1,721,068 research outputs found
Management of hepatocellular carcinoma recurrence after liver surgery and thermal ablations: state of the art and future perspectives
No full textDespite the improvements in surgical and medical therapy for hepatocellular carcinoma (HCC), recurrence still represents a major issue. Up to 70% of patients can experience HCC recurrence after liver resection (LR), as well as 20% of them even after liver transplantation (LT). The patterns of recurrence are different according to both the time and the location. Similarly, the risk factors and the management can change not only according to these patterns, but also according to the underlying liver condition and to the first treatment performed. Deep knowledge of such correlation is fundamental, since prevention and effective management of recurrence are undoubtedly the most important strategies to improve the outcomes of HCC treatment. Without adjuvant therapy, maintaining very close monitoring during the first 2 years in order to diagnose curable recurrence and continue this monitoring beyond 5 years because late recurrences exist, remains our only possibility today. Surgery represents the cornerstone treatment for HCC, including both LT and LR. However, new interesting therapeutic opportunities are coming from immunotherapy that has shown encouraging results also in the adjuvant setting. In such a complex and evolutionary scenario, the aim of this review is to summarize current strategies for the management of HCC recurrence, focusing on the different possible scenarios, as well as on future perspective
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
Discovery of Pancreatic Cancer Biomarkers Using Non-Destructive OMICS Technology
No full textLe cancer du pancréas est la quatrième cause de décès lié au cancer dans les pays occidentaux. Si la résection chirurgicale complète est le seul traitement curatif, moins de 30% des patients reséqués sont vivants à 5 ans. Le cancer du pancréas est souvent découvert à un stade avancé en termes d’extension et de retentissement pour le patient sans option thérapeutique curative. Ce constat est en partie lié à l’absence de biomarqueur sensible et spécifique permettant un diagnostic précoce de l’adénocarcinome du pancréas. Compte tenu des progrès de la technologie OMICS, plusieurs études ont identifié des biomarqueurs solubles (sanguins, urinaires, salivaires) via la spectrométrie de masse avec des résultants décevant en pratique clinique. Ces études ont concerné des échantillons tumoraux issus de pièces opératoires ou de biopsie de tumeur localement avancées ou métastatiques, non représentatifs du cancer du pancréas au stade précoce. L’analyse des tumeurs de tout stade impose l’accès aux échantillons issus de biopsie pancréatique lors du diagnostic qui demeurent indisponibles pour les chercheurs en raison d’une faible quantité de matériel et de son caractère précieux sur le plan clinique.Le Dr Turtoi a récemment co-développé une nouvelle méthode, conservatrice de l’échantillon sanitaire, nommée EXPEL, consistant en un rinçage sous pression d’un échantillon unique obtenu par biopsie fine, permettant au décours, un examen anatomopathologique standard et l’extraction des protéines, métabolites, ARN et ADN.En pratique clinique, la plupart des patients présentant une lésion suspecte du pancréas ont une écho-endoscopie avec biopsie fine à l’aiguille + aspiration. Le contenu de l’aiguille est ensuite rincé dans une solution de conservation nommée Preservcyt®. Apres extraction des biopsies/cellules du patient, ce liquide de conservation est systématiquement jeté.Mon travail de thèse a consisté, dans un premier, en l’étude PanEXPEL1, incluant 58 patients. Dans ce travail nous avons montré que ce Preservcyt® est riche en protéines ce qui nous a permis d’isoler une signature diagnostique de 19 protéines avec une sensibilité et une spécificité de 0.917 et 0.853 respectivement. Sa valeur prédictive positive du cancer du pancréas était de 100% chez les patients de plus de 54 ans.Dans un second temps, j’ai mis pu obtenir un financement et mettre en place l’étude clinico-biologique prospective PanEXPEL2 qui inclura 200 patients présentant une lésion suspecte du pancréas requérant une écho-endoscopie/biopsie avec analyse protéomique du Preservcyt® ainsi qu’une collection sérique appariée.Les perspectives de cette approche sont la mise en place de tests diagnostiques ou d’évaluation de la réponse à la chimiothérapie tout comme le développement de nouvelles thérapies (thérapies ciblées, immunothérapie).Pancreatic cancer is the 4th cause of cancer-related death in Western countries. While complete surgical resection is the only curative treatment, less than 30% of resected patients are alive at 5 years. Pancreatic cancer is often diagnosed at an advanced stage without any curative therapeutic option. This finding is linked to the absence of sensitive and specific biomarkers allowing early diagnosis of pancreatic cancer. Given the progress of OMICS technology, several studies have identified soluble biomarkers (blood, urine, saliva) via mass spectrometry, however none have been translated into clinical practice. These studies investigated tumor samples from surgical specimens or from locally advanced or metastatic tumor biopsies, not representative of early-stage pancreatic cancer. Analysis of tumors of early stage requires access to pancreatic biopsy specimens destined for diagnosis, which remain unavailable for research due to the small amount of tissue and its clinically valuable nature.Dr Turtoi (IRCM, Montpellier) recently co-developed a new method, conservative of the sanitary sample, called EXPEL, consisting of rinsing under pressure of a single sample obtained by fine needle biopsy, allowing in the course of a standard pathological examination and the extraction of proteins, metabolites, RNA and DNA.In clinical practice, most patients with a suspicious lesion of the pancreas have endoscopic ultrasound with fine needle/biopsy. This needle content is then rinsed in a preservative solution called