1,720,959 research outputs found
Ibrutinib therapy downregulates AID enzyme and proliferative fractions in chronic lymphocytic leukemia
No full textActivation-induced cytidine deaminase (AID) initiates somatic hypermutation and class switch recombination of the immunoglobulin genes. As a trade-off for its physiological function, AID also contributes to tumor development through its mutagenic activity. In chronic lymphocytic leukemia (CLL), AID is overexpressed in the proliferative fractions (PFs) of the malignant B lymphocytes, and its anomalous expression has been associated with a clinical poor outcome. Recent preclinical data suggested that ibrutinib and idelalisib, 2 clinically approved kinase inhibitors, increase AID expression and genomic instability in normal and neoplastic B cells. These results raise concerns about a potential mutagenic risk in patients receiving long-term therapy. To corroborate these findings in the clinical setting, we analyzed AID expression and PFs in a CLL cohort before and during ibrutinib treatment. We found that ibrutinib decreases the CLL PFs and, interestingly, also reduces AID expression, which correlates with dampened AKT and Janus Kinase 1 signaling. Moreover, although ibrutinib increases AID expression in a CLL cell line, it is unable to do so in primary CLL samples. Our results uncover a differential response to ibrutinib between cell lines and the CLL clone and imply that ibrutinib could differ from idelalisib in their potential to induce AID in treated patients. Possible reasons for the discrepancy between preclinical and clinical findings, and their effect on treatment safety, are discussed.Fil: Morande, Pablo Elías. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sivina, Mariela. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Uriepero, Angimar. Instituto Pasteur de Montevideo; UruguayFil: Seija, Noé. Instituto Pasteur de Montevideo; UruguayFil: Berca, Catalina. Instituto Pasteur de Montevideo; UruguayFil: Fresia, Pablo. Instituto Pasteur de Montevideo; UruguayFil: Landoni, Ana Inés. Ministerio de Salud.Hospital Maciel. Administración de los Servicios de Salud del Estado; UruguayFil: Di Noia, Javier M.. University of Montreal; Canadá. Cliniques de Montreal. Institut de Recherches. Division of Immunity and Viral Infections; CanadáFil: Burger, Jan A.. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Oppezzo, Pablo. Instituto Pasteur de Montevideo; Urugua
LPL protein in Chronic Lymphocytic Leukaemia have different origins in Mutated and Unmutated patients. Advances for a new prognostic marker in CLL
Get PDFLipoprotein lipase (LPL) mRNA expression in chronic lymphocytic leukaemia (CLL) is associated with an unmutated immunoglobulin profile and poor clinical outcome. We evaluated the subcellular localization of LPL protein in CLL cells that did or did not express LPL mRNA. Our results show that LPL protein is differently located in CLL cells depending on whether it is incorporated from the extracellular medium in mutated CLL or generated de novo by leukaemic cells of unmutated patients. The specific quantification of endogenous LPL protein correlates with mRNA expression levels and mutational IGHV status, suggesting LPL protein as a possible reliable prognostic marker in CLL.Fil: Prieto, Daniel. Instituto Pasteur de Montevideo; Uruguay. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Seija, Noé. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Uriepero, Angimar. Instituto Pasteur de Montevideo; UruguayFil: Souto-Padron, Thais. Universidade Federal do Rio de Janeiro; BrasilFil: Oliver, Carolina. Universidad de la República; UruguayFil: Irigoin, Victoria. Universidad de la República; UruguayFil: Guillermo, Cecilia. Universidad de la República; UruguayFil: Navarrete, Marcelo A.. Universidad de Magallanes; ChileFil: Inés Landoni, Ana. Ministerio de Salud. Administración Servicios de Salud del Estado. Hospital Maciel; UruguayFil: Dighiero, Guillermo. Ministerio de Salud. Administración Servicios de Salud del Estado. Hospital Maciel; UruguayFil: Gabus, Raúl. Ministerio de Salud. Administración Servicios de Salud del Estado. Hospital Maciel; UruguayFil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Oppezzo, Pablo. Instituto Pasteur de Montevideo; Urugua
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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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