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Abstract Species composition of the healthy adult gut microbiota tends to be stable over time. Destabilization of the gut microbiome under the influence of different factors is the main driver of the microbial dysbiosis and subsequent impacts on host physiology. Here, we used metagenomics data from a Swedish longitudinal cohort, to determine the stability of the gut microbiome and uncovered two distinct microbial species groups; persistent colonizing species (PCS) and transient colonizing species (TCS). We validated the continuation of this grouping, generating gut metagenomics data for additional time points from the same Swedish cohort. We evaluated the existence of PCS/TCS across different geographical regions and observed they are globally conserved features. To characterize PCS/TCS phenotypes, we performed bioreactor fermentation with faecal samples and metabolic modeling. Finally, using chronic disease gut metagenome and other multi-omics data, we identified roles of TCS in microbial dysbiosis and link with abnormal changes to host physiology.

Abstract Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate that STRling and ExpansionHunter accurately detect FGF14 expansions from short-read genome data using outlier approaches. By combining long-range PCR and nanopore sequencing in 169 patients with cerebellar ataxia and 802 controls, we compare FGF14 expansion alleles, including interruptions and flanking regions. Uninterrupted AAG expansions are significantly enriched in patients with ataxia from a lower threshold (180–200 repeats) than previously reported based on expansion size alone. Conversely, AAGGAG hexameric expansions are equally frequent in patients and controls. Distinct 5’ flanking regions, interruptions and pre-repeat sequences correlate with repeat size. Furthermore, pure AAG (pathogenic) and AAGGAG (non-pathogenic) repeats form different secondary structures. Regardless of expansion size, SCA27B is a recognizable clinical entity characterized by frequent episodic ataxia and downbeat nystagmus, similar to the presentation observed in a family with a previously unreported nonsense variant (SCA27A). Overall, this study suggests that SCA27B is a major overlooked cause of adult-onset ataxia, accounting for 23–31% of unsolved patients. We strongly recommend re-evaluating pathogenic thresholds and integrating expansion sequencing into the molecular diagnostic process.

Calcined kaolinitic clays are known to be very reactive pozzolans, and combined with limestone can enable significant clinker substitution in cementitious systems. Thermal activation of kaolinitic clays takes place when the hydroxyl groups are removed, leading to formation of an amorphous reactive structure. There are several technologies for clay activation, but the most used at industrial scale are flash and stationary calcination. The objective of this paper is to investigate the impact of the calcination regime on the properties of the calcined product. It presents the results of an experimental program carried out with a kaolinitic clay calcined at a flash calciner and at a laboratory furnace. Calcination brings about a drop in specific surface, and an increase of average diameter due to agglomeration, an effect more pronounced in stationary calcination. No major differences were found at the heat of hydration, CH consumption and phase assemblage for the fully dehydroxylated material. The flash calcined material had slightly better results mainly due to a finer PSD compared with the one stationary calcined. No major difference was found in water demand and compressive strength for both regimes. As expected, the main impact of the calcination regime is the agglomeration.

Abstract Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.

This study aims to assess the level of sustainability in vegetable-based agrifood production systems in Benin and to propose actions to enhance sustainability, food safety, and year-round production in the vegetable production systems. Semi-structured interviews were conducted with 200 vegetable farmers in contrasting agroecological areas (with areas of extensive production of staples and intensive production of vegetables), using the “Indicateur de Durabilité des Exploitations Agricoles” (IDEA) framework (an on-farm sustainability index). Most of the surveyed vegetable farmers produced a wide range of crops, including leafy vegetables (amaranth, African eggplant, and African basil) and peppers, grown by more than 50% of the farmers. The average scores achieved by the vegetable farms regarding three dimensions of sustainability—ecological, social, and economic—were 35, 41, and 63, respectively, out of a maximum score of 100. All three sustainability dimensions of the vegetable farms were, on average, at a low level and improvements were needed for them to reach an acceptable standard. The vegetable farms located in the south of Benin had, on average, a higher sustainability score than those in the north: around 50% of vegetable farms in the south had a medium score, while the sustainability level of almost 75% of vegetable farms in the north was low. Interventions seeking to improve the sustainability of vegetable farms in Benin should focus on the promotion and adoption of eco-responsible practices that improve on-farm biodiversity, water conservation, and the effective allocation and management of land and labor, to mitigate the environmental impacts of vegetable production.

Abstract Few studies have considered the influence of motor sign asymmetry on motivated behaviors in de novo drug-naïve Parkinson’s disease (PD). We tested whether motor sign asymmetry could be associated with different motivated behavior patterns in de novo drug-naïve PD. We performed a cross-sectional study in 128 de novo drug-naïve PD patients and used the Ardouin Scale of Behavior in Parkinson’s disease (ASBPD) to assess a set of motivated behaviors. We assessed motor asymmetry based on (i) side of motor onset and (ii) MDS-UPDRS motor score, then we compared right hemibody Parkinson’s disease to left hemibody Parkinson’s disease. According to the MDS-UPDRS motor score, patients with de novo right hemibody PD had significantly lower frequency of approach behaviors (p = 0.031), including nocturnal hyperactivity (p = 0.040), eating behavior (p = 0.040), creativity (p = 0.040), and excess of motivation (p = 0.017) than patients with de novo left hemibody PD. Patients with de novo left hemibody PD did not significantly differ from those with de novo right hemibody PD regarding avoidance behaviors including apathy, anxiety and depression. Our findings suggest that motor sign asymmetry may be associated with an imbalance between motivated behaviors in de novo drug-naïve Parkinson’s disease.

Summary: Gender equality has been a crosscutting issue in Horizon 2020 with three objectives: gender balance in decision-making, gender balance and equal opportunities in project teams at all levels, and inclusion of the gender dimension in research and innovation content. Between 2017 and 2022, the EU funded, in collaboration with national agencies, 13 transnational projects under “GENDER-NET Plus” that explored how to best integrate both sex and gender into studies ranging from social sciences, humanities, and health research. As the projects neared completion, forty researchers from these interdisciplinary teams met in November 2022 to share experiences, discuss challenges, and consider the best ways forward to incorporate sex and gender in research. Here, we summarize the reflections from this workshop and provide some recommendations for i) how to plan the studies (e.g., how to define sex and/or gender and their dimensions, rationale for the hypotheses, identification of data that can best answer the research question), ii) how to conduct them (e.g., adjust definitions and dimensions, perform pilot studies to ensure proper use of terminology and revise until consensus is achieved), and iii) how to analyze and report the findings being mindful of any real-world impact.

