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Abstract Recent large-scale seismological observations have shown that off-fault strain localization and foreshock migration could serve as an early warning of an impending earthquake. However, this process is still largely unknown. In this study, state-of-the-art friction experiments were conducted in a oil-confined biaxial shear apparatus to investigate the link between stick-slip nucleation and off-fault deformation. Our findings indicate that there is a direct link between stick-slip nucleation and off-fault deformation, provided that the fault is conditionally unstable (a − b

The High Performance Computing (HPC) domain aims to optimize code to use the latest multicore and parallel technologies including specific processor instructions. In this computing framework, portability and reproducibility are key concepts. A way to handle these requirements is to use Linux containers. These "light virtual machines" allow users to encapsulate applications within its environment in processes. Containers have been recently highlighted because they provide multi-infrastructure environnement for both developers and system administrators. Furthermore, they offer reproducibility due to image building files. Two container solutions are emerging: Docker for micro-services and Singularity for computing applications. We present here the Com-puteOps project which investigates the container benefits for HPC applications.

Abstract Background Improvements in oxygenation and lung mechanics with prone position (PP) in patients with acute respiratory distress syndrome (ARDS) are inconstant. The objectives of the study were (i) to identify baseline variables, including the recruitment-to-inflation ratio (R/I), associated with a positive response to PP in terms of oxygenation (improvement of the ratio of arterial oxygen partial pressure over the inspired oxygen fraction (PaO2/FiO2) ≥ 20 mmHg) and lung mechanics; (ii) to evaluate whether the response to the previous PP session is associated with the response to the next session. Methods In this prospective, observational, single-center study in patients who underwent PP for ARDS due to COVID-19, respiratory variables were assessed just before PP and at the end of the session. Respiratory variables included mechanical ventilation settings and respiratory mechanics variables, including R/I, an estimate of the potential for lung recruitment compared to lung overinflation. Results In 50 patients, 201 PP sessions lasting 19 ± 3 h were evaluated. Neuromuscular blockades were used in 116 (58%) sessions. The PaO2/FiO2 ratio increased from 109 ± 31 mmHg to 165 ± 65 mmHg, with an increase ≥ 20 mmHg in 142 (71%) sessions. In a mixed effect logistic regression, only pre-PP PaO2/FiO2 (OR 1.12 (95% CI [1.01–1.24])/every decrease of 10 mmHg, p = 0.034) in a first model and improvement in oxygenation at the previous PP session (OR 3.69 (95% CI [1.27–10.72]), p = 0.017) in a second model were associated with an improvement in oxygenation with PP. The R/I ratio (n = 156 sessions) was 0.53 (0.30–0.76), separating lower- and higher-recruiters. Whereas PaO2/FiO2 improved to the same level in both subgroups, driving pressure and respiratory system compliance improved only in higher-recruiters (from 14 ± 4 to 12 ± 4 cmH2O, p = 0.027, and from 34 ± 11 to 38 ± 13 mL/cmH2O, respectively, p = 0.014). Conclusions A lower PaO2/FiO2 at baseline and a positive O2-response at the previous PP session are associated with a PP-induced improvement in oxygenation. In higher-recruiters, lung mechanics improved along with oxygenation. Benefits of PP could thus be greater in these patients.

Abstract Obesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. We aimed to characterize in mice the sex-dependent effects of a high fat diet on these parameters. Male and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota, plasma adipokines and white adipose tissue response have been assessed. Both male and female HFD mice exhibited an increase of body weight and fat mass gain and glucose intolerance compared to SD mice. However, only male HFD mice tended to develop insulin resistance associated to increased Tnfα and Ccl2 mRNA expression in perigonadal adipose tissue. By contrast, only female HFD mice showed significant intestinal hyperpermeability that was associated with more markedly altered colonic inflammatory response. Cecal microbiota richness was markedly reduced in both sexes (Observed species) with sex-dependent modifications at the phyla or family level, e.g. decreased relative abundance of Bacillota and Lachnospiraceae in females, increased of Bacteroidaceae in males. Interestingly, some of these microbiota alterations were correlated with peripheral metabolic and inflammatory markers. In conclusions, male and female mice exhibit different responses to a high fat diet with specific changes of gut microbiota, intestinal barrier function, colonic and white adipose tissue inflammation, metabolic markers and body weight gain. The underlying mechanisms should be deciphered in further investigations.

Abstract The Kramers escape problem is a paradigmatic model for the kinetics of rare events, which are usually characterized by Arrhenius law. So far, analytical approaches have failed to capture the kinetics of rare events in the important case of non-Markovian processes with long-term memory, as occurs in the context of reactions involving proteins, long polymers, or strongly viscoelastic fluids. Here, based on a minimal model of non-Markovian Gaussian process with long-term memory, we determine quantitatively the mean FPT to a rare configuration and provide its asymptotics in the limit of a large energy barrier E. Our analysis unveils a correction to Arrhenius law, induced by long-term memory, which we determine analytically. This correction, which we show can be quantitatively significant, takes the form of a second effective energy barrier $$E^{\prime} \, < \, E$$ E ′ < E and captures the dependence of rare event kinetics on initial conditions, which is a hallmark of long-term memory. Altogether, our results quantify the impact of long-term memory on rare event kinetics, beyond Arrhenius law.

Abstract Background Rapid point-of-care tests for malaria are now widely used in many countries to guide the initial clinical management of patients presenting with febrile illness. With China having recently achieved malaria elimination, better understanding regarding the identity and distribution of major non-malarial causes of febrile illnesses is of particular importance to inform evidence-based empirical treatment policy. Methods A systematic review of published literature was undertaken to characterise the spectrum of pathogens causing non-malaria febrile illness in China (1980–2015). Literature searches were conducted in English and Chinese languages in six databases: Ovid MEDLINE, Global Health, EMBASE, Web of Science™ – Chinese Science Citation Database SM, The China National Knowledge Infrastructure (CNKI), and WanFang Med Online. Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. The number of published articles, reporting a given pathogen were presented, rather than incidence or prevalence of infection. Results A total of 57,181 records from 13 provinces of China where malaria used to be endemic were screened, of which 392 met selection criteria and were included in this review. The review includes 60 (15.3%) records published from 1980 to 2000, 211 (53.8%) from 2001 to 2010 and 121 (30.9%) from 2011 to 2015;. Of the 392 records, 166 (42.3%) were from the eastern region of China, 120 (30.6%) were from the south-west, 102 (26.0%) from south-central, and four (1.0%) were multi-regional studies. Bacterial infections were reported in 154 (39.3%) records, viral infections in 219 (55.9%), parasitic infections in four (1.0%), fungal infections in one (0.3%), and 14 (3.6%) publications reported more than one pathogen group. Participants of all ages were included in 136 (34.7%) studies, only adults in 75 (19.1%), only children in 17 (4.3%), only neonates in two (0.5%) and the age distribution was not specified in 162 (41.3%) records. The most commonly reported bacterial pathogens included Typhoidal Salmonella (n = 30), Orientia/ Rickettsia tsutsugamushi (n = 31), Coxiella burnetii (n = 17), Leptospira spp. (n = 15) and Brucella spp. (n = 15). The most commonly reported viral pathogens included Hantavirus/Hantaan virus (n = 89), dengue virus (DENV) (n = 76 including those with unknown serovars), Japanese encephalitis virus (n = 21), and measles virus (n = 15). The relative lack of data in the western region of the country, as well as in in neonates and children, represented major gaps in the understanding of the aetiology of fever in China. Conclusions This review presents a landscape of non-malaria pathogens causing febrile illness in China over 36 years as the country progressed toward malaria elimination. These findings can inform guidelines for clinical management of fever cases and infection surveillance and prevention, and highlight the need to standardize operational and reporting protocols for better understanding of fever aetiology in the country.

