1,720,968 research outputs found
GeneFEAST: the pivotal, gene-centric step in functional enrichment analysis interpretation
Get PDFSummary: GeneFEAST, implemented in Python, is a gene-centric functional enrichment analysis summarization and visualization tool that can be applied to large functional enrichment analysis (FEA) results arising from upstream FEA pipelines. It produces a systematic, navigable HTML report, making it easy to identify sets of genes putatively driving multiple enrichments and to explore gene-level quantitative data first used to identify input genes. Further, GeneFEAST can juxtapose FEA results from multiple studies, making it possible to highlight patterns of gene expression amongst genes that are differentially expressed in at least one of multiple conditions, and which give rise to shared enrichments under those conditions. Thus, GeneFEAST offers a novel, effective way to address the complexities of linking up many overlapping FEA results to their underlying genes and data, advancing gene-centric hypotheses, and providing pivotal information for downstream validation experiments. Availability and implementation: GeneFEAST GitHub repository: https://github.com/avigailtaylor/GeneFEAST; Zenodo record: 10.5281/zenodo.14753734; Python Package Index: https://pypi.org/project/genefeast; Docker container: ghcr.io/avigailtaylor/genefeast
Obesity: a perfect storm for carcinogenesis
No full textObesity-related cancers account for 40% of the cancer cases observed in the USA and obesity is overtaking smoking as the most widespread modifiable risk factor for carcinogenesis. Here, we use the hallmarks of cancer framework to delineate how obesity might influence the carcinogenic hallmarks in somatic cells. We discuss the effects of obesity on (a) sustaining proliferative signaling; (b) evading growth suppressors; (c) resisting cell death; (d) enabling replicative immortality; (e) inducing angiogenesis; (f) activating invasion and metastasis; (g) reprogramming energy metabolism; and (h) avoiding immune destruction, together with its effects on genome instability and tumour-promoting inflammation. We present the current understanding and controversies in this evolving field, and highlight some areas in need of further cross-disciplinary focus. For instance, the relative importance of the many potentially causative obesity-related factors is unclear for each type of malignancy. Even within a single tumour type, it is currently unknown whether one obesity-related factor consistently plays a predominant role, or if this varies between patients or, even in a single patient with time. Clarifying how the hallmarks are affected by obesity may lead to novel prevention and treatment strategies for the increasingly obese population
WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma
Get PDFPurpose
Despite recent advances, approximately 50% of patient with metastatic melanoma eventually succumb to the disease. Patients with melanomas harboring a BRAF mutation (BRAFMut) have a worse prognosis than those with wildtype (BRAFWT) tumors. Unexpectedly, interim AVAST-M Phase III trial data reported benefit from adjuvant anti-VEGF bevacizumab only in the BRAFMut group. We sought to find mechanisms underpinning this sensitivity.
Methods
We investigated this finding in vitro and in vivo using melanoma cell lines and clones generated by BRAFV600E knock-in on a BRAFWT background.
Results
Compared with BRAFWT cells, isogenic BRAFV600E clones secreted more VEGF and exhibited accelerated growth rates as spheroids and xenografts, which were more vascular and proliferative. Recapitulating AVAST-M findings, bevacizumab affected only BRAFV600E xenografts, inducing significant tumor growth delay, reduced vascularity and increased necrosis. We identified 814 differentially expressed genes in isogenic BRAFV600E/BRAFWT clones. Of 61 genes concordantly deregulated in clinical melanomas ROR2 was one of the most upregulated by BRAFV600E. ROR2 was shown to be RAF-MEK regulated in BRAFV600E cells and its depletion suppressed VEGF secretion down to BRAFWT levels. The ROR2 ligand WNT5A was also overexpressed in BRAFMut melanomas, and in ROR2-overexpressing BRAFV600E cells MEK inhibition downregulated WNT5A and VEGF secretion.
Conclusions
These data implicate WNT5A-ROR2 in VEGF secretion, vascularity, adverse outcomes and bevacizumab sensitivity of BRAFMut melanomas, suggesting that this axis has potential therapeutic relevance
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
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
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