NCube/papyrus huggingface dataset:
L’efficacité du CD154 monomérique dans le traitement des complications thrombotiques

CD154 has emerged as an important player in the pathogenesis of several autoimmune diseases, as well as vascular dysfunctions. CD154 is a member of the tumour necrosis factor family of pivotal importance in humoral immunity. However, CD154 also shares critical inflammatory functions through its interaction with its classical CD40 receptor or recently identified binding partners, namely αIIbβ3, α5β1 and αMβ2. These responses imply CD154 as a key factor in chronic inflammatory disorders including autoimmune diseases and thrombosis. Disrupting the interaction of CD154 with its receptors through anti-CD154 Abs significantly inhibits the development of these diseases, albeit serious side effects have been associated with these therapies. To overcome these adverse effects, other approaches such as knockout, antisense oligonucleotide and siRNA targeting were developed. These approaches were focused on the CD154/CD40 interaction and did not address the interaction of CD154 with its other receptors. Thus, there is a need for novel CD154 treatments for the prevention/abrogation of inflammatory or autoimmune diseases that address all CD154 receptors. Our group profoundly investigated the structural/functional interaction of CD154 with its various receptors. Given the importance of the trimeric structure of CD154 for its biological activity, we generated monomeric form of the molecule that can specifically bind to one receptor without inducing intracellular activation. This agent represents a potential therapeutic tool for the treatment of CD154-mediated diseases such as thrombotic events.

Keyphrases: CD154, Mutant, Receptor, Monomer, Thrombosis
Analyse critique de la présence des contraceptifs longue durée réversibles en Haïti

This project addresses the institutional dimension of contraceptive choice and questions the presence and prevalence in Haiti of two long-acting reversible hormonal contraceptives (LARCs): Depo-Provera injections and subcutaneous implants. The theoretical approach adopted is that of critical humanitarian anthropology and makes use of the concept of "dispositif" in French (translated in "apparatus" by Dreyfus Rabinow in 1984) put forward by Michel Foucault (1975-76) in order to analyze the different elements that are articulated within the Global health system as it unfolds in Haiti. An analysis of the available literature identified three explanatory paradigms for LARC contraceptives in Haiti : biomedical discourse, administrative structure and funding model of the global contraceptive system. The analysis of biomedical discourse provides insight into the different consensuses surrounding the use of LARC contraceptives in developing countries, while revealing the impact of WHO as a normative body in the context of the various controversies surrounding side effects associated with progesterone and long-term contraceptive technologies. The administrative structure that governs the delivery of contraceptives to women living in Haiti makes it possible to understand that LARC contraceptives go hand in hand with a demedicalized approach to contraception. Finally, the program funding model captures the impact of contraceptive donations on the supply of contraceptive programs in Haiti, as well as the predominance of philanthropic organizations on the biomedical orientation of global health programs. In discussion, the paper presents critical anthropological reflections and questions the adequacy of LARC contraceptives in Haiti because of the health impacts of these drugs, the concerns of Haitians and the need to challenge the biomedical model in family planning.

Keyphrases: Haïti, contraception, anthropology, critical, humanitarianism, development, Haiti, women, reproductive health, contraception
“Invasive” and “Non-invasive” Technologies in Neuroscience Communication

This paper analyzes a common distinction in neuroscience communication: the labels “invasive” and “non-invasive” attributed to brain-observation technologies. Because an implicit or explicit value judgment accompanies the term “non-invasive,” it has been used to promote technological progress, especially new brain-imaging techniques that have appeared in recent decades. This study’s material comes from interactions between some expert scientists and the political sphere. Expert reports on neuroscience from different advisory bodies in the French public sector have been collected and analyzed for use of the distinction between invasive and non-invasive. The paper shows that the meaning of these widely used labels varies according to the context, e.g., status of discourse, technologies compared, or stakeholders engaged in the discussion. The definition of what is understood as invasive or non-invasive becomes a strategic issue and can thus vary according to the methodologies favoured by experts participating in national advisory boards or councils.