Abstract Background This study explores the potential role of Thioredoxin-interacting protein (TXNIP) silencing in endothelial colony-forming cells (ECFCs) within the scope of age-related comorbidities and impaired vascular repair. We aim to elucidate the effects of TXNIP silencing on vasculogenic properties, paracrine secretion, and neutrophil recruitment under conditions of metabolic stress. Methods ECFCs, isolated from human blood cord, were transfected with TXNIP siRNA and exposed to a high glucose and β-hydroxybutyrate (BHB) medium to simulate metabolic stress. We evaluated the effects of TXNIP silencing on ECFCs’ functional and secretory responses under these conditions. Assessments included analyses of gene and protein expression profiles, vasculogenic properties, cytokine secretion and neutrophil recruitment both in vitro and in vivo. The in vivo effects were examined using a murine model of hindlimb ischemia to observe the physiological relevance of TXNIP modulation under metabolic disorders. Results TXNIP silencing did not mitigate the adverse effects on cell recruitment, vasculogenic properties, or senescence induced by metabolic stress in ECFCs. However, it significantly reduced IL-8 secretion and consequent neutrophil recruitment under these conditions. In a mouse model of hindlimb ischemia, endothelial deletion of TXNIP reduced MIP-2 secretion and prevented increased neutrophil recruitment induced by age-related comorbidities. Conclusions Our findings suggest that targeting TXNIP in ECFCs may alleviate ischemic complications exacerbated by metabolic stress, offering potential clinical benefits for patients suffering from age-related comorbidities.

Abstract High and low pathogenicity avian influenza viruses (HPAIV, LPAIV) are the primary causes of poultry diseases worldwide. HPAIV and LPAIV constitute a major threat to the global poultry industry. Therefore, early detection and well-adapted surveillance strategies are of the utmost importance to control the spread of these viruses. Volatile Organic Compounds (VOCs) released from living organisms have been investigated over the last decades as a diagnostic strategy. Mass spectrometry instruments can analyze VOCs emitted upon viral infection. Selected ion flow tube mass spectrometry (SIFT-MS) enables direct analysis of cell headspace in less than 20 min. As a proof-of-concept study, we investigated the ability of a SIFT-MS coupled sparse Partial Least Square-Discriminant Analysis analytical workflow to discriminate IAV-infected cells. Supernatants of HPAIV, LPAIV, and control cells were collected from 1 to 72 h post-infection and analyzed using our analytical workflow. At each collection point, VOCs' signatures were first identified based on four independent experiments and then used to discriminate the infectious status of external samples. Our results indicate that the identified VOCs signatures successfully discriminate, as early as 1-h post-infection, infected cells from the control cells and differentiated the HPAIV from the LPAIV infection. These results suggest a virus-dependent VOCs signature. Overall, the external samples' status was identified with 96.67% sensitivity, 100% specificity, and 97.78% general accuracy.

Abstract Meiotic rapid prophase chromosome movements (RPMs) require connections between the chromosomes and the cytoskeleton, involving SUN (Sad1/UNC-84)-domain-containing proteins at the inner nuclear envelope (NE). RPMs remain significantly understudied in plants, with respect to their importance in the regulation of meiosis. Here, we demonstrate that Arabidopsis thaliana meiotic centromeres undergo rapid (up to 500 nm/s) and uncoordinated movements during the zygotene and pachytene stages. These centromere movements are not affected by altered chromosome organization and recombination but are abolished in the double mutant sun1 sun2. We also document the changes in chromosome dynamics and nucleus organization during the transition from leptotene to zygotene, including telomere attachment to SUN-enriched NE domains, bouquet formation, and nucleolus displacement, all of which were defective in sun1 sun2. These results establish A. thaliana as a model species for studying the functional implications of meiotic RPMs and demonstrate the mechanistic conservation of telomere-led RPMs in plants.

Grape berry mycobiota is a complex and diverse ecosystem that is constantly evolving during the different berry ripening stages of vines, as well as in musts and wines, which can ultimately impact wine sensorial properties and thus overall product quality. To better characterise the role of this mycobiota in wine off-odours, we studied for the first time changes in Pinot Noir and Meunier grape and must mycobiota and carried out sensorial analyses in the resulting wines, with a focus on fresh mushroom aroma. Grapes from three berry ripening stages, fruit set, veraison and harvest, were collected without sorting bunches from 31 parcels, then laboratory-scale grape crushing was performed to obtain musts, followed by micro-winemaking. For all sample types, both culture-dependent and -independent strategies were used to decipher both species and genus level mycobiota composition. After the winemaking process, sensorial analyses detected 9 laboratory wines with fresh mushroom aroma off-odours. Musts that generated these spoiled wines contained higher total fungal counts, especially Penicillium spp., compared to other musts. A total of seven Penicillium species, including one unidentified Penicillium sp., was detected using the culture dependent approach; this genus represented up to 100 % of all fungal counts in musts linked to FMA wines. Fungal interactions inferred using co-occurrence networks revealed positive interactions between Vishniacozyma, Cladosporium and Penicillium in musts, indicating the possible implication of these three genera in FMA production. Negative interactions were observed in musts between the two yeast genera, Starmerella and Pichia, with Penicillium, Botrytis, Vishniacozyma and Cladosporium, as well as between Metschnikowia with Botrytis and Vishniacozyma. Starmerella, Pichia and Metschnikowia may thus be potential biocontrol candidates for use against Botrytis and Penicillium grape contamination.

