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    Enhancer of Zeste Homolog 2 (EZH2) and Global H3K27 Trimethylation Expression During Progression of Thyroid Cancer

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    Background: EZH2 is a histone lysine methyltransferase that is a member of the polycomb group protein family. EZH2 plays an important role in the epigenetic maintenance of H3K27 trimethylation (H3K27me3). Abnormal EZH2 expression has been associated with various cancers. We examined the expression of EZH2 and H3K27me3 to determine their roles in thyroid cancer progression. Design: Anaplastic thyroid carcinomas (ATC, n=35), poorly differentiated thyroid carcinomas (PDTC, n=21), papillary thyroid carcinomas (PTC, n=28), follicular variant of papillary thyroid carcinomas (FVPTC, n=29), follicular thyroid carcinomas (FTC, n=28), follicular adenomas (FA, n=31) and normal thyroids (NT, n=10) on a tissue microarray (TMA) were analyzed by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded tissues. Antibodies to EZH2 (Novus, 1:100) and H3K27me3 (Cell Signaling, 1:200) were used. IHC was scored based on the intensity and percentage of nuclear staining. Survival analysis was performed using the statistical computing software R. Results: Both EZH2 and H3K27me3 showed strong nuclear staining. The highest level of EZH2 expression was observed in ATC (97%) followed by PDTC (90%). Levels were lower in FA (71%), FTC (64%), PTC (79%) and FVPTC (79%). EZH2 expression was significantly higher in ATC than in well-differentiated carcinomas (P<0.04). H3K27me3 expression was high in both benign and malignant thyroid tumors as well as in NT. H3K27me3 expression was not significantly different in higher-grade tumors compared to well-differentiated carcinomas and FA. The carcinoma types expressing the highest levels of EZH2 (ATC and PDTC) had worse prognoses than the carcinoma types with lower expression (P<0.001). Conclusions: EZH2 is expressed in thyroid malignancies, and its expression correlates with higher-grade tumors. EZH2 effects may also include H3K27me3-independent mechanisms. Our findings suggest that EZH2 may play an important role in thyroid tumor progression

    Long Non-Coding RNA MALAT1 Expression in Thyroid Tissues and Tumors

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    Background: Long non-coding RNAs (lncRNAs) participate in transcription and in epigenetic or post-transcriptional regulation of gene expression, and may contribute to carcinogenesis. MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1), a lncRNA that participates in the regulation of cell cycle and migration, is known to be deregulated in multiple cancers. Some studies suggest MALAT1 may function as both an oncogene and a tumor suppressor. We analyzed the expression of the MALAT1in thyroid tumors and compared its expression to miR-146b-5p, a microRNA known to be deregulated in papillary thyroid cancer. Design: Tissue microarrays (TMAs) were constructed with formalin-fixed paraffin-embedded (FFPE) tissues of normal thyroid ( NT, n=10), nodular goiters (NG, n=10), follicular adenoma (FA, n=32), follicular carcinoma (FCA, n=28), papillary thyroid carcinoma ( PTC n=28), follicular variant of papillary thyroid carcinoma( FVPTC, n=29), poorly differentiated thyroid carcinomas (PDC, n=21) and anaplastic thyroid carcinoma (ATC, n=35). TMA sections were analyzed by in situ hybridization (ISH) using RNAscope technology with a MALAT1 probe (Advanced Cell Diagnostics). ISH for miR-146b-5p was also performed on the same set of TMAs (Exiqon). qRT-PCR was performed on a subset of the TMA cases (n=16). The results of the MALAT1 TMA ISH were analyzed with Vectra imaging technology, Nuance® and inForm ® software. Results: MALAT1 was highly expressed in NT, NG and in benign and malignant thyroid tumors predominantly in the nucleus, but also in the cytoplasm. The highest levels of MALAT1 wwere observed in PTCs which was significantly higher than in NT (p=0.014) and FVPTC (p=0.016). In contrast NT expressed higher levels of MALAT1 than PDC (p=0.015) or ATC (p<0.001). qRT-PCR analyses supported the ISH findings. Expression of miR-146b-5p was highest in PTC (89%) followed by FVPTC (41%) and was lowest in ATC (8%). Conclusions: MALAT1 is highly expressed in NT tissues and thyroid tumors with increased expression during progression from NT to PTCs. However both MALAT1 and miR-146b-5p are downregulated in ATC compared to PTCs, suggesting that MALAT1 may function both as an oncogene and as a tumor suppressor in different thyroid tumors and that non-coding RNAs may regulate the development of PTCs and ATCs. Category: Endocrine Patholog

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

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    “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

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    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

    Dispelling the Myths Behind First-author Citation Counts

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    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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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
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