1,720,997 research outputs found

    Loss of dimethylated H3K27 (H3K27me2) expression is not a specific marker of malignant peripheral nerve sheath tumor (MPNST): An immunohistochemical study of 137 cases, with emphasis on MPNST and melanocytic tumors

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    Introduction: Loss-of-function mutations in EED and SUZ12, core components of the polycomb repressive complex 2 (PRC2), occur in >90% of sporadic and radiation-associated malignant peripheral nerve sheath tumors (MPNST) and in roughly 70% of NF1-related tumors. PRC2 inactivation results in loss of H3K27me3 expression and aberrant downstream transcription. H3K27me3 expression is lost in 40-90% of spindle cell MPNST but is not specific. A single study has suggested that dimethylated H3K27 (H3K27me2) is a more specific marker of MPNST.Methods: We compared the expression of H3K27me3 and H3K27me2 by immunohistochemistry in a series of MPNST (n = 26), neurofibroma (n = 11), conventional dermatofibrosarcoma protuberans (n = 8), fibrosarcomatous dermatofibrosarcoma protuberans (n = 7), spindle cell rhabdomyosarcoma (n = 6), high-risk solitary fibrous tumor (n = 9), dedifferentiated chondrosarcoma (n = 7), synovial sarcoma (n = 9), diffuse midline glioma, H3K27-altered (n = 13), conventional diffuse astrocytoma (n = 2), conventional cutaneous melanoma (n = 8), uveal melanoma (n = 8), cellular blue nevus (n = 17) and melanoma arising in blue nevus (n = 6).Results: H3K27me3 and H3K27me2 expression patterns were concordant in 115/137 (84%) with 85 cases (62%) expressing both markers and 30 cases (22%) showing loss of both. Discordant results were seen in 22 cases (H3K27me3 loss with retained H3K27me2, 10 cases (7%); H3K27me3 expression with H3K27me2 loss, 12 cases (9%)). H3K27me2 loss was not specific for MPNST and was also seen in certain other tumors, in particular those in the "blue nevus family".Conclusion: We conclude that H3K27me2 loss is not specific for MPNST, and like H3K27me3, should be used in the appropriate clinicopathologic, immunohistochemical and molecular genetic context. Loss of H3K27me2 with retained H3K27me3 is a common feature of "blue nevus family" melanocytic tumors known to harbor GNAQ/GNA11 mutations

    Dataset for reporting of thymic epithelial tumours:recommendations from the International Collaboration on Cancer Reporting (ICCR)

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    Aims: Thymic epithelial tumours (TET), including thymomas and thymic carcinomas and thymic neuroendocrine neoplasms, are malignant neoplasms that can be associated with morbidity and mortality. Recently, an updated version of the World Health Organization (WHO) Classification of Thoracic Tumours 5th Edition, 2021 has been released, which included various changes to the classification of these neoplasms. In addition, in 2017 the Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) published the 8th Edition Staging Manual which, for the first time, includes a TNM staging that is applicable to thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms. Methods and Results: To standardize reporting of resected TET and thymic neuroendocrine neoplasms the accrediting bodies updated their reporting protocols. The International Collaboration on Cancer Reporting (ICCR), which represents a collaboration between various National Associations of Pathology, updated its 2017 histopathology reporting guide on TET and thymic neuroendocrine neoplasms accordingly. This report will highlight important changes in the reporting of TET and thymic neuroendocrine neoplasms based on the 2021 WHO, emphasize the 2017 TNM staging, and also comment on the rigour and various uncertainties for the pathologist when trying to follow that staging. Conclusion: The ICCR dataset provides a comprehensive, standardized template for reporting of resected TET and thymic neuroendocrine neoplasms.</p

    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

    TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by upregulating claudin-1 in non-small-cell lung cancer cells

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    Lung cancer is the most frequent cause of cancer-related deaths worldwide, but its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. However, our research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. In this study, we analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of non-small-cell lung cancer cell lines. To identify the molecules and signaling pathways with which TUSC3 might interact, we completed immunoblotting, quantitative polymerase chain reaction, microarray, co-immunoprecipitation, and immunofluorescence assays. We demonstrated that TUSC3 knockdown leads to decreased proliferation, migration, and invasion, and reduced xenograft tumor growth of non-small-cell lung cancer cell lines, whereas opposite results were observed with overexpression of TUSC3. In addition, TUSC3 knockdown suppressed epithelial-mesenchymal transition by downregulating the expression of claudin-1, which plays an indispensable role in EMT progress. On the contrary, overexpression of TUSC3 significantly enhanced EMT progress by upregulating claudin-1 expression. Overall, our observations suggest that TUSC3 accelerates cancer growth and induces the epithelial-mesenchymal transition in non-small-cell lung cancer cells; we also identified claudin-1 as a target of TUSC3

    Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

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    Thoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered

    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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