Abstract Background Previous retrospective research has shown that maintaining prone positioning (PP) for an average of 40 h is associated with an increase of survival rates in intubated patients with COVID-19-related acute respiratory distress syndrome (ARDS). This study aims to determine whether a cumulative PP duration of more than 32 h during the first 2 days of intensive care unit (ICU) admission is associated with increased survival compared to a cumulative PP duration of 32 h or less. Methods This study is an ancillary analysis from a previous large international observational study involving intubated patients placed in PP in the first 48 h of ICU admission in 149 ICUs across France, Belgium and Switzerland. Given that PP is recommended for a 16-h daily duration, intensive PP was defined as a cumulated duration of more than 32 h during the first 48 h, whereas standard PP was defined as a duration equal to or less than 32 h. Patients were followed-up for 90 days. The primary outcome was mortality at day 60. An Inverse Probability Censoring Weighting (IPCW) Cox model including a target emulation trial method was used to analyze the data. Results Out of 2137 intubated patients, 753 were placed in PP during the first 48 h of ICU admission. The intensive PP group (n = 79) had a median PP duration of 36 h, while standard PP group (n = 674) had a median of 16 h during the first 48 h. Sixty-day mortality rate in the intensive PP group was 39.2% compared to 38.7% in the standard PP group (p = 0.93). Twenty-eight-day and 90-day mortality as well as the ventilator-free days until day 28 were similar in both groups. After IPCW, there was no significant difference in mortality at day 60 between the two-study groups (HR 0.95 [0.52–1.74], p = 0.87 and HR 1.1 [0.77–1.57], p = 0.61 in complete case analysis or in multiple imputation analysis, respectively). Conclusions This secondary analysis of a large multicenter European cohort of intubated patients with ARDS due to COVID-19 found that intensive PP during the first 48 h did not provide a survival benefit compared to standard PP.

In controlled phase II trials, major prognostic factors need to be well balanced between arms. The main procedures used are SPBR (Stratified Permuted Block Randomization) and minimization. First, we provide a systematic review of the treatment allocation procedure used in gastrointestinal oncology controlled phase II trials published in 2019. Second, we performed simulations using data from six phase II studies to measure the impacts of imbalances and bias on the efficacy estimations. From the 40 articles analyzed, all mentioned randomization in both the title and abstract, the median number of patients included was 109, and 77.5% were multicenter. Of the 27 studies that reported at least one stratification variable, 10 included the center as a stratification variable, 10 used minimization, 9 used SBR, and 8 were unspecified. In real data studies, the imbalance increased with the number of centers. The total and marginal imbalances were higher with SBR than with minimization, and the difference increased with the number of centers. The efficiency estimates per arm were close to the original trial estimate in both procedures. Minimization is often used in cases of numerous centers and guarantees better similarity between arms for stratification variables for total and marginal imbalances in phase II trials.

Abstract Background The rates of maternal and neonatal deaths in Madagascar are among the highest in the world. In response to a request for additional training from obstetrical care providers at the Ambanja district hospital in north-eastern Madagascar, a partnership of institutions in Switzerland and Madagascar conducted innovative training on respectful emergency obstetric and newborn care using e-learning and simulation methodologies. The training focused on six topics: pre-eclampsia, physiological childbirth, obstetric maneuvers, postpartum hemorrhage, maternal sepsis, and newborn resuscitation. Cross-cutting themes were interprofessional communication and respectful patient care. Ten experienced trainers participated in an e-training-of-trainers course conducted by the Swiss partners. The newly-trained trainers and Swiss partners then jointly conducted the hybrid remote/in-person training for 11 obstetrical care providers in Ambanja. Methods A mixed methods evaluation was conducted of the impact of the training on participants’ knowledge and practices. Trainees’ knowledge was tested before, immediately after, and 6 months after the training. Focus group discussions were conducted to elicit participants’ opinions about the training, including the content and pedagogical methods. Results Trainees’ knowledge of the six topics was higher at 6 months (with an average of 71% correct answers) compared to before the training (62%), although it was even higher (83%) immediately after the training. During the focus group discussions, participants highlighted their positive impressions of the training, including its impact on their sense of professional effectiveness. They reported that their interprofessional relationships and focus on respectful care had improved. Simulation, which was a new methodology for the participants native to Madagascar, was appreciated for its engaging and active format, and they enjoyed the hybrid delivery of the training. Participants (including the trainers) expressed a desire for follow-up engagement, including additional training, and improved access to more equipment. Conclusion The evaluation showed improvements in trainees’ knowledge and capacity to provide respectful emergency care to pregnant women and newborns across all training topics. The hybrid simulation-based training method elicited strong enthusiasm. Significant opportunity exists to expand the use of hybrid onsite/remote simulation-based training to improve obstetrical care and health outcomes for women and newborns in Madagascar and elsewhere.

Abstract Background Alveolar soft part sarcoma is a rare tumour of soft tissues, mostly localized in muscles or deep soft tissues of the extremities. In rare occasions, this tumour develops in deep tissues of the abdomen or pelvis. Case presentation In this case report, we described the case of a 46 year old man who developed a primary splenic alveolar soft part sarcoma. The tumour displayed typical morphological alveolar aspect, as well as immunohistochemical profile notably TFE3 nuclear staining. Detection of ASPSCR1 Exon 7::TFE3 Exon 6 fusion transcript in molecular biology and TFE3 rearrangement in FISH confirmed the diagnosis. Conclusion We described the first case of primary splenic alveolar soft part sarcoma, which questions once again the cell of origin of this rare tumour.

Abstract Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation states. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.

Objective Gut microbes and microbe-dependent metabolites (eg, tryptophan-kynurenine-serotonin pathway metabolites) have been linked to systemic inflammation, but the microbiota-metabolite-inflammation axis remains uncharacterised in children. Here we investigated whether gut microbiota features and circulating metabolites (both microbe-dependent and non-microbe-dependent metabolites) associated with circulating inflammation markers in children.Methods We studied children from the prospective Gen3G birth cohort who had data on untargeted plasma metabolome (n=321 children; Metabolon platform), gut microbiota (n=147; 16S rRNA sequencing), and inflammation markers (plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1, and tumour necrosis factor-α) measured at 5–7 years. We examined associations of microbial taxa and metabolites—examining microbe-dependent and non-microbe-dependent metabolites separately—with each inflammatory marker and with an overall inflammation score (InfSc), adjusting for key confounders and correcting for multiple comparisons. We also compared the proportion of significantly associated microbe-dependent versus non-microbe-dependent metabolites, identified a priori (Human Microbial Metabolome Database), with each inflammation marker.Results Of 335 taxa tested, 149 were associated (qFDR

