CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner

Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-β−/− T reg cells into nude mice suppressed NK cell–mediated cytotoxicity, reduced NKG2D receptor expression, and accelerated the growth of tumors that are normally controlled by NK cells. Conversely, the depletion of mouse T reg cells exacerbated NK cell proliferation and cytotoxicity in vivo. Human NK cell–mediated tumor recognition could also be restored by depletion of T reg cells from tumor-infiltrating lymphocytes. These findings support a role for T reg cells in blunting the NK cell arm of the innate immune system

Rapport d\u27analyse ­ Enquête : Les données de la recherche à l\u27université ParisSaclay, panorama et perspectives

Cette enquête, proposée par l’ensemble du réseau des bibliothèques et centres de documentation et le Comité de pilotage de la Science Ouverte de l’Université Paris-Saclay en 2021, s’inscrit dans un contexte dynamique de Science Ouverte prônant l’obligation de publication des données de la recherche selon les principes FAIR (Facilement trouvable, Accessible, Interopérable, Réutilisable)

Standardization of in vitro digestibility and DIAAS method based on the static INFOGEST protocol

Background: The FAO recommends the digestible indispensable amino acid score (DIAAS) as the measure for protein quality, for which the true ileal digestibility needs to be assessed in humans or pigs. However, due to high costs and ethical concerns, the FAO strongly encourages as well the development of validated in vitro methods, which complement the in vivo experiments. Method: Recently, an in vitro workflow, based on the validated static INFOGEST protocol, was developed and compared towards in vivo data. In parallel to the validation with in vivo data, the repeatability and reproducibility of the in vitro protocol were tested in an international ring trial (RT) with the aim to establish an international ISO standard method within the International Dairy Federation (IDF). Five different dairy products (skim milk powder, whole milk powder, whey protein isolate, yoghurt, and cheese) were analyzed in 32 different laboratories from 18 different countries, across 4 continents. Results: in vitro protein digestibilities based on Nitrogen, free R-NH2, and total amino acids as well as DIAAS values were calculated and compared to in vivo data, where available. Conclusion: The in vitro method is suited for quantification of digestibility and will be further implemented to other food matricesinfo:eu-repo/semantics/publishedVersio