Abstract Background Crime scene investigation (CSI) in general means the standard procedures and techniques used for processing and reconstructing of scene of crime. In Palestine, the competent authorities delegated by law to carry out the task of research and investigation of crimes and inspection at the crime scene are the officers granted by law the status of the judicial police. CSIs face numerous challenges that affect every worker involved. These challenges arise from legal, administrative, security, and technical aspects. This study aimed to point out the challenges faced by field police personnel during CSI in Palestine. To achieve the aims of this study, a validated and reliable questionnaire was developed. The study sample consisted of 354 crime scene investigators and officers affiliated with the Palestinian Civil Police (PCP) across all governorates of the West Bank. Results In addition to the training of CSI officers, and shortage of equipment, the findings of this study indicate that there are many challenges amplified by the Israeli occupation facing PCP officers concerning crime scene management and technical procedures during CSIs such as the collection, transportation, and storage of forensic evidence. Overlapping responsibilities and difficulties in coordinating specialized agencies working at the crime scene are also factors that should be better studied. Conclusion This study invites decision-makers within the Palestinian police agencies to prioritize efforts to address the significant challenges encountered by workers at crime scenes. They should give special attention on enhancing training programs and providing the necessary tools and devices for effective crime scene work. It also recommends Palestinian representatives at international stage to highlight the obstacles facing workers at crime scenes due to the occupation.

Abstract Background Porcine reproductive and respiratory syndrome (PRRS) is a viral disease with worldwide distribution and an enormous economic impact. To control PRRS virus (PRRSV) infection, modified live vaccines (MLVs) are widely used in the field, mainly administered via an intramuscular (IM) route. Currently, some MLVs are authorized for intradermal (ID) administration, which has many practical and welfare advantages. The objectives of the study were to compare the immune responses (systemic in blood and mucosal in lungs) and vaccine efficacy in preventing challenge strain transmission after IM or needle-free ID immunization of piglets with an MLV against PRRSV-1 (MLV1). Methods Groups of sixteen 5-week-old specific pathogen-free piglets were vaccinated with Porcilis PRRS® (MSD) either by an IM (V+ IM) or ID route (V+ ID) using an IDAL®3G device or kept unvaccinated (V-). Four weeks after vaccination, in each group, 8 out of the 16 piglets were challenged intranasally with a PRRSV-1 field strain, and one day later, the inoculated pigs were mingled by direct contact with the remaining 8 sentinel noninoculated pigs to evaluate PRRSV transmission. Thus, after the challenge, each group (V+ IM, V+ ID or V-) included 8 inoculated and 8 contact piglets. During the postvaccination and postchallenge phases, PRRSV replication (RT–PCR), PRRSV-specific antibodies (ELISA IgG and IgA, virus neutralization tests) and cell-mediated immunity (ELISPOT Interferon gamma) were monitored in blood and bronchoalveolar lavages (BALs). Results Postvaccination, vaccine viremia was lower in V+ ID pigs than in V+ IM pigs, whereas the cell-mediated immune response was detected earlier in the V+ ID group at 2 weeks postvaccination. In the BAL fluid, a very low mucosal immune response (humoral and cellular) was detected. Postchallenge, the vaccine efficacy was similar in inoculated animals with partial control of PRRSV viremia in V+ ID and V+ IM animals. In vaccinated sentinel pigs, vaccination drastically reduced PRRSV transmission with similar estimated transmission rates and latency durations for the V+ IM and V+ ID groups. Conclusions Our results show that the tested MLV1 induced a faster cell-mediated immune response after ID immunization two weeks after vaccination but was equally efficacious after IM or ID immunization towards a challenge four weeks later. Considering the practical and welfare benefits of ID vaccination, these data further support the use of this route for PRRS MLVs.

Ce doped Lu3Al5O12 (Ce:LuAG) transparent ceramics are considered as promising color converters for solid-state lighting because of their excellent luminous efficiency, high thermal quenching temperature, and good thermal stability. However, Ce:LuAG ceramics mainly emit green light. The shortage of red light as well as the expensive price of Lu compounds are hindering their application for white lighting. In this work, transparent (Lu,Gd)3Al5O12–Al2O3 (LuGAG–Al2O3) nanoceramics with different replacing contents of Gd3+ (10%–50%) were successfully elaborated via a glass-crystallization method. The obtained ceramics with full nanoscale grains are composed of the main LuGAG crystalline phase and secondary Al2O3 phase, exhibiting eminent transparency of 81.0%@780 nm. After doping by Ce3+, the Ce:LuGAG–Al2O3 nanoceramics show a significant red shift (510 nm→550 nm) and make up for the deficiency of red light component in the emission spectrum. The Ce:LuAG–Al2O3 nanoceramics with 20% Gd3+ show high internal quantum efficiency (81.5% in internal quantum efficiency (IQE), 96.7% of Ce:LuAG–Al2O3 nanoceramics) and good thermal stability (only 9% loss in IQE at 150 ℃). When combined with blue LED chips (10 W), 0.3%Ce:LuGAG–Al2O3 nanoceramics with 20% Gd3+ successfully realize the high-quality warm white LED lighting with a color coordinate of (0.3566, 0.435), a color temperature of 4347 K, CRI of 67.7, and a luminous efficiency of 175.8 lm·W−1. When the transparent 0.3%Ce:LuGAG–Al2O3 nanoceramics are excited by blue laser (5 W·mm−2), the emission peak position redshifts from 517 to 570 nm, the emitted light exhibits a continuous change from green light to yellow light, and then to orange-yellow light, and the maximum luminous efficiency is up to 234.49 lm·W−1 (20% Gd3+). Taking into account the high quantum efficiency, good thermal stability, and excellent and adjustable luminous properties, the transparent Ce:LuGAG–Al2O3 nanoceramics with different Gd3+ substitution contents in this paper are believed to be promising candidates for high-power white LED/LD lighting.

To achieve its energy transition, the French government is planning to install floating wind farms in the Mediterranean Sea in the Gulf of Lion. In order to study the effects of such installations on the ecosystem, A trophic model was developed to study the evolution of biomass and ecological network indicators (ENA). Four scenarios were designed in order to simulate 1/the “reef effect” caused by the new hard substrate created by the wind farm structure, 2/the association of the reef effect with the reserve effect caused by the closure of the wind farm to fishing, 3/the impact of regular harvesting of sessile organisms from the hard substrate by fishermen and, 4/the impact of the transfer of these organisms to the seafloor. Our study suggests changes in the ecosystem structure and functioning after the introduction of a wind farm, where low trophic level groups became more important in the functioning of the trophic web, the ecosystem maturity decreased, and the overall activity and diversity increased. The biomass of some pelagic and demersal groups increased. Overall, the introduction of large wind farm platforms will transform the local ecosystem, enhancing the overall production which will likely provide benefits to local fisheries focused on higher trophic level groups.

Background A risk model has been proposed to provide a patient individualized estimation of risk for major clinical events (heart failure events, ventricular arrhythmia, all‐cause mortality) in patients with transposition of the great arteries and atrial switch surgery. We aimed to externally validate the model. Methods and Results A retrospective, multicentric, longitudinal cohort of 417 patients with transposition of the great arteries (median age, 24 years at baseline [interquartile range, 18–30]; 63% men) independent of the model development and internal validation cohort was studied. The performance of the prediction model in predicting risk at 5 years was assessed, and additional predictors of major clinical events were evaluated separately in our cohort. Twenty‐five patients (5.9%) met the major clinical events end point within 5 years. Model validation showed good discrimination between high and low 5‐year risk patients (Harrell C index of 0.73 [95% CI, 0.65–0.81]) but tended to overestimate this risk (calibration slope of 0.20 [95% CI, 0.03–0.36]). In our population, the strongest independent predictors of major clinical events were a history of heart failure and at least mild impairment of the subpulmonary left ventricle function. Conclusions We reported the first external validation of a major clinical events risk model in a large cohort of adults with transposition of the great arteries. The model allows for distinguishing patients at low risk from those at intermediate to high risk. Previous episode of heart failure and subpulmonary left ventricle dysfunction appear to be key markers in the prognosis of patients. Further optimizing risk models are needed to individualize risk predictions in patients with transposition of the great arteries.