Keyphrases: scientific communication, scientific responsibility, brain imaging technologies, body representation, neuroethics
Rationalisation de contrats de services en imagerie médicale

Medical imaging activities are extremely diverse, complex, but crucial to the diagnosis of a patient. There is no need to emphasize that the engineering behind the magnetic resonance, x-ray, γ scan, ultrasound and other diagnostic imaging systems, is profoundly elaborated. Under the roof of most health centers, several thousand examinations involving these technologies are performed, every day. For this reason, among others, it is unacceptable for this type of equipment to be the subject of repetitive service interruptions. It is common to note that within the same health facility, similar equipment can be paired to irrationally distinct service agreements. This is one of the reasons why the management of specialized medical equipment maintenance activities and the contracts that governs them should not be overlooked. The lack of conductive lines for an effective and rational management of contracts such as those related to medical imaging directly affects the administrative, technical and clinical aspects of hospitals. This document mainly studies the multi-vendor service agreement format as a mean of rationalizing multiple service contracts in the medical imaging field. Little documentation on the subject, particularly regarding healthcare, generates the need for a global enhancement procedure that takes into account the many issues involved. The solutions proposed therein apply not only to equipment intended for the medical imaging discipline, but also to any other equipment subject to service agreements.

Keyphrases: GMAO, EMS, service agreement, medical imaging, remote diagnostic, multi-vendor, service improvement, CMMS, medical equipment
Archéologies de soi et marges de la modernité. L’écriture de l’enfance dans « Du côté de chez Swann » et « Mort à crédit »

From the thematically and chronologically close works that are "Du côté de chez Swann" and "Mort à crédit", this article tries to think together the autobiographical dimension of the coming-­‐ of-­‐age story with the discovery of the modern world that is orchestrated and put to crisis within those novels. The starting point of this reflection is to be found in the literary theories of the philosophical archeology of Foucault, for whom literature is a redistribution of the signs of the society and also a margin in which the order of history comes to fail and to be redistributed. In Proust’s as in Celine’s works, childhood’s naivety is reloaded with a primitively charged critique that allows a reflexive resumption of existence and writing.

Keyphrases: Proust, Marcel
Impact d’un module d’enseignement de la sédation procédurale, basé sur la simulation à haute fidélité, sur la performance des résidents non- anesthésiologistes pour la prise en charge des complications respiratoires liées à la sédation : étude prospective, randomisée en simple insu

A Hi-Fi simulation-based sedation course improves the performance of non-anesthesiology residents for the management of airway complications, compared with self-learning.  A randomized, controlled, single blinded trial.  Background: Sedation is a depression of consciousness ranging from anxiolysis to something less than general anesthesia. It is used by non-anesthesiologists to facilitate stressful or painful diagnostic tests and minor surgeries. The primary complications of procedural sedation impact the airway and respiratory system. Early diagnosis and adequate management of airway complications may prevent negative outcomes such as hypoxic brain damage or death. We investigated whether a simulation-based sedation course improved the performance of non-anesthesiology residents for the management of airway and respiratory complications during sedation, compared with self-learning. Methods: Thirty-two residents, without prior airway management experience, underwent a pre-test revolving around a HI-FI scenario of a complicated procedural sedation case. Residents were subsequently randomized to either attend an oriented debriefing including a theoretical course and a practical workshop with a low fidelity mannequin (Group E) or to simply view a video on sedation management (group C). A post-test that included a different sedation Hi-Fi scenario with airway complication, was carried out 21 days later. All scenarios were adapted to include realistic elements for all students from the various participating specialties. Residents’ performance was assessed by two evaluators who viewed the recorded scenarios without knowledge of the order in which they were conducted or of the participants’ group. It was rated according to a pre-established performance grid that was developed by simulation experts using the Delphi technique. The results are compared by a Wilcoxon rank test, or by a Mann-Whitney rank test.  Results: A significant improvement in performance was noted by both evaluators in group E (Evaluator A: 14,31∓2,30 vs 17,00∓1,59. Evaluator B: 12,38 ∓1,96 vs 14,94∓1,48. p<0.0001). A slight performance improvement was also noted in the control group, but this was not statistically significant (Evaluator A: 14,63∓1,40 vs 15,81∓1,79. Evaluator B: 13,31∓2,21 vs 14,75∓1,88). There was a significant positive correlation between the results of the evaluators. Conclusion : Our sedation crash course, based mainly on high-fidelity simulation, has allowed non-anesthesiology residents to improve their performance, and provided them with a safe way of managing procedural sedation and related airway and respiratory complications, compared to self-learning.