Assistive Robotic arm control using point of gaze Estimation

RÉSUMÉ: Les avancées récentes de la robotique permettent aux personnes atteintes de troubles musculosquelettiques de s'équiper d'un bras robotique d'assistance pouvant être placé sur leur fauteuil motorisé. Il a été démontré que ces bras robotiques améliorent l'autonomie et l'habileté de ces personnes, notamment pour accomplir les tâches importantes du quotidien, telles que se nourrir seul. Cependant, certains problèmes perdurent, en particulier le fait que le temps pour accomplir les manoeuvres à l'aide d'un bras robotique reste encore élevé, en particulier pour les personnes atteintes de troubles musculo-squelettiques. Une des manoeuvres les plus longues est l'approche et la saisie d'un objet, car elle demande de contrôler 6 degrés de liberté à l'aide d'une manette commandant seulement 3 axes à la fois. Aussi, le contrôle à l'aide de manettes demande un haut niveau de dextérité, souvent difficile à atteindre par les utilisateurs ciblés. Pour résoudre ces problématiques, l'objectif de ce projet est de développer une solution de contrôle du bras robotique d'assistance à l'aide d'un système de suivi du regard de l'utilisateur. Pour ce faire, il est nécessaire de suivre les yeux de l'utilisateur et d'en déduire la direction du regard, de reconstruire la scène en face de l'utilisateur par stéréovision, d'y faire la correspondance entre la direction du regard et les objets présents dans la scène pour finalement planifier la trajectoire du bras robotique pour atteindre l'objet et le prendre. La solution finale détaillée dans cette thèse permet donc de faire l'approche et la prise d'objet automatique en estimant la direction du regard de l'utilisateur et en détectant les objets en face de ce dernier. Ce système n'est aucunement intrusif car il ne nécessite pas que le bénéficiaire porte un objet comme des lunettes. Il fonctionne en présence d'illumination du soleil, ce qui n'est pas le cas d'autres types de système. Il permet aussi de prendre des objets sans contrainte sur leur type et ne nécessite aucune calibration par utilisateur. Utilisant un modèle original d'estimation de la direction du regard et mettant en place un système de détection et sélection d'objets basé sur la détection de surface plane telle une table et de l'allure de l'objet par apprentissage profond en parallèle, le système permet de planifier une trajectoire automatiquement en évitant les collisions avec la scène. À la suite d'essais exécutés dans le contexte de cette thèse, il est possible de constater une réduction du temps pour accomplir une tâche de préhension d'un objet d'environ 72.0% pour un taux de succès de 90% , tout en obtenant un score de satisfaction élevé d'en moyenne 4.6 sur 5 selon un questionnaire complété par les participants. ABSTRACT: In recent years, advances in robotics allow people suffering from upper limb disabilities to equip their motorized wheelchair with an assistive robotic arm. These are generally controlled through a specialized joystick device using filters and calibrated specifically to the user's force and disability. These robotic arms have been proven to improve the autonomy of their users, especially to accomplish tasks of daily living such as eating. However, some issues still persist, such as that manipulating the robotic arm is still time intensive for the users, especially in the case of approaching and grasping an object, since it requires moving the robotic arm in 6 degrees of freedom using a joystick that typically provides only 3 axes of motion. Also, joystick controls are complicated and require a high degree of dexterity, which is often lacking in potential users. Furthermore, the learning curve for using this technology is steep and the adaptation time is often too long, which leads to low adoption rates for potential users. To mitigate these issues, this PhD project aims to develop a control system for assistive robotic arms using user point of gaze estimation and gazed-at object detection using computer vision. This implies that the developed system must estimate the gaze direction and origin of the user, reconstruct the scene in 3D in front of the user, detect objects in the scene and match the user's gaze to the best fitting object. The developed system must also be able to generate a valid and collision-free path to the object, leading to a grasping motion, thus being able to automatically approach and grasp an object that is gazed-at by the user. The system described in this thesis is non-intrusive since it does not require the user to wear any devices, instead relying on mounting points on the user's motorized wheelchair. It is also less sensitive to lighting conditions, working with direct sunlight which is not the case for most of the available gaze control systems in the literature. Furthermore, it allows the grasping of objects independent of their type, as long as it is found to fit inside the robot's gripper. The developed system uses a novel gaze estimation deep learning model and an object detection subsystem that uses both the detection of a flat surface such as a table and a deep learning segmentation model based on object classes in parallel, allowing for robust object detection. From the data collected through device trials performed in the context of this PhD thesis, the system has demonstrated a 72.0% reduction in the time to grasp varied objects over to the same tasks performed with a joystick, while keeping a high success rate of 90% and a high satisfaction score of 4.6 out of 5

Immunoregulatory properties of clinical grade mesenchymal stromal cells: evidence, uncertainties, and clinical application.

International audienceMesenchymal stromal cell (MSC)-based therapy holds great promise for treating immune disorders and for regenerative medicine in agreement with their paracrine trophic and immunosuppressive activities. Various processes have been developed worldwide to produce clinical grade MSCs but, so far, it is not known if one given MSC is more efficient than another. In addition, while their broad activity on innate and adaptative immune cell subsets is now widely admitted, the precise mechanisms supporting their immunoregulatory capacities are still a matter of debate. Finally, quantitative immunological potency assays correlated to clinical efficacy and clinically relevant immunomonitoring approaches for MSC-treated patients are sorely needed. Multiple parameters could influence the immunomodulatory potential of therapeutic MSCs. The most important challenge is now to differentiate, within a high number of poorly comparable and even contradictory pre-clinical studies, the parameters that could have some clinical impact from those that are only due to uncontrolled experimental variability. Importantly, besides MSC-related differences, primarily linked to production processes, several important variables associated with immune assays themselves, including selection of effector immune cells, activation signals, and read-out techniques, should be carefully considered to obtain solid results with potential therapeutic application. In this review, we establish a core of common and reproducible immunological properties of MSCs, shed light on technical issues concerning immunomodulatory potential assessment, and put them into perspective when considering clinical application