Objectif : Cet article a pour objectif d’appréhender la perception que les parties prenantes ont de la politique d’offre des microcrédits des Institutions de Microfinance (IMF) dans un pays en développement en contexte post covid. Méthodologie : Les données de l’étude empirique sont collectées grâce aux entretiens semi-directifs réalisés avec deux catégories de parties prenantes des IMF, à savoir les clients et les dirigeants. Les entretiens qui ont lieu entre les mois de Novembre 2022 et Mars 2023, se déroulent dans les villes de Yaoundé et Douala au Cameroun. Résultats : L’analyse de contenu des discours révèle que, la pertinence des problèmes posés par la clientèle, est déconstruite par les dirigeants des IMF. L’étude suppose que cette déconstruction, appréhendée comme une forme voilée de résistance au changement, constitue un frein majeur à la réalisation de la mission sociale originelle des IMF dans l’aire d’expérimentation de l’étude. Originalité : L’essentiel des travaux sur les IMF en contexte africain et au Cameroun en particulier traite de la performance sociale sans réellement prendre en compte la perception des parties prenantes. L’originalité dans cette recherche vient de ce que, nous avons adopté une approche inductive pour appréhender la perception des parties prenantes des IMF en termes de portée sociale.

Abstract This case illustrates chest scars after piston-based chest compression device resuscitation and raises the awareness of the potential benefits of following up survivors of critical illness.

Abstract With climate projections questioning the future survival of stony corals and their dominance as tropical reef builders, it is critical to understand the adaptive capacity of corals to ongoing climate change. Biological mediation of the carbonate chemistry of the coral calcifying fluid is a fundamental component for assessing the response of corals to global threats. The Tara Pacific expedition (2016–2018) provided an opportunity to investigate calcification patterns in extant corals throughout the Pacific Ocean. Cores from colonies of the massive Porites and Diploastrea genera were collected from different environments to assess calcification parameters of long-lived reef-building corals. At the basin scale of the Pacific Ocean, we show that both genera systematically up-regulate their calcifying fluid pH and dissolved inorganic carbon to achieve efficient skeletal precipitation. However, while Porites corals increase the aragonite saturation state of the calcifying fluid (Ωcf) at higher temperatures to enhance their calcification capacity, Diploastrea show a steady homeostatic Ωcf across the Pacific temperature gradient. Thus, the extent to which Diploastrea responds to ocean warming and/or acidification is unclear, and it deserves further attention whether this is beneficial or detrimental to future survival of this coral genus.

Abstract Background COVID-19-associated acute respiratory distress syndrome (ARDS) supported by veno-venous extra-corporal membrane oxygenation (vv-ECMO) results in a high in-hospital mortality rate of more than 35%. However, after cannulation, no prognostic factor has been described to guide the management of these patients. The objective was to assess the association between static respiratory compliance over the first 10 days post-vv-ECMO implantation on 180-day mortality. Results In this multicentric retrospective study in three ECMO referral centers, all patients with COVID-19-associated ARDS supported by vv-ECMO were included from 03/01/2020 to 12/31/2021. Patients were ventilated with ultra-protective settings targeting a driving pressure lower than 15 cmH2O. 122 patients were included. Median age was 59 IQR (52–64), 83 (68%) were male, with a median body mass index of 33 (28–37) kg/m2. Delay between first symptoms to vv-ECMO implantation was 16 (10–21) days. Six-month death was 48%. Over the first ten days, compliance increased in 180 day survivors [from 18 (12–25) to 20 (15–27) mL/cmH2O] compared to non-survivors [from 12 (9–20) to 10 (8–14) mL/cmH2O, p interaction

Abstract Background In prior research, we identified and prioritized ten measures to assess research performance that comply with the San Francisco Declaration on Research Assessment, a principle adopted worldwide that discourages metrics-based assessment. Given the shift away from assessment based on Journal Impact Factor, we explored potential barriers to implementing and adopting the prioritized measures. Methods We identified administrators and researchers across six research institutes, conducted telephone interviews with consenting participants, and used qualitative description and inductive content analysis to derive themes. Results We interviewed 18 participants: 6 administrators (research institute business managers and directors) and 12 researchers (7 on appointment committees) who varied by career stage (2 early, 5 mid, 5 late). Participants appreciated that the measures were similar to those currently in use, comprehensive, relevant across disciplines, and generated using a rigorous process. They also said the reporting template was easy to understand and use. In contrast, a few administrators thought the measures were not relevant across disciplines. A few participants said it would be time-consuming and difficult to prepare narratives when reporting the measures, and several thought that it would be difficult to objectively evaluate researchers from a different discipline without considerable effort to read their work. Strategies viewed as necessary to overcome barriers and support implementation of the measures included high-level endorsement of the measures, an official launch accompanied by a multi-pronged communication strategy, training for both researchers and evaluators, administrative support or automated reporting for researchers, guidance for evaluators, and sharing of approaches across research institutes. Conclusions While participants identified many strengths of the measures, they also identified a few limitations and offered corresponding strategies to address the barriers that we will apply at our organization. Ongoing work is needed to develop a framework to help evaluators translate the measures into an overall assessment. Given little prior research that identified research assessment measures and strategies to support adoption of those measures, this research may be of interest to other organizations that assess the quality and impact of research.

Introduction Human albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites.Methods and analysis ALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis.Ethics and dissemination The trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion.Trial registration number NCT05056220 EU CT: 2022-501006-34-01

Onions (Allium cepa L.) are the second most commonly produced and consumed vegetable worldwide due to their economic, nutritional, and medicinal benefits. However, drought hinders vegetative growth, lowers yields and bulb quality, reduces photosynthetic activity, and alters the onion plant’s metabolism. This review provides a summary of global research on the impact of drought on onions. It specifically seeks to shed light on aspects that remain unclear and generate research avenues. Relevant scientific articles were sourced from the AGORA database, Web of Science (WoS), and search engines such as Google Scholar, Scopus, MEDLINE/PubMed, and SCImago to achieve this objective. A total of 117 scientific articles and documents related to onion and drought were critically examined. The review revealed agromorphological, physiological, biochemical, and genomic studies depicting factors that contribute to drought tolerance in onion genotypes. However, there was little research on the physiological, biochemical, and genetic characteristics of drought tolerance in onions, which need to be deepened to establish its adaptation mechanisms. Understanding the mechanisms of onion response to water stress will contribute to fast-tracking the development of drought-tolerant genotypes and optimize onion production. Future research should be more focused on investigating onion drought tolerance mechanisms and structural and functional genomics and identifying genes responsible for onion drought tolerance.

