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Abstract Background BK-polyomavirus (BKpyV) nephropathy (BKVN) is associated with end-stage kidney disease in kidney and non-kidney solid organ transplantation, with no curative treatment. Case presentation A 45-year-old woman with a past medical history of double lung transplantation subsequently developed end-stage kidney disease, of undetermined origin. One month after receiving a kidney transplant, a diagnosis of early BKVN was suspected, and in retrospect was a reasonable cause for the loss of her native kidneys. Minimisation of immunosuppression, achieved through extracorporeal photopheresis, allowed clearance of BKpyV and so prevented nephropathy. Both lung and kidney grafts had a satisfactory and stable function after one year of follow-up, with no rejection. Conclusions Extracorporeal photopheresis may have facilitated minimisation of immunosuppression and BKpyV clearance without lung allograft rejection.

Abstract Plasma growth differentiation factor-15 (GDF-15) levels increase with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) but the underlying mechanism remains poorly defined. Using male mouse models of obesity and MASLD, and biopsies from carefully-characterized patients regarding obesity, type 2 diabetes (T2D) and MASLD status, we identify adipose tissue (AT) as the key source of GDF-15 at onset of obesity and T2D, followed by liver during the progression towards metabolic dysfunction-associated steatohepatitis (MASH). Obesity and T2D increase GDF15 expression in AT through the accumulation of macrophages, which are the main immune cells expressing GDF15. Inactivation of Gdf15 in macrophages reduces plasma GDF-15 concentrations and exacerbates obesity in mice. During MASH development, Gdf15 expression additionally increases in hepatocytes through stress-induced TFEB and DDIT3 signaling. Together, these results demonstrate a dual contribution of AT and liver to GDF-15 production in metabolic diseases and identify potential therapeutic targets to raise endogenous GDF-15 levels.

Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment. Here, we show that microextrusion bioprinting can reproducibly generate distinct cancer and stromal compartments integrating cells relevant to human pathology. Our findings unveil the functional maturation of this millimeter-sized model, showcasing the development of a hypoxic cancer core and an increased surface proliferation. Maturation was also driven by the presence of cancer-associated fibroblasts (CAF) that induced elevated microvascular-like structures complexity. Such modulation was concomitant to extracellular matrix remodeling, with high levels of collagen and matricellular proteins deposition by CAF, simultaneously increasing tumor stiffness and recapitulating breast cancer fibrotic development. Importantly, our bioprinted model faithfully reproduced response to treatment, further modulated by CAF. Notably, CAF played a protective role for cancer cells against radiotherapy, facilitating increased paracrine communications. This model holds promise as a platform to decipher interactions within the microenvironment and evaluate stroma-targeted drugs in a context relevant to human pathology.

