1,721,394 research outputs found
Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome
No full textThymocytes and thymic epithelial cell (TEC) cross-talk is crucial to preserve thymic architecture and function, including maturation of TECs and dendritic cells, and induction of mechanisms of central tolerance.We have analyzed thymic maturation and organization in 9 infants with various genetic defects leading to complete or partial block in T-cell development. Profound abnormalities of TEC differentiation (with lack of AIRE expression) and severe reduction of thymic dendritic cells were identified in patients with Tnegative severe combined immunodeficiency, reticular dysgenesis, and Omenn syndrome. The latter also showed virtual absence of thymic Foxp3 T cells. In contrast, an IL2RG-R222C hypomorphic mutation
permissive for T-cell development allowed for TEC maturation, AIRE expression, and Foxp3 T cells. Our data provide
evidence that severe defects of thymopoiesis impinge on TEC homeostasis and may affect deletional and nondeletional
mechanisms of central tolerance, thus favoring immune dysreactive manifestations, as in Omenn syndrome
ARTEMIS AND LIGASE 4 ARE DISPENSABLE FOR THE GENERATION OF HUMAN INDUCED PLURIPOTENT STEM CELLS
No full textThe challenges presented by haematopoietic stem cell transplantation in children with primary immunodeficiency
No full text\ua9 The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected] OR BACKGROUND: For many primary immunodeficiencies (PIDs), haematopoietic stem cell transplantation (HSCT) offers treatment to cure disease. However, patients with PID present a unique set of challenges when considering HSCT. SOURCES OF DATA: Review of recent literature. AREAS OF AGREEMENT: The most significant recent impact on successful outcome is introduction of newborn screening programmes for diagnosis of severe combined immunodeficiency-wider adoption of screening in an increasing number of countries will see further improvements. Other PIDs have better outcomes when treated earlier, before development of co-morbidities-early referral for consideration of HSCT is important. Evolution of conditioning regimens is improving short- and long-term toxicities-targeted busulfan and low-toxicity myeloablative treosulfan regimens deliver good survival with reduced short-term toxicities. AREAS OF CONTROVERSY: The most radical development, still in clinical trials, is the use of mono-antibody-based conditioning, which eliminates the requirement for chemotherapy and is likely to become much more important in HSCT for non-malignant disease in the future. GROWING POINTS: Multidisciplinary working for optimum care is essential. AREAS TIMELY FOR DEVELOPING RESEARCH: International collaborations are important to learn about rare presentations and complications, and to formulate the most effective and safe treatment strategies
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
Severe combined immunodeficiency: Newborn screening and the BCG vaccination
No full text\ua9 Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.Severe combined immunodeficiency (SCID) presents in infancy and, if untreated, is fatal by 12-18 months. Infants appear healthy at birth, but develop persistent infection, progressive pneumonitis and malabsorption-induced growth failure, due to enteric viral infection, often with persistent vaccine-strain rotavirus. Live vaccines are contraindicated, although most eligible infants receive BCG and rotavirus vaccine before receiving a SCID diagnosis. For most patients, haematopoietic cell transplantation (HCT) is the treatment of choice and curative. However, HCT mortality is significantly increased when infection or organ damage is present. In infection-free infants, survival1 and neurodevelopmental outcome2 are significantly better
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
Primary immune regulatory disorders: Undiagnosed needles in the haystack?
Get PDF\ua9 2022. The Author(s). Primary Immune Regulatory Disorders (PIRD) describe a group of conditions characterized by loss of normal inflammatory control and immune tolerance mechanisms, with autoimmunity as a predominant clinical feature. PIRD can arise due to defects in the number or function of regulatory T-lymphocytes, defects in the immune mechanisms required to \u27turn off\u27 inflammation such as in perforin-dependent cytotoxicity or alterations in cytokine signalling pathways. Diagnosis of PIRD is a significant challenge to physicians due to their rarity, complexity, and diversity in clinical manifestations. Many of these individual conditions lack a genotype-phenotype correlation and display incomplete penetrance. However, establishing a diagnosis is integral in optimizing patient management, including the use of individualized treatment approaches. Increasing awareness among physicians is necessary as patients are likely to present to different subspecialties. Due to the rarity of these conditions, worldwide collaboration and data-sharing is essential to improve our knowledge of the clinical spectrum and disease course in PIRD, and to optimize therapeutic strategies including identification of which patients can benefit from hematopoietic stem cell transplant
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
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