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Jean-Christophe Lagier,1,2 Matthieu Million,1,2 Sébastien Cortaredona,1,3 Léa Delorme,1 Philippe Colson,1,2 Pierre-Edouard Fournier,1,3 Philippe Brouqui,1,2 Didier Raoult,1,2 Philippe Parola1,3 On behalf of the IHU Task Force1IHU-Méditerranée Infection, Marseille, France; 2MEPHI, Aix Marseille Université, Institut de Recherche pour le Développement, Assistance Publique Hôpitaux de Marseille, Marseille, France; 3VITROME, Aix Marseille Université, Institut de Recherche pour le Développement, Assistance Publique Hôpitaux de Marseille, Service de Santé des Armées, Marseille, FranceCorrespondence: Philippe Parola, Institut Hospitalo-Universitaire Méditerranée Infection, 19-21 Boulevard Jean Moulin, Marseille, 13005, France, Tel + 33 0 4 13 73 24 01, Fax + 33 0 4 13 73 24 02, Email philippe.parola@univ-amu.fr Jean-Christophe Lagier, Email jeanchristophe.lagier@ap-hm.frObjectives: We evaluated the 6-week mortality of SARS-CoV-2 hospitalized patients treated using a standardized protocol in 2020 in Marseille, France.Methods: A retrospective monocentric cohort study was conducted in the standard hospital wards at the Institut Hospitalo-Universitaire Méditerranée Infection, between March and December 2020 in adults with SARS-CoV-2 PCR-proven infection.Results: Of the 2111 hospitalized patients (median age, 67 [IQR 55– 79] years; 1154 [54.7%] men), 271 were transferred to the intensive care unit (12.8%) and 239 died (11.3%; the mean age of patients who died was 81.2 (± 9.9)). Treatment with hydroxychloroquine plus azithromycin (HCQ-AZ), used in 1270 patients, was an independent protective factor against death (0.68 [0.52 – 0.88]). This effect was consistent for all subgroups of age, comorbidities, severity of the disease and comedications with zinc or corticosteroids. Zinc was independently protective against death (0.39 [0.23 – 0.67]), in a subgroup analysis of patients treated with HCQ-AZ without dexamethasone. The use of high-flow oxygen therapy in elderly patients who were not eligible for intensive care unit transfer saved 19 patients (33.9%).Conclusions: In our 2020 cohort, treating COVID-19 with HCQ-AZ was associated with lower mortality. These results need to be analyzed in the context of academic discussions about observational studies versus randomized clinical trials. More data will deserve to be analyzed in the SARS-Cov 2 variants, vaccination and post-vaccination era.Keywords: SARS-CoV-2, COVID-19, hydroxychloroquine, azithromycin

This study sought to understand how state-level policies inform and promote the implementation of restorative justice in education (RJE). A content analysis of 60 laws revealed that definitions, structures, and supports varied greatly, causing us to question whether policies support a systematic implementation of RJE and how policies can prevent the misuse of RJE as an alternative system of punishment. We recommend that laws clearly define the paradigm shift underlying RJE, and provide sustained support to promote a realignment of policies and practices with attention to incorporating measures of accountability to larger values surrounding equity and justice.

Because the COVID-19 pandemic has been implicated in increased mental health concerns for families of low income, we aimed to describe maternal perspectives about the pandemic's impact on their kindergartener's mental health during the 2020-2021 school year. We conducted 22 in-depth, semi-structured interviews with U.S. mothers with low income who had kindergarten-age children (50% male and 50% female). All participants were female, ranging in age from 24 to 44 years, and reported the following ethnic/racial identities: non-Hispanic Black or African American (41%), Hispanic of any race (36%) and non-Hispanic, White (23%). With a team comprising multiple researchers from varied disciplines (e.g., medicine, education and public health) our analytic process used an iterative approach for developing and revising codes and themes until we reached thematic saturation. Most mothers described negative impacts on social, behavioural and emotional aspects of mental health. Some described positive social impacts, including strengthened family relationships. Mothers described no positive changes to behavioural or emotional aspects of mental health. Maternal perspectives suggest the importance of prioritising access to screening and treating mental health needs to support children's kindergarten transition, mitigate pandemic impacts and plan for future disruptions.

