78 research outputs found

    Avant-propos

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    Mouvement majeur de notre histoire, le gallicanisme se présente comme une culture spécifique, à la croisée du droit, de l’ecclésiologie et de l’histoire. Participant de la révolution intellectuelle et institutionnelle des xvi et xviie siècles - notamment dans ses conséquences historiographiques, juridiques et érudites - Y habitus gallican est d’emblée tourné vers le passé pour trouver un précédent et éditer des preuves historiques qui légitiment un axiome présent, et surtout une autorité auto..

    Radiomics in neuro-oncological clinical trials

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    The development of clinical trials has led to substantial improvements in the prevention and treatment of many diseases, including brain cancer. Advances in medicine, such as improved surgical techniques, the development of new drugs and devices, the use of statistical methods in research, and the development of codes of ethics, have considerably influenced the way clinical trials are conducted today. In addition, methods from the broad field of artificial intelligence, such as radiomics, have the potential to considerably affect clinical trials and clinical practice in the future. Radiomics is a method to extract undiscovered features from routinely acquired imaging data that can neither be captured by means of human perception nor conventional image analysis. In patients with brain cancer, radiomics has shown its potential for the non-invasive identification of prognostic biomarkers, automated response assessment, and differentiation between treatment-related changes from tumour progression. Despite promising results, radiomics is not yet established in routine clinical practice nor in clinical trials. In this Viewpoint, the European Organization for Research and Treatment of Cancer Brain Tumour Group summarises the current status of radiomics, discusses its potential and limitations, envisions its future role in clinical trials in neuro-oncology, and provides guidance on how to address the challenges in radiomics

    Diaphragm movement sensor for phrenic nerve monitoring during cryoballoon procedures: the first clinical evaluation

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    Background and aimsRight phrenic nerve palsy is the most frequent complication of cryoballoon procedures. The SMARTFREEZE™ console (Boston Scientific, St. Paul, MN, USA) has integrated a new tool for diaphragm monitoring—the Diaphragm Movement Sensor; however, it has not been evaluated in clinical practice. We aimed to assess the diagnostic performance of the Diaphragm Movement Sensor based on compound motor action potential data recorded simultaneously.MethodsThirty consecutive patients (mean age 63.2 ± 10.2 years) were included. We simultaneously recorded the compound motor action potential and the Diaphragm Movement Sensor during cryoapplications in the right pulmonary veins. The right phrenic nerve was paced at 60 per minute, 12 V and 2.9 ms. Compound motor action potential monitoring with a 30% decrease cutoff for the diagnosis of phrenic nerve threatening was considered the gold standard. The Diaphragm Movement Sensor decrease threshold was also set at 30%.ResultsConsidering compound motor action potential monitoring, phrenic nerve threatening occurred 11 times (in seven patients) among 84 cryoapplications (13.1%) at the right pulmonary veins. The sensitivity and specificity of the Diaphragm Movement Sensor were, respectively, 33% (95% CI: 7%–70%) and 49% (95% CI: 38%–61%; P < 0.001). The predictive positive and negative values for the Diaphragm Movement Sensor were, respectively, 7% (95% CI: 2%–20%) and 86% (95% CI: 72%–95%). The Diaphragm Movement Sensor gave an erroneous diagnosis in 44/84 cryoapplications (52.4%).ConclusionsThe diagnostic performance of the Diaphragm Movement Sensor is low, and the relevance of its use in clinical practice may be debated

    The Role of Disordered Ribosomal Protein Extensions in the Early Steps of Eubacterial 50 S Ribosomal Subunit Assembly

