1,721,253 research outputs found
Characterisation of autoreactives B cells in Sjögren's syndrome
No full textLes LB jouent un rôle central dans le syndrome de Sjögren primitif (SSp), cependant très peu d’études ont été réalisées sur les caractéristiques des LB auto-réactifs qui sécrètent des autoanticorps contre l'auto-antigène SSA.Nous avons cherché à caractériser les LB circulants spécifiques de la SSA (LB SSA+), afin de mieux comprendre les mécanismes conduisant à la rupture de la tolérance chez les patients atteints du SSp.En utilisant une méthode de cytométrie en flux, basée sur la spécificité du BCR, nous avons détecté et caractérisé phénotypiquement les LB SSA+ circulants chez des patients atteints de SSp et chez des contrôles sains (HCs). Nous avons testé leur capacité à sécréter des immunoglobulines spécifiques de la SSA in vitro après stimulation. Ensuite, nous avons réalisé une première expérience de profilage transcriptionnel de ces cellules par RNA seq unicellulaire afin de mieux comprendre le rôle des LB auto-réactifs chez les sujets sains.L'analyse du phénotype a montré une expansion d'un sous-ensemble de LB naïfs CD19+IgD+CD27-CD21low/-CD11c-SSA+ avec un BCR régulé à la baisse chez les patients atteints de SSp.Les LB SSA+ étaient également enrichis parmi les LB mémoires non commutés IgMlow chez les patients, ainsi que dans les LB mémoires DN (IgD-CD27-) et commutés des différents isotypes. Les LB SSA+ triés, provenant d'un sujet sain, étaient capables de sécréter in vitro des immunoglobulines IgM mais pas IgG anti-SSA, contrairement aux LB SSA+ provenant de patients atteints de SSp, qui sont capables de sécréter des autoanticorps IgG spécifiques de SSA. Sur le plan transcriptomtique, les DEG du cluster enrichi en LB SSA+ ont montré une régulation positive des gènes HLA impliqués dans la présentation de l'antigène ainsi qu’une régulation négative du BCR par la surexpression de CD72.Nos résultats suggèrent que les LB SSA+ auto-réactifs, chez les patients atteints de SSP, sont enrichis dans le compartiment mémoire, ce qui suggère qu'ils échappent aux différents points de contrôle de la tolérance périphérique et se différencient in vivo encellules sécrétant des anticorps anti-SSA.B cells play a central role in primary Sjögren's syndrome (pSS), but little is known about the autoreactive B cells that secrete autoantibodies against the autoantigen SSA. Here, we aimed to characterize the circulating SSAspecific B cells (SSA+ B cells), in order to better understand the mechanisms leading to the breakdown of self-tolerance in patients with pSS.Using a flow-cytometry-based method, we detected and phenotypically characterized SSA+ B cells among peripheral blood mononuclear cells (PBMCs) collected from patients with pSS and from healthy controls (HCs). We tested their ability to secrete SSA-specific immunoglobulins in vitro following stimulation. Then, we performed a first experience of transcriptional profiling of these cells by single-cell RNA seq to understand further the characteristics of these autoreactive B cells in healthy subjects.Phenotype analysis showed an expansion of a CD19+IgD+CD27-CD21low/-CD11c-SSA+ naïve B-cell subset with a downregulated B cell receptor in pSS patients.SSA+ B cells were also enriched within the IgMlow unswitched memory B-cell subset in patients, as well as in double negative (IgD-CD27-) and switched memory B cells of the different isotypes. Sorted SSA+ B cells from HCs were able to secrete in vitro IgM but not IgG anti-SSA immunoglobulins contrary to SSA+ B cells from pSS patients, that were able to secrete IgG autoantibodies. From the scRNA-seq analysis in a healthy subject, we obtained 6 clusters with 2 enriched in SSA+ B cells. DEG from clusters enriched with SSA+ B cells, showed upregulation of HLA genes implicated in the antigen presentation and negative regulation of BCR.Our results show that autoreactive SSA+ B cells in pSS patients maturate and reach the memory compartment, suggesting that they escape to the different layers of peripheral tolerance checkpoints and differentiate in vivo into anti-SSA antibody-secreting cells
Quantification automatique de la sécheresse oculaire par intelligence artificielle au cours du syndrome de Sjögren
No full textLe syndrome de Sjögren est une maladie du système immunitaire dont les deux symptômes communs sont la sécheresse des yeux et de la bouche. La gêne occasionnée par les symptômes de sécheresse oculaire affecte la vie quotidienne, entraîne une diminution de 30% des activités et touche 95% des patients atteints du syndrome de Sjögren [1]. La sécheresse oculaire est également un trouble multifactoriel indépendant dont la prévalence peut atteindre 50% [2]. L’inflammation de la surface oculaire entraîne une gêne, une fatigue et, globalement, une baisse de la qualité de vie [2, 3]. Les thérapies traditionnelles permettent de gérer les symptômes et d’éviter les dommages permanents. Il est donc essentiel de classer et de suivre l’évolution de la DED. Les méthodes existantes qui permettent de diagnostiquer et de quantifier les DED présentent des inconvénients communs : reproductibilité, invasivité et imprécision. Nous avons passé en revue les méthodes classiques et celles qui intègrent l’automatisation pour mesurer l’étendue de la DED : [4]. Cette étude a montré que la DED n’a pas encore bénéficier de ce que l’intelligence artificielle (IA) a à offrir. En utilisant des examens de la surface oculaire à la lampe à fente, nous avons cherché à améliorer la quantification du score d’Oxford [5]. La méthode que nous proposons utilise l’apprentissage non supervisé pour recaler les images des examens dans un système de coordonnées commun. En apprenant simultanément le mouvement de la caméra et la profondeur, nous sommes en mesure de suivre la surface oculaire en 3D, de compenser le mouvement de l’oeil et de visualiser l’oeil entier. La source