Keyphrases: high-fidelity simulation, sedation, simulation based medical education
Développement de méthodes analytiques par LC-MS/MS pour la caractérisation de l’activité et de l’expression des CYP450s chez l’humain

This research project is divided into two sections, both aiming at the development of sensitive and specific LC-MS methods to evaluate activity and expression of CYP450 and finally, looking at their clinical application. The first section of this research project focuses on the development of analytical methods by LC-MS/MS for a seven CYP450 probe-drug cocktail. Although these cocktails have shown value they also suffer from many limitations. Our objective was to develop and validate highly sensitive and selective LC-MS/MS assays allowing the determination of CYP1A2, 2B6, 2C9, 2C19, 2D6, 3A4/5 and 2E1 activities following administration of low oral doses of a modified CYP450 probe-drug cocktail in patients. These methods can be used to phenotype CYP450 activities, evaluate inter-individual variabilities, study the impact of pathological conditions on drug metabolism and elimination, and evaluate drug-drug interactions. Our CYP450 cocktail assays have been successfully applied to phenotype CYP450 activities in type 2 diabetic patients. The second section of this project aims at the development of a LC-HRMS method for the characterization and absolute quantification of CYP1A1, 1A2, 1B1, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2, 3A4, 3A5, 3A7 and 4F2 in the human small intestine. Our hypothesis suggests that CYP450 isoenzymes found along the small intestine can significantly affect the first-pass effect of certain drugs administered orally and thus influence their pharmacological and/or toxic effects. My participation in this project allowed to identify proteotypic peptides by in silico and in vitro digestion and to develop LC-HRMS methods allowing the absolute quantification of CYP450. This project is a first step in the characterization of the main CYP450 along the small intestine. This project will allow a better understanding of inter-individual variability in drug response associated with intestinal absorption of drugs, a better prediction of variability in drug bioavailability and to develop more complex pharmacokinetic models.

Keyphrases: LC-MS/MS, CYP450 probe-drug cocktail, Drug metabolism, Proteomic, Phenotyping
Mise en place d’un nouveau test de perméabilité membranaire à l’aide de la glycoprotéine-P reconstituée dans des protéoliposomes

Cellular membranes play an important role in the absorption and distribution of drugs in the human body. They contain different membrane transporters, which are responsible for the pharmacokinetic properties of drugs, as well as the safety and efficiency of their diffusion. When developing a new drug, it is thus of utmost importance to study the way that it will interact with the transporters present within the body. The aim of this study was to evaluate a new tool for measuring permeability in order to understand the function and mecanisms of P-glycoprotein (P-gp). P-gp is a transporter that is responsible for the rejection of many different compounds found in various drugs. This study thus seeks to use proteoliposomes to develop non-cellular models of membrane permeability including efflux and uptake transporters. This novel model of permeability will be utilized to study the underlying mechanisms of membrane permeability to xenobiotics.  The human P-gp was produced, extracted and purified using two different expression systems: MDCK-MDR1 cells (Madin-Darby canine kidney cells transfected with the human MDR1 gene) and Pichia pastoris. Both expression systems were studied in order to compare the strengths and weaknesses of each system. We then tested different methods of reconstituting the P-gp into protéoliposomes. Finally, we measured the level of ATPase activity using different substrates.  The protocols of cell culture, extraction and purification of both expression systems were accomplished in a laboratory during this study. These results demonstrated that expressing P-gp using yeast was more effective than that of mammalian cells. Furthermore, working with Pichia pastoris offers multiple advantages: expressing P-gp was easier, faster and cheaper than working with mammalian cells. The first measurements of ATPase activity using reconstituted P-gp proteoliposomes were promising, however they proved difficult to reproduce due to the possible degradation of the membrane protein.Further studies in this project will look to evaluate another ABC membrane transporter, BCRP. This smaller protein should prove to be more stable than P-gp, facilitating experimentation.