ABSTRACT The aim of this study was to evaluate the proportion of resistance to a temocillin, tigecycline, ciprofloxacin, and chloramphenicol phenotype called t2c2 that resulted from mutations within the ramAR locus among extended-spectrum β-lactamases-Enterobacterales (ESBL-E) isolated in three intensive care units for 3 years in a French university hospital. Two parallel approaches were performed on all 443 ESBL-E included: (i) the minimal inhibitory concentrations of temocillin, tigecycline, ciprofloxacin, and chloramphenicol were determined and (ii) the genomes obtained from the Illumina sequencing platform were analyzed to determine multilocus sequence types, resistomes, and diversity of several tetR-associated genes including ramAR operon. Among the 443 ESBL-E strains included, isolates of Escherichia coli (n = 194), Klebsiella pneumoniae (n = 122), and Enterobacter cloacae complex (Ecc) (n = 127) were found. Thirty-one ESBL-E strains (7%), 16 K. pneumoniae (13.1%), and 15 Ecc (11.8%) presented the t2c2 phenotype in addition to their ESBL profile, whereas no E. coli presented these resistances. The t2c2 phenotype was invariably reversible by the addition of Phe-Arg-β-naphthylamide, indicating a role of resistance-nodulation-division pumps in these observations. Mutations associated with the t2c2 phenotype were restricted to RamR, the ramAR intergenic region (IR), and AcrR. Mutations in RamR consisted of C- or N-terminal deletions and amino acid substitutions inside its DNA-binding domain or within key sites of protein–substrate interactions. The ramAR IR showed nucleotide substitutions involved in the RamR DNA-binding domain. This diversity of sequences suggested that RamR and the ramAR IR represent major genetic events for bacterial antimicrobial resistance.IMPORTANCEMorbimortality caused by infectious diseases is very high among patients hospitalized in intensive care units (ICUs). A part of these outcomes can be explained by antibiotic resistance, which delays the appropriate therapy. The transferable antibiotic resistance gene is a well-known mechanism to explain the high rate of multidrug resistance (MDR) bacteria in ICUs. This study describes the prevalence of chromosomal mutations, which led to additional antibiotic resistance among MDR bacteria. More than 12% of Klebsiella pneumoniae and Enterobacter cloacae complex strains presented mutations within the ramAR locus associated with a dysregulation of an efflux pump called AcrAB-TolC and a porin: OmpF. These dysregulations led to an increase in antibiotic output notably tigecycline, ciprofloxacin, and chloramphenicol associated with a decrease of input for beta-lactam, especially temocillin. Mutations within transcriptional regulators such as ramAR locus played a major role in antibiotic resistance dissemination and need to be further explored.

Abstract Objectives We aimed to analyze the risk factors for management failure of BC after pediatric liver transplantation (pLT) by retrospectively analyzing primary pLT performed between 1997 and 2018 (n = 620 patients). Results In all, 117/620 patients (19%) developed BC. The median (range) follow-up was 9 (1.4–21) years. Patient survival at 1, 5 and 10 years was 88.9%, 85.7%, 84.4% and liver graft survival was 82.4%, 77.4%, and 74.3% respectively. Graft not patient survival was impaired by BC (p = 0.01). Multivariate analysis identified the number of dilatation courses > 2 (p = 0.008), prolonged cold ischemia time (p = 0.004), anastomosed multiple biliary ducts (p = 0.019) and hepatic artery thrombosis (p = 0.01) as factors associated with impaired graft survival. The number of dilatation courses > 2 (p 2) radiologic dilatation courses are associated with impaired graft survival and management failure. Overall, graft but not patient survival was impaired by BC.

Abstract Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP+ CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8+ T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment. Single cell analysis, spatial transcriptomics and immunohistochemistry reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) is the most affected by chemotherapy. Moreover, functional assays demonstrate that ECM-myCAF isolated from HGSOC reduce CD8+ T-cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, efficient inhibition after treatment of YAP1-signaling pathway in the ECM-myCAF cluster could enhance CD8+ T-cell cytotoxicity. Altogether, these data pave the way for therapy targeting YAP1 in ECM-myCAF in HGSOC.

The geometry of the compact convex set of all n×nn\times n doubly stochastic matrices, a structure frequently referred to as the Birkhoff polytope, has been an active subject of research as of late. Geometric characteristics such as the Chebyshev center and the Chebyshev radius with respect to the operator norms from ℓnp{\ell }_{n}^{p} to ℓnp{\ell }_{n}^{p} and the Schatten pp-norms, both for the range 1≤p≤∞1\le p\le \infty , have only recently been studied in depth. In this article, we continue in this vein by determining the diameter of the Birkhoff polytope with respect to the metrics induced by the aforementioned matrix norms.

Abstract Background Inhaled sedation during invasive mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) has received increasing attention. However, inhaled sedation devices increase dead-space ventilation and an undesirable effect is the increase in minute ventilation needed to maintain CO2 removal. A consequence of raising minute ventilation is an increase in mechanical power (MP) that can promote lung injury. However, the effect of inhaled sedation devices on MP remains unknown. Methods We conducted a bench study to assess and compare the effects of three devices delivering inhaled sevoflurane currently available in ICU (AnaConDa-50 mL (ANA-50), AnaConDa-100 mL (ANA-100), and MIRUS) on MP by using a test lung model set with three compliances (20, 40, and 60 mL/cmH2O). We simulated lung-protective ventilation using a low tidal volume and two levels of positive end-expiratory pressure (5 and 15 cmH2O) under ambient temperature and dry conditions. Following the insertion of the devices, either the respiratory rate or tidal volume was increased in 15%-steps until end-tidal CO2 (EtCO2) returned to the baseline value. MP was calculated at baseline and after EtCO2 correction using a simplified equation. Results Following device insertion, the EtCO2 increase was significantly greater with MIRUS (+ 78 ± 13%) and ANA-100 (+ 100 ± 11%) than with ANA-50 (+ 49 ± 7%). After normalizing EtCO2 by adjusting minute ventilation, MP significantly increased by more than 50% with all inhaled sedation devices compared to controls. The lowest increase in MP was observed with ANA-50 (p 50% with all devices after normalizing EtCO2 by adjusting minute ventilation. Conclusion Inhaled sedation devices substantially increased MP in this bench model of protective ventilation, which might limit their benefits in ARDS.

Abstract Rationale Patients with anorexia nervosa (AN) often present sleep disorders and circadian hormonal dysregulation. The role of the microbiota–gut–brain axis in the regulation of feeding behavior has emerged during the last decades but its relationships with the circadian rhythm remains poorly documented. Thus, we aimed to characterize the circadian clock genes expression in peripheral and central tissues in the activity-based anorexia mouse model (ABA), as well as the dynamics of the gut–microbiota composition. Methods From day 1 to day 17, male and female C57Bl/6 mice were submitted or not to the ABA protocol (ABA and control (CT) groups), which combines a progressive limited access to food and a free access to a running wheel. At day 17, fasted CT and ABA mice were euthanized after either resting (EoR) or activity (EoA) phase (n = 10–12 per group). Circadian clock genes expression was assessed by RT-qPCR on peripheral (liver, colon and ileum) and central (hypothalamic suprachiasmatic nucleus or SCN) tissues. Cecal bacterial taxa abundances were evaluated by qPCR. Data were compared by two-way ANOVA followed by post-tests. Results ABA mice exhibited a lower food intake, a body weight loss and an increase of diurnal physical activity that differ according with the sex. Interestingly, in the SCN, only ABA female mice exhibited altered circadian clock genes expression (Bmal1, Per1, Per2, Cry1, Cry2). In the intestinal tract, modification of clock genes expression was also more marked in females compared to males. For instance, in the ileum, female mice showed alteration of Bmal1, Clock, Per1, Per2, Cry1, Cry2 and Rev-erbα mRNA levels, while only Per2 and Cry1 mRNAs were affected by ABA model in males. By contrast, in the liver, clock genes expression was more markedly affected in males compared to females in response to ABA. Finally, circadian variations of gut–bacteria abundances were observed in both male and female mice and sex-dependent alteration were observed in response to the ABA model. Conclusions This study shows that alteration of circadian clock genes expression at both peripheral and central levels occurs in response to the ABA model. In addition, our data underline that circadian variations of the gut–microbiota composition are sex-dependent.