Christos Tsamasiotis,1 Gaelle Fiard,2 Pierre Bouzat,3 Patrice François,1 Guillaume Fond,4 Laurent Boyer,4 Bastien Boussat1,5 1Department of Clinical Epidemiology, Grenoble-Alps University Hospital; Laboratory TIMC-IMAG, UMR 5525 Joint Research Unit, National Center for Scientific Research, Faculty of Medicine, Grenoble Alps University, Grenoble, France; 2Department of Urology, Grenoble Alpes University Hospital, CNRS, Grenoble INP, TIMC, Université Grenoble Alpes, Grenoble, France; 3Department of Anaesthesia and Intensive Care, Centre Hospitalier Universitaire Grenoble, University Grenoble Alpes; INSERM U1216, Grenoble Institut Neurosciences, Grenoble, France; 4AP-HM, Aix-Marseille University, School of Medicine - La Timone Medical Campus, UR3279: Health Service Research and Quality of Life Center (CEReSS), Marseille, France; 5O’Brien Institute for Public Health, University of Calgary, Calgary, Alberta, CanadaCorrespondence: Bastien Boussat, Service d’épidémiologie et évaluation médicale, CHU Grenoble-Alpes, Boulevard de la Chantourne, La Tronche, 38700, France, Tel +33 4 76 76 69 96, Email bboussat@chu-grenoble.frBackground: Given the increasing focus on patient safety in healthcare systems worldwide, understanding the impact of Continuous Quality Improvement Programs (QIPs) is crucial. QIPs, including Morbidity and Mortality Conferences (MMCs) and Experience Feedback Committees (EFCs), have been identified as effective strategies for enhancing patient safety culture. These programs engage healthcare professionals in the identification and analysis of adverse events to foster a culture of safety (ie the product of individual and group value, attitudes, and perceptions about quality and safety). This study aimed to determine whether patient safety culture differed regarding care provider participation in MMCs and EFCs activities.Methods: A cross-sectional web-only survey was conducted in 2022 using the Hospital Survey on Patient Safety Culture (HSOPS) among 4780 employees at an 1836-bed, university-affiliated hospital in France. We quantified the mean differences in the 12 HSOPS dimension scores according to MMCs and EFCs participation, using Cohen d effect size. We performed a multivariate analysis of variance to examine differences in dimension scores after adjusting for background characteristics.Results: Of 4780 eligible employees, 1457 (30.5%) participated in the study. Among the respondents, 571 (39.2%) participated in MMCs or EFCs activities. Participants engaged in MMCs or EFCs reported significantly higher scores in six out of twelve HSOPS dimensions, particularly in “Nonpunitive response to error”, “Feedback and communication about error”, and “Organizational learning” (Overall effect size = 0.14, 95% confidence interval = 0.11 to 0.17, P< 0.001). Notably, involvement in both MMCs and EFCs was associated with higher improvements in patient safety culture compared to non-participation or singular involvement in either program. However, certain dimensions such as “Staffing”, “Hospital management support”, and “Hospital handoffs and transition” showed no significant association with MMCs or EFCs participation, highlighting broader systemic challenges.Conclusion: The study confirms the positive association between participation in MMCs or EFCs and an enhanced culture of patient safety, emphasizing the importance of such programs in fostering an environment conducive to learning, communication, and nonpunitive responses to errors. While MMCs or EFCs are effective in promoting certain aspects of patient safety culture, addressing broader systemic challenges remains crucial for comprehensive improvements in patient safety.Keywords: patient safety culture, quality improvement programs, morbidity and mortality conferences, experience feedback committees

Abstract Key Message Understanding the impact of extreme drought on the canopy fuel moisture content (CFMC) is crucial to anticipate the effects of climate change on wildfires. Our study demonstrates that foliage mortality, caused by leaf embolism, can substantially diminish CFMC during drought on Pinus halepensis Mill. and Quercus ilex L. It emphasizes the importance of considering plant hydraulics to improve wildfire predictions. Context Canopy fuel moisture content (CFMC), which represents the water-to-dry mass ratio in leaves and fine twigs within the canopy, is a major factor of fire danger across ecosystems worldwide. CFMC results from the fuel moisture content of living foliage (live fuel moisture content, LFMC) and dead foliage (dead fuel moisture content, DFMC) weighted by the proportion of foliage mortality in the canopy (α Dead ). Understanding how LFMC, α Dead , and ultimately CFMC are affected during extreme drought is essential for effective wildfire planning. Aims We aimed to understand how plant hydraulics affect CFMC for different levels of soil water deficit, examining its influence on both LFMC and α Dead . Methods We conducted a drought experiment on seedlings of two Mediterranean species: Aleppo pine (Pinus halepensis Mill.) and Holm oak (Quercus ilex L.). Throughout the drought experiment and after rewatering, we monitored CFMC, LFMC, and α Dead along with other ecophysiological variables. Results LFMC exhibited a significant decrease during drought, and as leaf water potentials reached low levels, α Dead increased in both species, thereby reducing CFMC. Distinct water use strategies resulted in species-specific variations in dehydration dynamics. Conclusion Our findings demonstrate that as drought conditions intensify, foliage mortality might become a critical physiological factor driving the decline in CFMC.

Abstract In recent years, there has been a surge in the development of methods for cell segmentation and tracking, with initiatives like the Cell Tracking Challenge driving progress in the field. Most studies focus on regular cell population videos in which cells are segmented and followed, and parental relationships annotated. However, DNA damage induced by genotoxic drugs or ionizing radiation produces additional abnormal events since it leads to behaviors like abnormal cell divisions (resulting in a number of daughters different from two) and cell death. With this in mind, we developed an automatic mitosis classifier to categorize small mitosis image sequences centered around one cell as “Normal” or “Abnormal.” These mitosis sequences were extracted from videos of cell populations exposed to varying levels of radiation that affect the cell cycle’s development. We explored several deep-learning architectures and found that a network with a ResNet50 backbone and including a Long Short-Term Memory (LSTM) layer produced the best results (mean F1-score: 0.93 ± 0.06). In the future, we plan to integrate this classifier with cell segmentation and tracking to build phylogenetic trees of the population after genomic stress.