Preservcyt®. After extraction of the patient's biopsies / cells, this conservation fluid is systematically discarded.My thesis work was in a first step, via the PanEXPEL1 study including 58 patients, to demonstrate that this Preservcyt® is rich in proteins and made it possible to isolate a diagnostic signature of 19 proteins with sensitivity and a specificity of 0.917 and 0.853 respectively. Its positive predictive value for pancreatic cancer was 100% in patients over 54 years of age.As a second step, I set up the prospective clinico-biological study PanEXPEL2 that will include more than 200 patients with a suspicious pancreatic lesion requiring endoscopic ultrasound/biopsy with proteomic analysis of Preservcyt® and matched serum collection.The perspectives for this approach are the development of diagnostic tests or evaluation of the response to chemotherapy as well as the development of targeted therapy (immunotherapy)
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
Oncogenic Cooperation and Metabolic Effects of FGF19 in Hepatocellular Carcinoma
No full textLe carcinome hépatocellulaire (CHC) est la tumeur maligne primitive hépatique la plus fréquente et se situe au 6e et 3ème rang en termes de fréquence et de mortalité liées au cancer, respectivement. La surexpression de FGF19 est un évènement fréquent dans les CHC humains et des molécules ciblant FGF19 ou son récepteur tyrosine kinase dans le foie (Fibroblast Growth Factor Receptor 4 FGFR4) sont en cours d’étude. Chez la souris l’exposition à des concentrations élevées de FGF19 au long cours provoque une tumorigénèse hépatique. Par ailleurs, FGF19 exerce de nombreux effets métaboliques ayant pour conséquence une protection contre l’insulinorésistance. Ainsi, des molécules analogues à FGF19 sont également en cours d’étude pour traitement de maladies métaboliques, comme la stéatohépatite non alcoolique (ou NASH pour Non alcoholic steatohepatitis). Dans ce contexte, notre projet avait pour but de mieux caractériser les effets oncogéniques et métaboliques de FGF19 dans un modèle de souris immunocompétentes.En utilisant la technique de transfection hydrodynamique des hépatocytes, nous avons obtenu des souris C57Bl6/J ayant une expression de FGF19 persistante, avec des concentrations circulantes supra-physiologiques, associée à l’inhibition de la voie de synthèse des acides biliaires. Nous avons découvert chez ces souris un phénotype de diabète insipide, caractérisé par une polydipsie et une dilution des urines persistant dans le temps. Cet effet est similaire à celui qui a déjà été décrit pour FGF21, une molécule appartenant à la même famille que FGF19. Cependant, l’effet de FGF19 est indépendant de FGF21 et est retrouvé également lorsqu’une tumeur surexprimant FGF19 est injectée par voie orthotopique.Par ailleurs, l’expression de FGF19, seule ou avec l’invalidation simultanée de p53 par la technique de CRISPR-Cas9, donne des CHC bien différenciés après 9-12 mois. La combinaison FGF19 avec une surexpression de C-Myc, avec ou sans l’invalidation de p53, induit le développement de volumineuses tumeurs moyennement différenciées apparaissant après 2-3 semaines seulement. La comparaison avec la tumorigenèse déclenchée par C-Myc seul ou par C-Myc/ CRISPR-p53, fait apparaître une coopération entre Myc et FGF19 donnant lieu à l’accélération très significative de l’oncogenèse par FGF19. L’analyse transcriptomique et histologique de ces tumeurs met en évidence une stimulation de la néoangiogénèse par FGF19. Enfin, dans un modèle de régime pourvoyeur de NASH, l’expression tumorale de FGF19 exerce un effet paradoxal : tout en accélérant la croissance tumorale, elle s’accompagne d’une amélioration histologique de la NASH.Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and ranks 6th and 3rd in terms of frequency and cancer mortality, respectively. Overexpression of FGF19 is a common event in human HCC and compounds targeting FGF19 or its receptor tyrosine kinase in the liver (Fibroblast Growth Factor Receptor 4 FGFR4) are being investigated. Studies in mice have shown that long term exposure to high levels of FGF19 causes hepatic tumorigenesis. In addition, FGF19 exerts numerous metabolic effects resulting in protection against insulin resistance. Thus, FGF19 analogs are under evaluation for treatment of metabolic diseases, such as non-alcoholic steatohepatitis (NASH). The aim of our study was to further characterize the oncogenic and metabolic effects of FGF19 in an immunocompetent mouse model.Using the technique of hydrodynamic gene transfer, we obtained C57Bl6/J mice with persistent hepatic expression of FGF19, displaying supra-physiological circulating concentrations of the hormone, associated with inhibition of the bile acid synthesis pathway. We discovered that these mice display a phenotype of diabetes insipidus, characterized by polydipsia and urine dilution persisting over time. This effect resembles that already described for FGF21, a molecule belonging to the same family as FGF19. However, the effect of FGF19 is independent of FGF21 and is also present when a tumor overexpressing FGF19 is injected orthotopically.Furthermore, FGF19 expression, alone or with simultaneous invalidation of p53 by CRISPR-Cas9 technology, gives rise to well-differentiated HCC after 9-12 months. The combination of FGF19 with C-Myc overexpression, with or without the invalidation of p53, induces the development of large, moderately differentiated tumors appearing after only 2-3 weeks. Comparison with tumorigenesis triggered by C-Myc alone or by C-Myc/ CRISPR-p53, reveals oncogenic cooperation between Myc and FGF19, resulting in a very significant acceleration of oncogenesis by FGF19. Transcriptomic and histological analyses of these tumors show that FGF19 stimulates neoangiogenesis. Finally, in a NASH-inducing diet model, tumor expression of FGF19 exerts a paradoxical effect: while accelerating tumor growth, it is accompanied by histological improvement of NASH
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
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