Abstract Background Sexually polymorphic cognition (SPC) results from the interaction between biological (birth-assigned sex (BAS), sex hormones) and socio-cultural (gender identity, gender roles, sexual orientation) factors. The literature remains quite mixed regarding the magnitude of the effects of these variables. This project used a battery of classic cognitive tests designed to assess the influence of sex hormones on cognitive performance. At the same time, we aimed to assess the inter-related and respective effects that BAS, sex hormones, and gender-related factors have on SPC. Methods We recruited 222 adults who completed eight cognitive tasks that assessed a variety of cognitive domains during a 150-min session. Subgroups were separated based on gender identity and sexual orientation and recruited as follows: cisgender heterosexual men (n = 46), cisgender non-heterosexual men (n = 36), cisgender heterosexual women (n = 36), cisgender non-heterosexual women (n = 38), gender diverse (n = 66). Saliva samples were collected before, during, and after the test to assess testosterone, estradiol, progesterone, cortisol, and dehydroepiandrosterone. Psychosocial variables were derived from self-report questionnaires. Results Cognitive performance reflects sex and gender differences that are partially consistent with the literature. Interestingly, biological factors seem to better explain differences in male-typed cognitive tasks (i.e., spatial), while psychosocial factors seem to better explain differences in female-typed cognitive tasks (i.e., verbal). Conclusion Our results establish a better comprehension of SPC over and above the effects of BAS as a binary variable. We highlight the importance of treating sex as a biological factor and gender as a socio-cultural factor together since they collectively influence SPC.

Abstract In Apicomplexa, rhoptry discharge is essential for invasion and involves an apical vesicle (AV) docking one or two rhoptries to a macromolecular secretory apparatus. Toxoplasma gondii is armed with 10–12 rhoptries and 5-6 microtubule-associated vesicles (MVs) presumably for iterative rhoptry discharge. Here, we have addressed the localization and functional significance of two intraconoidal microtubule (ICMT)-associated proteins instrumental for invasion. Mechanistically, depletion of ICMAP2 leads to a dissociation of the ICMTs, their detachment from the conoid and dispersion of MVs and rhoptries. ICMAP3 exists in two isoforms that contribute to the control of the ICMTs length and the docking of the two rhoptries at the AV, respectively. This study illuminates the central role ICMTs play in scaffolding the discharge of multiple rhoptries. This process is instrumental for virulence in the mouse model of infection and in addition promotes sterile protection against T. gondii via the release of key effectors inducing immunity.

The Surface Water and Ocean Topography (SWOT) mission was launched on 16 December 2022 to measure water levels over both open ocean and inland waters. To achieve these objectives, the SWOT Payload contains an innovative Ka-band radar interferometer, called KaRIn, completed with a nadir altimeter called POSEIDON-3C that was switched on a month after launch and a few days before KaRIn. POSEIDON-3C measurements provide a link between large-scale phenomena and high resolution. The POSEIDON-3C design is based on POSEIDON-3B, its predecessor on board JASON-3. It is also a dual-frequency radar altimeter operating in C- and Ku-bands, but with some improvements to enhance its performance. Even though it is a Low Resolution Mode altimeter, its performance over open ocean, inland waters and coastal zones are indeed excellent. This paper first describes the POSEIDON-3C design and its modes with a focus on its new features and the Digital Elevation Model that drives its open-loop tracking mode. Then, we assess the in-flight performances of the altimeter from an instrumental point of view. For that purpose, special and routine calibrations have been realized. They show the good performance and stability of the radar. In-flight assessments thus provide confidence when it comes to ensuring excellent altimeter measurement stability throughout the mission duration.

Gait analysis is essential for evaluating walking patterns and identifying functional limitations. Traditional marker-based motion capture tools are costly, time-consuming, and require skilled operators. This study evaluated a 3D Marker-less Motion Capture (3D MMC) system using pose and depth estimations with the gold-standard Motion Capture (MOCAP) system for measuring hip and knee joint angles during gait at three speeds (0.7, 1.0, 1.3 m/s). Fifteen healthy participants performed gait tasks which were captured by both systems. The 3D MMC system demonstrated good accuracy (LCC > 0.96) and excellent inter-session reliability (RMSE < 3°). However, moderate-to-high accuracy with constant biases was observed during specific gait events, due to differences in sample rates and kinematic methods. Limitations include the use of only healthy participants and limited key points in the pose estimation model. The 3D MMC system shows potential as a reliable tool for gait analysis, offering enhanced usability for clinical and research applications.

Background/Objectives: In paediatric liver transplantation, donor–recipient compatibility depends on graft size. We explored whether the graft weight can be predicted using the donor’s biometric parameters. Methods: We used seven easily available biometric variables in 142 anonymised paediatric and adult donors, with data collected between 2016 and 2022. The whole or partial liver was transplanted in our hospital from these donors. We identified the variables that had the strongest correlation to our response variable: whole liver graft weight. Results: In child donors, we determined two linear models: using donor weight and height on the one hand and using donor weight and right liver span on the other hand. Both models had a coefficient of determination R2 = 0.86 and p-value < 10−5. We also determined two models in adult donors using donor weight and height (R2 = 0.33, p < 10−4) and donor weight and sternal height (R2 = 0.38, p < 10−4). The models proved valid based on our external dataset of 245 patients from two institutions. Conclusions: In clinical practise, our models could provide rapidly accessible estimates to determine whole graft dimension compatibility in liver transplantation in children and adults. Determining similar models predicting the left lobe and lateral segment weight could prove invaluable in paediatric transplantation.

Abstract Caspase recruitment-domain containing protein 9 (CARD9) is a key signaling pathway in macrophages but its role in atherosclerosis is still poorly understood. Global deletion of Card9 in Apoe -/- mice as well as hematopoietic deletion in Ldlr -/- mice increases atherosclerosis. The acceleration of atherosclerosis is also observed in Apoe -/- Rag2 -/- Card9 -/- mice, ruling out a role for the adaptive immune system in the vascular phenotype of Card9 deficient mice. Card9 deficiency alters macrophage phenotype through CD36 overexpression with increased IL-1β production, increased lipid uptake, higher cell death susceptibility and defective autophagy. Rapamycin or metformin, two autophagy inducers, abolish intracellular lipid overload, restore macrophage survival and autophagy flux in vitro and finally abolish the pro-atherogenic effects of Card9 deficiency in vivo. Transcriptomic analysis of human CARD9-deficient monocytes confirms the pathogenic signature identified in murine models. In summary, CARD9 is a key protective pathway in atherosclerosis, modulating macrophage CD36-dependent inflammatory responses, lipid uptake and autophagy.

