1,720,992 research outputs found

    Single-cell characterisation of T lymphocyte immune responses in spondyloarthropathy

    Get PDF
    The spondyloarthropathies (SpA) are a collection of inflammatory disorders of undetermined etiology affecting the joints and connective tissues, however existing evidence suggests a role for the microbiome, CD4 and CD8 T cells in disease pathogenesis. A CD154 activation based functional assay was first used to quantify and characterise CD4+ memory T cell populations reactive to a panel of 13 microbes found at mucosal barrier sites, predominantly gut bacteria. Peripheral blood mononuclear cells (PBMC) from 31 SpA, 17 rheumatoid arthritis (RA) and 14 healthy controls, as well as synovial fluid mononuclear cells (SFMC) from 9 SpA patients were separated and stimulated overnight with a panel of microbial lysates. Cells were then stained for CD154, TNFα, IFNγ, IL-17A, GM-CSF, IL-22 and IL-2 and analysed by flow cytometry. Single-cell RNA sequencing (scRNA-seq) was then used to characterise S. typhimurium-reactive synovial Th memory cells from a psoriatic arthritis (PsA) patient, in addition to ex vivo CD4 and CD8 memory T cells from the peripheral blood and synovial fluid of 6 PsA patients. The frequency of Th memory cells reactive to microbes capable of inducing a type 17/17.1 response were enriched in SpA synovial fluid relative to blood, and scRNA-seq analysis revealed a trajectory along which Th17.1 cells could differentiate into a "stem-like" memory pool capable of proliferation or into a Th17 regulatory phenotype. Pronounced clonal expansions of ex vivo CD8 memory T-cells within the joints of PsA patients were also identified by scRNA-seq. They exhibited distinct gene expression profiles including cycling, activation, tissue homing and tissue residency markers. Pseudotime analysis of these clonal CD8 populations identified trajectories in which tissue residency can represent an intermediate developmental state giving rise to activated, cycling and exhausted CD8 populations. Comparing T cell clonality across patients further revealed specificity convergence of clones against a putative common antigen. A role for gut microbes in SpA pathogenesis was supported by the higher frequency of Th17 cells reactive to Salmonella typhimurium found in SpA synovial fluid compared with SpA peripheral blood, and characterisation of these cells revealed trajectories of differentiation which could potentially be targeted to skew Th17.1 responses towards a regulatory phenotype. The identification of pro-inflammatory and clonally expanded CD8 T cells by scRNA-seq also suggests an antigen driven expansion of pathogenic CD8 T cells in PsA

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Get PDF
    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

    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

    Appropriate Similarity Measures for Author Cocitation Analysis

    Get PDF
    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

    Get PDF
    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

    No full text
    Nao informado

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

    No full text
    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
    corecore