Summary: Background: SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10–60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability. Methods: We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor. Findings: A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p

Category: Bunion; Other Introduction/Purpose: Hallux Valgus correction with Minimally Invasive Surgery (MIS) is a popular procedure due to its potential advantages such as shorter operative time and quicker recovery than open surgery. Third-generation Minimally Invasive Chevron Akin (MICA) osteotomy has shown excellent clinical and radiological outcomes. The optimal fixation criteria are 3-point fixation (medial cortex, lateral cortex, and the lateral half of the 1st metatarsal head) for the proximal screws and 2-point fixation (medial cortex and central position in the 1st metatarsal head) for the distal one. To address the steep learning curve of the free hand technique, we describe a new guided trajectory system for third-generation MICA to increase precision and reduce the risk of suboptimal K-wire or screw placement. Early radiological outcomes and complications were reported. Methods: From April 2022 to January 2023, 13 consecutive MICAs were performed on 11 female patients (bilateral in 2 patients) with an average age of 61 by a single fellowship-trained foot and ankle orthopaedic surgeon who developed the device. These were the 13 first cases performed with the new device. Preoperative and postoperative intermetatarsal angle (IMA), hallux valgus angle (HVA), distal metatarsal articular angle (DMAA) and tibial sesamoid position (TSP) were measured in all patients using weight-bearing radiographs. Also evaluated in the postoperative radiographs were the number of cortical purchase of the screws and their position in the metatarsal head. Additionally, any difficulties or intraoperative complications and operative time were reported. All parameters were analysed with the one-tailed non-parametric Wilcoxon test. Results: All the radiographic parameters improved significantly. The median IMA improved from 14.5 degrees (interquartile range [IQR]: 11.5-16) to 5 degrees (IQR: 4.0-6.0) (p < 0.005). The median HVA also decreased from 27.5 degrees (IQR: 25.3-34.5) to 7.0 degrees (IQR: 4.0-8.5) (p < 0.005). The median DMAA fell from 15.5 degrees (IQR: 13.3-19.3) to 6.0 degrees (IQR: 6.0-8.0) (p < 0.005). The median TSP was 2 (IQR: 2-3) pre-operatively and 0 (IQR : 0-1) (p < 0.005) post-operatively. All the proximal screws for Chevron osteotomy had 3-point fixation and the distal anti-rotation screws had 2-point fixation No intraoperative complications were reported. The mean operative time was 52 (SD:10,4) minutes. Conclusion: Our study demonstrates the successful use of a guided trajectory system for minimally invasive bunion correction with optimal screw placement, good early radiological outcomes, and without extensive operating time. The absence of intraoperative complications or difficulties further confirms the efficacy of this system. Our findings suggest that the use of a guided trajectory system can potentially improve the consistency and success of third-generation MICA procedures. These results emphasize the benefits of incorporating guided trajectory systems in bunion correction surgeries and their potential to improve patient outcomes.

Category: Bunion; Other Introduction/Purpose: The Lapidus procedure (first tarsometatarsal joint (TMT1) fusion) is an established treatment for correcting hallux valgus with 1st ray hypermobility. The original Lapidus (OL) technique involves fusing the TMT1 joint and first metatarsal base to the second, while the modified Lapidus (ML) technique involves fusing only the TMT1 joint. The purpose of this study was to investigate whether the ML procedure results in an early loss of correction. Methods: This retrospective study analyzed the outcomes of 45 feet in 40 patients with hallux valgus who underwent either the ML (21 feet) or OL (24 feet) procedure between 2014 and 2022 at a single center. All fixations were performed with 3.5 cortical screws, except for 9 cases that were fixed with a plantar locking plate. Differences in the immediate postoperative (6 weeks) and postoperative (6 months) intermetatarsal angle (IMA) and hallux valgus angle (HVA) were analyzed using Mann-Whitney tests, and complications were reported. Results: The mean preoperative IMA and HVA for the OL were 15.8° ± 3.5° and 36.4° ± 9.5°, respectively, and 14.5° ± 2.3° and 33.0° ± 7.0° for the ML. The immediate postoperative IMA and HVA were similar for both procedures (7.2° ± 2.0° and 7.7° ± 4.3° for OL, 7.3° ± 2.1° and 8.5° ± 5.5° for ML). Although from 6 weeks to 6 months postoperatively, the loss of correction of the HVA did not differ between both procedures (4.2° for OL, 5,6° for ML), the IMA loss of correction was significantly higher in the ML (1.1° ± 1.4° vs 0.5° ± 1.1°) (p < 0.05). One case of delayed union was reported in the OL group, but it did not require revision. Conclusion: The study results suggest that the ML procedure does not provide the same stability as the OL procedure in the early postoperative period, as there was a significantly greater early loss of correction of the IMA at 6 months postoperatively in the ML group compared to the OL group. Although there were no differences in the loss of correction of the HVA angle (HVA), an observed loss of 5 degrees remains a concern. Further studies are necessary to better understand the indications of the modified and original procedures.

Abstract Sequencing of B-cell and T-cell immune receptor repertoires helps us to understand the adaptive immune response, although it only provides information about the clonotypes (lineages) and their frequencies and not about, for example, their affinity or antigen (Ag) specificity. To further characterize the identified clones, usually with special attention to the particularly abundant ones (dominant), additional time-consuming or expensive experiments are generally required. Here, we present an extension of a multiscale model of the germinal center (GC) that we previously developed to gain more insight in B-cell repertoires. We compare the extent that these simulated repertoires deviate from experimental repertoires established from single GCs, blood, or tissue. Our simulations show that there is a limited correlation between clonal abundance and affinity and that there is large affinity variability among same-ancestor (same-clone) subclones. Our simulations suggest that low-abundance clones and subclones, might also be of interest since they may have high affinity for the Ag. We show that the fraction of plasma cells (PCs) with high B-cell receptor (BcR) mRNA content in the GC does not significantly affect the number of dominant clones derived from single GCs by sequencing BcR mRNAs. Results from these simulations guide data interpretation and the design of follow-up experiments.

