribution in the topics: Population & Galaxy. The organization has 118293 authors who have published 282289 publications receiving 14497093 citations. The organization is also known as: Cambridge University & Cambridge.
Topics: Population, Galaxy, Context (language use), Gene, Transplantation
Papers published on a yearly basis
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Wellcome Trust Sanger Institute1, J. Craig Venter Institute2, George Washington University3, University of Glasgow4, University of Oxford5, Newcastle University6, University of Bordeaux7, University of Cambridge8, Oregon Health & Science University9, University of Dundee10, Imperial College London11, Case Western Reserve University12, Yale University13, Université catholique de Louvain14, University of Iowa15, Wellcome Trust16
TL;DR: Comparisons of the cytoskeleton and endocytic trafficking systems of Trypanosoma brucei with those of humans and other eukaryotic organisms reveal major differences.
Abstract: African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including ∼900 pseudogenes and ∼1700 T. brucei–specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
1,631 citations
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Harvard University1, University of California, Los Angeles2, Chiba University3, University of Liverpool4, Katholieke Universiteit Leuven5, Hochschule Hannover6, University of Cambridge7, The Chinese University of Hong Kong8, Princess Margaret Cancer Centre9, Merck & Co.10, National Taiwan University11, Kindai University12
TL;DR: Pembrolizumab was effective and tolerable in patients with advanced hepatocellular carcinoma who had previously been treated with sorafenib and is undergoing further assessment in two phase 3, randomised trials as a second-line treatment.
Abstract: Summary Background Immune checkpoint blockade therapy has shown promising results in patients with advanced hepatocellular carcinoma. We aimed to assess the efficacy and safety of pembrolizumab in this patient population. Methods KEYNOTE-224 is a non-randomised, multicentre, open-label, phase 2 trial that is set in 47 medical centres and hospitals across ten countries. Eligible patients had pathologically confirmed hepatocellular carcinoma; had previously been treated with sorafenib and were either intolerant to this treatment or showed radiographic progression of their disease after treatment; an Eastern Cooperative Oncology Group performance status of 0–1; adequate organ function, and were Child-Pugh class A. Participants received 200 mg pembrolizumab intravenously every 3 weeks for about 2 years or until disease progression, unacceptable toxicity, patient withdrawal, or investigator decision. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response in all patients who received at least one dose of pembrolizumab, which was radiologically confirmed by use of the Response Evaluation Criteria in Solid Tumors version 1.1 by central review. Safety was also assessed in all treated patients. This trial is ongoing but closed to enrolment and is registered with ClinicalTrials.gov number NCT02702414. Findings Between June 7, 2016, and Feb 9, 2017, we screened 169 patients with advanced hepatocellular carcinoma, of whom 104 eligible patients were enrolled and treated. As of data cutoff on Feb 13, 2018, 17 (16%) patients were still receiving pembrolizumab. We recorded an objective response in 18 (17%; 95% CI 11–26) of 104 patients. The best overall responses were one (1%) complete and 17 (16%) partial responses; meanwhile, 46 (44%) patients had stable disease, 34 (33%) had progressive disease, and six (6%) patients who did not have a post-baseline assessment on the cutoff date were considered not to be assessable. Treatment-related adverse events occurred in 76 (73%) of 104 patients, which were serious in 16 (15%) patients. Grade 3 treatment-related events were reported in 25 (24%) of the 104 patients; the most common were increased aspartate aminotransferase concentration in seven (7%) patients, increased alanine aminotransferase concentration in four (4%) patients, and fatigue in four (4%) patients. One (1%) grade 4 treatment-related event of hyperbilirubinaemia occurred. One death associated with ulcerative oesophagitis was attributed to treatment. Immune-mediated hepatitis occurred in three (3%) patients, but there were no reported cases of viral flares. Interpretation Pembrolizumab was effective and tolerable in patients with advanced hepatocellular carcinoma who had previously been treated with sorafenib. These results indicate that pembrolizumab might be a treatment option for these patients. This drug is undergoing further assessment in two phase 3, randomised trials as a second-line treatment in patients with hepatocellular carcinoma. Funding Merck & Co, Inc.
1,630 citations
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TL;DR: The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA.
Abstract: Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a 'liquid biopsy' for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.
1,630 citations
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07 Dec 2015
TL;DR: The FEniCS Project is a collaborative project for the development of innovative concepts and tools for automated scientific computing, with a particular focus on the solution of differential equations by finite element methods.
Abstract: The FEniCS Project is a collaborative project for the development of innovative concepts and tools for automated scientific computing, with a particular focus on the solution of differential equations by finite element methods. The FEniCS Projects software consists of a collection of interoperable software components, including DOLFIN, FFC, FIAT, Instant, UFC, UFL, and mshr. This note describes the new features and changes introduced in the release of FEniCS version 1.5.
1,628 citations
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TL;DR: Improving macroautophagy with drugs such as rapamycin could offer a tractable therapeutic strategy for a number of late-onset neurodegenerative diseases.
Abstract: Many late-onset neurodegenerative diseases, including Parkinson's disease and Huntington's disease, are associated with the formation of intracellular aggregates by toxic proteins. It is therefore crucial to understand the factors that regulate the steady-state levels of these 'toxins', at both the synthetic and degradation stages. The degradation pathways acting on such aggregate-prone cytosolic proteins include the ubiquitin-proteasome system and macroautophagy. Dysfunction of the ubiquitin-proteasome or macroautophagy pathways might contribute to the pathology of various neurodegenerative conditions. However, enhancing macroautophagy with drugs such as rapamycin could offer a tractable therapeutic strategy for a number of these diseases.
1,626 citations
Authors
Showing all 119522 results
Name | H-index | Papers | Citations |
---|---|---|---|
Albert Hofman | 267 | 2530 | 321405 |
Zhong Lin Wang | 245 | 2529 | 259003 |
Solomon H. Snyder | 232 | 1222 | 200444 |
Trevor W. Robbins | 231 | 1137 | 164437 |
George Davey Smith | 224 | 2540 | 248373 |
Nicholas J. Wareham | 212 | 1657 | 204896 |
Cyrus Cooper | 204 | 1869 | 206782 |
Eric B. Rimm | 196 | 988 | 147119 |
Martin White | 196 | 2038 | 232387 |
Simon D. M. White | 189 | 795 | 231645 |
Michael Rutter | 188 | 676 | 151592 |
George Efstathiou | 187 | 637 | 156228 |
Mark Hallett | 186 | 1170 | 123741 |
David H. Weinberg | 183 | 700 | 171424 |
Paul G. Richardson | 183 | 1533 | 155912 |