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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
Diagnostic, prognostic and therapeutic potential of synovial tissue biology analysis
No full textLa polyarthrite rhumatoïde (PR) est la plus fréquente des maladies auto-immunes et touche 0.1 % de la population. Sur le plan physiopathologique, la membrane synoviale, qui recouvre l'articulation, est le siège de remaniements inflammatoires avec un infiltrat de cellules immunitaires. Malgré l'existence de nombreuses thérapies ciblant directement différentes molécules de l'inflammation, certains patients présentent une réponse insuffisante ou un échappement secondaire aux traitements. Dans la première partie de cette thèse, nous nous sommes intéressés à mieux caractériser les cellules infiltrant le tissu synovial dans la PR, en ajoutant à un score histologique de synovite couramment utilisé des marquages d'immunohistochimie ciblant les cellules de l'immunité innée et adaptative, améliorant ainsi ses performances diagnostiques. Le domaine de l'épigénétique et en particulier l'étude des micro-acides desoxiribonucléiques (mi-ARN) est en plein essor dans de nombreuses disciplines et notamment en ~Cancérologie. Dans la seconde partie de ce travail, nous nous• sommes focalisés sur l'étude différentielle des mi-ARN au sein de la synovite en fonction du phénotype érosif ou non de la PR. Nous avons identifié un mi-ARN (miR-17-5p) capable d'exercer un effet anti-inflammatoire in vitro et ainsi qu'anti érosif in vivo dans le modèle murin d'arthrite induite au collagène. En conclusion, ces travaux permettent dans un premier temps la description d'un nouveau score histologique pour évaluation de la synovite ainsi que la mise en évidence de différences d'expression synoviale des mi-ARN dans la PR en fonction de son caractère érosif ou non. Un des mi-ARN identifié a montré des caractéristiques prometteuses dans un essai pré-clinique.Rheumatoid arthritis (RA) is the most common autoimmune disease, affecting 0.1 % of the population. From the biological perspective, the synovial membrane is the key organ involved in RA pathophysiology and is the site of an immune cells' infiltration. Despite the development of several therapies targeting different molecules of inflammation, some patients still display an insufficient response or secondary failure of treatment. ln the first part of this work, we were interested in better characterizing cells infiltrating synovial tissue in RA. We added immunohistochemistry staining targeting innate and adaptive immune cells to a commonly used histological synovitis score, thus improving its diagnostic performance. The field of epigenetics and in particular the study of micro-RNA has expended rapidly in many biological disciplines and particularly in cancerology. ln the second part of this work, we focused on the differential expression of miRNAs in RA synovitis depending on the erosive or non-erosive phenotype. We identified one candidate (miR-17-5p) exerting an anti-inflammatory effect in vitro along with an anti- erosive effect in vivo in the collagen-induced 'arthritis mice model. Overall, this work allowed to describe a new histological synovitis score and demonstrated differential synovial tissue expression of mi-RNA according to RA phenotype. One of the identified mi-RNA showed promising characteristics in a preclinical trial
Expression and therapeutic interest of Interleukin-38 in Rheumatoid Arthritis : basic antagonist of interleukin 36 or novel inhibitor of inflammation?
