1,720,960 research outputs found
A computational approach to identify predictive gene signatures in Triple Negative Breast Cancer
Microarray technology has been extensively used to detect patterns in gene expression that stem from regulatory interactions. Seminal studies demonstrated that the synergistic use of microarray-based techniques and bioinformatics analysis of genomic data might not only further the understanding of pathological phenotypes, but also provide lists of genes to dissect a disease into distinct groups, with different diagnostic or prognostic characteristics. Nonetheless, optimism for microarray-based technologies as clinical tools has suffered of both perceptual and real setbacks. Criticism is largely on the ground of general non-reproducibility of gene signatures and the inability to replicate results.
The research activity illustrated in this thesis aimed at fulfilling methodological gaps still hampering the identification of gene signatures with proved prognostic and predictive value and, finally, affecting their reliability, reproducibility, and applicability. Specifically, we developed computational methods to efficiently merge gene expression profiles of tumors from multiple, independent, retrospective studies and to construct meta-datasets storing high throughput gene expression profiles and clinical information from thousands cancer patients. Moreover, we expanded on the concept of gene signature and derived consensus signatures, i.e. linear weighted combinations of gene signatures that, singularly, recapitulate independent signaling pathways or specific molecular mechanisms, while intertwined together render a more comprehensive molecular model of tumor progression or chemo-resistance.
This approach has been applied to breast cancer, in general, and to triple negative breast cancer (TNBC), in particular, and resulted in the identification of gene signature combinations with increased robustness and power to predict cancer progression or response to therapy over the use of single signatures
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
A multifactorial ‘Consensus Signature’ by in silico analysis to predict response to neoadjuvant anthracycline-based chemotherapy in triple-negative breast cancer
BACKGROUND: Owing to the complex processes required for anthracycline-induced cytotoxicity, a prospectively defined multifactorial Consensus Signature (ConSig) might improve prediction of anthracycline response in triple-negative breast cancer (TNBC) patients, whose only standard systemic treatment option is chemotherapy.
AIMS: We aimed to construct and evaluate a multifactorial signature, comprising measures of each function required for anthracycline sensitivity in TNBC.
METHODS: ConSigs were constructed based on five steps required for anthracycline function: drug penetration, nuclear topoisomerase IIα (topoIIα) protein location, increased topoIIα messenger RNA (mRNA) expression, apoptosis induction, and immune activation measured by, respectively, HIF1α or SHARP1 signature, LAPTM4B mRNA, topoIIα mRNA, Minimal Gene signature
or YWHAZ mRNA, and STAT1 signature. TNBC patients treated with neoadjuvant anthracycline-based chemotherapy without taxane were identified from publicly available gene expression data derived with Affymetrix HG-U133 arrays (training set). In silico analyses of correlation between gene expression data and pathological complete response (pCR) were performed using receiver-operating characteristic curves. To determine anthracycline specificity, ConSigs were assessed in patients treated with anthracycline plus taxane. Specificity, sensitivity, positive and negative predictive value, and odds ratio (OR) were calculated for ConSigs. Analyses were repeated in two validation gene expression data sets derived using different microarray platforms.
RESULTS: In the training set, 29 of 147 patients had pCR after anthracycline-based chemotherapy. Various combinations of components were evaluated, with the most powerful anthracycline response predictors being ConSig1: (STAT1+topoIIα mRNA +LAPTM4B) and ConSig2: (STAT1+topoIIα mRNA+HIF1α). ConSig1 demonstrated high negative predictive value (85%) and high OR
for no pCR (3.18) and outperformed ConSig2 in validation sets for anthracycline specificity. CONCLUSIONS: With further validation, ConSig1 may help refine selection of TNBC patients for anthracycline chemotherapy
Dispelling the Myths Behind First-author Citation Counts
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
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