lumineuse fixée à la caméra constitue un défi et une perturbation lors de l’apprentissage de l’égomotion. Ce problème a été résolu par la segmentation sémantique et l’ajout d’un nouveau signal de supervision : la losse de reconstruction sémantique. Nous avons également utilisé la forme de l’oeil comme une connaissance préalable que nous pouvons inclure comme une contrainte. Ceci a été mis en oeuvre par une perte d’ajustement de forme ; les formes étant deux sphères se croisant l’une l’autre. Notre recalage a montré une amélioration quantitative et qualitative avec chaque contribution. Nous avons également calculé la fiabilité inter-juges des annotations des points ponctués (zones endommagées). Notre méthode s’est rapprochée le plus de ce qui peut être considéré comme une erreur humaine. La méthode de recalage proposée a également été utilisée pour une tâche de prétraitement, la sélection des images. Une fois appliquée à la classification automatique du score d’Oxford, notre méthode a également amélioré les résultats. Cette amélioration valide le fait que les fortes variations de couleur/illumination présentes dans les examens constituent une perturbation pour toute tâche d’apprentissage profond. Nous avons surmonté ce problème dans les deux tâches grâce à nos contributions et à la méthode proposée.Sjögren’s syndrome is an immune system disorder with two common symptoms, dry eyes and a dry mouth. The discomfort of dry eye symptoms affects daily lives, results in 30% activity impairment and affects 95% of Sjögren patients [1]. Dry eye disease (DED) is also an independent multifactorial disorder with a prevalence of up to 50% [2]. The ocular surface inflammation causes discomfort, fatigue and overall, a lower quality of life [2, 3]. Traditional therapies help manage the symptoms and avoid permanent damage. Hence, it is pivotal to grade and follow the development of DED. A common drawback in existingmethods that diagnose and quantify DED is reproducibility, invasivity and inaccuracy.We reviewed classical methods and those that incorporate automation to measure the extent of DED [4]. The study showed that DED has yet to benefit from what Artificial Intelligence (AI) has to offer. Using slit-lamp examinationsof the ocular surface we aimed to improve the quantification of the Oxford score [5]. Our proposed method uses unsupervised learning to register frames from the examinations to a common coordinate system. By learning the camera motion and depth simultaneously we are able to track the ocular surface in 3-D, compensate for eye motion and visualise the full eye. The lightsource attached to the camera is a challenge and a disturbance when learning egomotion. This was solved through semantic segmentation and adding a new supervision signal: semantic reconstruction loss. We also used the advantage of estimatingthe shape of the eye as prior knowledge we could include as a constraint. This was implemented through a shape fitting loss; the shapes being two spheres intersecting each other. Our registration showed quantitative and qualitative improvement with each contribution. We also calculated the inter-rater reliability of the punctate dots (damaged areas) annotations. Our method came closest to what can be considered human error. The proposed registration method was also used for a pre-processing task, frame selection. Once applied to automated Oxford score classification, our method improved the results as well. The improvement validates that the strong color/illumination variances present in the examinations are a disturbance for any deep learning task. We overcame this in both tasks via our contributions and proposed method
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
Mysterious uncoupled clinical symptoms and interferon signature in Sjögren’s syndrome: limitations of current approaches for unravelling complexity?
No full textInternational audienc
Clinical Presentation and Treatment Response in ACPA-negative Rheumatoid Arthritis
No full textInternational audienceRheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and potential extra-articular manifestations. This review compares the presentation and treatment response between anti-citrullinated protein antibodies (ACPA)-positive and ACPA-negative RA patients. The incidence of seronegative RA (rheumatoid factor (RF)-negative and ACPA-negative) has increased in recent decades, emphasizing the need for new diagnostic biomarkers.Diagnostically, ACPA is highly specific for RA, yet many patients remain ACPA-negative. The absence of RF and ACPA in RA should trigger further analysis to test alternative diagnosis, in particular when new symptoms arise. Emerging biomarkers like anti-PAD4 and anti-CarP antibodies provide additional diagnostic value, identifying some ACPA-negative patients. Clinically, ACPA-negative patients often exhibit higher disease activity at diagnosis, with more swollen joints and elevated CRP levels. They also tend to have fewer pulmonary and ocular manifestations compared to ACPA-positive patients. Radiographically, ACPA-positive patients are at a higher risk for joint erosions over time.Response to treatment also differs according to ACPA status. Abatacept and rituximab have demonstrated greater efficacy in ACPA-positive patients, showing better disease activity control and higher treatment retention rates. Continuous re-evaluation is crucial for ACPA-negative patients, especially when first-line treatments like methotrexate are ineffective, to rule out RA mimickers and adjust the treatment approach accordingly.These findings underscore the importance of personalized treatment strategies in RA management
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
Is primary Sjögren's syndrome an orphan disease? A critical appraisal of prevalence studies in Europe.
No full textInternational audienc
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
- …
