1,720,964 research outputs found
Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer
Get PDFBackground
Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding sites to chromatin have been used to inform functional annotations of SNPs.
Results
Here we establish criteria for enhancer mapping which are applicable to other diseases and traits to achieve the optimal tissue-specific enrichment of PC risk SNPs. We used stratified Q-Q plots and Fisher test to assess the differential enrichment of SNPs mapping to specific categories of enhancers. We find that BRD4 is the key discriminant of tissue-specific enhancers, showing that it is more powerful than AR binding information to capture PC specific risk loci, and can be used with similar effect in breast cancer (BC) and applied to other diseases such as schizophrenia.
Conclusions
This is the first study to evaluate the enrichment of epigenetic readers in genome-wide associations studies for SNPs within enhancers, and provides a powerful tool for enriching and prioritizing PC and BC genetic risk loci. Our study represents a proof of principle applicable to other diseases and traits that can be used to redefine molecular mechanisms of human phenotypic variation
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Lifestyle, biochemical, and genetic risk factors for prostate cancer
Get PDFDespite considerable research there are no established risk factors for prostate cancer beyond age, family history, ethnicity, genetic factors, and insulin-like growth factor I. However, evidence from existing studies of risk factors for prostate cancer suggest that many lifestyle and biochemical exposures, and genetic vari- ants may be risk factors for prostate cancer.
Exposures investigated in this thesis are: vasectomy status, microseminoprotein- beta (MSP), human kallikrein 2 (HK2), and the lactase persistence SNP, rs4988235. Additionally, this thesis contains an analysis of how germline polymorphism, in- cluding rs4988235, may determine the intake of dairy produce.
Vasectomy has been implicated as a risk factor for total and aggressive prostate cancer. However, vasectomy was not associated with risk of prostate cancer overall (hazards ratio (HR): 1.05; [95% CI 0.96-1.15]), with risk for high grade or advanced stage tumours (1.01; [0.84-1.21] & 0.83; [0.64-1.07], respectively), or for death from prostate cancer (0.88; [0.68-1.12]) in 84,753 men in the European Prospective Investigation into Cancer and Nutrition (EPIC).
A previous prospective study in the Multi-Ethnic Cohort found a significant pro- tective association of MSP with prostate cancer. In a nested case-control study (1,871 cases & 1,871 controls) plasma MSP concentrations in EPIC were inversely associated with prostate cancer risk after adjusting for total prostate-specific anti- gen (PSA) concentration (odds ratio (OR) for highest versus lowest fourth of MSP = 0.65; [95% CI 0.51-0.84], p-trend = 0.001). No heterogeneity in this associa- tion was observed by tumor stage or histological grade. Mendelian randomisation (MR) analyses suggest a causal protective association of MSP with prostate can- cer risk (OR per unit increase in MSP for MR: 0.96; [95% CI 0.95-0.97]).
Although HK2 has previously been found to improve discrimination for prostate cancer in predictive models, there has been no large prospective investigation of the association of HK2 with prostate cancer in men without elevated PSA. However, in EPIC plasma HK2 concentrations were not associated with prostate cancer risk independent of circulating concentrations of PSA in a nested case- control study (2,867 cases & 2,867 controls) (OR for highest versus lowest fourth of HK2 before adjustment for PSA = 7.09; [95% CI 5.82-8.65], p-trend = 0.001 vs. after adjustment for PSA = 1.29; [0.98-1.67], p-trend = 0.1). Further, there was no evidence that including HK2 in a model of prostate cancer risk based on PSA and age improved discrimination for prostate cancer overall or for high grade tumours (overall area under the curve (AUC): 0.816 vs. 0.816 or high-grade AUC: 0.752 vs. 0.752).
The lactase persistence SNP, rs4988235, has previously been investigated in the estimation of prostate cancer risk as a marker of dairy intake. In these analyses rs4988235 was not associated with prostate cancer risk overall (per-allele OR: 1.01; [95% CI 0.99-1.04]), with risk for high grade or advanced stage tumours (0.99; [0.95-1.04] and 0.99; [0.93-1.04], respectively), or for death from prostate
cancer (0.96; [0.90-1.03]) in the PRACTICAL consortium, a large (48,471 cases & 29,866 controls) prostate cancer genetics consortium. Further, in UK Biobank (up to 41,514 men) rs4988235 was only associated with the intake of dairy milk (diâµerence between CC and TT: 19.9 g/d; [12.8-26.9]) and not the intake of other dairy products (yogurt, ice cream, and cheese).
It is possible that alternative germline polymorphisms may determine diâµerences in the intake of dairy milk, which may be useful for future MR studies into prostate cancer risk. However, no SNPs were genome-wide significant in relation to the intake of dairy milk in a discovery GWAS in the UK Biobank (22,041 men). Further, putative associations for SNPs significant at the lower tentative genome- wide significance threshold (p < 10-5) were not replicated when investigated in an independent sample of men from the UK Biobank (50,701 men).
In conclusion, there is no strong evidence that vasectomy, HK2, or the lactase persistence SNP as a marker of dairy intake, are associated with prostate cancer risk. Given the null GWAS for dairy milk intake, rs4988235 remains the strongest known genetic determinant of dairy milk intake. Lastly, observational and MR results provide compelling evidence that MSP is a potentially causal protective factor for prostate cancer risk. Future research should focus on replicating the putative causal association of MSP with prostate cancer and better understanding the purported role of MSP in tumour suppression or pathogen defense.</p
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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