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Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, and the neuromuscular junction. In amyotrophic lateral sclerosis, where motor neuron function is progressively lost, Schwann cell function may also be impaired. Recently, important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported. This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles, marking, to our knowledge, the first instance of such treatment. An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis. After initial diagnosis, the patient underwent a combination of generic riluzole, sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis, and taurursodiol. The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function. We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired (senescent) and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles, cultured expanded from a cadaver donor improved their growth capacity in vitro. After a period of observation lasting 10 weeks, during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored, the patient received weekly consecutive infusions of 1.54 × 1012 (×2), and then consecutive infusions of 7.5 × 1012 (×6) allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline. None of the infusions were associated with adverse events such as infusion reactions (allergic or otherwise) or changes in vital signs. Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend. A more sensitive in-house assay suggested possible inflammasome activation during the disease course. A trend for clinical stabilization was observed during the infusion period. Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles. Initial findings suggest that this approach is safe.

Aim: Transition from pediatric to adult healthcare is a critical period. Recommendations have pointed to greater preparation of youths and families and better coordination. Considerations such as patient values and preferences may – if not taken into consideration – impede uptake of clinical recommendations. This survey-based study aimed to better understand challenges, needs, and intervention preferences of youths and parents during transition. Methods: Two online surveys were designed to investigate challenges, needs, and intervention preferences of youths with a chronic or rare condition and parents during transition. The youth survey included the French translation of the Transition Readiness Assessment Questionnaire (TRAQ). Additional questions were derived from an interview-based study and aimed to grasp issues related to human flourishing in addition to more conventional clinical issues related to the transition process. Descriptive statistics were used and ANOVAs to detect differences between the groups when applicable. Results: 86 youths and 94 parents completed the survey. Average scores for TRAQ subscales were high except for “Tracking health issues” and “Appointment keeping”. Youths and parents reported being able to give their opinion. Parents were judged to be slightly over-involved. Ongoing involvement of parents in health management was desired. Awareness of differences between pediatric and adult healthcare was high, but a source of notable concern (e.g., accessibility of different medical and professional services). Information on transition was lacking. Installing a pivot-person, visits to the adult hospital, meeting other youths, and accessing transition videos were supported interventions. Conclusion: Transition readiness can be high, but significant challenges can still be present and salient. Youths and adults want to be involved and informed to prepare actively for transition through meetings or adapted materials.

A growing body of critical care research draws on real-world data from electronic health records (EHRs). The bedside clinician has myriad data sources to aid in clinical decision-making, but the lack of data sharing and harmonization standards leaves much of this data out of reach for multi-institution critical care research. The Society of Critical Care Medicine (SCCM) Discovery Data Science Campaign convened a panel of critical care and data science experts to explore and document unique advantages and opportunities for leveraging EHR data in critical care research. This article reviews and illustrates six organizing topics (data domains and common data elements; data harmonization; data quality; data interoperability and digital infrastructure; data access, sharing, and governance; and ethics and equity) as a data science primer for critical care researchers, laying a foundation for future publications from the SCCM Discovery Data Harmonization and Sharing Guiding Principles Panel.

L’entreprise EDF, en tant qu’aménageur d’infrastructures majeures et gestionnaire de plus de 30 000 hectares de foncier terrestre en France continentale, collabore depuis plus de dix ans avec les Conservatoires botaniques nationaux sur l’origine du matériel végétal utilisé dans ses projets d’aménagement, de réhabilitation post-chantier et de restauration écologique. Cette collaboration se traduit notamment par un partenariat national initié dès la création en 2015 de la marque « Végétal local ». Cette dernière, animée par le réseau des Conservatoires botaniques nationaux, l’Afac-Agroforesteries et Plante & Cité, vise à garantir l’utilisation de matériel végétal adapté au territoire où les projets sont mis en place, dans un souci de protection de la diversité génétique. L’article présente la vision d’EDF sur la structuration de la filière, qui se distingue par un réseau d’animateurs locaux, un lien avec les acteurs de l’économie des territoires et une forte implication du monde de la formation et de la recherche. Un retour d’expérience sur les projets portés par EDF avec du « Végétal local « permet de mettre en lumière les avantages de la marque, mais aussi les défis qui vont de pair avec son utilisation.