Introduction Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications.Methods and analysis The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age

At the cell surface, the actin cytoskeleton and the plasma membrane interact reciprocally in a variety of processes related to the remodeling of the cell surface. The actin cytoskeleton has been known to modulate membrane organization and reshape the membrane. To this end, actin-membrane linking molecules play a major role in regulating actin assembly and spatially direct the interaction between the actin cytoskeleton and the membrane. While studies in cells have provided a wealth of knowledge on the molecular composition and interactions of the actin-membrane interface, the complex molecular interactions make it challenging to elucidate the precise actions of the actin-membrane linkers at the interface. Synthetic reconstituted systems, consisting of model membranes and purified proteins, have been a powerful approach to elucidate how actin-membrane linkers direct actin assembly to drive membrane shape changes. In this review, we will focus only on several actin-membrane linkers that have been studied by using reconstitution systems. We will discuss the design principles of these reconstitution systems and how they have contributed to the understanding of the cellular functions of actin-membrane linkers. Finally, we will provide a perspective on future research directions in understanding the intricate actin-membrane interaction.

Microorganisms play an important role in maintaining the proper functioning of river ecosystems and are promising candidates for environmental indicators. They are also highly sensitive to environmental changes. It is necessary to have basic knowledge about them in order to know the ecological status of river ecosystem. To our knowglege, there is very little information on the status of microorganisms in surface water of the Seine River, although the Seine River is one of the rivers that suffers the greatest impact from humain activities in the world due to a weak dilution effect. It is therefore necessary to carry out a microbial analysis to assess the ecological status of the Seine River and to use it as a reference to compare with the future state when, for instance, new disinfection technologies of wastewater are implemented.To this end, the microbial communities of the Seine surface water were analyzed, taking into account the spatial effect, including the tributaries, and from upstream to downstream of the Paris conurbation and the temporal aspect, with a monitoring over 4 seasons. The results showed that the microbiome of the water is highly diverse and involved a variety of functions. The main phyla making up the surface water microbiome were Proteobacteria, Actinobacteriota, Firmicutes, Bacteroidota, while other minor phyla were Deinococcota, Patescibacteria, Gemmatimonadota, Cyanobacteria, Bdellovibrionota, Acidobacteriota, Campilobacterota, Myxococcota, and Desulfobacterota. Overall, the microbial community did not change spatially (with the exception of some minor differences between upstream and downstream), but did vary seasonally. The main factors influencing this microbiome were temperature, nitrate and orthophosphate concentrations. The main predicted functions were related to cell metabolism, in particular carbohydrates, amino acids, lipids, energy, vitamins and cofactors, and cell mobility. The microbial compositions showed a strong balance between microbial groups and were involved in the degradation of recalcitrant compounds.

Tyrosine kinase inhibitors (TKI) directed against MET have been recently approved to treat advanced non-small cell lung cancer (NSCLC) harbouring activating MET mutations. This success is the consequence of a long characterization of MET mutations in cancers, which we propose to outline in this review. MET, a receptor tyrosine kinase (RTK), displays in a broad panel of cancers many deregulations liable to promote tumour progression. The first MET mutation was discovered in 1997, in hereditary papillary renal cancer (HPRC), providing the first direct link between MET mutations and cancer development. As in other RTKs, these mutations are located in the kinase domain, leading in most cases to ligand-independent MET activation. In 2014, novel MET mutations were identified in several advanced cancers, including lung cancers. These mutations alter splice sites of exon 14, causing in-frame exon 14 skipping and deletion of a regulatory domain. Because these mutations are not located in the kinase domain, they are original and their mode of action has yet to be fully elucidated. Less than five years after the discovery of such mutations, the efficacy of a MET TKI was evidenced in NSCLC patients displaying MET exon 14 skipping. Yet its use led to a resistance mechanism involving acquisition of novel and already characterized MET mutations. Furthermore, novel somatic MET mutations are constantly being discovered. The challenge is no longer to identify them but to characterize them in order to predict their transforming activity and their sensitivity or resistance to MET TKIs, in order to adapt treatment.

Background The COVID-19 pandemic affected all WHO member states. We compared and contrasted the COVID-19 treatment guidelines of each member state with the WHO COVID-19 therapeutic guidelines.Methods Ministries of Health or accessed National Infectious Disease websites and other relevant bodies and experts were contacted to obtain national guidelines (NGs) for COVID-19 treatment. NGs were included only if they delineated specific pharmacological treatments for COVID-19, which were stratified by disease severity. We conducted a retrospective review using the adapted Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG) survey checklist and a derived comparative metric based on the WHO guidelines was performed.Results COVID-19 therapeutics NGs could be obtained from 109 of the 194 WHO member states. There was considerable variation in guidelines and in disease severity stratifications. Therapeutic recommendations in many NGs differed substantially from the WHO guidelines. Overall in late 2022, 93% of NGs were recommending at least one treatment which had proved to be ineffective in large randomised trials, and was not recommended by WHO. Corticosteroids were not recommended in severe disease in nearly 10% of NGs despite overwhelming evidence of their benefit. NGs from countries with low-resource settings showed the greatest divergence when stratified by gross domestic product per year, Human Development Index and the Global Health Security Index.Discussion Our study is limited to NGs that were readily accessible, and it does not reflect the availability of recommended medicines in the field. Three years after the start of the SARS-CoV-2 pandemic, available COVID-19 NGs vary substantially in their therapeutic recommendations, often differ from the WHO guidelines, and commonly recommend ineffective, unaffordable or unavailable medicines.

Introduction: Although, there is an increasing focus on inactive or extinct seafloor massive sulfide (SMS) deposits driven by the possibility of marine mining, only few studies have been devoted to them so far. The Trans-Atlantic Geotraverse (TAG) hydrothermal field is probably one of the best-studied hydrothermal systems even if the relict SMS deposits known since the mid-1980s have not been thoroughly explored.Objectives: The main objective of this study was to describe the characteristics of these so-called inactive sites.Methods: During four different expeditions, we acquired high-resolution acoustic data and performed numerous human occupied vehicle (HOV) dive operations including extensive rock sampling and in-situ temperature measurements.Results and Discussion: We discovered thirteen new hydrothermal mounds including six large (i.e. > 5,000 m2) deposits making the TAG hydrothermal field one of the largest accumulation of hydrothermal materials (21.1 Mt) known on the seafloor. However, copper and zinc grades of the largest SMS deposits remain low (i.e. < 1.4 wt%) even compared to on-land volcanogenic massive sulfide deposits. Additionally, eight areas of diffuse hydrothermal fluid flow were identified challenging the presumed inactivity of these SMS deposits and, for the first time, emphasizing the importance of low temperature (LT) hydrothermal activity in whole the TAG field. Inactive and weakly active SMS deposits exhibit a large diversity of surface mineralization (e.g. sulfides, Fe-Mn mineralization, jasper) illustrating complexity of hydrothermal activities but also different ageing history. Several mounds no longer have visible sulfide chimneys and are covered by a widespread layer of manganese and iron oxyhydroxides attesting the longevity of diffuse fluid flow at specific locations even long after last high-temperature (HT) hydrothermal activity has ceased. This contrasts with SMS deposits that are devoid of extensive LT precipitates but characterized by standing or topped sulfide chimney indicating a relatively abrupt cessation of HT hydrothermal activity.Conclusion: Together these results allow us to propose evolution models to explain the diversity of active, weakly active and inactive SMS deposits in the TAG hydrothermal field.