Keyphrases: Protéoliposome, P-glycoprotein, MDCK-MDR1, Pichia pastoris, Proteoliposome, Membrane transporters, Membrane permeability
Les effets du fentanyl sur la douleur et la motricité suite à une hémorragie intracérébrale induite chez le rat

The pain associated with traumatic brain injury is linked with the central nervous system sensitization and chronic cephalalgia when pain is not treated. However, analgesics in human patient must be done with caution since they are associated with cognitive and motor deficits. The present study aims to assess the efficiency of fentanyl to treat pain and evaluate motor behaviors on a rat model of intracerebral hemorrhage (IH).   Twenty-one male Sprague-Dawley rats underwent a stereotaxic surgery to produce a collagenase-induced IH with an injection of 2 µL of colagenase (0.5 UI) in the right caudoputamen nucleus. The control group (n=6) received saline subcutaneously (SC), and experimental groups received either 5 (n=6), 10 (n=6), or 20 (n=3) µg/kg of fentanyl SC, 2h following surgery and on the 2 subsequent days. The rat grimace scale, a neurological examination, balance beam test and rotarod test were performed for 5 consecutive days postoperatively to evaluate pain and motor performance. At the end of the experimentation, the animals were euthanized, the brains were collected and evaluated to determine hematoma volume, the number of reactive astrocytes and necrotic neurons.  When compared to controls, the grimace scale has showed that 5 µg/kg fentanyl significantly alleviated pain on day 2 only (p<0.01) and that 10 µg/kg alleviated pain on days 1 (p<0.01), 2 (p<0.001), and 3 (p<0.01). For the rotarod test, only the 10 µg/kg group showed significant decreases in performance on days 5 (p<0.05) and 6 (p<0.02). The neurologic exam was not significantly different between groups, but only the hopping test showed a poor recuperation for the 5 and 10 µg/kg fentanyl group when compared to saline (p<0.01). During brains exams, no differences were found between groups for the results of the 3 parameters.  Fentanyl, at a dose of 10 µg/kg SC, has provided a substantial analgesia following a collagenase-induced intracerebral hemorrhage in rats; however it can alter motor performance following analgesic treatments.

Keyphrases: Céphalalgie, Histopathologie, Analgesia, Cephalalgia, Grimace scale, Histopathology, Neurological exam, Rats
Récurrence de mammite clinique chez la vache laitière : incidence, facteurs de risque et impacts

Clinical mastitis (CM) is one of the most common and most costly diseases of dairy cows in dairy herds. A frustrating aspect of CM is its recurrent nature. Currently, no study has reported in an exhaustive and comprehensive manner information about risk of recurrent CM, risk factors for CM recurrence and its impacts. However, the information about CM recurrence in dairy cows were investigated in many, but disconnected studies. Therefore, a scoping review was conducted to synthesize knowledge on risk of recurrent CM, its risk factors, and negative impacts. Two databases (PubMed and CAB Abstracts), and one search platform (Web of Science) were searched to identify relevant English or French scientific literature published after 1989. Fifty-seven articles were selected for qualitative synthesis. Description of recurrent CM, its negative impacts, and risk factors were reported in 33, 19, and 37 selected studies, respectively. Then, meta-analysis and meta-regression analysis were applied to compute risk ratio (RR) comparing risk of CM in cows that experienced one CM case in the current lactation to risk of CM of healthy cows. The total number of lactations followed and the number of lactations with ≤ 1 and ≤ 2 CM cases were reported in nine studies and the information was used in meta-analysis. These nine studies were then separated into two groups based on recurrent CM definition; those requiring only 24 h and those requiring ≥ 5 d between two CM cases to consider a CM case as a new CM event. For studies requiring only 24 h, cows that already had one CM case in the current lactation had a 1.5 times higher RR for recurrent CM than healthy cows. However, for studies using ≥ 5 d between two CM cases, risk of repeated cases of CM was not different in cows that suffered one CM case in a given lactation as compared with healthy cows (RR: 0.99; 95% CI: 0.86, 1.1). In this study, milk yield reduction and increased risk of mortality and culling were identified as important negative impacts of recurrent CM. Moreover, the most important CM recurrence risk factors were older dairy cow, high-producing dairy cow, and not having cure of treatment following initial CM case. A better understanding of the cow’s, pathogens’ and herd’s characteristics associated with recurrent CM events may possibly help controlling these recurrent events, decrease the associated costs as well as reduce amounts of antibiotics used on dairy farms. Moreover, these knowledges may be also useful in predicting the probability of a repeated CM event and could, therefore, be used to develop tools to inform dairy producer’s CM-related management decisions.