BackgroundLung cancer is the leading cause of cancer death worldwide, with poor survival despite recent therapeutic advances. A better understanding of the complexity of the tumor microenvironment is needed to improve patients’ outcome.MethodsWe applied a computational immunology approach (involving immune cell proportion estimation by deconvolution, transcription factor activity inference, pathways and immune scores estimations) in order to characterize bulk transcriptomics of 62 primary lung adenocarcinoma (LUAD) samples from patients across disease stages. Focusing specifically on early stage samples, we validated our findings using an independent LUAD cohort with 70 bulk RNAseq and 15 scRNAseq datasets and on TCGA datasets.ResultsThrough our methodology and feature integration pipeline, we identified groups of immune cells related to disease stage as well as potential immune response or evasion and survival. More specifically, we reported a duality in the behavior of immune cells, notably natural killer (NK) cells, which was shown to be associated with survival and could be relevant for immune response or evasion. These distinct NK cell populations were further characterized using scRNAseq data, showing potential differences in their cytotoxic activity.ConclusionThe dual profile of several immune cells, most notably T-cell populations, have been discussed in the context of diseases such as cancer. Here, we report the duality of NK cells which should be taken into account in conjunction with other immune cell populations and behaviors in predicting prognosis, immune response or evasion.

Fermentation alters the protein content and composition of foods. To characterize fungal catabolism of peanut proteins, defatted peanut flour was fermented by Rhizopus oryzae (R. oryzae) for up to 48 h and evaluated by SDS-PAGE, mass spectrometry, and antibody binding. A clear change in peanut protein migration was observed by SDS-PAGE after 16 h of fermentation. Mass spectrometric analysis indicated changes in allergen peptides and R. oryzae proteins. Several low molecular weight allergen fragments produced during fermentation were identified by mass spectrometry. Immunoassays using anti-peanut allergen antibodies demonstrated reduced allergen content as early as 16 h of fermentation. However, ELISA with peanut allergic IgE indicated only slightly reduced allergen binding even after 48 h. These results indicate that while R. oryzae fermentation efficiently metabolizes peanut allergens, significant IgE binding remains in lower molecular mass peptides, and therefore R. oryzae fermented peanut products would not be safe for peanut allergic individuals.

Our article aims to identify the pragmatics of science fiction texts, the way in which they are perceived and handled by readers, especially students. SF literature tends to inscribe in the text the figure of the reader-investigator, or even of the suspicious reader. While any literary reading in general requires this kind of investigation, if only to resolve the inferences necessary for comprehension, SF would require more effort because of the semantic oddities designed to represent the science-fictional universe more or less distanced from the readers’ real reference point. This article looks at cultural and didactic approaches to the study of utopias and extraordinary journeys from the classical period to more contemporary dystopias, as well as resistant texts and the paradigm of the reader subject. A whole arsenal of tried and tested teaching methods can be used to study science fiction in the classroom.

The aim of this article is to provide some answers to the question of the use and content of science fiction (SF) in the teaching of literature, from the historical perspective of French secondary education. It shows that SF – since the 1970s – has been a constant subject of teaching in French secondary schools, first approached in a marginal way, then taking on a greater role – particularly in school textbooks – as curricula changed and children’s literature was introduced into the school corpus (1980s). The time milestones selected enable us to identify the main trends according to periods corresponding to developments initiated either by research or by official national education programs. An analysis of examples shows that, from the 1970s, SF was regularly the subject of pedagogical and didactic proposals. In a first approach, the examples selected are each time situated at the junction of applied university research and analyzed classroom experiences. A second section analyzes the use of SF in a panel of textbooks at the turn of the millennium. The third part of the study offers reflections on more contemporary teaching. The constant presence of SF in French language teaching is nonetheless minor, whatever the period considered.

Objective: The aim of this study was to compare the magnitude and the predictors of the placebo response in an internet versus onsite randomised controlled trials (RCTs) in people with hand osteoarthritis (HOA). Method: This study is a post-hoc analysis based on one internet RCT (RADIANT) and previously published onsite RCTs for HOA identified through a rigorous searching and selection strategy. The magnitude of the placebo response in the two different types of RCTs were compared using heterogeneity statistics and forest plots visualisation. Classic placebo predictors as well as a combined model, defined with data from onsite RCTs, were tested to predict the placebo response. Results: We analysed the dataset from RADIANT and fourteen previously published onsite RCTs. None of the analyses showed a significant difference between the placebo response for the internet versus onsite RCTs. The “classic” placebo predictors combined in a multivariate predictive model correlated significantly with the placebo response measured in RADIANT study. Conclusion: Despite the absence of face-to-face interactions with the study personnel, there is no evidence that either the magnitude or the predictors of the placebo response of this internet RCT differ from those of onsite RCTs. This analysis is considered as a first step towards evaluating the difference between these designs and strengthens the argument that internet RCTs remain an acceptable alternative way to assess the efficacy of an active treatment in comparison to a placebo.