Abstract Understanding what makes a community vulnerable to invasion is integral to the successful management of invasive species. Our understanding of how characteristics of resident plant interactions, such as the network architecture of interactions, can affect the invasibility of plant communities is limited. Using a simulation model, we tested how successfully a new plant invader established in communities with different network architectures of species interactions. We also investigated whether species interaction networks lead to relationships between invasibility and other community properties also affected by species interaction networks, such as diversity, species dominance, compositional stability and the productivity of the resident community. We found that higher invasibility strongly related with a lower productivity of the resident community. Plant interaction networks influenced diversity and invasibility in ways that led to complex but clear relationships between the two. Heterospecific interactions that increased diversity tended to decrease invasibility. Negative conspecific interactions always increased diversity and invasibility, but increased invasibility more when they increased diversity less. This study provides new theoretical insights into the effects of plant interaction networks on community invasibility and relationships between diversity and invasibility. Combined with increasing empirical evidence, these insights could have useful implications for the management of invasive plant species.

Abstract Circulating free tumor DNA (ctDNA) analysis is gaining popularity in precision oncology, particularly in metastatic breast cancer, as it provides non-invasive, real-time tumor information to complement tissue biopsies, allowing for tailored treatment strategies and improved patient selection in clinical trials. Its use in early breast cancer has been limited so far, due to the relatively low sensitivity of available techniques in a setting characterized by lower levels of ctDNA shedding. However, advances in sequencing and bioinformatics, as well as the use of methylome profiles, have led to an increasing interest in the application of ctDNA analysis in early breast cancer, from screening to curative treatment evaluation and minimal residual disease (MRD) detection. With multiple prospective clinical trials in this setting, ctDNA evaluation may become useful in clinical practice. This article reviews the data regarding the analytical validity of the currently available tests for ctDNA detection and the clinical potential of ctDNA analysis in early breast cancer.

Véritables portes d’entrée du football, les ports contribuent fortement à la diffusion du jeu en Bretagne au début du xxe siècle. Toutefois, les différents types d’activité portuaire (pêche, chantiers navals et arsenaux) posent la question de l’existence d’un modèle portuaire. Existe-t-il un football des ports en Bretagne ? Pas si sûr. En position d’ouverture au monde, le port favorise les rencontres, les échanges et l’acculturation aux innovations comme le football. Mais les ports conservent une singularité, une identité forte qui renvoie à ces espaces à nul autre pareil : un tout petit monde caractérisé par une géographie sociale fermée. Il n’en demeure pas moins qu’il existe en Bretagne un football arrivé par le port, des clubs construits dans le port, suscitant puissance une identification. Angle mort de l’histoire maritime régionale, le football donne à voir sous un jour nouveau les sociétés portuaires bretonnes.

Humoral immunity is a major waypoint towards chronic allograft dysfunction in lung transplantation (LT) recipients. Though allo-immunization and antibody-mediated rejection (AMR) are well-known entities, some diagnostic gaps need to be addressed. Morphological analysis could be enhanced by digital pathology and artificial intelligence-based companion tools. Graft transcriptomics can help to identify graft failure phenotypes or endotypes. Donor-derived cell free DNA is being evaluated for graft-loss risk stratification and tailored surveillance. Preventative therapies should be tailored according to risk. The donor pool can be enlarged for candidates with HLA sensitization, with strategies combining plasma exchange, intravenous immunoglobulin and immune cell depletion, or with emerging or innovative therapies such as imlifidase or immunoadsorption. In cases of insufficient pre-transplant desensitization, the effects of antibodies on the allograft can be prevented by targeting the complement cascade, although evidence for this strategy in LT is limited. In LT recipients with a humoral response, strategies are combined, including depletion of immune cells (plasmapheresis or immunoadsorption), inhibition of immune pathways, or modulation of the inflammatory cascade, which can be achieved with photopheresis. Altogether, these innovative techniques offer promising perspectives for LT recipients and shape the 21st century’s armamentarium against AMR.