Abstract Fluctuations of consciousness and their rhythmicities have been rarely studied in patients with a disorder of consciousness after acute brain injuries. 24-h assessment of brain (EEG), behaviour (eye-opening), and circadian (clock-controlled hormones secretion from urine) functions was performed in acute brain-injured patients. The distribution, long-term predictability, and rhythmicity (circadian/ultradian) of various EEG features were compared with the initial clinical status, the functional outcome, and the circadian rhythmicities of behaviour and clock-controlled hormones. Here we show that more physiological and favourable patterns of fluctuations are associated with a higher 24 h predictability and sharp up-and-down shape of EEG switches, reminiscent of the Flip-Flop model of sleep. Multimodal rhythmic analysis shows that patients with simultaneous circadian rhythmicity for brain, behaviour, and hormones had a favourable outcome. Finally, both re-emerging EEG fluctuations and homogeneous 24-h cycles for EEG, eye-opening, and hormones appeared as surrogates for preserved functionality in brainstem and basal forebrain, which are key prognostic factors for later improvement. While the recovery of consciousness has previously been related to a high short-term complexity, we suggest in this exploratory study the importance of the high predictability of the 24 h long-term generation of brain rhythms and highlight the importance of circadian body-brain rhythms in awakening.

Abstract Our goal was to investigate the effects of head-thorax elevation (HUP) during chest compressions (CC) on lung ventilation. A prospective study was performed on seven human cadavers. Chest was automatically compressed-decompressed in flat position and during progressive HUP from 18 to 35°. Lung ventilation was measured with electrical impedance tomography. In each cadaver, 5 sequences were randomly performed: one without CC at positive end-expiratory pressure (PEEP) 0cmH2O, 3 s with CC at PEEP0, 5 or 10cmH2O and 1 with CC and an impedance threshold device at PEEP0cmH2O. The minimal-to-maximal change in impedance (VTEIT in arbitrary unit a.u.) and the minimal impedance in every breathing cycle (EELI) the) were compared between flat, 18°, and 35° in each sequence by a mixed-effects model. Values are expressed as median (1st–3rd quartiles). With CC, between flat, 18° and 35° VTEIT decreased at each level of PEEP. It was 12416a.u. (10,689; 14,442), 11,239 (7667; 13,292), and 6457 (4631; 9516), respectively, at PEEP0. The same was true with the impedance threshold device. EELI/VTEIT significantly decreased from − 0.30 (− 0.40; − 0.15) before to − 1.13 (− 1.70; − 0.61) after the CC (P = 0.009). With HUP lung ventilation decreased with CC as compared to flat position. CC are associated with decreased in EELI.

Abstract A new sensitive method to determine polonium-210 (210Po) and lead-210 (210Pb) in a diversity of environmental samples was developed. For fresh and marine waters, Po was pre-concentrated using a titanium (III) hydroxide (Ti(OH)3) co-precipitation. Solid environmental samples were digested with nitric acid (HNO3) and hydrogen peroxide (H2O2). The alpha thin layer source was prepared using CuS micro-precipitation and 210Po was measured by alpha spectrometry. Lead-210 was left to decay for up to a year and indirectly measured via its progeny, 210Po. The chemical recoveries for 210Po and 210Pb were high, 90% and 97%, respectively, for a large variety of samples and a very low minimum detectable activity (MDA) was obtained. The method was validated using standardized solutions and certified reference materials.

Cet article s’interroge sur l’oubli dont est victime la pratique du rugby dans la France de l’Ouest. Les recherches menées dans le cadre d’une thèse d’histoire montrent la présence de nombreuses équipes avant la Grande Guerre. La concurrence du football, les difficultés financières et l’éloignement contribuent à fragiliser et à provoquer la disparition de plusieurs clubs. Toutefois, le rugby se maintient dans certaines villes et reste un sport populaire. L’historiographie du rugby a le plus souvent délaissé cet espace considérant que ce sport n’y avait pas été implanté ou que la greffe britannique y avait échoué. Il s’agit également de comprendre les raisons de l’échec de la mémoire de la pratique du rugby dans la France de l’Ouest.

Abstract Respiratory diseases are a health and economic concern for poultry production worldwide. Given global economic exchanges and migratory bird flyways, respiratory viruses are likely to emerge continuously in new territories. The primary aim of this study was to investigate the major pathogens involved in respiratory disease in Tunisian broiler poultry and their epidemiology. Between 2018 and 2020, broilers farms in northeastern Tunisia were monitored, and 39 clinically diseased flocks were sampled. Samples were screened for five viral and three bacterial respiratory pathogens using a panel of real-time PCR assays. The reemergence of H9N2 low pathogenic avian influenza virus (LPAIV) in commercial poultry was reported, and the Northern and Western African GI lineage strain was typed. The infectious bronchitis virus (IBV) GI-23 lineage and the avian metapneumovirus (aMPV) subtype B also were detected for the first time in broilers in Tunisia. H9N2 LPAIV was the most detected pathogen in the flocks tested, but rarely alone, as 15 of the 16 H9N2 positive flocks were co-infected. Except for infectious laryngotracheitis virus (ILTV), all of the targeted pathogens were detected, and in 61% of the respiratory disease cases, a combination of pathogens was identified. The major combinations were H9N2 + aMPV (8/39) and H9N2 + IBV (6/39), showing the high contribution of H9N2 LPAIV to the multifactorial respiratory diseases. This field survey provided evidence of the emergence of new respiratory viruses and the complexity of respiratory disease in Tunisia. A comprehensive and continuous surveillance strategy therefore is needed to better control respiratory pathogens in Tunisia.

This work concerns the autonomous navigation of non-holonomic ground mobile robots in a GPS-denied environment. The objective was to locate, in a global frame, without GPS, anonymous ground mobile robots starting from two consecutive aerial images captured by a single fixed webcam. The effectiveness of deep learning by a MultiLayer Perceptron in an indexed localization was compared to the methods studied in previous works. The ability of a robot to determine the position of other non-indexed robots was also performed. The structure and parameters of the network and the choice of the points taken into account during the learning phase to obtain a local optimum are presented. The results, obtained from simulated and experimental data, are compared to those obtained with more classical methods for different sampling periods (time between images).