Stray light (SL) control is an important aspect in the development of optical instruments. Iterations are necessary between design and analysis phases, where ray tracing simulations are performed for performance prediction. This process involves trial and error, requiring to be able to perform rapid evaluation of SL properties. The limitation is that accurate SL simulations require sending many rays, which can be time consuming. In this paper, we use deep learning to improve the accuracy of SL maps even when obtained with very few rays. Two different deep learning methods are used, an autoencoder and an EAM. The training process is performed by generating a large database of artificial SL maps, with different noise levels reproduced with a Poisson distribution. Once the training completed, we show that the autoencoder performs the best and improves significantly the accuracy of SL maps. Even with extremely small number of rays, it recovers complex SL patterns which are not visible on raw ray traced maps. This method thus enables more efficient iterations between design and analysis. It is also useful for developing SL correction algorithms, as it requires tracing SL maps under large number of illumination conditions in a reasonable amount of time.

Summary: Background: Eighty percent of global cardiovascular disease (CVD) is projected to occur in low- and middle -income countries (LMICs), yet local epidemiological data are scarce. We provide the first population-based, adjudicated CVD prevalence estimates in Port-au-Prince, Haiti to describe the spectrum of heart disease and investigate associated risk factors. Methods: Demographic, medical history, clinical, imaging and laboratory data were collected among adults recruited using multistage random sampling from 2019 to 2021. Prevalent CVD (heart failure, stroke, ischemic disease) were adjudicated using epidemiological criteria similar to international cohorts. Multivariable Poisson regressions assessed relationships between risk factors and prevalent CVD. Findings: Among 3003 participants, median age was 40 years, 58.1% were female, 70.2% reported income

Abstract HIV-1 infection causes severe alterations of gut mucosa, microbiota and immune system, which can be curbed by early antiretroviral therapy. Here, we investigate how treatment timing affects intestinal memory B-cell and plasmablast repertoires of HIV-1-infected humans. We show that only class-switched memory B cells markedly differ between subjects treated during the acute and chronic phases of infection. Intestinal memory B-cell monoclonal antibodies show more prevalent polyreactive and commensal bacteria-reactive clones in late- compared to early-treated individuals. Mirroring this, serum IgA polyreactivity and commensal-reactivity are strongly increased in late-treated individuals and correlate with intestinal permeability and systemic inflammatory markers. Polyreactive blood IgA memory B cells, many of which egressed from the gut, are also substantially enriched in late-treated individuals. Our data establish gut and systemic B-cell polyreactivity to commensal bacteria as hallmarks of chronic HIV-1 infection and suggest that initiating treatment early may limit intestinal B-cell abnormalities compromising HIV-1 humoral response.

OBJECTIVES:. Early signs of bleeding are often masked by the physiologic compensatory responses delaying its identification. We sought to describe early physiologic signatures of bleeding during the blood donation process. SETTING:. Waveform-level vital sign data including electrocardiography, photoplethysmography (PPG), continuous noninvasive arterial pressure, and respiratory waveforms were collected before, during, and after bleeding. SUBJECTS:. Fifty-five healthy volunteers visited blood donation center to donate whole blood. INTERVENTION:. After obtaining the informed consent, 3 minutes of resting time was given to each subject. Then 3 minutes of orthostasis was done, followed by another 3 minutes of resting before the blood donation. After the completion of donating blood, another 3 minutes of postbleeding resting time, followed by 3 minutes of orthostasis period again. MEASUREMENTS AND MAIN RESULTS:. From 55 subjects, waveform signals as well as numerical vital signs (heart rate [HR], respiratory rate, blood pressure) and clinical characteristics were collected, and data from 51 subjects were analyzable. Any adverse events (AEs; dizziness, lightheadedness, nausea) were documented. Statistical and physiologic features including HR variability (HRV) metrics and other waveform morphologic parameters were modeled. Feature trends for all participants across the study protocol were analyzed. No significant changes in HR, blood pressure, or estimated cardiac output were seen during bleeding. Both orthostatic challenges and bleeding significantly decreased time domain and high-frequency domain HRV, and PPG amplitude, whereas increasing PPG amplitude variation. During bleeding, time-domain HRV feature trends were most sensitive to the first 100 mL of blood loss, and incremental changes of different HRV parameters (from 300 mL of blood loss), as well as a PPG morphologic feature (from 400 mL of blood loss), were shown with statistical significance. The AE group (n = 6) showed decreased sample entropy compared with the non-AE group during postbleed orthostatic challenge (p = 0.003). No significant other trend differences were observed during bleeding between AE and non-AE groups. CONCLUSIONS:. Various HRV-related features were changed during rapid bleeding seen within the first minute. Subjects with AE during postbleeding orthostasis showed decreased sample entropy. These findings could be leveraged toward earlier identification of donors at risk for AE, and more broadly building a data-driven hemorrhage model for the early treatment of critical bleeding.