There is a need for increased collaboration between mental health providers who work with children and youth to increase continuity of care across settings. While schools can be an optimal location for mental health support, school psychologists often have to work with clinical providers given the increases in youth mental health needs and the shortage of school-based providers. This study used an online survey with a mixed-methods approach to understand the collaboration practices of school and clinical psychologists. A sample of 57 practitioners in the United States were asked to provide their perceptions of the roles of their interagency providers, their collaboration practices, and the benefits or barriers in the collaboration process. Findings indicated differences in providers' perceptions of the quality of assessments conducted and the importance of particular psychological practices to the roles of clinical and school psychologists. Content analysis of open-ended responses found that while providers acknowledge the benefits of collaboration there was distrust among providers. Implications for training programs and future research directions are discussed.

This article describes the evolution of a required Master of Library and Information Science (MLIS) research methods course moving to a focus on evidence-based library and information practice (EBLIP). It describes how a research methods course was revised, beginning with results from a "typical" course review and morphing into work that is now informing a broader program review. Implications of this work include a reconsideration of how best to provide a quality education while allowing for grace for faculty and students.

The purpose of this paper is to identify key characteristics and forms that both research approaches use within the applied field of education. In this paper, we ask--how are CPAR and IS-GR similar and different? And, can tools or propositions from each be used in tandem within a research project? We invite readers to consider useful frameworks created to address problems of practice. Drawing strength from our diverse backgrounds (fields of study and professional roles), we aim to identify clear overlaps and divergent perspectives between the two approaches to aid scholarly practitioners in making informed decisions about the research frameworks they choose to take up to address pressing problems of practice in education.

The purpose of this article is to examine ways in which the COVID-19 pandemic impacted the adoption and perception of virtual programs in Indiana public school districts. This mixed-methods sequential explanatory study focuses on beliefs held by Indiana public school superintendents and virtual program administrators regarding the growth of virtual education during the COVID-19 pandemic. Subjects received surveys regarding their views surrounding virtual education. Subjects who volunteered participated in semi-structured interviews conducted in web-based meetings. This study provides a snapshot of the state of virtual education in Indiana, including the perceptions held by school administrators at the end of the 2020-21 school year. COVID-19 significantly affected virtual education in Indiana. Participants cited a need to provide educational options during a pandemic as the primary reason for implementing a virtual program. Additionally, participants noted significant challenges of virtual education while acknowledging an overwhelming need to maintain district enrollment during the pandemic through the utilization of a virtual program. This study identifies factors that will impact school districts should enrollment in virtual education programs remain strong. This provides an opportunity for districts to address these areas and ensure effective virtual education programming.

We report a large-scale outbreak of Mycoplasma pneumoniae respiratory infections encompassing 218 cases (0.8% of 26,449 patients tested) during 2023–2024 in Marseille, France. The bacterium is currently circulating and primarily affects children

Various hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated proteins can increase, we studied mouse ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle. ZFAND5s AN1 Zn-finger domain interacts with the Rpt5 ATPase and its C terminus with Rpt1 ATPase and Rpn1, a ubiquitin-binding subunit. Upon proteasome binding, ZFAND5 widens the entrance of the substrate translocation channel, yet it associates only transiently with the proteasome. Dissociation of ZFAND5 then stimulates opening of the 20S proteasome gate. Using single-molecule microscopy, we showed that ZFAND5 binds ubiquitylated substrates, prolongs their association with proteasomes, and increases the likelihood that bound substrates undergo degradation, even though ZFAND5 dissociates before substrate deubiquitylation. These changes in proteasome conformation and reaction cycle can explain the accelerated degradation and suggest how other proteasome activators may stimulate proteolysis.

