1,721,010 research outputs found
The Presence of Combined BRAF, TP53 and PIK3CA Mutations Have Prognostic Impact in the Hobnail Variant of Papillary Thyroid Carcinoma
No full textBackground: Hobnail variant of papillary carcinoma (HPTC) represents a recently described aggressive and rare group of moderately differentiated thyroid tumors with poorly understood pathogenesis. Molecular data in this group of tumors are heterogeneous, possibly reflecting the rarity of this entity, and there is the need for a more detailed molecular characterization of these tumors. The objective of the study was to define a comprehensive molecular typing of HPTC.
Design: Twelve cases of HPTC, including eight primary tumors and four lymph node metastases, from eight patients selected through the files of University of Turin, Italy, have been screened for N-K-H-RAS, BRAF, TP53, PIK3CA and NOTCH1 gene mutations generating locus-specific amplicon libraries with tagged primers for the above genes. Sequencing was conducted on the Roche/454 GS junior system and quality-filtered reads were analyzed with the GS Amplicon Variant Analyzer (AVA 2.7, 454 Life Sciences). Molecular data were compared with clinical-pathologic data and follow up.
Results: The patients included 5 women and 3 men. Ages ranged from 31 to 87 years. All twelve cases of HPTC showed more than 30% hobnail features. BRAF and HRAS mutations were by far the most common genetic alterations in HPTC (41.7% and 33.3% respectively). V600E BRAF mutation was detected both in primary and metastasis in two patients and in one primary tumor in one patient. TP53 deleterious mutations were found in two primary HPTC and in one metastasis. PIK3CA gene mutations was found in 3 cases and KRAS in one case. No mutation was detected in the NRAS and NOTCH1 genes. Interestingly, only the three patients (37.5%) who died of disease after a mean of 30.6 months, showed the same complex molecular characterization constituted by the presence of combined mutations.
Conclusions: The present study confirms that HPTC are genetically heterogeneous and complex. The presence of combined mutations in BRAF, TP53 and PIK3CA genes appear to have a negative prognostic factor. The detection of these multiple mutations by molecular profiling should be clinically relevant for the prognostic stratification and treatment of these patients
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
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
Long Non-Coding RNA MALAT1 Expression in Thyroid Tissues and Tumors
No full textBackground: 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
MALAT1 Long Non-coding RNA Expression in Thyroid Tissues: Analysis by In Situ Hybridization and Real-Time PCR
Full text linkLong non-coding RNAs (lncRNAs) are important for transcription and for epigenetic or posttranscriptional regulation of gene expression and may contribute to carcinogenesis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an lncRNA involved in the regulation of the cell cycle, cell proliferation, and cell migration, is known to be deregulated in multiple cancers. Here, we analyzed the expression of MALAT1 on 195 cases of benign and malignant thyroid neoplasms by using tissue microarrays for RNA in situ hybridization (ISH) and real-time PCR. MALAT1 is highly expressed in normal thyroid (NT) tissues and thyroid tumors, with increased expression during progression from NT to papillary thyroid carcinomas (PTCs) but is downregulated in poorly differentiated thyroid cancers (PDCs) and anaplastic thyroid carcinomas (ATCs) compared to NT. Induction of epithelial to mesenchymal transition (EMT) by transforming growth factor (TGF)-beta in a PTC cell line (TPC1) led to increased MALAT1 expression, supporting a role for MALAT1 in EMT in thyroid tumors. This is the first ISH study of MALAT1 expression in thyroid tissues. It also provides the first piece of evidence suggesting MALAT1 downregulation in certain thyroid malignancies. Our findings support the notion that ATCs may be molecularly distinct from low-grade thyroid malignancies and suggest that MALAT1 may function both as an oncogene and as a tumor suppressor in different types of thyroid tumors
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