Abstract Background Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. Methods This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for

Abstract The phylum Apicomplexa comprises important eukaryotic parasites that invade host tissues and cells using a unique mechanism of gliding motility. Gliding is powered by actomyosin motors that translocate host-attached surface adhesins along the parasite cell body. Actin filaments (F-actin) generated by Formin1 play a central role in this critical parasitic activity. However, their subcellular origin, path and ultrastructural arrangement are poorly understood. Here we used cryo-electron tomography to image motile Cryptosporidium parvum sporozoites and reveal the cellular architecture of F-actin at nanometer-scale resolution. We demonstrate that F-actin nucleates at the apically positioned preconoidal rings and is channeled into the pellicular space between the parasite plasma membrane and the inner membrane complex in a conoid extrusion-dependent manner. Within the pellicular space, filaments on the inner membrane complex surface appear to guide the apico-basal flux of F-actin. F-actin concordantly accumulates at the basal end of the parasite. Finally, analyzing a Formin1-depleted Toxoplasma gondii mutant pinpoints the upper preconoidal ring as the conserved nucleation hub for F-actin in Cryptosporidium and Toxoplasma. Together, we provide an ultrastructural model for the life cycle of F-actin for apicomplexan gliding motility.

Abstract With almost 700 000 estimated cases each year in the United States and Europe, Lyme borreliosis (LB), also called Lyme disease, is the most common tick-borne illness in the world. Transmitted by ticks of the genus Ixodes and caused by bacteria Borrelia burgdorferi sensu lato, LB occurs with various symptoms, such as erythema migrans, which is characteristic, whereas others involve blurred clinical features such as fatigue, headaches, arthralgia, and myalgia. The diagnosis of Lyme borreliosis, based on a standard two-tiered serology, is the subject of many debates and controversies, since it relies on an indirect approach which suffers from a low sensitivity depending on the stage of the disease. Above all, early detection of the disease raises some issues. Inappropriate diagnosis of Lyme borreliosis leads to therapeutic wandering, inducing potential chronic infection with a strong antibody response that fails to clear the infection. Early and proper detection of Lyme disease is essential to propose an adequate treatment to patients and avoid the persistence of the pathogen. This review presents the available tests, with an emphasis on the improvements of the current diagnosis, the innovative methods and ideas which, ultimately, will allow more precise detection of LB.

Abstract Background 3-methylmethcathinone (3-MMC) has been available on the European drug market for several years, but an increase in its availability seems to have occurred around 2020, associated with reports of harm and death. We aimed to analyze the composition of the supposed 3-MMC samples purchased and its concordance with the assumed composition of the drug. Methods A prospective multicenter (n = 6) study was conducted between February 2021 and September 2021 in Auvergne-Rhone-Alpes, France. The inclusion criteria were: 3-MMC users over 18 years of age in contact with a community-based organization (CBO) called AIDES. Consumption was evaluated with an anonymized questionnaire and samples of 3-MMC powder were analyzed with a combination of qualitative (GC–MS) and quantitative methods (UPLC-MS/MS), to compare the assumed and real compositions of the products purchased. Results We studied 45 samples provided by 33 users. The study population was predominantly male (91%), with a median age of 40 years, most were university graduates and regular users of 3-MMC. Intravenous drug use was reported by 15.2% of the population. Most of the users bought their 3-MMC online via the Clear Web. Drug testing was requested by 86% of the users, highlighting the need for this type of harm reduction strategy. The purity of the 3-MMC powder samples tested ranged from 21 to 98%. Other NPS drugs, such as 4-CEC (4-chloroethcathinone), 4-MMC, and 2-fluorodeschloroketamine (2-FDCK), supplied as methoxphenidine (MXP), were also detected. Conclusion This prospective study shows that 3-MMC purity and dose vary considerably. It also describes the characteristics of 3-MMC users and their expectations of a drug-checking program. Our data suggest that drug-checking services may be useful in this population. Health associations and laboratories should work together to help increase access to such programs.

Background: Artificial urinary sphincter (AUS) is a gold standard treatment in male stress urinary incontinence but remains poorly used in elderly patients. Objective: To assess the efficacy, safety, and reoperation-free survival of AUS implantation in male patients over 75 yr of age. Design, setting, and participants: We retrospectively reviewed the charts of all 1233 non-neurological male AUS implantations between 2005 and 2020 at 13 French centers. We compared 330 patients ≥75 yr old (GROUP75+) with 903 patients

ABSTRACTHigh pathogenicity avian influenza viruses (HPAIVs) H5Nx of clade 2.3.4.4b have been circulating increasingly in both wild and domestic birds in recent years. In turn, this has led to an increase in the number of spillover events affecting mammals. In November 2022, an HPAIV H5N1 caused an outbreak in a zoological park in the south of France, resulting in the death of a Tibetan black bear (Ursus thibetanus) and several captive and wild bird species. We detected the virus in various tissues of the bear and a wild black-headed gull (Chroicocephalus ridibundus) found dead in its enclosure using histopathology, two different in situ detection techniques, and next-generation sequencing, all performed on formalin-fixed paraffin-embedded tissues. Phylogenetic analysis performed on the hemagglutinin gene segment showed that bear and gull strains shared 99.998% genetic identity, making the bird strain the closest related strain. We detected the PB2 E627K mutation in minute quantities in the gull, whereas it predominated in the bear, which suggests that this mammalian adaptation marker was selected during the bear infection. Our results provide the first molecular and histopathological characterization of an H5N1 virus infection in this bear species.IMPORTANCEAvian influenza viruses are able to cross the species barrier between birds and mammals because of their high genetic diversity and mutation rate. Using formalin-fixed paraffin-embedded tissues, we were able to investigate a Tibetan black bear's infection by a high pathogenicity H5N1 avian influenza virus at the molecular, phylogenetic, and histological levels. Our results highlight the importance of virological surveillance programs in mammals and the importance of raising awareness among veterinarians and zookeepers of the clinical presentations associated with H5Nx virus infection in mammals.

With his Sententiae, diuisiones, colores rhetorum et oratorum, published around 30 CE, Seneca the Elder, father of the Stoic philosopher Seneca, produced an anthology of excerpts from declamations (forensic or deliberative mock speeches) by 116 different declaimers (teachers, students and non-professional practitioners) who lived during the reigns of Augustus and Tiberius. By citing these declaimers, Seneca intended to offer an informed and critical view of their qualities and shortcomings, and to memorialize the emerging literary genre of declamation. But his text also lends itself to a more social reading. By mining the Sententiae, diuisiones, colores for mentions of direct contact between declaimers, and by applying the methodology of network analysis, it becomes possible to read the anthology as a depiction of a structured intellectual milieu. The aim of this article is to identify and reconstruct a set of social relationships within the declamatory world described in the anthology, using mentions of criticism (where one declaimer comments on the performance of another) as markers of relationships. After explaining the goals and biases of Seneca and their impact on his depiction of the declamatory milieu, this article expounds a method for: 1) identifying concrete links between declaimers with a reasonable degree of certainty; 2) building a set of usable data based on these findings; and 3) assessing the significance of the expected results given the incompleteness of the anthology. It then reconstructs and plots this particular declamatory network, identifying its central figures and mapping its main relational structures.