Abstract Background In France, physician-assisted suicide or euthanasia are not legal but are still debated. French intensive care unit (ICU) health care workers (HCWs) have an insider’s perspective on the global quality of the patient’s end-of-life, whether it occurs in ICU or not. However, their opinion about euthanasia/physician-assisted suicide remains unknown. The aim of this study is to investigate the opinion of French ICU HCWs about physician-assisted suicide/euthanasia. Results A total of 1149 ICU HCWs participated to a self-administered anonymous questionnaire: 411 (35.8%) physicians and 738 (64.2%) non-physicians. Among them, 76.5% indicated they were in favor of legalizing euthanasia/physician-assisted suicide. Non-physicians HCWs were significantly more in favor of the legalization of euthanasia/physician assisted suicide than physicians (87% vs 57.8% p

In the context of climate change and the reduction of mineral nitrogen (N) inputs applied to the field, winter oilseed rape (WOSR) will have to cope with low-N conditions combined with water limitation periods. Since these stresses can significantly reduce seed yield and seed quality, maintaining WOSR productivity under a wide range of growth conditions represents a major goal for crop improvement. N metabolism plays a pivotal role during the metabolic acclimation to drought in Brassica species by supporting the accumulation of osmoprotective compounds and the source-to-sink remobilization of nutrients. Thus, N deficiency could have detrimental effects on the acclimation of WOSR to drought. Here, we took advantage of a previously established experiment to evaluate the metabolic acclimation of WOSR during 14 days of drought, followed by 8 days of rehydration under high- or low-N fertilization regimes. For this purpose, we selected three leaf ranks exhibiting contrasted sink/source status to perform absolute quantification of plant central metabolites. Besides the well-described accumulation of proline, we observed contrasted accumulations of some “respiratory” amino acids (branched-chain amino acids, lysineand tyrosine) in response to drought under high- and low-N conditions. Drought also induced an increase in sucrose content in sink leaves combined with a decrease in source leaves. N deficiency strongly decreased the levels of major amino acids and subsequently the metabolic response to drought. The drought-rehydration sequence identified proline, phenylalanine, and tryptophan as valuable metabolic indicators of WOSR water status for sink leaves. The results were discussed with respect to the metabolic origin of sucrose and some amino acids in sink leaves and the impact of drought on source-to-sink remobilization processes depending on N nutrition status. Overall, this study identified major metabolic signatures reflecting a similar response of oilseed rape to drought under low- and high-N conditions.

Modeling of infectious diseases at the livestock-wildlife interface is a unique subset of mathematical modeling with many innate challenges. To ascertain the characteristics of the models used in these scenarios, a scoping review of the scientific literature was conducted. Fifty-six studies qualified for inclusion. Only 14 diseases at this interface have benefited from the utility of mathematical modeling, despite a far greater number of shared diseases. The most represented species combinations were cattle and badgers (for bovine tuberculosis, 14), and pigs and wild boar [for African (8) and classical (3) swine fever, and foot-and-mouth and disease (1)]. Assessing control strategies was the overwhelming primary research objective (27), with most studies examining control strategies applied to wildlife hosts and the effect on domestic hosts (10) or both wild and domestic hosts (5). In spatially-explicit models, while livestock species can often be represented through explicit and identifiable location data (such as farm, herd, or pasture locations), wildlife locations are often inferred using habitat suitability as a proxy. Though there are innate assumptions that may not be fully accurate when using habitat suitability to represent wildlife presence, especially for wildlife the parsimony principle plays a large role in modeling diseases at this interface, where parameters are difficult to document or require a high level of data for inference. Explaining observed transmission dynamics was another common model objective, though the relative contribution of involved species to epizootic propagation was only ascertained in a few models. More direct evidence of disease spill-over, as can be obtained through genomic approaches based on pathogen sequences, could be a useful complement to further inform such modeling. As computational and programmatic capabilities advance, the resolution of the models and data used in these models will likely be able to increase as well, with a potential goal being the linking of modern complex ecological models with the depth of dynamics responsible for pathogen transmission. Controlling diseases at this interface is a critical step toward improving both livestock and wildlife health, and mechanistic models are becoming increasingly used to explore the strategies needed to confront these diseases.

Summary: Background: To resist the autoimmune attack characteristic of type 1 diabetes, insulin producing pancreatic β cells need to evade T-cell recognition. Such escape mechanisms may be conferred by low HLA class I (HLA-I) expression and upregulation of immune inhibitory molecules such as Programmed cell Death Ligand 1 (PD-L1). Methods: The expression of PD-L1, HLA-I and CXCL10 was evaluated in the human β cell line, ECN90, and in primary human and mouse pancreatic islets. Most genes were determined by real-time RT-PCR, flow cytometry and Western blot. Activator and inhibitor of the AKT signaling were used to modulate PD-L1 induction. Key results were validated by monitoring activity of CD8+ Jurkat T cells presenting β cell specific T-cell receptor and transduced with reporter genes in contact culture with the human β cell line, ECN90. Findings: In this study, we identify tryptophan (TRP) as an agonist of PD-L1 induction through the AKT signaling pathway. TRP also synergistically enhanced PD-L1 expression on β cells exposed to interferon-γ. Conversely, interferon-γ-mediated induction of HLA-I and CXCL10 genes was down-regulated upon TRP treatment. Finally, TRP and its derivatives inhibited the activation of islet-reactive CD8+ T cells by β cells. Interpretation: Collectively, our findings indicate that TRP could induce immune tolerance to β cells by promoting their immune evasion through HLA-I downregulation and PD-L1 upregulation. Funding: Dutch Diabetes Research Foundation, DON Foundation, the Laboratoire d’Excellence consortium Revive (ANR-10-LABX-0073), Agence Nationale de la Recherche (ANR-19-CE15-0014-01), Fondation pour la Recherche Médicale (EQ U201903007793–EQU20193007831), Innovative Medicines Initiative INNODIA and INNODIA HARVEST, Aides aux Jeunes Diabetiques (AJD) and Juvenile Diabetes Research Foundation Ltd (JDRF).

Transparent Ce:lutetium aluminum garnet (Ce:Lu3Al5O12, Ce:LuAG) ceramics have been regarded as potential scintillator materials due to their relatively high density and atomic number (Zeff). However, the current Ce:LuAG ceramics exhibit a light yield much lower than the expected theoretical value due to the inevitable presence of LuAl antisite defects at high sintering temperatures. This work demonstrates a low-temperature (1100 ℃) synthetic strategy for elaborating transparent LuAG–Al2O3 nanoceramics through the crystallization of 72 mol% Al2O3–28 mol% Lu2O3 (ALu28) bulk glass. The biphasic nanostructure composed of LuAG and Al2O3 nanocrystals makes up the whole ceramic materials. Most of Al2O3 is distributed among LuAG grains, and the rest is present inside the LuAG grains. Fully dense biphasic LuAG–Al2O3 nanoceramics are highly transparent from the visible region to mid-infrared (MIR) region, and particularly the transmittance reaches 82% at 780 nm. Moreover, LuAl antisite defect-related centers are completely undetectable in X-ray excited luminescence (XEL) spectra of Ce:LuAG–Al2O3 nanoceramics with 0.3–1.0 at% Ce. The light yield of 0.3 at% Ce:LuAG–Al2O3 nanoceramics is estimated to be 20,000 ph/MeV with short 1 μs shaping time, which is far superior to that of commercial Bi4Ge3O12 (BGO) single crystals. These results show that a low-temperature glass crystallization route provides an alternative approach for eliminating the antisite defects in LuAG-based ceramics, and is promising to produce garnet-based ceramic materials with excellent properties, thereby meeting the demands of advanced scintillation applications.

