1,721,032 research outputs found
Hematopoietic stem cell gene therapy for the cure of blood diseases: primary immunodeficiencies
No full textGene therapy for Wiskott Aldrich Syndrome
No full textThe Wiskott-Aldrich Syndrome (WAS) is a monogenic X-linked primary immunodeficiency characterised also by thrombocytopenia, eczema, and a high susceptibility to develop tumours and autoimmunity. WAS patients have a severely reduced life expectancy, unless they undergo a successful HLA-matched haematopoietic stem cell (HSC) transplantation. However, several WAS patients lack a compatible donor and complications, such as autoimmunity, can arise in a significant fraction of HSC transplanted patients. Administration of WAS gene-corrected autologous HSC represents an alternative therapeutic approach, potentially applicable to all WAS patients. To this aim, several gene therapy approaches for WAS using initially gamma-retroviral vectors (RVs) and subsequently HIV-based lentiviral vectors (LVs) have been developed. In the present review, we will first describe the results of the preclinical studies conducted in the murine model of WAS and then discuss the outcome of different phase I/II clinical trials using RV or LV- transduced HSC. Both gene therapy approaches led to restored WASP expression, correction of functional defects and clinical improvement. While RV-mediated gene therapy was associated with a high occurrence of leukaemia, results obtained in the first patients treated with LV-based HSC gene therapy indicate a safer risk-benefit profile
Correction to: A Case of Two Adult Brothers with Wiskott‐Aldrich Syndrome, One Treated with Gene Therapy and One with HLA‐Identical Hematopoietic Stem Cell Transplantation (Journal of Clinical Immunology, (2022), 42, 2, (421-425), 10.1007/s10875-021-01157-6)
No full textDue to typesetting mistake, some entries of Table 1 were not properly aligned to their corresponding rows. The original version has been corrected
Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency.
No full textPURPOSE OF REVIEW:
The present review describes the recent progress in the treatment of adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) using autologous gene-modified hematopoietic stem cells, comparing immune reconstitution with respect to allogeneic transplant and discussing differences with gene therapy for SCID-X1.
RECENT FINDINGS:
Since 2000, more than 30 ADA-SCID patients have been treated with gene therapy worldwide, with successful outcome in most cases, consisting of progressive immune reconstitution, efficient systemic detoxification, and long-term multilineage engraftment. Gene therapy resulted in restoration of thymic activity and T-cell functions, although the kinetic of reconstitution was slower compared with standard bone marrow transplant. Unlike allogeneic transplant from alternative donors, survival after gene therapy is excellent. In comparison with SCID-X1, ADA-SCID gene therapy presents a better safety profile and engraftment of multilineage transduced stem/progenitor cells, thanks to the use of nonmyeloablative preconditioning. New approaches using safer integrating vectors are being developed, which may lead to safer and effective gene therapy for ADA-SCID and other genetic disorders.
SUMMARY:
In the last decade, gene therapy has been developed as a successful and safe alternative strategy for patients affected by ADA-SCID lacking a compatible sibling donor. The application of innovative vector technology might further improve its efficacy and safety profile
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
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
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