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    Beta-Catenin Alterations in Postchemotherapy Yolk Sac Tumor, Postpubertal-Type With Enteroblastic Features

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    Postchemotherapy postpubertal -type yolk sac tumors (YST) with glandular and solid phenotypes are aggressive and commonly resistant to systemic chemotherapy. These neoplasms show morphologic features that significantly overlap with those of somatic carcinomas with "enteroblastic" or "fetal" phenotype (the preferred terminology depends on the site of origin). They often present as late or very late recurrences, and their diagnosis is challenging because they frequently affect patients in an age group at risk for carcinomas of somatic origin. Recently, we incidentally identified examples of postchemotherapy glandular and solid YST with "enteroblastic" phenotypes and nuclear expression of beta-catenin, prompting us to further evaluate the prevalence of this phenomenon. We found nuclear expression of beta-catenin in 10 (29%) of 34 such tumors. A subset of cases with nuclear beta-catenin expression was further analyzed with a DNA sequencing panel (n = 6) and fluorescence in situ hybridization for isochromosome 12p [i(12p); n = 5]. Sequencing identified exon 3 CTNNB1 variants in 3 (50%) of 6 analyzed cases, and fluorescence in situ hybridization was positive for i(12p) in 5 of 5 cases. In conclusion, a significant subset of postchemotherapy YST with glandular or solid architecture and "enteroblastic" phenotype demonstrates beta-catenin alterations, suggesting that activation of Wnt signaling may play a role in the progression of these neoplasms. Moreover, nuclear beta-catenin expression in these tumors represents a potential diagnostic pitfall given that carcinomas of true somatic origin with overlapping morphology may also be positive for this marker. (c) 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies

    The absence of FOXA2 and HNF1β expression in vasculogenic mesenchymal lesions of germ cell origin suggests an evolutionary pathway similar to that of sarcomatoid yolk sac tumor

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    : Vasculogenic mesenchymal lesions (VMLs) are uncommon phenotypes of germ cell tumor (GCT) origin that are mostly found after chemotherapy of mediastinal yolk sac tumor (YST). These lesions typically lack expression of classical YST markers [α-fetoprotein (AFP) and glypican-3 (GPC3)]. FOXA2 and HNF1β are key inducers of the YST phenotype and co-operate to promote transcription of genes involved in YST development (AFP, GPC3, GATA3, among others). Immunohistochemical studies have shown that FOXA2 and HNF1β are more sensitive than AFP, GPC3, and GATA3 for conventional phenotypes of YST, whereas they are typically negative in sarcomatoid YST. In this study, assessment of VMLs showed that they do not express FOXA2 and HNF1β to a significant degree. These results suggest that the combined downregulation of FOXA2 and HNF1β may underlie the transformation of YST to "mesenchymal" phenotypes, with additional (still undefined) processes determining the final phenotype (sarcomatoid YST or VMLs)

    β-Catenin alterations in testicular Leydig cell tumour: a immunohistochemical and molecular analysis

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    Background: Testicular Leydig cell tumours (LCTs) are the most common type of sex cord-stromal tumour in men, representing 1%-3% of all testicular neoplasms. Among testicular sex cord-stromal tumours, CTNNB1 mutations and nuclear expression of beta-catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of beta-catenin alterations remain incompletely understood in this tumour type. Methods: In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using beta-catenin immunohistochemistry and DNA sequencing. Results: Immunohistochemistry revealed focal or multifocal nuclear beta-catenin expression in 47% of the tumours. Diffuse nuclear beta-catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of beta-catenin-positive and beta-catenin-negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional beta-catenin-positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively. Conclusion: These results demonstrate that beta-catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of beta-catenin in this tumour type

    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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