Abstract Background Genome-wide association studies have identified ATP2B4 as a severe malaria resistance gene. Recently, 8 potential causal regulatory variants have been shown to be associated with severe malaria. Methods Genotyping of rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452 was performed in 154 unrelated individuals (79 controls and 75 mild malaria patients). rs10751450, rs10751451 and rs10751452 were genotyped by Taqman assays, whereas the fragment of the ATP2B4 gene containing the remaining SNPs was sequenced. Logistic regression analysis was used to assess the association between the SNPs and mild malaria. Results The results showed that mild malaria was associated with rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452. The homozygous genotypes for the major alleles were associated with an increased risk of mild malaria. Furthermore, the haplotype containing the major alleles and that containing the minor alleles were the most frequent haplotypes. Individuals with the major haplotypes had a significantly higher risk of mild malaria compared to the carriers of the minor allele haplotype. Conclusions ATP2B4 polymorphisms that have been associated with severe malaria are also associated with mild malaria.

Abstract Background An external control arm is a cohort of control patients that are collected from data external to a single-arm trial. To provide an unbiased estimation of efficacy, the clinical profiles of patients from single and external arms should be aligned, typically using propensity score approaches. There are alternative approaches to infer efficacy based on comparisons between outcomes of single-arm patients and machine-learning predictions of control patient outcomes. These methods include G-computation and Doubly Debiased Machine Learning (DDML) and their evaluation for External Control Arms (ECA) analysis is insufficient. Methods We consider both numerical simulations and a trial replication procedure to evaluate the different statistical approaches: propensity score matching, Inverse Probability of Treatment Weighting (IPTW), G-computation, and DDML. The replication study relies on five type 2 diabetes randomized clinical trials granted by the Yale University Open Data Access (YODA) project. From the pool of five trials, observational experiments are artificially built by replacing a control arm from one trial by an arm originating from another trial and containing similarly-treated patients. Results Among the different statistical approaches, numerical simulations show that DDML has the smallest bias followed by G-computation. In terms of mean squared error, G-computation usually minimizes mean squared error. Compared to other methods, DDML has varying Mean Squared Error performances that improves with increasing sample sizes. For hypothesis testing, all methods control type I error and DDML is the most conservative. G-computation is the best method in terms of statistical power, and DDML has comparable power at $$n=1000$$ n = 1000 but inferior ones for smaller sample sizes. The replication procedure also indicates that G-computation minimizes mean squared error whereas DDML has intermediate performances in between G-computation and propensity score approaches. The confidence intervals of G-computation are the narrowest whereas confidence intervals obtained with DDML are the widest for small sample sizes, which confirms its conservative nature. Conclusions For external control arm analyses, methods based on outcome prediction models can reduce estimation error and increase statistical power compared to propensity score approaches.

Measurement(s) mock community • Metagenomic profiling Technology Type(s) Illumina HiSeq 3000 • ThermoFisher Ion Proton and GeneStudio S5 • MGI DNBseq G400 and T7 • Oxford Nanopore Sequencing • PacBio Sequel System • Genome mapping and assembly Sample Characteristic - Organism Synthetic microbial communities • Bacteria • Archaea

In this interview, Hervé Mazurel looks back on his career, between philosophy and history, which has led him to take an interest in the history of the body, the senses and sensibilities. In light of the “cultural and historical diversity of the ways of feeling and sensing”, he proposes a long-term reflection on the place of touch within the sensory order.

Abstract Introduction Paediatric patients with disorders that involve brain functioning are particularly vulnerable with respect to including them in shared decision‐making. Current tools are mostly paper or digital patient information. We lay the groundwork for improving engagement with a concept that we coined ‘the Self‐Portrait’. The main goals were to identify (1) obstacles and (2) design parameters that enable patient participation. Methods A research‐through‐design approach was utilized in nine patients with brain‐related disorders (4–12 years), 15 parents and 15 medical professionals, involving contextual research (interviews and observations) within the paediatric hospital and patients' homes and codesign. Sensitizing materials and early instances of design solutions were deployed as catalysts for communication. Five rounds of enriched interviews and design reviews were thematically analysed to answer the research questions. Results Obstacles to child involvement were related to children's level of understanding, the time and energy necessary for information processing and lack of perceived relevance of the information. Patients' engagement is supported by design features that extend the time frame of interaction beyond the consultation, transfer information interactively and give control and influence during the consultation. Conclusion Obstacles were detected that complicate child engagement, which differ between stakeholders. Promising design features were identified that have the potential to play an important role in enabling active child involvement. These findings show that applying principles of human‐centred design research and codesign can bring together patients, parents and medical professionals around a tool that provides a shared language and focus, which are prerequisites to increase child engagement. Patient or Public Contribution Patients, parents and clinicians contributed as design informants during contextual research and design reviews. Clinicians provided feedback on the initial outcomes of thematic analysis. Two researchers assisted in consensus sessions during the thematic analysis.

Deposition of Siberian wildfire aerosols, which contained nitrogen, enhanced phytoplankton growth in the eastern Eurasian Basin of the Arctic Ocean in summer 2014, suggest satellite-based ocean color data and atmospheric transport modeling.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infected patients mainly displays pulmonary and oronasal tropism; however, the presence of the virus has also been demonstrated in the stools of patients and consequently in wastewater treatment plant effluents, raising the question of the potential risk of environmental contamination (such as seawater contamination) through inadequately treated wastewater spillover into surface or coastal waters even if the environmental detection of viral RNA alone does not substantiate risk of infection. Therefore, here, we decided to experimentally evaluate the persistence of the porcine epidemic diarrhea virus (PEDv), considered as a coronavirus representative model, in the coastal environment of France. Coastal seawater was collected, sterile-filtered, and inoculated with PEDv before incubation for 0 to 4 weeks at four temperatures representative of those measured along the French coasts throughout the year (4, 8, 15, and 24°C). The decay rate of PEDv was determined using mathematical modeling and was used to determine the half-life of the virus along the French coast in accordance with temperatures from 2000 to 2021. We experimentally observed an inverse correlation between seawater temperature and the persistence of infectious viruses in seawater and confirm that the risk of transmission of infectious viruses from contaminated stool in wastewater to seawater during recreational practices is very limited. The present work represents a good model to assess the persistence of coronaviruses in coastal environments and contributes to risk evaluation, not only for SARS-CoV-2 persistence, but also for other coronaviruses, specifically enteric coronaviruses from livestock. IMPORTANCE The present work addresses the question of the persistence of coronavirus in marine environments because SARS-CoV-2 is regularly detected in wastewater treatment plants, and the coastal environment, subjected to increasing anthropogenic pressure and the final receiver of surface waters and sometimes insufficiently depurated wastewater, is particularly at risk. The problem also arises in the possibility of soil contamination by CoV from animals, especially livestock, during manure application, where, by soil impregnation and runoff, these viruses can end up in seawater. Our findings are of interest to researchers and authorities seeking to monitor coronaviruses in the environment, either in tourist areas or in regions of the world where centralized systems for wastewater treatment are not implemented, and more broadly, to the scientific community involved in “One Health” approaches.