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    Although during the past decade research has shown the functional importance of disorder in proteins, many of the structural and dynamics properties of intrinsically unstructured proteins (IUPs) remain to be elucidated. This review is focused on the role of the extensions of the ribosomal proteins in the early steps of the assembly of the eubacterial 50 S subunit. The recent crystallographic structures of the ribosomal particles have revealed the picture of a complex assembly pathway that condenses the rRNA and the ribosomal proteins into active ribosomes. However, little is know about the molecular mechanisms of this process. It is thought that the long basic r-protein extensions that penetrate deeply into the subunit cores play a key role through disorder-order transitions and/or co-folding mechanisms. A current view is that such structural transitions may facilitate the proper rRNA folding. In this paper, the structures of the proteins L3, L4, L13, L20, L22 and L24 that have been experimentally found to be essential for the first steps of ribosome assembly have been compared. On the basis of their structural and dynamics properties, three categories of extensions have been identified. Each of them seems to play a distinct function. Among them, only the coil-helix transition that occurs in a phylogenetically conserved cluster of basic residues of the L20 extension appears to be strictly required for the large subunit assembly in eubacteria. The role of α helix-coil transitions in 23 S RNA folding is discussed in the light of the calcium binding protein calmodulin that shares many structural and dynamics properties with L20

    Contribution à l'étude du système adénosinergique en pathologie cardiovasculaire

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    L'adénosine est un nucléoside ubiquitaire issu de la déphosphorylation de l'ATP qui est libéré par les cellules endothéliales et les myocytes lors de l'hypoxie, de l'ischémie ou du stress oxydatif. Elle exerce un contrôle puissant sur les systèmes nerveux, immunitaire et cardiovasculaire par l'intermédiaire de quatre récepteurs membranaires : A1R, A2AR, A2BR et A3R. La compréhension de l'implication du système adénosinergique dans le système cardiovasculaire implique la possibilité technique d'un dosage de l'adénosine endogène et la quantification de l'expression de ses récepteurs. L'adénosine ayant globalement une action hypotensive (via les récepteurs A2AR) et chronotrope négative (via les récepteurs A1R), nous nous sommes intéressés à son implication chez les patients présentant des syncopes neurocardiogéniques, la bradycardie et l'hypotension étant 2 signes cardinaux dans ce syndrome. Les manifestations cliniques de cette affection peuvent être reproduites par le test d'inclinaison (HUT) et/ou le test à l'ATP. Dans un premier temps nous avons réalisé des dosages d'adénosine plasmatiques chez ces patients au moment d'un test d'inclinaison. Les concentrations en adénosine étaient élevées chez les patients présentant un test positif. Par la suite, nous avons comparé les concentrations en adénosine plasmatiques et l'expression des récepteurs A2A en fonction du résultat du test d'inclinaison et du test à l'ATP.Adenosine is a ubiquitous nucleoside that comes from the dephosphorylation of ATP and which is released during hypoxia or oxidative stress, by endothelial cells and myocytes. Adenosine interacts on its cell surface receptors, namely A1R, A2AR, A2BR and A3R, to exert physiological effects on target tissues. Our knowledge about the adenosinergic system was improved because of our ability to measure adenosine plasma levels and to quantify its receptors expression. Because adenosine, via A1 or A2A receptor activation leads to bradycardia and hypotension, we first tried to understand the implication of the adenosinergic system in patients with neurocardiogenic syncope (NMS for neutrally mediated syncope). Indeed, this syndrome is characterized by relative or absolute bradycardia associated with a drop in blood pressure and a loss of consciousness. The symptomatology can be reproduced by the tilt test (HUT) or by the intravenous administration of ATP (ATP test). First, we measured adenosine plasma levels in patients with NMS just before and during HUT. We found that adenosine plasma levels were higher in patients with a positive HUT. Then, we compared adenosine plasma levels and the expression of A2A receptors in patients with NMS depending on the result of HUT and ATP-test. We found that elevated adenosine plasma levels and A2A receptors overexpression were associated with positive HUT. On the opposite, low adenosine plasma levels and normal expression of A2A receptor were associated with positive ATP test

    Adénosine endogène et expression des récepteurs A2a au cours de l'infarctus du myocarde

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    AIX-MARSEILLE2-BU MĂ©d/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
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