1,721,095 research outputs found

    BIOLOGICAL AND CLINICAL RELEVANCE OF MIRNA EXPRESSION SIGNATURES IN PRIMARY PLASMA CELL LEUKEMIA

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    Purpose: Plasma cell leukemia (PCL) is a very aggressive and rare hematological malignancy that can be distinguished into primary (pPCL), originating de novo, or secondary (sPCL), arising as a leukemic transformation of multiple myeloma (MM). Genomic and clinical differences between pPCL and MM have been demonstrated, mainly based on retrospective studies. This study was aimed at investigating the involvement of miRNAs in pPCL and their possible relationship with higher tumor aggressiveness. Experimental design: MiRNA expression profiles were analyzed in highly-purified malignant plasma cells from 18 pPCL cases included in a prospective clinical trial. MiRNA expression patterns were evaluated in comparison with a representative series of multiple myeloma (MM) patients, in relation to the most recurrent chromosomal abnormalities (as assessed by fluorescence in situ hybridization and single nucleotide polymorphism-array analysis), and in association with clinical outcome. MiRNA expression was also integrated with gene expression profiles and computational prediction of miRNA target genes in pPCL and MM samples in order to identify putative target genes of deregulated miRNAs. The functional role of a few identified miRNAs in plasma cell dyscrasia pathogenesis was explored by transfection of synthetic pre/anti-miRNAs in multiple myeloma cell lines. Results: We identified a series of deregulated miRNAs in pPCL (42 up- and 41 down-regulated) in comparison with MM. Some of them, based on their reported functions or putative target genes computed by integrative analysis, might have a role in the pathobiology of pPCL, such as miR-21, that was found to promote in vitro growth of MM cell lines. As regards chromosomal aberrations, the expression of some miRNAs mapped to hot-spot altered regions was associated with DNA copy number of the corresponding genomic loci; furthermore, TP53 deletion, a frequent cytogenetic lesion in our pPCL cohort, was found associated with a trend of down-regulation of miR-34a, whose tumor suppressor activity was demonstrated for the first time also in the context of MM. Finally, four miRNAs (miR-497, miR-106b, miR-181a* and miR-181b) were identified having expression levels correlated with treatment response, and four (miR-92a, miR-330-3p, miR-22, and miR-146a) with clinical outcome. Conclusions: Overall, this study provides insights into the possible contribution of miRNAs in the pathogenesis of pPCL and suggests targets for future therapeutic investigations

    Long non-coding RNAs in normal and malignant hematopoiesis

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    Long non coding RNAs (lncRNAs) are defined as ncRNAs of more than 200 nt in length. They are involved in a large spectrum of biological processes, such as maintenance of genome integrity, genomic imprinting, cell differentiation, and development by means of mechanisms that remain to be fully elucidated. Besides their role in normal cellular physiology, accumulating evidence has linked lncRNA expression and functions to cancer development and progression. In this review, we summarize and discuss what is known about their expression and roles in hematopoiesis with a particular focus on their cell-type speciï¬city, functional interactions, and involvement in the pathobiology of hematological malignancies

    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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    MicroRNAs in the Pathobiology of Multiple Myeloma

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    MicroRNAs (miRNAs) are small non-coding RNAs that bind to the 3'untranslated region of target mRNAs and lead to translation repression or mRNA degradation, thus regulating important cell processes. MiRNA deregulation has been identified in virtually all types of cancer, and miRNA profiling has proved useful in cancer diagnosis, prognosis and response to therapy. So far, limited but important evidence of miRNA impaired expression has been reported in multiple myeloma (MM), suggesting implications in the pathogenesis and biology of the disease. In this review, we present a general overview of the role of miRNAs in B-cell development and associated malignancies, focusing on those most extensively characterized. We fully describe seminal studies on miRNA expression in MM, highlighting the correlations of their deregulation with pathogenesis and with distinct molecular subgroups, as well as their role in prognostic stratification. The data obtained in MM, supported by the consolidated role of miRNAs in cancer and their potential effectiveness in therapy, all provide a solid rationale for the more accurate characterization of their deregulation and the development of effective means of selectively delivering miRNAs and anti-miRNAs to myeloma cells in therapeutic approache

    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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