1,720,978 research outputs found
NOTCH1 mutations are associated with low CD20 expression in Chronic Lymphocytic Leukemia: evidences for a NOTCH1-mediated epigenetic regulatory mechanism
Full text linkChronic lymphocytic leukemia (CLL) is a heterogeneous disease with highly variable clinical courses and survivals ranging from months to decades. Recently, it has been reported that stabilizing mutations of NOTCH1 are recurrently associated with CLL, being identified in about 10% of CLL at diagnosis and with higher frequencies in chemorefractory CLL, CLL in advanced disease phases, and in Richter Syndrome. All NOTCH1 mutations disrupt the C-terminal PEST domain, causing an accumulation of a stabilized NOTCH1 isoform. By taking advantage of a large retrospective cohort of CLL cases (n=463), for a subset of which clinical data was available, we confirm that NOTCH1 mutations behave as independent prognosticator, identifying a high-risk subset characterized by unfavourable prognosis and poor overall survival. We further demonstrate that the presence of NOTCH1 mutations also identifies a CLL subset which does not benefit from addition of rituximab in the context of a maintenance therapy after first-line treatment with fludarabine. These results are in keeping with recently published data, reporting that the NOTCH1 mutated subset of CLL patients does not benefit from the addition of rituximab to chemotherapeutic treatment with fludarabine plus cyclophosphamide. As the reasons for this different clinical behaviour remained to be elucidated, considering that the response to rituximab treatment in B cell neoplasms directly depends upon CD20 expression, we investigated whether NOTCH1 mutations could affect CD20 expression in CLL. By taking advantage of a wide CLL series (n=692), we demonstrated that NOTCH1 mutated CLL cells (87/692) were characterized by lower CD20 expression and lower relative lysis induced by rituximab in-vitro. Consistently, CD20 expression by CLL cells was up-regulated in-vitro by exposure to γ-secretase inhibitors, and the stable transfection of the NOTCH1 intracellular domain (NICD) into CLL-like cells resulted in a strong downregulation of both CD20 protein and transcript. By using these NICD transfectants, we investigated the protein interactions of RBPJ, a transcription factor acting either as activator or repressor of NOTCH1 pathway when respectively bound to NICD or histone deacetylases (HDACs). Compared to controls, NICD transfectants had RBPJ preferentially complexed to NICD, and showed higher levels of HDACs interacting with the promoter of the CD20 gene. Finally, treatment with the HDAC inhibitor valproic acid upregulated CD20 in both NICD transfectants and primary CLL cells. In conclusion, NOTCH1 mutations are associated with low CD20 levels in CLL and are responsible for a dysregulation of HDAC-mediated epigenetic repression of CD20 expression. In conclusion, in the present thesis we i) confirm that NOTCH1 mutations are an independent prognosticator of overall survival in CLL; ii) identify a CLL subset, characterized by the presence of NOTCH1 mutations, that do not benefit from addition of rituximab to chemotherapeutic treatment; iii) provide a proof of concept that NOTCH1 mutations responsible for a truncated NOTCH1 protein are associated with low CD20 expression levels in CLL by a dysregulated HDAC-dependent repression mechanism. This low CD20 levels may be, in turn, responsible for the specific immunoresistance to rituximab-based treatments, such as FCR, of NOTCH1 mutated CLL
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
Hepatitis C virus-associated B-cell lymphomas: The importance of the new direct antiviral agent therapy
No full textHepatitis C virus (HCV) is a hepatotropic and lymphotropic virus, responsible for both chronic hepatitis and extra-hepatic manifestations. Multiple epidemiologic, clinical, biological, and molecular studies have suggested that HCV plays a causal role also in the development of several lymphoproliferative disorders, either benign, such as mixed cryoglobulinemia, or malignant, such as B-cell non-Hodgkin lymphomas (NHL). Chronic viral antigenic stimulation of B-lymphocytes plays a fundamental basic role from the on -set of lymphoma to its final steps. In the past, several studies demonstrated that the association of pe-gylated interferon plus ribavirin was able to eradicate HCV, with subsequent regression of indolent B-cell low-grade NHL. Other studies have demonstrated that direct antiviral agents (DAAs) therapy have some efficacy in HCV-associated NHL, particularly in patients with low-grade NHL or marginal zone-lymphoma, but these results need to be confirmed in larger studies with longer follow-up. The response rate of an-tiviral therapy seems favorable also in high grade NHL when DAAs therapy is administered in combina-tion with chemotherapy and therefore antiviral therapy should be considered as a first-line approach in HCV-related NHL.(c) 2022 Published by Elsevier Inc
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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