1,721,049 research outputs found
Multi-cancer early detection: searching for evidence
No full textIn cancer screening, there is probably not a one-fits-all solution. On the contrary, screening interventions should be tailored individually to reflect, among others, patient history, comorbidities and environmental risk factors, and any MCED testing should be used in the context of this paradigm. In conclusion, the jury is still out on the utility of the Galleri test in clinical practice
Challenging the dogma: why reviewers should be allowed to use AI tools
No full textAs artificial intelligence (AI) continues to advance rapidly, the central question is no longer whether it will be integrated into peer review, but rather how its use can be effectively managed and harnessed to ensure fairness to authors while enhancing the efficiency and value of the editorial process. Several practical considerations lead to a simple conclusion. AI should be permitted in peer-review, not clandestinely, but openly, under safeguards that protect confidentiality and preserve human judgment. A policy framework emphasizing confidentiality, transparency, and scope limits, remains valuable, but must be refined. A workable approach should include four key principles, i.e., secure infrastructure, flexible disclosure, human primacy, and parity with authors
Rethinking internal quality control: the time is now
No full textThe analytical quality of laboratory results, and particularly the improvement due to better efforts to comply with analytical performance specifications and to adopt better internal quality control and external quality assessment/proficiency testing systems, should be notified in some universally agreed means to clinicians, to allow better and more evidence-based interpretation and utilization of laboratory information. This, in turn, should ultimately assure a better quality of care and enhanced patient safety
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
Metrological characterization of candidate primary reference methods for the enumeration of lipoprotein particles and the absolute quantification of glycated hemoglobin HbA1c
No full textEn biologie clinique, disposer de mesures fiables et comparables, indépendamment du temps et du laboratoire, est primordial afin de permettre une prise en charge et un suivi adaptés des patients. Le moyen privilégié est d’établir la traçabilité métrologique des résultats de mesure aux unités du système international (SI), notamment par le biais de méthodes de référence et de matériaux de référence certifiés d’ordre supérieur. Ces travaux de thèse se sont attachés à caractériser deux méthodes de référence primaires candidates. Une méthode d’énumération absolue des lipoprotéines par ES-DMA pour l’évaluation du risque cardiovasculaire a été développée et caractérisée. Les résultats obtenus ont mis en évidence certaines limitations instrumentales rendant l’établissement de la traçabilité au SI difficile. Malgré les avantages certains de cette méthode pour l’analyse avancée de lipoprotéines, la fidélité et la robustesse des mesures ne sont pas suffisantes pour la considérer comme méthode de référence primaire. Une méthode de quantification de l’hémoglobine glyquée HbA1c, un biomarqueur du diabète sucré, par LC-MS/MS associée à la dilution isotopique a été mise en place et validée. La traçabilité au SI des résultats de dosage a été établie, toutefois, les incertitudes de mesures demeurent élevées et la comparabilité avec la méthode de référence IFCC reste à évaluer sur un nombre plus significatif d’échantillons et de laboratoires. Pour conclure, ces travaux ont mis en évidence les défis associés à la mise en place de nouvelles chaînes de traçabilité ainsi que les problématiques liées au développement de méthodes de référence primaires pour le dosage de biomarqueurs complexes.Ensuring reliability and between-laboratory comparability of in-vitro diagnostic test results is essential for appropriate and internationally harmonized decision making and patient follow-up. To this end, a privileged way is to establish results metrological traceability to the international system of units (SI) through the development of primary reference methods and higher order reference materials. This thesis aimed at characterizing two candidate primary reference procedures.A method for lipoprotein absolute quantification by ES-DMA for cardiovascular diseases risk assessment was developed and characterized. Results evidenced some advantages of this method compared to other advanced lipoprotein testing assays, but some instrumental weaknesses make the establishment of results traceability to the SI difficult in the current state-of-the-art. Precision and robustness are additionally not sufficient for this method to be considered as a primary reference method.A method for the quantification of glycated hemoglobin HbA1c, a biomarker of diabetes mellitus, by LC/MS/MS associated to isotopic dilution was implemented and validated. Results traceability to the SI units could successfully be established. However, measurement uncertainties remain large and comparability with the IFCC reference method is still to be further assessed on a significant number of samples and laboratories.To conclude, this study highlighted the challenges associated with the implementation of new traceability chains and the difficulties related to the development and characterization of primary reference procedures for the quantification of complex biological markers
Study of intracellular metabolism of carbamylated proteins
No full textLa réaction de carbamylation, comme les réactions de glycation, d’oxydation ou de carbonylation, fait partie des modifications post-traductionnelles non enzymatiques des protéines. Elle correspond à la fixation d’acide isocyanique sur les groupements aminés des protéines et conduit à la formation de produits de carbamylation, dont fait partie l’homocitrulline. Des études in vitro ont mis en évidence le caractère délétère de la carbamylation des protéines sur leur structure et leur fonction. Des études in vivo ont montré l’accumulation tissulaire des produits de carbamylation au cours de l’insuffisance rénale chronique et du vieillissement. Cependant, peu de travaux ont porté sur la carbamylation des protéines intracellulaires.Ce travail a porté sur l’étude de la carbamylation des protéines intracellulaires, leur impact sur la cellule ainsi que leur devenir. De plus, un mécanisme de réparation des protéines carbamylées a été recherché.Nous avons montré, par une approche quantitative et qualitative, que les protéines intracellulaires pouvaient être carbamylées dans des conditions physiologiques et que leur carbamylation était augmentée en présence de cyanate ou d’urée. Nous avons également montré que les cellules étaient capables d’éliminer les protéines carbamylées, en impliquant le protéasome. Un phénomène de décarbamylation a été mis en évidence, ce qui ouvre des possibilités pour la mise en place de stratégies visant à limiter ou à inverser la carbamylation.The carbamylation reaction, like glycation, oxidation or carbonylation reactions, is a non-enzymatic post-translational modification of proteins. It corresponds to the binding of isocyanic acid to protein amino groups and leads to the formation of carbamylation-derived products (CDPs), such as homocitrulline. In vitro studies have demonstrated the deleterious effect of carbamylation of proteins on their structure and function. In vivo studies have shown tissue accumulation of CDPs during chronic kidney disease and aging. However, studies on the carbamylation of intracellular proteins are lacking.This work was devoted to the study of the carbamylation of intracellular proteins, their impact on cell and their fate. In addition, a mechanism for repairing carbamylated proteins has been investigated.Our results showed, by quantitative and qualitative approaches, that intracellular proteins were carbamylated in physiological conditions and that their carbamylation rate was increased in the presence of cyanate or urea. We also have shown that cells were able to remove carbamylated proteins by a mechanism involving the proteasome. A phenomenon of decarbamylation has been highlighted, which opens up possibilities for the implementation of strategies to limit or reverse carbamylation
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
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