1,720,994 research outputs found
Thyroid hormone therapy in differentiated thyroid cancer
No full textSurgery-with or without postoperative radioiodine-is the standard of care for most patients with differentiated thyroid carcinoma (DTC). Thyroid hormone replacement therapy is the mainstay of long-term medical management. Patients treated with total thyroidectomy and some who undergo lobectomy alone require thyroid hormone therapy to restore euthyroidism with normal serum thyroid-stimulating hormone (TSH) levels. Because TSH acts as a growth factor for thyroid follicular cells (including those that are neoplastic), it can potentially affect the onset and/or progression of follicular-cell derived thyroid cancer. For this reason, some patients are placed on thyroid hormone therapy at doses that suppress secretion of TSH (suppression therapy). This mini-review looks at the potential benefits and risks of this practice in patients diagnosed with DTC. Aggressive TSH-suppressive therapy is of little or no benefit to the vast majority of patients with DTC. Practice guidelines, therefore, recommend a graded algorithm in which the potential benefits of suppression are weighed against the associated cardiovascular and skeletal risks. Large randomized controlled studies are needed to confirm the presumed oncological benefits of TSH-suppression and its causal role in adverse cardiac, skeletal, and quality of life effects and to assess the efficacy of TSH normalization in reversing or reducing these effects
Rare germline variants in DNA repair-related genes are accountable for papillary thyroid cancer susceptibility
No full textBackground: Understanding the molecular mechanisms underlying papillary thyroid cancer (PTC) proved to be vital not only for diagnostic purposes but also for tailored treatments. Despite the strong evidence of heritability, only a small subset of alterations has been implicated in PTC pathogenesis. To this reason, we used targeted next-generation sequencing (NGS) to identify candidate variants implicated in PTC pathogenesis, progression, and invasiveness. Methods: A total of 42 primary PTC tissues were investigated using a targeted next-generation sequencing (NGS) panel enlisting 47 genes involved in DNA repair and tumor progression. Results: We identified 57 point mutations in 78.5% of samples (n = 32). Thirty-two somatic mutations were identified exclusively in known thyroid cancer genes (BRAF, KRAS, NRAS, and TERT). Unpredictably, 45% of the all identified mutations (n = 25) resulted to be germline, most affecting DNA repair genes. Interestingly, none of the latter variants was in the main population databases. Following ACMG classification, 20% of pathogenic/likely pathogenic and 68% of variant of unknown significance were identified. Conclusions: Overall, our results support the hypothesis that rare germline variants in DNA repair genes are accountable for PTC susceptibility. More data, including the segregation analysis in affected families, should be collected before definitely annotate these alterations and to establish their potential prognostic and treatment implications
SEaCorAl: Identifying and contrasting the regulation-correlation bias in RNA-Seq paired expression data of patient groups
Full text linkThe Cancer Genome Atlas database offers the possibility of analyzing genome-wide expression RNA-Seq cancer data using paired counts, that is, studies where expression data are collected in pairs of normal and cancer cells, by taking samples from the same individual. Correlation of gene expression profiles is the most common analysis to study co-expression groups, which is used to find biological interpretation of -omics big data. The aim of the paper is threefold: firstly we show for the first time, the presence of a “regulation-correlation bias” in RNA-Seq paired expression data, that is an artifactual link between the expression status (up- or down-regulation) of a gene pair and the sign of the corresponding correlation coefficient. Secondly, we provide a statistical model able to theoretically explain the reasons for the presence of such a bias. Thirdly, we present a bias-removal algorithm, called SEaCorAl, able to effectively reduce bias effects and improve the biological significance of correlation analysis. Validation of the SEaCorAl algorithm is performed by showing a significant increase in the ability to detect biologically meaningful associations of positive correlations and a significant increase of the modularity of the resulting unbiased correlation network
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
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
Effective TRIAC treatment of a THRβ-mutated patient with thyroid hormone resistance
No full textResistance to thyroid hormone (RTH) is a rare autosomal dominant disease characterized by an alteration of thyroid hormone negative feedback, usually as a consequence of a mutation in the thyroid hormone receptor-b gene (THRβ). It is characterized by high variability of clinical manifestations, ranging from isolated abnormal thyroid function tests without symptoms to severe and impaired clinical conditions. Here we report the case of a woman who was diagnosed with RTHβ when she was 35 years old and was treated with 3,5,3-triiodiothyroacetic acid (TRIAC) because of the onset of clinical symptoms of hyperthyroidism. This therapy has been effective in controlling thyrotoxicosis for 5 years. After this time the patient developed an autoimmune hyperthyroidism, with TSH receptor autoantibodies appearance, which caused a loss of efficacy of the drug in controlling the disease. The development of different pathophysiological mechanisms of thyrotoxicosis, as in this case, could be the reason for both variability of disease manifestations and of loss of response to drug therapy
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