Keyphrases: Dairy cow, Clinical mastitis, Recurrence, Systematic review, Meta-analysis
Modèles chirurgicaux de douleur arthrosique : évaluation fonctionnelle, biomarqueurs spinaux et développement de nouveaux modèles

The exact aetiology of osteoarthritic pain is only partially understood and the use of animal models is fundamental in the pathophysiological investigation and the development of therapeutic modalities, particularly the creation of a pathological chronic pain model. In the investigation of OA knee pain in rats, the intra-articular injection of sodium mono-iodo-acetate (MIA) is an overrepresented model.  However, this does not represent the natural disease in humans since the disease is acute, chemically induced, and temporary. We hypothesized that surgical models have the advantage of using mechanisms with better resemblance to the natural post-traumatic osteoarthritis. The model of transection of the cranial cruciate ligament, destabilization of the medial meniscus (partial medial meniscotomy) and their combination were evaluated in a pilot study with the objective to compare the pain behaviour and spinal neuromarkers between the surgical and MIA models. Surgical induction was accompanied by measurable neurophysiological changes associated with pathological pain and lasting longer than the MIA model, an advantage that can be applied in the evaluation of therapeutic modalities. Simple surgical models have proved to be without interest as they present temporary functional impairment without neuroproteomics modification.

Keyphrases: Neuropeptides, Pain, Osteoarthritis, Animal model, Sodium mono-iodo-acetate, Functional evaluations, Biomarkers, Neuropeptides
Le rôle de la région variable du 3’ UTR dans la réplication du virus de l’hépatite C

The hepatitis C virus (HCV), a member of the Flaviviridae, contains a single (+) strand linear RNA genome which incorporates one long open reading frame flanked by two untranslated regions known as the 5’UTR and 3’UTR. These regions contain structures known to function in the regulation of HCV translation and replication. The 3’UTR is the focus of this research project. Its tripartite structure consists of a variable region (VR), a poly (U/UC) region and the X-tail. Our laboratory recently identified a VR sequence forming a duplex structure with a distal sequence located in the NS5B gene. Because NS5B encodes the viral polymerase, and seeing that the 3’UTR is involved in viral replication, we postulated that this duplex may function in controlling the level of HCV RNA replication. To test this hypothesis, we constructed HCV 1b mutants in the respective VR and NS5B annealing sequences to disrupt complementarity and prevent duplex formation. We also created a mutant with complementary mutations at both sites to reconstitute the duplex. RNA from these constructs was synthesized in vitro and transfected into Huh7.5 cells. Following a 9-day incubation period, RNA from all transfected cultures was harvested and HCV RNA was quantified by RT-qPCR. The data indicate an increase of 5.3X and 3.4X for HCV viral RNA harvested from cultures with disrupted 3’UTR-VR and NS5B, respectively, relative to wild-type HCV 1b, whereas the reconstituted HCV construct yielded a 2.6X increase in viral RNA. While these figures do not reach statistical significance, they suggest that the duplex structure modulates HCV replication downward. Further pursuit of this work is necessary to better elucidate the role of the VR-NS5B duplex structure on HCV replication.

Keyphrases: Flaviviridae, 3’UTR, VR, NS5B, Interactions distales, HCV, Distal interactions, Replication, RNA structures