Inspections of 48 photovoltaic (PV) modules within a 302.4 kWp solar array were undertaken to expose the presence of defects after 12 years of operation under the harsh environmental conditions of Djibouti. To this end, a multiple-technique testing protocol was conducted including visual inspection (VI), infrared thermography (IR), current-voltage curve characterization (I-V), ultraviolet fluorescence (UVFL) and electroluminescence imaging (EL). The main visible degradation features observed were discoloration, bubbling and snail trails with occurrences of 100%, 93.7% and 2.1% respectively. According to the IR imaging results, hotspots were observed on cells affected by snail trails. IR was combined with convolutional neural network (CNN) techniques to automatically detect the different classes of failures that PV modules may experience. EL imaging reveals that the cracks of the cells underlie the observed snail trails during visual inspection and UVFL imaging. In addition, a decrease in STC power was observed after 12 yr of operation with a median reaching 5.5% corresponding to an average degradation rate of 0.46%/years. Conclusively, fault diagnosis with combined approaches of imaging and electrical techniques is crucial to prevent defects and minimize the investment losses; this will ensure uninterrupted power generation, extended service life and high safety of photovoltaic modules.

Abstract Observations suggest that the tropical Pacific Ocean has lost oxygen since the 1960s leading to the expansion of its oxygen minimum zone (OMZ). Attribution to anthropogenic forcing is, however, difficult because of limited data availability and the large natural variability introduced by the Pacific Decadal Oscillation (PDO). Here, we evaluate the PDO influence on oxygen dynamics and OMZ extent using observations and hindcast simulations from two global ocean circulation models (NEMO‐PISCES, MOM6‐COBALT). In both models, the tropical Pacific oxygen content decreases by about 30 Tmol.decade−1 and the OMZ volume expands by 1.3 × 105 km3.decade−1 during PDO positive phases, while variations of similar magnitude but opposite sign are simulated during negative phases. Changes in equatorial advective oxygen supply, partially offset by biological demand, control the oxygen response to PDO. Observations which cover 39% of the tropical Pacific volume only partially capture spatio‐temporal variability, hindering the separation of anthropogenic trend from natural variations.

Abstract Background The reduction of maternal mortality in developing countries such as the Democratic Republic of Congo (DRC) still raises many questions. Indeed, this large country in the heart of Africa ranks 4th among the eight countries that alone account for more than 50% of maternal deaths in the world, behind India, Nigeria and Pakistan. However, there is no up-to-date data on maternal mortality in eastern DRC. This study measures the mortality rate rate in health facilities in eastern DRC and identifies the associated risk factors. Methods This analytical epidemiological study was based on retrospective data materna deaths recorded in 59 health facilities, in three health zones in the southern part of Maniema province in east DRC. The study was conducted from July 1, 2015 to June 30, 2020. Descriptive, bi and multivariate analyses were used. Results The maternal mortality rate was estimated at 620 deaths per 100,000 live births, of which 46% of maternal deaths were related to a parturients’ delayed decision in seeking healthcare in time (first delay). Maternal deaths were significantly associated with extreme ages (≤ 19 years and ≥ 40 years: p =

Abstract Background The increasing temperatures due to climate change around the world poses a serious threat to sustainable crop production. The growing adverse effects of heat stress are putting global food security at great risk. Crop improvement for adaptation to increased temperatures is therefore of paramount importance. This study aims at assessing the effects of heat stress in relation to agro-morphological and physiological traits of six rice varieties. The study was carried out in the Township of Glazoué, a rice-growing area in Benin. The experiments were laid in randomized complete block design with three replications. Two types of stress were imposed: high-temperature stress in the dry season and optimal temperatures in the rainy season. The calculated mean values of morphological, physiological, and agronomic traits were used to estimate heritability, genetic advance, PCA, and correlation. Results The results showed that heat stress had a significant (p ≤ 0.01) influence on plant height, leaf length, number of tillers, number of internodes, days to flowering, and days to maturity, 1000-seed weight, and yield per plant. The heat stress had significantly delayed the flowering of all the varieties when compared to the controls. The highest values of 1000-seed weight (34. 67 g) were recorded for BRIZ-8B while the lowest (25.33 g) were recorded for NERICA-L20. The highest values for the genotypic coefficient of variation (43.05%) and phenotypic coefficient of variation (99.13%) were recorded for yield per plant under heat stress. The topmost broad-sense heritability was recorded for grain width (92.72%), followed by days to maturity (69.33%), days to flowering (68.50%), number of grains per panicle (57.35%), and yield (54.55%). Conclusions These results showed that BRIZ-8B and BRIZ-10B were the most tolerant to high temperature amongst the six varieties assessed and potentially could be recommended to farmers for production under high temperature and be used in breeding programs to improve heat tolerance in rice.

Antibodies play a crucial role in activating protective immunity against malaria by interacting with Fc-gamma receptors (FcγRs). Genetic variations in genes encoding FcγRs can affect immune cell responses to the parasite. In this study, our aim was to investigate whether non-coding variants that regulate FcγR expression could influence the prevalence of Plasmodium falciparum infection. Through bioinformatics approaches, we selected expression quantitative trait loci (eQTL) for FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B genes encoding FcγRs (FCGR), in whole blood. We prioritized two regulatory variants, rs2099684 and rs1771575, located in open genomic regions. These variants were identified using RegVar, ImmuNexUT, and transcription factor annotations specific to immune cells. In addition to these, we genotyped the coding variants FCGR2A/rs1801274 and FCGR2B/rs1050501 in 234 individuals from a malaria-endemic area in Burkina Faso. We conducted age and family-based analyses to evaluate associations with the prevalence of malarial infection in both children and adults. The analysis revealed that the regulatory rs1771575-CC genotype was predicted to influence FCGR2B/FCGR2C/FCGR3A transcripts in immune cells and was the sole variant associated with a higher prevalence of malarial infection in children. In conclusion, this study identifies the rs1771575 cis-regulatory variant affecting several FcγRs in myeloid and neutrophil cells and associates it with the inter-individual capacity of children living in Burkina Faso to control malarial infection.

Recent attention has highlighted the importance of oral microbiota in human health and disease, e.g., in Parkinson’s disease, notably using shotgun metagenomics. One key aspect for efficient shotgun metagenomic analysis relies on optimal microbial sampling and DNA extraction, generally implementing commercial solutions developed to improve sample collection and preservation, and provide high DNA quality and quantity for downstream analysis. As metagenomic studies are today performed on a large number of samples, the next evolution to increase study throughput is with DNA extraction automation. In this study, we proposed a semi-automated DNA extraction protocol for human salivary samples collected with a commercial kit, and compared the outcomes with the DNA extraction recommended by the manufacturer. While similar DNA yields were observed between the protocols, our semi-automated DNA protocol generated significantly higher DNA fragment sizes. Moreover, we showed that the oral microbiome composition was equivalent between DNA extraction methods, even at the species level. This study demonstrates that our semi-automated protocol is suitable for shotgun metagenomic analysis, while allowing for improved sample treatment logistics with reduced technical variability and without compromising the structure of the oral microbiome.