Abstract Background Hepatitis E is a potentially serious infection in organ recipients, with an estimated two-thirds of cases becoming chronic, and with a subsequent risk of cirrhosis and death. In Europe, transmission occurs most often through the consumption of raw or undercooked pork, more rarely through blood transfusion, but also after solid organ transplantation. Here we describe a case of Hepatitis E virus (HEV) infection transmitted following kidney transplantation and review the literature describing cases of HEV infection transmitted by solid organ transplantation. Case presentation Three weeks after kidney transplantation, the patient presented with an isolated minimal increase in GGT and hepatic cytolysis 6 months later, leading to the diagnosis of genotype 3c hepatitis E, with a plasma viral load of 6.5 log10IU/mL. In retrospect, HEV RNA was detected in the patient's serum from the onset of hepatitis, and in the donor's serum on the day of donation, with 100% identity between the viral sequences, confirming donor-derived HEV infection. Hepatitis E had a chronic course, was treated by ribavirin, and relapsed 10 months after the end of treatment. Discussion Seven cases of transmission of HEV by solid organ transplantation have been described since 2012 without systematic screening for donors, all diagnosed at the chronic infection stage; two patients died. HEV organ donor transmission may be underestimated and there is insufficient focus on immunocompromised patients in whom mild liver function test impairment is potentially related to hepatitis E. However, since HEV infection is potentially severe in these patients, and as evidence accumulates, we believe that systematic screening of organ donors should be implemented for deceased and living donors regardless of liver function abnormalities, as is already the case in the UK and Spain. In January 2024, the French regulatory agency of transplantation has implemented mandatory screening of organ donors for HEV RNA.

Abstract Background Mobile upright PET devices have the potential to enable previously impossible neuroimaging studies. Currently available options are imagers with deep brain coverage that severely limit head/body movements or imagers with upright/motion enabling properties that are limited to only covering the brain surface. Methods In this study, we test the feasibility of an upright, motion-compatible brain imager, our Ambulatory Motion-enabling Positron Emission Tomography (AMPET) helmet prototype, for use as a neuroscience tool by replicating a variant of a published PET/fMRI study of the neurocorrelates of human walking. We validate our AMPET prototype by conducting a walking movement paradigm to determine motion tolerance and assess for appropriate task related activity in motor-related brain regions. Human participants (n = 11 patients) performed a walking-in-place task with simultaneous AMPET imaging, receiving a bolus delivery of F18-Fluorodeoxyglucose. Results Here we validate three pre-determined measure criteria, including brain alignment motion artifact of less than

This study addresses the challenges inherent in preserving archaeological waterlogged wood, which is prone to deformation and decay if not stabilized immediately after recovery. Conventional preservation methods, such as impregnation with polyethylene glycol (PEG) solutions, often result in undesirable dimensional changes. To obtain exact spatio-temporal information on the deformations during the conservation process, a photogrammetric monitoring system, utilizing a stereo camera facing from air into the liquid, attached to an automated biaxial measurement unit is proposed. Special target heads were developed and attached to the wood to provide deformation points. Refraction correction was applied to the imaging model by ray tracing, and indirect flat lighting was used to mitigate turbidity. The system observed logs from a wooden track from the first century, subject to conservation. Subject of investigation were the influence of refraction negligence and scale definition in a bundle geometry, similar to bathymetric aerial setups. Results show that refraction correction is imperative for good results. Furthermore, scale definition with highly accurately determined scale bars and inclusion of relative orientation constraints provide further accuracy improvements.

Abstract Background The aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes. Methods We performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR. We used a composite primary outcome for COVID-19 including increased need for oxygen since the hospital admission, ICU transfer, and in-hospital mortality. We assessed by univariate and multivariate analyses the risk factors for poor outcomes. Results Overall, we included 91 LTx who contracted COVID-19. The COVID-19 in-hospital mortality rate reached 4.4%. By hierarchical clustering, we found a strong and independent association between the composite poor outcome and the discontinuation of at least one immunosuppressive molecule among tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus. Obesity (OR = 16, 95%CI (1.96; 167), p = 0.01) and chronic renal failure (OR = 4.6, 95%CI (1.4; 18), p = 0.01) were also independently associated with the composite poor outcome. Conversely, full vaccination was protective (OR = 0.23, 95%CI (0.046; 0.89), p = 0.047). Conclusion The administration of immunosuppressive drugs such as tacrolimus, cyclocporine or everolimus can have a protective effect in LTx with COVID-19, probably related to their intrinsic antiviral capacity.

