1,721,423 research outputs found

    Tregs: hype or hope for allogeneic hematopoietic stem cell transplantation?

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    The discovery of T regulatory cells has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. Basic immunology is rapidly elucidating the complex biology of these cells even though the difficulties in purifying or even expanding them in vitro represent a major limitation to the development of clinical studies. The clinical benefit potentially associated with this therapeutic approach remains to be demonstrated. Meanwhile, several drugs used for the treatment of hematologic malignancies or for other purposes have been shown to upregulate the number and function of Tregs in vivo. In the near future, both ex vivo or in vivo expanded T cells are likely to enter the therapeutic armamentarium of clinical transplantation.Bone Marrow Transplantation advance online publication, 20 March 2017; doi:10.1038/bmt.2017.30

    Inflammation and myeloproliferative neoplasms

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    Myeloproliferative neoplasms (MPN) include three main entities: Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Myelofibrosis (MF). MPN represent a unique model of the relationship between the clonal development of a hematologic malignancy and chronic inflammation. The neoplastic clone is the main driver of this inflammatory reaction as demonstrated by the curative effect of allogeneic stem cell transplantation which leads not only to a complete restore of the hematopoiesis, but also to regression of bone marrow fibrosis. The neoplastic clone and its differentiated progeny are also the main source of an indirect paracrine secretion of inflammatory cytokines released by different normal cells present within the tumor microenvironment. In the end, the cytokine storm within the bone marrow niche leads to fibrosis. In addition, chronic inflammation is responsible of the constitutional symptoms which negatively affect the quality of life of MPN patients and represents a major driver for the development of premature atherosclerosis and disease progression. Here we describe the available data about the link between MPN and chronic inflammation in animal models as well as in clinical studies. We also review the practical value of including acute phase inflammatory proteins such as high sensitivity C-reactive protein (hs-CRP) and pentraxin 3 (PTX-3) in prognostic stratification of MPN patients. Interestingly, the plasma levels of these proteins is often increase in MPN patients and this may be important when considering the well-established link between these two inflammatory proteins and the risk of both arterial and venous thrombosis. Although the available drugs are unable to eradicate the malignant clone, the ability to identify patient with a high inflammatory burden and an adverse molecular profile is important to advise therapy with ruxolitinib or even allogeneic stem cell transplantation that currently represents the only potentially curative option for these diseases

    ROLE OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

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    Adult acute lymphoblastic leukemia (ALL) is a heterogeneous disease, due to the expression of different biological and clinical risk factors, for which allogeneic stem cell transplantation (alloHSCT) is an effective consolidation therapy. The non-relapse mortality of alloHSCT remains significantly higher compared with that of conventional chemotherapy; therefore, one of the main challenges in the care of ALL is to establish a more precise prognostic definition to select patients who could take advantage from an alloHSCT. Currently, the use of minimal residual disease following induction and early consolidation therapy has improved the prognostic accuracy in defining ALL risk class. In Philadelphia-positive ALL, the introduction of tyrosine kinase inhibitors pre and post alloHSCT appears to improve outcomes significantly and, in the absence of specifically designed clinical trials, alloHSCT remains the most effective post- remission therapy. Nowadays, alloHSCT can be performed according to different modalities encompassing the use of different conditioning regimens, as well as different donors and stem cell source, with a significant accessibility to transplant

    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
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