We report an index patient with complete insensitivity to pain and a history of painless fractures, joint hypermobility, and behavioral problems. The index patient descends from a family with notable cases among his maternal relatives, including his aunt and his mother’s first cousin, both of whom suffer from congenital insensitivity to pain. The patient had normal results for prior genetic testing: fragile-X syndrome testing, chromosomal microarray analysis, and exome sequencing. Optical genome mapping detected a homozygous deletion affecting the noncoding 5′ untranslated region (UTR) and the first non-coding exon of the SCN9A gene in all affected family members, compatible with recessive disease transmission. Pathogenic homozygous loss-of-function variants in the SCN9A gene are associated with impaired pain sensation in humans. Optical genome mapping can thus detect pathogenic structural variants in patients without molecular etiology by standard diagnostic procedures and is a more accessible diagnostic tool than short-read or long-read whole-genome sequencing.

Abstract Objective The objective of this study was to evaluate users’ driving performances with a Power Wheelchair (PWC) driving simulator in comparison to the same driving task in real conditions with a standard power wheelchair. Methods Three driving circuits of progressive difficulty levels (C1, C2, C3) that were elaborated to assess the driving performances with PWC in indoor situations, were used in this study. These circuits have been modeled in a 3D Virtual Environment to replicate the three driving task scenarios in Virtual Reality (VR). Users were asked to complete the three circuits with respect to two testing conditions during three successive sessions, i.e. in VR and on a real circuit (R). During each session, users completed the two conditions. Driving performances were evaluated using the number of collisions and time to complete the circuit. In addition, driving ability by Wheelchair Skill Test (WST) and mental load were assessed in both conditions. Cybersickness, user satisfaction and sense of presence were measured in VR. The conditions R and VR were randomized. Results Thirty-one participants with neurological disorders and expert wheelchair drivers were included in the study. The driving performances between VR and R conditions were statistically different for the C3 circuit but were not statistically different for the two easiest circuits C1 and C2. The results of the WST was not statistically different in C1, C2 and C3. The mental load was higher in VR than in R condition. The general sense of presence was reported as acceptable (mean value of 4.6 out of 6) for all the participants, and the cybersickness was reported as acceptable (SSQ mean value of 4.25 on the three circuits in VR condition). Conclusion Driving performances were statistically different in the most complicated circuit C3 with an increased number of collisions in VR, but were not statistically different for the two easiest circuits C1 and C2 in R and VR conditions. In addition, there were no significant adverse effects such as cybersickness. The results show the value of the simulator for driving training applications. Still, the mental load was higher in VR than in R condition, thus mitigating the potential for use with people with cognitive disorders. Further studies should be conducted to assess the quality of skill transfer for novice drivers from the simulator to the real world. Trial registration Ethical approval n $$^\circ$$ ∘ 2019-A001306-51 from Comité de Protection des Personnes Sud Mediterranée IV. Trial registered the 19/11/2019 on ClinicalTrials.gov in ID: NCT04171973.

Abstract Background Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months. Case presentation To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time. Conclusion This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.

The Olympic/Paralympic Games are world events that promote countries and their participants, and more particularly, those winning medals. The potential link between a country’s scientific productivity and its podium wins remains unknown for the Paralympic Games. This study aimed to (1) quantify the link between the production of Paralympic scientific articles and the medals won by countries during Summer/Winter Paralympic Games between 2012 and 2022, and (2) select the five most important articles published for all Paralympic sports. A bibliographic search of the Web of Science, PubMed, and Google Scholar databases was conducted. From the 1351 articles identified, 525 fulfilled the inclusion/exclusion criteria. The results showed a greater (7x) production of scientific articles relating to the Summer Paralympics compared to those relating to the Winter Paralympics. For the Summer Paralympics, there was a strong correlation (r = 0.79) between the number of medals and the number of scientific articles produced by a given country, while a low correlation (r = 0.12) was observed for the Winter Paralympics. Biomechanics-related articles represent almost 50% of the overall Paralympic publications. In conclusion, there is a strong link between scientific productivity and the number of medals won for the 2012–2022 Paralympic Games. Parasport Federations are strongly encouraged to promote the publication of more Paralympic research articles.

Abstract Outbreaks of West Nile virus (WNV) occur periodically, affecting both human and equine populations. There are no vaccines for humans, and those commercialised for horses do not have sufficient coverage. Specific antiviral treatments do not exist. Many drug discovery studies have been conducted, but since rodent or primate cell lines are normally used, results cannot always be transposed to horses. There is thus a need to develop relevant equine cellular models. Here, we used induced pluripotent stem cells to develop a new in vitro model of WNV-infected equine brain cells suitable for microplate assay, and assessed the cytotoxicity and antiviral activity of forty-one chemical compounds. We found that one nucleoside analog, 2′C-methylcytidine, blocked WNV infection in equine brain cells, whereas other compounds were either toxic or ineffective, despite some displaying anti-viral activity in human cell lines. We also revealed an unexpected proviral effect of statins in WNV-infected equine brain cells. Our results thus identify a potential lead for future drug development and underscore the importance of using a tissue- and species-relevant cellular model for assessing the activity of antiviral compounds.

