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Deciphering full omics of pituitary tumors : classification, diagnostic and pronostic
No full textLes adénomes hypophysaires sont des tumeurs bénignes développées aux dépends de l'hypophyse. Elles sont fréquentes (5% de la population). Leur phénotype varie selon : - l'agressivité tumorale, c'est-à-dire la taille, la vitesse de croissance, l'invasion et la compression des structures adjacentes - la sécrétion hormonale, c'est-à-dire le type de sécrétion (prolactine, hormone croissance, corticotropine, thyréostimuline), et son intensité. La classification actuelle de ces tumeurs repose essentiellement sur l'histologie (classification de l'organisation mondiale de la santé (OMS) 2017). Cette classification s'appuie sur le profil d'expression de facteurs de transcription spécifiques de chaque lignage ante-hypophysaire : lignage PIT1 (adénomes lacto- somato- et thyréotropes), lignage TPIT (adénomes corticotropes) et lignage SF1 (adénomes gonadotropes). Cette classification reflète mal l'agressivité tumorale. L'objectif essentiel de cette thèse était de fournir la première classification génomique des adénomes hypophysaires. Pour cela, une caractérisation clinique, histologique et génomique de 134 PitNETs de tous les sous-types a été effectué, combinant mutations (séquençage d'exome), transcriptome (séquençage des ARNm), miRnome (séquençage des microARN), anomalies chromosomiques (puces SNP) et méthylome de l'ADN (puces méthylome). Une analyse indépendante de chaque omique a été effectuée puis une analyse intégrée combinée. L'analyse des profils chromosomiques ont décrit trois groupes : profil avec perte étendue sur le génome, profil avec peu d'altérations et profil avec des gains étendus sur le génome. Ces altérations étaient liées au type sécrétoire (moins d'anomalies dans les tumeurs gonadotropes), mais indépendantes de l'agressivité. L'analyse épigénétique (miRnome et méthylome ) discriminait nettement le lignage PIT1 des autres lignages, avec principalement un profil d'hypométhylation globale du génome, et un profil miRNA spécifique. L'hypométhylation était corrélée à l'instabilité chromosomique et à la surexpression d'éléments transposables. L'analyse transcriptome a retrouvé en classification non supervisée six groupes, associés au sous-type histologique et à la sécrétion. On retrouvait globalement les même conclusions que l'OMS, avec des précisions supplémentaires : - le type « null-cell » était fusionné avec les gonadotropes - les corticotropes silencieux formaient un groupe différent des corticotropes sécrétants, en rapport avec une transdifférenciation gonadique. - au sein des adénomes corticotropes sécrétants, les mutés USP8 formaient un sous-groupe à part. - les thyréotropes et les plurihormonaux-Pit1 étaient classés ensemble, avec la plupart des somatotropes à granules éparses. - les adénomes mixtes GH-PRL étaient dans le même groupe que les adénomes somatotropes, et distincts des adénomes lactotropes. Au sein des adénomes somatotropes, les mutés GNAS formaient un sous-groupe à part. Dans le cadre d'une analyse intégrée combinant toutes ces approches d'omics, les adénomes hypophysaires ont été projetés dans une représentation multidimensionnelle. Dans cette représentation moléculaire non supervisée, la classification reprenant les 6 groupes du transcriptome et le statut mutationnel GNAS et USP8 forme des groupes plus homogènes et mieux séparés que la classification histologique OMS 2017. Sur le plan clinique, l'agressivité des tumeurs apparaissait comme un déterminant moins fort de la classification moléculaire que le lignage hypophysaire. Au sein des adénomes corticotropes, les adénomes avec sécrétion franche et sans mutation USP8 formaient un sous-groupe plus agressif tant cliniquement qu'en terme de transcriptome (signature de prolifération). Cette thèse dévoile des aspects nouveaux de la biologie des adénomes hypophysaires.Ces données importantes devraient ouvrir la voie à de nouveaux axes de recherches.Pituitary adenomas are benign tumors developed from the pituitary gland. They are common (5% of the population). Their phenotype varies according to: - tumor aggressiveness, ie size, rate of growth, invasion and compression of adjacent structures - the hormonal secretion, ie the type of secretion (prolactin, growth hormone, corticotropin, thyreostimulin), and its intensity. The current classification of these tumors is based primarily on histology (World Health Organization (WHO) classification 2017). This classification is based on the expression profile of specific transcription factors of each ante-pituitary lineage: PIT1 lineage for lacto- somato- thyrotroph adenomas, TPIT lineage for corticotroph adenomas and SF1 lineage for gonadotroph adenomas. This classification does not reflect the aggressiveness of the tumor. The main objective of this thesis was to provide the first genomic classification of pituitary adenomas. For this, a clinical, histological and genomic characterization of 134 PitNETs of all subtypes was performed, combining mutations (exome sequencing), transcriptome (mRNA sequencing), miRnome (microRNA sequencing), chromosomal abnormalities (SNP microarrays),and DNA methylome (methylome chips). An independent analysis of each omic was carried out then an integrated analysis combining all the methods. Analysis of the chromosome profiles described three groups: one with extensive loss on the genome, one with few alterations and one with extensive gains on the genome. These alterations were associated to the secretory type (less anomaly in gonadotropic tumors), but independent of aggressiveness. Epigenetic analysis (miRnome and methylome) clearly discriminated the PIT1 lineage from other lineages, mainly with a global genome hypomethylation profile, and a specific miRNA profile. Hypomethylation was correlated with chromosomal instability and overexpression of transposable elements. The transcriptome analysis found in unsupervised classification six groups, associated with histological subtype and secretion. The same conclusions were found overall as WHO, with additional details: - the "null-cell" type was merged with gonadotrophs -silent corticotrophs formed a different group from secreting corticotrophs, related to a gonadal transdifferentiation. Within the secretory corticotropic adenomas, the USP8 mutants formed a separate subgroup. -the thyrotropic and the plurihormonal PIT1 were classified together with most of the sparsely granulated somatotrophs. -the mixed GH-PRL adenomas were in the same group as the somatotroph adenomas, and distinct from the lactotroph adenomas. Within the somatotroph adenomas, the GNAS mutated formed a separate subgroup. As part of an integrated analysis combining all these omics approaches, pituitary adenomas were projected into a multidimensional representation. In this unsupervised molecular representation, the classification based on the six transcriptome groups and the mutation status GNAS and USP8 forme more homogeneous and better separated groups than the histological classification OMS 2017. Clinically, tumor aggressiveness appeared to be a weaker determinant of the molecular classification than the pituitary lineage. Within corticotropic adenomas, USP8-wild type adenomas formed a more aggressive subgroup both clinically and at the transcriptome level (proliferative signature). This thesis unveils new aspects of the biology of pituitary adenomas. It is also the first unsupervised molecular classification of pituitary adenomas. These important data should pave the way for new lines of research
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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