1,721,122 research outputs found
The pathogenesis of rheumatoid arthritis
No full textSignificant recent progress in understanding rheumatoid arthritis (RA) pathogenesis has led to improved treatment and quality of life. The introduction of targeted-biologic and -synthetic disease modifying anti-rheumatic drugs (DMARDs) has also transformed clinical outcomes. Despite this, RA remains a life-long disease without a cure. Unmet needs include partial response and non-response to treatment in many patients, failure to achieve immune homeostasis or drug free remission, and inability to repair damaged tissues. RA is now recognized as the end of a multi-year prodromal phase in which systemic immune dysregulation, likely beginning in mucosal surfaces, is followed by a symptomatic clinical phase. Inflammation and immune reactivity are primarily localized to the synovium leading to pain and articular damage, but is also associated with a broader series of comorbidities. Here, we review recently described immunologic mechanisms that drive breach of tolerance, chronic synovitis, and remission
Ankylosing spondylitis
No full textAnkylosing spondylitis (AS) belongs to the group of diseases known as the <i>spondyloarthropathies</i> or, better, <i>spondyloarthritides</i>. This group of disorders constitutes a family of related but heterogeneous conditions, rather than a single disease with different clinical manifestations..
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
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Transcriptional Topology & Epigenetic Trajectory: A Translational Informatics Approach to the Characterization of Rheumatoid Arthritis
No full textRheumatoid arthritis (RA) is an autoimmune disease that begins as systemic dysregulation of the immune system and progresses to an inflammatory attack on the synovial joints. This body of research represents the application of translational bioinformatics methods to understand both the transcriptional topology of the rheumatoid synovium and the epigenetic trajectory of lymphocytes in RA. In chapter 1, we demonstrate the inability of the current, purportedly optimal, single-cell disaggregation protocol to accurately assay transcription in the synovium. Using RNAseq to evaluate transcription, we apply multiple disaggregation protocols to RA and OA synovial tissue and demonstrate that alternative protocols characterize transcription with greater fidelity, with implications for single-cell methods applied to adhesive tissue.
In chapter 2, we present a novel application of Laser Capture Microdissection followed by RNAseq (LCM-RNAseq) to accurately describe the transcriptional topology of the rheumatoid synovium. This method facilitates progress towards spatial investigation of transcription in the synovium but avoids the need for an adhesive-tissue-optimized, single-cell disaggregation protocol. By applying LCM-RNAseq to 7 RA samples and 7 controls (synovial tissue derived from osteoarthritis patients), we demonstrate that the lining, sublining, and vessel compartments of the rheumatic synovium each contribute unique aspects of the transcriptional signature that generates the inflammatory phenotype characteristic of symptomatic RA.
In chapters 3 and 4, we report the cross-sectional and longitudinal results, respectively, of the Targeting Immune Responses for Prevention of Rheumatoid Arthritis (TIP-RA) consortium’s study of the epigenetic changes in RA progression. Here we report a genome-wide analysis of methylation among ACPA- Controls, ACPA+ At-Risk, and Early RA. In this study, participants were followed for up to 5 years, with blood samples taken annually and at RA diagnosis. Peripheral blood mononuclear cells (PBMCs) were separated into CD19+ B cells, memory CD4+ T cells, and naïve CD4+ T cells using antibodies and magnetic beads. Genome-wide methylation within each cell lineage was assayed using the Illumina MethylationEPIC v1.0 beadchip.
In chapter 3, initial cross-sectional analysis at baseline reveals that the ACPA+ “At-Risk” methylome exhibits non-specific methylome dysregulation while Early RA epigenetic changes occur in a more coherent manner. In chapter 4, with the additional knowledge of which ACPA+ “At-Risk” participants would develop clinical RA and those that would not (“Pre-RA” and “Non-converters”, respectively), we perform an additional cross-sectional comparison. We find DMLs that distinguish the Pre-RA methylome from ACPA+ Non-converters, which closely resembles ACPA- Controls. Longitudinal analysis shows that ACPA- Control and ACPA+ Non-converter methylomes are relatively constant. In contrast, the Pre-RA methylome remodels along a dynamic “RA methylome trajectory” characterized by epigenetic changes in active regulatory elements
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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