Summary: Background: Red blood cell (RBC) transfusions are frequent in patients after cardiac surgery. This study assessed whether a bundle of care including pre-operative and post-operative administration of erythropoietin (EPO) with intravenous iron supplementation, and restrictive transfusion adjusted for ScvO2 could result in reduced postoperative transfusions. Methods: In this single-centre, randomised, open-label, parallel-group controlled pilot study, patients undergoing elective cardiac surgery with high risk of transfusion in a University Hospital were enrolled by the investigator and the randomisation procedure using a central internet-based system was made by the clinical research assistant. Since the trial was open-label, no masking was used. Patients were assigned (1:1) to either the STOP group (40,000 IU subcutaneous EPO combined with 20 mg/kg intravenous ferric carboxymaltose if Hb

CAG trinucleotide repeat expansions cause several neurodegenerative diseases, including Huntington's disease and spinocerebellar ataxia. RNAs with expanded CAG repeats contribute to disease in two unusual ways. First, these repeat-containing RNAs may agglomerate in the nucleus as foci that sequester several RNA-binding proteins. Second, these RNAs may undergo aberrant repeat-associated non-AUG (RAN) translation in multiple frames and produce aggregation-prone proteins. The relationship between RAN translation and RNA foci, and their relative contributions to cellular dysfunction, are unclear. Here, we show that CAG repeat-containing RNAs that undergo RAN translation first accumulate at nuclear foci and, over time, are exported to the cytoplasm. In the cytoplasm, these RNAs are initially dispersed but, upon RAN translation, aggregate with the RAN translation products. These RNA-RAN protein agglomerates sequester various RNA-binding proteins and are associated with the disruption of nucleocytoplasmic transport and cell death. In contrast, RNA accumulation at nuclear foci alone does not produce discernable defects in nucleocytoplasmic transport or cell viability. Inhibition of RAN translation prevents cytoplasmic RNA aggregation and alleviates cell toxicity. Our findings demonstrate that RAN translation-induced RNA-protein aggregation correlates with the key pathological hallmarks observed in disease and suggest that cytoplasmic RNA aggregation may be an underappreciated phenomenon in CAG trinucleotide repeat expansion disorders.

Abstract Background Breastfeeding has long-lasting effects on children’s cognition, behavioral, mental and physical health. Previous research shows parental characteristics (e.g., education, race/ethnicity, income level) are associated with breastfeeding initiation and duration. Further, research shows significant variation in access to community resources by race/ethnicity. It is unclear how community resources may impact breastfeeding practices and how this might intersect with maternal race/ethnicity. Methods This study combined nationally-representative data from the Study of Attitudes and Factors Effecting Infant Care (SAFE), which surveyed US mothers immediately after the infant’s birth and at two to six months of infant age, with the Child Opportunity Index (COI) 2.0, a census tract measure of community resources associated with child development, to explore the association between community resources and breastfeeding initiation and whether this varies based on maternal race/ethnicity and country of birth. The SAFE Study used a stratified, two-stage, clustered design to obtain a nationally representative sample of mothers of infants, while oversampling Hispanic and non-Hispanic (NH) Black mothers. The SAFE study enrolled mothers who spoke English or Spanish across 32 US birth hospitals between January 2011 and March 2014. Results After accounting for individual characteristics, mothers residing in the highest-resourced communities (compared to the lowest) had significantly greater likelihood of breastfeeding. Representation in higher-resourced communities differed by race/ethnicity. Race/ethnicity did not significantly moderate the association between community resources and breastfeeding. In examining within race/ethnic groups, however, community resources were not associated with non-US born Black and Hispanic mothers’ rates of breastfeeding, while they were with US born Black and Hispanic mothers. Conclusions Findings suggest that even health behaviors like breastfeeding, which we often associate with individual choice, are connected to the community resources within which they are made. Study implications point to the importance of considering the impact of the contextual factors that shape health and as a potential contributor to understanding the observed race/ethnicity gap.

