1,720,972 research outputs found

    Assessment of mammary adiposity in breast cancer using digital pathology

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    L'obesità è un fattore di rischio significativo per molti tumori, compreso il carcinoma della mammella. I pazienti con carcinoma della mammella che sono sovrappeso o obesi hanno un aumentato rischio di recidiva e di mortalità correlata al tumore. Sebbene siano state proposte diverse ipotesi per descrivere i meccanismi biologici alla base dell’interazione tra obesità e carcinoma della mammella, i progressi nella comprensione del microambiente tumorale e del ruolo degli adipociti presenti in esso e della loro rilevanza per lo sviluppo e la progressione tumorale o per l'emergere di resistenze alle terapie sono ancora limitati. Parallelamente alle importanti scoperte sull'obesità come fattore di rischio per diverse malattie e tipi di tumore, i ricercatori hanno iniziato a utilizzare la patologia digitale per caratterizzare il microambiente tumorale. Studi pionieristici hanno scoperto l'esistenza di un tipo particolare di adipociti chiamati adipociti associati al tumore presenti nel microambiente di tumori che crescono a stretto contatto con il tessuto adiposo. Nel momento in cui è stata scritta questa tesi, solo pochi studi con piccole coorti di pazienti e spesso, un numero limitato di adipociti analizzati, per lo più distanti dal tumore, hanno mostrato la rilevanza del tessuto adiposo e degli adipociti come componente del microambiente tumorale. Tuttavia, allo stato attuale manca ancora una conoscenza approfondita del ruolo degli adipociti nel carcinoma della mammella. Lo studio presentato in questa tesi descrive le potenzialità della patologia digitale e fornisce una rappresentazione dello stato dell'arte sui software con algoritmi dedicati per la misurazione degli adipociti, con una attenzione per gli adipociti presenti nel microambiente di carcinomi mammari. Oltre a stabilire criteri istopatologici per l'analisi degli adipociti, i risultati presentati dimostrano che è possibile effettuare l'analisi degli adipociti associati al tumore come di quelli distanti, utilizzando un software di patologia digitale. Inoltre, abbiamo mostrato che gli adipociti associati al tumore sono più piccoli degli adipociti distanti, riflettendo il processo di delipidazione subito dagli stessi. Infine, l'indice di massa corporea del paziente è associato alle dimensioni degli adipociti distanti e associati al tumore, fornendo nuove prospettive per la valutazione dell'adiposità mammaria di un paziente. I dati qui presentati, sono preliminari per un cambiamento diretto nella pratica clinica, ma forniscono i criteri per eseguire l'analisi degli adipociti su coorti più ampie di pazienti ed evidenziano l’importanza della valutazione del tessuto adiposo nella gestione del carcinoma della mammella.Increased adiposity is a significant risk factor for many cancers, including breast cancer. Patients with breast cancer who are overweight or obese have an increased risk of recurrence, and breast cancer-related mortality. While several hypotheses have been proposed to explain the biological mechanisms that drive the obesity-breast cancer interconnections, progress in our understanding of the adipose tissue tumor microenvironment and its relevance to breast cancer initiation and progression or the emergence of resistance to therapy has been limited. In parallel to major breakthroughs on the increased adiposity as risk factor for several diseases and cancers, researchers have begun to utilize digital pathology to characterize the tumor microenvironment in diverse types of adipose tissue-rich neoplasia. Pioneering studies have uncovered the existence of a peculiar type of adipocytes named cancer-associated adipocytes in the microenvironment of tumors that grow in close contact with adipose tissue. At the time this thesis was started, only a few studies with small cohorts of patients and often, a limited number of adipocytes analyzed, mostly distant from the tumor, have shown the importance of the adipose tissue tumor microenvironment. However, an in-depth knowledge was currently lacking for breast cancer. The work presented here harnesses the strength of digital pathology and state of the art of adipocyte measurement tools to analyze adipocytes in the adipose tissue microenvironment of breast cancer. Beyond providing histopathological criteria for adipocyte analysis, these results suggest that the analysis of mammary cancer-associated adipocytes is feasible using image analysis software. Moreover, our analyses reveal that cancer-associated adipocytes are smaller than distant adipocytes, reflecting the delipidation process undergone by cancer-associated adipocytes. The body mass index of the patient is associated with the size of distant and cancer-associated adipocytes giving new insights in the evaluation of mammary adiposity of a patient. The data presented here are too preliminary to derive practice-changing evidence but provide the basis for performing adipocyte analysis on larger number of patients and support the concept that the evaluation of adipose tissue should be taken into account in breast cancer management

    Squalene epoxidase as a promising metabolic target in cancer treatment

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    Oncogenic alteration of the cholesterol synthesis pathway is a recognized mechanism of metabolic adaptation. In the present review, we focus on squalene epoxidase (SE), one of the two rate-limiting enzymes in cholesterol synthesis, retracing its history since its discovery as an antimycotic target to its description as an emerging metabolic oncogene by amplification with clinical relevance in cancer. We review the published literature assessing the association between SE over-expression and poor prognosis in this disease. We assess the works demonstrating how SE promotes tumor cell proliferation and migration, and displaying evidence of cancer cell demise in presence of human SE inhibitors in in vitro and in vivo models. Taken together, robust scientific evidence has by now accumulated pointing out SE as a promising novel therapeutic target in cancer treatment

    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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