Institution
Guy's and St Thomas' NHS Foundation Trust
Healthcare•London, United Kingdom•
About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.
Topics: Population, Medicine, Randomized controlled trial, Cancer, Breast cancer
Papers published on a yearly basis
Papers
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TL;DR: The SCARE Guideline is presented, consisting of a 14-item checklist that will improve the reporting quality of surgical case reports, and was approved by the participants.
1,648 citations
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Christopher J L Murray1, Ryan M Barber, Kyle J Foreman2, Ayse Abbasoglu Ozgoren +608 more•Institutions (251)
TL;DR: Patterns of the epidemiological transition with a composite indicator of sociodemographic status, which was constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population, were quantified.
1,609 citations
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Wellcome Trust Sanger Institute1, Wellcome Trust2, Katholieke Universiteit Leuven3, University of East Anglia4, Guy's and St Thomas' NHS Foundation Trust5, Academia Sinica6, Singapore General Hospital7, Netherlands Cancer Institute8, University of Queensland9, University of British Columbia10, Erasmus University Rotterdam11, Harvard University12, University of Cambridge13, Claude Bernard University Lyon 114, Curie Institute15, Royal Brisbane and Women's Hospital16, University of Amsterdam17, Université libre de Bruxelles18, The Breast Cancer Research Foundation19, Cambridge University Hospitals NHS Foundation Trust20, Oslo University Hospital21
TL;DR: Strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade are found, and multiple mutational signatures are observed, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides.
Abstract: All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.
1,606 citations
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TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
1,600 citations
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TL;DR: Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.
Abstract: background Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. methods To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. results New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. conclusions Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.
1,582 citations
Authors
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Name | H-index | Papers | Citations |
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Christopher J L Murray | 209 | 754 | 310329 |
Bruce M. Psaty | 181 | 1205 | 138244 |
Giuseppe Remuzzi | 172 | 1226 | 160440 |
Mika Kivimäki | 166 | 1515 | 141468 |
Simon I. Hay | 165 | 557 | 153307 |
Theo Vos | 156 | 502 | 186409 |
Ali H. Mokdad | 156 | 634 | 160599 |
Steven Williams | 144 | 1375 | 86712 |
Igor Rudan | 142 | 658 | 103659 |
Mohsen Naghavi | 139 | 381 | 169048 |
Christopher D.M. Fletcher | 138 | 674 | 82484 |
Martin McKee | 138 | 1732 | 125972 |
David A. Jackson | 136 | 1095 | 68352 |
Graham G. Giles | 136 | 1249 | 80038 |
Yang Liu | 129 | 2506 | 122380 |