No full textLes IL-36α, β et γ sont des cytokines appartenant à la famille de l’IL-1. Elles sont exprimées notamment dans la peau et sont impliquées dans la pathogenèse du psoriasis. Leurs inhibiteurs connus ou hypothétiques l’IL-36Ra et l’IL-38 agissent en limitant l’inflammation. Dans la polyarthrite rhumatoïde (PR) et la maladie de Crohn, l’expression et le rôle de ces cytokines sont encore débattues. Les travaux de cette thèse se consacrent à l’étude du profil d’expression des IL-36 et de leurs inhibiteurs ainsi qu’à déterminer l’impact d’une surexpression de l’IL-38 in vivo et in vitro. La première étude a été réalisée chez les patients atteints de PR en comparaison avec les patients psoriasiques et ceux atteints de maladie de Crohn ainsi que dans les modèles murins correspondants. Cette étude a montré que ces cytokines étaient exprimées majoritairement par les kératinocytes et les macrophages mais possédaient cependant des profils d’expression distincts. Elle a également permis d’identifier un sous-groupe de patients pour lesquelles les IL-36 pourraient avoir un rôle important et pourraient représenter une cible en clinique. La seconde partie de la thèse a permis de montrer un effet anti-inflammatoire d’une surexpression de l’inhibiteur IL-38 dans différents modèles d’arthrite in vivo et dans des macrophages in vitro. Les thérapies basées sur l’inhibition de cytokines ont déjà prouvé leur efficacité en clinique et sont une cible thérapeutique très prometteuse. Cette thèse a pour objectifs d’une part de mieux comprendre la biologie des nouvelles cytokines de la famille de l’IL-1 et d’autre part de participer à la découverte de nouvelles cibles thérapeutiques dans les pathologies inflammatoires chroniques telles que la PR.IL-36α, β and γ are cytokines belonging to the IL-1 family. IL- 36 are expressed especially in the skin and are involved in the pathogenesis of psoriasis. Their inhibitors (well-known or hypothetical) IL-36Ra and IL-38 act in reducing inflammation. In rheumatoid arthritis (RA) and Crohn's disease, the expression and role of these cytokines need to be elucidated. This thesis is dedicated to the study of IL-36 agonists and antagonists expression profile and the better understanding of in vivo and in vitro impact of IL-38 overexpression. The firts study was conducted in patients with RA in comparison with psoriasis and Crohn's disease patients as well as in the corresponding relevant murine models. This study showed that these cytokines were expressed predominantly by keratinocytes and macrophages but had distinct expression profiles. A subgroup of patients for which the IL-36 could have an important role and may represent a clinical target was also identified. In the second part of the thesis, we demonstrated an anti-inflammatory effect following overexpression of the inhibitor IL-38 in several in vivo arthritis models and in macrophages in vitro. Cytokine neutralization based therapies have already proven effective in the clinic and are still a promising therapeutic target. This thesis aims firstly to better understand the biology of new IL-1 family cytokines and also to participate in the discovery of new therapeutic targets in chronic inflammatory diseases such as RA
Study of the composition of the calcific deposits and mechanisms leading to them in the calcific tendonitis of the rotator cuff
No full textLa tendinopathie calcifiante est une cause fréquente de douleurs d’épaule. Elle est due à des dépôts d’apatite au sein des tendons de la coiffe. Sa physiopathologie est actuellement peu connue. L’objectif de cette thèse était de déterminer les mécanismes impliqués dans la constitution des dépôts et les facteurs régulant cette minéralisation pathologique. L’étude de tondons calcifiés prélevés sur cadavres a montré la présence d’une métaplasie fibro-cartilagineuse autour des dépôts contenant des cellules de type chondrocytaire produisant de la phosphatase alcaline et de l’ENPP1, deux enzymes clé de la minéralisation. In vitro, les ténocytes humains issues de la coiffe des rotateurs ont la capacité de produire des dépôts d’apatite et ceci de manière dépendante de la phosphatase alcaline. Ces cellules sur-exprimaient alors des marqueurs spécifiques des chondrocytes hypertophiques (Collagène de type X, MMP13). L’analyse de poudres calciques prélévées sur des patients souffrant de tendinopathie calcifiante a montré un enrichissement significatif en protéines associées au développement de l’os et du cartilage. Parmi celles-ci, nous avons identifié le Pigment Epithelium Derived Factor (PEDF), connue pour favoriser la minéralisation osseuse. Bien qu’il ait été identifié dans les poudres calciques et les cellules chondrocytaires présentes autour des dépôts, il n’a pas montré d’effet pro-minéralisant in vitro sur les ténocytes humains.Calcific tendonitis is a frequent cause of shoulder pain. It is due to apatite deposits within the rotator cuff tendons. Its cause is currently poorly known. The objectives of this thesis were to better characterize the cells and mechanisms involved in depositing apatite crystals in human tendons. Histologic sections of cadaveric calcified tendons showed that calcifications were amorphous areas surrounded by a fibrocartilaginous metaplasia containing hypertrophic chondrocyte-like cells that expressed alkaline phosphatase and ENPP1, two key enzymes of the mineralization process. In vitro, tenocytes extracted from human rotator cuff were able to mineralize in an alkaline phosphatase-dependent manner. These cells expressed type X COLLAGEN and MMP13, hypertrophic chondrocytes markers. Finally, analysis of calcific powders extracted from patients suffering from calcific tendonitis showed a significant enrichment of proteins involved in bone and cartilage development. Among them, we identified Pigment Epithelium Derived Factor (PEDF). PEDF is able to promote bone mineralization. While it was identified in calcific powders and chondrocyte-like cells surrounding the deposits, it was not able to increase the mineralisation of human tenocytes in vitro
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 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
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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