BackgroundThe COVID-19 pandemic had a global impact on people life, notably because of lockdown periods. This could particularly affected patients suffering from hip fracture, who could have been more isolated during these periods. We aim at evaluating the impact of the COVID-19 period (including lockdown periods) on quality of life (QOL) in older adult patients 90 days after a surgery for a hip fracture.Subject and methodsAncillary study of the prospective randomized controlled HiFIT study. We compared the QOL measured at 90 days after a hip fracture surgery using the EuroQOL-5 dimensions 3 levels (EQ-5D), the Perceived Quality of life (PQOL) and the Instrumental Activities of Daily Living (IADL) in patients included in the Hifit study before and during the COVID-19 pandemic.ResultsThe characteristics of the 161 patients included before and of the 213 included during the COVID period (including 122 (57%) during COVID with containment periods and 91 (43%) during COVID without containment periods) were similar (mean age 84 ± 10 years; 282 (75%) women). The majority (81%) of the patients alive at 90 days had returned to their previous place of residence in both periods. During the COVID period, EQ-5D showed better patient pain/discomfort and anxiety/depression levels. The PQOL happiness was not different, with around 81% of the patient being “happy” or “very happy” during the two periods and the IADL was also similar during the two periods. In the multivariate analysis odd ratios of having poorer outcomes were increased before COVID for pain/discomfort (OR 2.38, 95%CI [1.41–4.15], p = 0.001), anxiety (OR 1.89 [1.12–3.21], p = 0.017) and mobility (1.69 [1.02–2.86], p = 0.044).ConclusionPatient’s quality of life measured using different scales was not altered during the COVID period compared to before COVID, 90 days after a hip fracture. Surprisingly, the Pain/Discomfort and Anxiety dimensions of the EQ-5D questionnaires were even better during the COVID period.Clinical trial registration:https://clinicaltrials.gov/ (NCT02972294).

Objectives Describe new opioid prescription claims, their clinical indications and annual trends among opioid naïve adults covered by the Quebec’s public drug insurance plan (QPDIP) for the fiscal years 2006/2007–2019/2020.Design and setting A retrospective observational study was conducted using data collected between 2006/2007 and 2019/2020 within the Quebec Integrated Chronic Disease Surveillance System, a linkage administrative data.Participants A cohort of opioid naïve adults and new opioid users was created for each study year (median number=2 263 380 and 168 183, respectively, over study period).Intervention No.Main outcome measure and analyses A new opioid prescription was defined as the first opioid prescription claimed by an opioid naïve adult during a given fiscal year. The annual incidence proportion for each year was then calculated and standardised for age. A hierarchical algorithm was built to identify the most likely clinical indication for this prescription. Descriptive and trend analyses were performed.Results There was a 1.7% decrease of age-standardised annual incidence proportion during the study period, from 7.5% in 2006/2007 to 5.8% in 2019/2020. The decrease was highest after 2016/2017, reaching 5.5% annual percentage change. Median daily dose and days’ supply decreased from 27 to 25 morphine milligram equivalent/day and from 5 to 4 days between 2006/2007 and 2019/2020, respectively. Between 2006/2007 and 2019/2020, these prescriptions’ most likely clinical indications increased for cancer pain from 34% to 48%, for surgical pain from 31% to 36% and for dental pain from 9% to 11%. Inversely, the musculoskeletal pain decreased from 13% to 2%. There was good consistency between the clinical indications identified by the algorithm and prescriber’s specialty or user’s characteristics.Conclusions New opioid prescription claims (incidence, dose and days’ supply) decreased slightly over the last 14 years among QPDIP enrollees, especially after 2016/2017. Non-surgical and non-cancer pain became less common as their clinical indication.