The use of quarry by-products can enable the commercialization of a clay building material (reconstituted earth) thanks to minimal valorized and perennial stocks of materials. This study shows that quarry by-products can be used to mix design a clay-based building material for the manufacture of CEB. These soils are composed of quarry tailing and clayey muds. Proctor and dry compressive strength tests have shown that the proportion of mud that achieves the highest possible compressive strength is a balance between increasing density through the aggregate arrangement, increasing clay activity, and decreasing density through the increase in water content. These tests resulted in the formulation of materials with compressive strengths of 5.8 MPa and 8.4 MPa at densities of 2135 kg/m3 and 2178 kg/m3. The influence of mud incorporation on the material granulometry and on its characteristics was also studied. Moreover, a model allowing us to link the compressive strength, the clay activity, and the dry density is proposed for the materials composed of quarry by-products. This model enables us to facilitate the mix design and the standardization of the earth material.

Background: Functional hallux limitus (FHLim) refers to a limitation of hallux dorsiflexion when the first metatarsal head is under load, whereas physiologic dorsiflexion is measured in the unloaded condition. Limited excursion of the flexor hallucis longus (FHL) in the retrotalar pulley has been identified as a possible cause of FHLim. A low-lying or bulky FHL muscle belly could be the cause of this limitation. However, to date, there are no published data regarding the association between clinical and anatomical findings. The purpose of this anatomical study is to correlate the presence of FHLim and objective morphologic findings through magnetic resonance imaging (MRI). Methods: Twenty-six patients (27 feet) were included in this observational study. They were divided into 2 groups, based on positive and negative Stretch Tests. In both groups, we measured on MRI the distance from the most inferior part of the FHL muscle belly and the retrotalar pulley as well as the cross-sectional area of the muscle belly 20, 30, and 40 mm proximal to the retrotalar pulley. Results: Eighteen patients had a positive Stretch Test and 9 patients had a negative Stretch Test. The mean distance between the most inferior part of the FHL muscle belly and the retrotalar pulley was 6.0 ± 6.4 mm for the positive group and 11.8 ± 9.4 mm for the negative group ( P = .039). The mean cross section of the muscle measured at 20, 30, and 40 mm from the pulley were 190 ± 90, 300 ± 112, and 395 ± 123 mm 2 for the positive group and 98 ± 44, 206 ± 72, and 294 ± 61mm 2 for the negative group ( P values .005, .019, and .017). Conclusion: Based on these findings, we can conclude that patients with FHLim do have a low-lying FHL muscle belly causing limited excursion in the retrotalar pulley. However, the mean volume of the muscle belly was comparable in both groups, and therefore bulkiness was not found to be a contributing factor. Level of Evidence: Level III, observational study.

HIV-1 infection results in the activation of inflammasome that may facilitate viral spread and establishment of viral reservoirs. We evaluated the effects of the caspase-1 inhibitor VX-765 on HIV-1 infection in humanized NSG mice engrafted with human CD34+ hematopoietic stem cells. Expression of caspase-1, NLRP3, and IL-1β was increased in lymph nodes and bone marrow between day 1 and 3 after HIV-1 infection (mean fold change (FC) of 2.08, 3.23, and 6.05, p

ObjectiveThe San Francisco Declaration on Research Assessment (DORA) advocates for assessing biomedical research quality and impact, yet academic organizations continue to employ traditional measures such as Journal Impact Factor. We aimed to identify and prioritize measures for assessing research quality and impact.MethodsWe conducted a review of published and grey literature to identify measures of research quality and impact, which we included in an online survey. We assembled a panel of researchers and research leaders, and conducted a two-round Delphi survey to prioritize measures rated as high (rated 6 or 7 by ≥ 80% of respondents) or moderate (rated 6 or 7 by ≥ 50% of respondents) importance.ResultsWe identified 50 measures organized in 8 domains: relevance of the research program, challenges to research program, or productivity, team/open science, funding, innovations, publications, other dissemination, and impact. Rating of measures by 44 panelists (60%) in Round One and 24 (55%) in Round Two of a Delphi survey resulted in consensus on the high importance of 5 measures: research advances existing knowledge, research plan is innovative, an independent body of research (or fundamental role) supported by peer-reviewed research funding, research outputs relevant to discipline, and quality of the content of publications. Five measures achieved consensus on moderate importance: challenges to research productivity, potential to improve health or healthcare, team science, collaboration, and recognition by professional societies or academic bodies. There was high congruence between researchers and research leaders across disciplines.ConclusionsOur work contributes to the field by identifying 10 DORA-compliant measures of research quality and impact, a more comprehensive and explicit set of measures than prior efforts. Research is needed to identify strategies to overcome barriers of use of DORA-compliant measures, and to "de-implement" traditional measures that do not uphold DORA principles yet are still in use.

Abstract Glucocorticoids (GCs) are widely prescribed for their anti-inflammatory and immunosuppressive properties as a treatment for a variety of diseases. The use of GCs is associated with important side effects, including diabetogenic effects. However, the underlying mechanisms of GC-mediated diabetogenic effects in β-cells are not well understood. In this study we investigated the role of glycogen synthase kinase 3 (GSK3) in the mediation of β-cell death and dysfunction induced by GCs. Using genetic and pharmacological approaches we showed that GSK3 is involved in GC-induced β-cell death and impaired insulin secretion. Further, we unraveled the underlying mechanisms of GC-GSK3 crosstalk. We showed that GSK3 is marginally implicated in the nuclear localization of GC receptor (GR) upon ligand binding. Furthermore, we showed that GSK3 regulates the expression of GR at mRNA and protein levels. Finally, we dissected the proper contribution of each GSK3 isoform and showed that GSK3β isoform is sufficient to mediate the pro-apoptotic effects of GCs in β-cells. Collectively, in this work we identified GSK3 as a viable target to mitigate GC deleterious effects in pancreatic β-cells.

In this study, we explore knowledge regimes shaping the ongoing transformation of medical identities. We accomplish this through a text-based analysis of published studies reporting on interventions into the membership, content, or process of morbidity and mortality rounds. Historically a site for physicians to discuss medical error, these rounds still feature strongly in efforts to improve patient safety. In this way, changes to morbidity and mortality rounds offer a window into shifting knowledge regimes being realized in clinical workplaces and sites of medical education. Following a systematic search process, our dataset included 54 studies published between 1992 and 2020. Using Foucault's concept of governmentality as a sensitizing device in our analysis of these texts, we found that morbidity and mortality rounds were being changed to align with the rationales and identities associated with evidence-based medicine, quality improvement/patient safety practices, or a combination of both. However, those combinations were not always smooth. In some ways, our analysis confirms the ongoing penetration of evidence-based medicine rationales in the profession of medicine. Our analysis also shows the competing dynamics of quality improvement and patient safety regimes. If the identities available for participants enrolled in evidence-based medicine include engaging as librarians or researchers, then the identities invited in the quality improvement/patient safety regimes centre around the notion of “safety scientists”. The future question is whether these belief systems and associated knowledge practices compete, complement, or mix together in some new configuration. Ultimately, we argue for further explorations of the changing nature of knowledge practices and associated knowledge regimes intersecting with the profession of medicine.