Abstract Background Peripheral nerve injuries (PNI) have been associated with prone positioning (PP) in mechanically ventilated (MV) patients with COVID-19 pneumonia. The aims of this retrospective study were to describe PNI prevalence 3 months (M3) after intensive care unit (ICU) discharge, whether patients survived COVID-19 or another critical illness, and to search for risk factors of PNI. Results A total of 55 COVID (62 [54–69] years) and 22 non-COVID (61.5 [48–71.5] years) patients were followed at M3, after an ICU stay of respectively 15 [9–26.5] and 13.5 [10–19.8] days. PNI symptoms were reported by 23/55 (42.6%) COVID-19 and 8/22 (36%) non-COVID-19 patients (p = 0.798). As the incidence of PNI was similar in both groups, the entire population was used to determine risk factors. The MV duration predicted PNI occurrence (OR (CI95%) = 1.05 (1.01–1.10), p = 0.028), but not the ICU length of stay, glucocorticoids, or inflammation biomarkers. Conclusion In the present cohort, PNI symptoms were reported in at least one-third of the ICU survivors, in similar proportion whether patients suffered from severe COVID-19 or not.

The evolution of SARS-CoV-2, the agent of COVID-19, has been remarkable for its high mutation potential, leading to the appearance of variants. Some mutations have never appeared in the published genomes, which represent consensus, or bona fide genomes. Here we tested the hypothesis that mutations that did not appear in consensus genomes were, in fact, as frequent as the mutations that appeared during the various epidemic episodes, but were not expressed because lethal. To identify these mutations, we analysed the genomes of 90 nasopharyngeal samples and the quasispecies determined by next-generation sequencing. Mutations observed in the quasispecies and not in the consensus genomes were considered to be lethal, what we called “outlaw” mutations. Among these mutations, we analysed the 21 most frequent. Eight of these “outlaws” were in the RNA polymerase and we were able to use a structural biology model and molecular dynamics simulations to demonstrate the functional incapacity of these mutated RNA polymerases. Three other mutations affected the spike, a major protein involved in the pathogenesis of COVID-19. Overall, by analysing the SARS-CoV-2 quasispecies obtained during sequencing, this method made it possible to identify “outlaws,” showing areas that could potentially become the target of treatments.

Preeclampsia is a severe complication of pregnancy, affecting an estimated 4 million women annually. It is one of the leading causes of maternal and fetal mortality worldwide, and it has life-long consequences. The maternal multisystemic symptoms are driven by poor placentation, which causes syncytiotrophoblastic stress and the release of factors into the maternal bloodstream. Amongst them, the soluble fms-like tyrosine kinase-1 (sFLT-1) triggers extensive endothelial dysfunction by acting as a decoy receptor for the vascular endothelial growth factor (VEGF) and the placental growth factor (PGF). Current interventions aim to mitigate hypertension and seizures, but the only definite treatment remains induced delivery. Thus, there is a pressing need for novel therapies to remedy this situation. Notably, CBP-4888, a siRNA drug delivered subcutaneously to knock down sFLT1 expression in the placenta, has recently obtained Fast Track approval from the Food and Drug Administration (FDA) and is undergoing a phase 1 clinical trial. Such advance highlights a growing interest and significant potential in gene therapy to manage preeclampsia. This review summarizes the advances and prospects of gene therapy in treating placental dysfunction and illustrates crucial challenges and considerations for these emerging treatments.

The purpose of this study is to examine the impact of professional development in co-teaching on teacher self-efficacy amongst general and special education rural high school teachers. A causal-comparative research design was used to survey 256 rural high school teachers from the South and Midwest regions of the U.S. to measure their self-efficacy in student engagement, instructional practices, and classroom management. One-way analysis and independent samples t-test were used to analyze these data using SPSS statistical software. The results indicated a significant difference between teachers with and without experience in a co-taught classroom regarding their efficacy in using instructional practices. Furthermore, ANOVA results indicated a significant difference in the number of hours of professional development a teacher received in co-teaching as it relates to their efficacy in student engagement, instructional practices, and classroom management. Further discussion and recommendations are also included.