Immunosuppression et cellules souches mésenchymateuses

Les cellules souches mésenchymateuses (CSM) possèdent des propriétés immunosuppressives très vastes liées à la production de facteurs solubles inductibles qui inhibent l’activation des principaux effecteurs de l’immunité. L’intérêt de ces propriétés a été confirmé dans des essais cliniques spectaculaires chez des patients atteints de la maladie du greffon contre l’hôte, une complication fréquente et grave des allogreffes de cellules souches hématopoïétiques. Depuis, les applications de ce potentiel anti-inflammatoire et immunosuppresseur des CSM ont été étendues à la médecine régénératrice puisque les capacités de réparation des CSM semblent étroitement liées à leurs propriétés immunologiques, démontrant tout l’intérêt d’une compréhension fine des interactions entre les CSM et les cellules immunitaires

Behavior Change Techniques in Popular Mobile Apps for Smoking Cessation in France: Content Analysis

International audienceBackground The mobile app market differs from country to country, and to date, no previous review of the content quality of smoking cessation apps has been conducted in France. Objective This study aimed to examine the general quality of the most popular smoking cessation apps in France and also determine the degree to which apps adhere to established behavioral and cognitive techniques (BCTs) proven effective in clinical practice. Methods A systematic research of smoking cessation apps was conducted in both the Google Play Store and Apple Store in the French market. The general quality of popular apps was rated with the Mobile App Rating Scale (MARS), and the therapeutic quality was assessed with the ratio of adherence of the behavior change technique taxonomy for smoking cessation treatment. Results A total of 14 mobile apps met all the inclusion criteria of the content analysis. The interrater reliability varied from “substantial” (0.79) to “almost perfect” (0.9) for the two measures. The mean MARS score was 3.5 out of 5 (median 3.6, IQR 0.6 [3.2-3.8]). The findings suggest that popular apps focus primarily on the functionality dimension of the MARS scale (4.2/5). The mean number of BCTs was 22, with a large difference between apps (minimum 4, maximum 38). At least half of the apps addressed motivation (8.8/14, 63%) and advised on using behavioral skills in order to quit smoking or stay a nonsmoker (8.7/14, 62%). However, only a handful of apps gathered important information (5.9/14, 42%) in order to deliver proper advice regarding the use of approved medication or the implementation of behavioral techniques (4.3/14, 31%). The mean MARS score was positively correlated with the price (r=0.70, P=.007) and the number of BCTs used (r=0.67, P=.01). User rating was not correlated with any quality scale (P=.67). Conclusions The content quality of popular smoking cessation apps in France varied by app type and price. Most popular apps propose in general good quality content but lack implementation of evidence-based BCTs associated with effectiveness on smoking cessation treatment. Further research is needed to evaluate the improvement in the content quality of smoking cessation apps in France

Medial thighplasty after massive weight loss: are there any risk factors for postoperative complications?

International audienceBACKGROUND: With the increasing incidence of obesity in Western societies, an increasing number of patients undergo bariatric surgery that leads to functional and aesthetic sequelae related to a rapid and massive weight loss, namely, skin and fat excess. The goal of surgical management after massive weight loss is to optimize the functional results obtained from bariatric surgery or diet by removal of the redundant skin folds. The authors report their experience with medial thighplasty after massive weight loss and identify factors predictive of postoperative complications. METHODS: This retrospective study investigated 53 patients who underwent surgery for medial thighplasty after massive weight loss. Data were collected through chart review and submitted to statistical analysis. RESULTS: The average weight loss before thighplasty was 43.5 ± 14.9 kg, and 39.6 % of the patients experienced at least one complication. The complications were seroma (9.4 %), wound dehiscence (20.8 %), scar migration (17 %), wound infection (5.7 %), and partial skin necrosis (1.9 %). The body mass index (BMI) before massive weight loss and the BMI before medial thighplasty were found to be risk factors for the development of a postoperative complication. CONCLUSION: Few guidelines exist for the optimization of care and safety in this complex patient population. The information from this retrospective study complements the current data from the literature and can help surgeons select patients eligible for medial thighplasty. This report shows that the BMI before medial thighplasty should be taken into consideration for patients willing to undergo a body-contouring procedure. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266

Introducing two databases of spoken French throughout adulthood

International audienc