Institution
Wellcome Trust Centre for Human Genetics
Facility•Oxford, United Kingdom•
About: Wellcome Trust Centre for Human Genetics is a facility organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 2122 authors who have published 4269 publications receiving 433899 citations.
Topics: Population, Genome-wide association study, Single-nucleotide polymorphism, Gene, Locus (genetics)
Papers published on a yearly basis
Papers
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TL;DR: In this article, a method that captures lineage-level associations even when locus-specific associations cannot be fine-mapped was proposed to detect genes and genetic variants underlying resistance to 17 antimicrobials in 3,144 isolates from four taxonomically diverse clonal and recombining bacteria.
Abstract: Bacteria pose unique challenges for genome-wide association studies because of strong structuring into distinct strains and substantial linkage disequilibrium across the genome(1,2). Although methods developed for human studies can correct for strain structure(3,4), this risks considerable loss-of-power because genetic differences between strains often contribute substantial phenotypic variability(5). Here, we propose a new method that captures lineage-level associations even when locus-specific associations cannot be fine-mapped. We demonstrate its ability to detect genes and genetic variants underlying resistance to 17 antimicrobials in 3,144 isolates from four taxonomically diverse clonal and recombining bacteria: Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Strong selection, recombination and penetrance confer high power to recover known antimicrobial resistance mechanisms and reveal a candidate association between the outer membrane porin nmpC and cefazolin resistance in E. coli. Hence, our method pinpoints locus-specific effects where possible and boosts power by detecting lineage-level differences when fine-mapping is intractable.
231 citations
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TL;DR: The anterior location of the mesoderm-derived hypochiasmatic cartilages, which are closely linked with the extra-ocular muscles, suggests that some tissues associated with the visual apparatus may have evolved independently of the rest of the "New Head".
230 citations
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TL;DR: The data suggest that Dll4 expression acts as a switch from the proliferative phase of angiogenesis to the maturation and stabilisation phase by blocking endothelial cell proliferation and allowing induction of a more mature, differentiated phenotype.
228 citations
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TL;DR: It is suggested that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions that appear associated with a higher risk of future neoplasia or colorectal cancer should be offered a one-off colonoscopic surveillance examination at 3 years.
Abstract: Serrated polyps have been recognised in the last decade
as important premalignant lesions accounting for
between 15% and 30% of colorectal cancers. There is
therefore a clinical need for guidance on how to manage
these lesions; however, the evidence base is limited. A
working group was commission by the British Society of
Gastroenterology (BSG) Endoscopy section to review the
available evidence and develop a position statement to
provide clinical guidance until the evidence becomes
available to support a formal guideline. The scope of the
position statement was wide-ranging and included:
evidence that serrated lesions have premalignant
potential; detection and resection of serrated lesions;
surveillance strategies after detection of serrated lesions;
special situations—serrated polyposis syndrome
(including surgery) and serrated lesions in colitis;
education, audit and benchmarks and research
questions. Statements on these issues were proposed
where the evidence was deemed sufficient, and reevaluated
modified via a Delphi process until >80%
agreement was reached. The Grading of
Recommendations, Assessment, Development and
Evaluations (GRADE) tool was used to assess the
strength of evidence and strength of recommendation
for finalised statements. Key recommendation: we
suggest that until further evidence on the efficacy or
otherwise of surveillance are published, patients with
sessile serrated lesions (SSLs) that appear associated
with a higher risk of future neoplasia or colorectal
cancer (SSLs ≥10 mm or serrated lesions harbouring
dysplasia including traditional serrated adenomas)
should be offered a one-off colonoscopic surveillance
examination at 3 years (weak recommendation, low
quality evidence, 90% agreement).
228 citations
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TL;DR: The authors have investigated the role of 3 microRNAs, including the hypoxia‐induced hsa‐miR‐210, as potential markers of Hypoxia or prognosis.
Abstract: BACKGROUND:
Hypoxia is an important mechanism of treatment resistance in head and neck squamous cell carcinoma (HNSCC). MicroRNAs are short noncoding RNAs that regulate multiple mRNAs and are frequently dysregulated in cancer. The authors have investigated the role of 3 microRNAs, including the hypoxia-induced hsa-miR-210, as potential markers of hypoxia or prognosis.
METHODS:
Three hypoxia-related microRNAs, hsa-miR-210, hsa-miR-21, and hsa-miR-10b, were measured in 46 samples from patients with HNSCC. Expression levels were correlated with clinicopathological variables and other markers of hypoxia: a published 99-gene hypoxia metagene, individual hypoxia-related genes such as TWIST1, and immunohistochemical expression of hypoxia-inducible factor 1 and its target gene carbonic anhydrase 9. We then performed survival analyses to investigate the prognostic significance of these microRNAs.
RESULTS:
Only the level of hsa-miR-210 was significantly correlated with other markers of hypoxia, including the 99-gene hypoxia metagene (rho = 0.67, P < .001). We found no association between hsa-miR-210, hsa-miR-21, or hsa-miR-10b and clinicopathological variables such as tumor size, differentiation, and stage. However, high levels of hsa-miR-210 were associated with locoregional disease recurrence (P = .001) and short overall survival (P = .008). hsa-miR-21 and hsa-miR-10b had no prognostic significance.
CONCLUSIONS:
Expression of hsa-miR-210 in head and neck cancer correlates with other approaches for assessing hypoxia and is associated with prognosis. This warrants further study as a classification marker of patients for therapies involving modulation of hypoxia. Cancer 2010. © 2010 American Cancer Society.
228 citations
Authors
Showing all 2127 results
Name | H-index | Papers | Citations |
---|---|---|---|
Mark I. McCarthy | 200 | 1028 | 187898 |
John P. A. Ioannidis | 185 | 1311 | 193612 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
Simon I. Hay | 165 | 557 | 153307 |
Robert Plomin | 151 | 1104 | 88588 |
Ashok Kumar | 151 | 5654 | 164086 |
Julian Parkhill | 149 | 759 | 104736 |
James F. Wilson | 146 | 677 | 101883 |
Jeremy K. Nicholson | 141 | 773 | 80275 |
Hugh Watkins | 128 | 524 | 91317 |
Erik Ingelsson | 124 | 538 | 85407 |
Claudia Langenberg | 124 | 452 | 67326 |
Adrian V. S. Hill | 122 | 589 | 64613 |
John A. Todd | 121 | 515 | 67413 |
Elaine Holmes | 119 | 560 | 58975 |