1,720,959 research outputs found
Expression of genes related to lipid handling and the obesity paradox in melanoma: database analysis
Full text linkBackground: Publicly available genomic and transcriptomic data in searchable databases allow researchers to investigate specific medical issues in thousands of patients. Many studies have highlighted the role lipids play in cancer initiation and progression and reported nutritional interventions aimed at improving prognosis and survival. Therefore, there is an increasing interest in the role that fat intake may play in cancer. It is known that there is a relationship between BMI and survival in patients with cancer, and that there is an association between a high-fat diet and increased cancer risk. In some cancers, such as colorectal cancer, obesity and high fat intake are known to increase the risk of cancer initiation and progression. On the contrary, in patients undergoing treatment for melanoma, a higher BMI unexpectedly acts as a protective factor rather than a risk factor; this phenomenon is known as the obesity paradox.
Objective: We aimed to identify the molecular mechanism underlying the obesity paradox, with the expectation that this could indicate new effective strategies to reduce risk factors and improve protective approaches.
Methods: In order to determine the genes potentially involved in this process, we investigated the expression values of lipid-related genes in patients with melanoma or colorectal cancer. We used available data from 2990 patients from 3 public databases (IST [In Silico Transcriptomics] Online, GEO [Gene Expression Omnibus], and Oncomine) in an analysis that involved 3 consecutive validation steps. Of this group, data from 1410 individuals were analyzed in the IST Online database (208 patients with melanoma and 147 healthy controls, as well as 991 patients with colorectal cancer and 64 healthy controls). In addition, 45 melanoma, 18 nevi, and 7 healthy skin biopsies were analyzed in another database, GEO, to validate the IST Online data. Finally, using the Oncomine database, 318 patients with melanoma (312 controls) and 435 patients with colorectal cancer (445 controls) were analyzed.
Results: In the first and second database investigated (IST Online and GEO, respectively), patients with melanoma consistently showed significantly (P<.001) lower expression levels of 4 genes compared to healthy controls: CD36, MARCO, FABP4, and FABP7. This strong reduction was not observed in patients with colorectal cancer. An additional analysis was carried out on a DNA-TCGA data set from the Oncomine database, further validating CD36 and FABP4.
Conclusions: The observed lower expression of genes such as CD36 and FABP4 in melanoma may reduce the cellular internalization of fat and therefore make patients with melanoma less sensitive to a high dietary fat intake, explaining in part the obesity paradox observed in patients with melanoma
Analysis of gene expression levels and their impact on survival in 31 cancer-types patients identifies novel prognostic markers and suggests unexplored immunotherapy treatment options in a wide range of malignancies
Full text linkBACKGROUND: Immunotherapy has dramatically improved cancer treatment by inhibiting or activating specific cell receptors, thus unleashing the host anti-tumor response. However, the engagement of the three main immune checkpoints so far identified, CTLA4, PD-1 and PD-L1, is effective in a fraction of patients, therefore novel targets must be identified and tested. METHODS: We focused our attention on the following nine highly relevant immune checkpoint (ICR) receptors: CTLA4, PD1, PD-L1, LAG3, TIM3, OX40, GITR, 4-1BB and TIGIT. All of them are targets of existing drugs currently under clinical scrutiny in several malignancies. Their expression levels were evaluated in patient tissues of 31 different cancer types vs. proper controls, in a total of 15,038 individuals. This analysis was carried out by interrogating public databases available on GEPIA2 portal and UALCAN portal. By the Principal Component Analysis (PCA) their ability to effectively discriminate patients form controls was then investigated. Expression of the nine ICRs was also related to overall survival in 31 cancer types and expressed as Hazard Ratio, on the GEPIA2 portal and validated, for melanoma patients, in patients-datasets available on PROGgene V2 portal. RESULTS: Significant differential expression was observed for each ICR molecule in many cancer types. A 7-molecules profile was found to specifically discriminate melanoma patients from controls, while two different 6-molecules profiles discriminate pancreatic cancer patients and Testicular Germ Cell Tumors from matched controls. Highly significant survival improvement was found to be related to the expression levels of all nine ICRs in a wide spectrum of malignancies. For melanoma analysis, the relation with survival observed in TCGA datasets was validated in independent GSE melanoma datasets. CONCLUSION: Analysis the nine ICR molecules demonstrates that their expression patterns may be considered as markers of disease and strong survival predictors in a variety of malignancies frequently associated to poor prognosis. Thus, the present findings are strongly advocating that exploratory clinical trials are worth to be performed, using available drugs, targeting these molecules. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03670-7
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Likelihood-type confidence regions for optimal sensitivity and specificity of a diagnostic test
Full text linkNew methods are proposed that provide approximate joint confidence regions for the optimal sensitivity and specificity of a diagnostic test, i.e., sensitivity and specificity corresponding to the optimal cutpoint as defined by the Youden index criterion. Such methods are semi-parametric or non-parametric and attempt to overcome the limitations of alternative approaches. The proposed methods are based on empirical likelihood pivots, giving rise to likelihood-type regions with no predetermined constraints on the shape and automatically range-respecting. The proposal covers three situations: the binormal model, the binormal model after the use of Box-Cox transformations and the fully non-parametric model. In the second case, it is also shown how to use two different transformations, for the healthy and the diseased subjects. The finite sample behaviour of our methods is investigated using simulation experiments. The simulation results also show the advantages offered by our methods when compared with existing competitors. Illustrative examples, involving three real datasets, are also provided
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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