The finite volume method (FVM) was used to model a tungsten inert gas (TIG) arc welding process. A two-dimensional axisymmetric model of arc plasma integrating fluid–solid coupling was developed by solving electromagnetic and thermal equations in both the gas domain and the solid cathode. In addition, two additional coupling equations were considered in the gaseous domain where the arc is generated. This model also included the actual geometry of torch components such as the gas diffuser, the nozzle, and the electrode. The model was assessed using numerous numerical examples related to the prediction of the argon plasma mass fraction, temperature distribution, velocity fields, pressure, and electric potential in the plasma. A new linearization method was developed for the source term in the energy conservation equation, allowing for the prediction of Joule effects without artificial conductibility. This new method enhances the efficiency of the classical approach used in the literature.

Abstract Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, a connection between excessive Ca2+ influx and photoreceptor loss has yet to be proven. Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes indicated links to several Ca2+-signalling related pathways. To explore these, rd1 and wt organotypic retinal explant cultures were treated with the intracellular Ca2+-chelator BAPTA-AM or inhibitors of different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the novel compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. Effects on the retinal activity of poly(ADP-ribose) polymerase (PARP), sirtuin-type histone-deacetylase, calpains, as well as on activation of calpain-1, and − 2 were monitored, cell death was assessed via the TUNEL assay. While rd1 photoreceptor cell death was reduced by BAPTA-AM, Ca2+-channel blockers had divergent effects: While inhibition of T-type VGCC and NCX promoted survival, blocking CNGCs and CRACs did not. The treatment-related activity patterns of calpains and PARPs corresponded to the extent of cell death. Remarkably, sirtuin activity and calpain-1 activation were linked to photoreceptor protection, while calpain-2 activity was related to degeneration. In support of this finding, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors. These results suggest that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCCs and NCX. High Ca2+-levels likely suppress protective activity of calpain-1 and promote retinal degeneration via activation of calpain-2. Overall, our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of targeting degenerative processes specifically to achieve a therapeutic benefit for IRDs. Video Abstract

As a vapor pressure-driven process, pervaporation (PV) shares several of the advantages of membrane distillation (MD), such as the ability to tackle high salinity waters and the possibility of integrating low grade heat sources to reduce energy consumption. Membrane scaling and pore wetting remain strong limitations to the implementation of MD desalination. In comparison, dense, non-porous PV membranes are considered. In this study, PV membranes made from NEXARTM, a sulfonated pentablock copolymer, were evaluated and compared to polytetrafluoroethylene (PTFE) MD membranes in a vacuum configuration. The membranes were tested using three solutions: 32 g L-1 sodium chloride (NaCl), a brackish water (8.4 g L-1) of high scaling potential, and 5.5 g L-1 NaCl with 1 mM sodium dodecyl sulfate. The NEXARTM membrane achieved a permeance of 93.1±44.6 kg m-2 h-1 bar-1 for the 32 g L-1 brine, which was almost 20% higher than the PTFE MD membrane. This permeance decreased in the presence of foulants; however, in contrast with the MD membrane, where scaling and surfactants induced pore wetting, the salt rejection for the NEXARTM PV membrane was constant at >99% for all water types. These results emphasize the robustness of PV as a process to deal with challenging saline waters.

Background: Gastroesophageal reflux disease (GERD) is highly prevalent after lung transplantation (LTx) and is suspected to favor the development of chronic lung allograft dysfunction (CLAD), almost of bronchiolitis obliterans syndrome (BOS) phenotype. The preventive effect of antireflux surgery (ARS) on BOS/CLAD onset in patients with GERD still remains debated. We compared the outcome (freedom from CLAD and graft survival) of patients with GERD with or without performed ARS (GERD-ARS and GERD-noARS groups) and those without GERD (noGERD group) in our LTx cohort. Methods: Data from 284 LTx recipients with available post-LTx pHmetry findings were reviewed (2001-2014). We focused on the outcome of 244 patients without CLAD at the date of pHmetry. Results: Among 244 stable patients at the date of pHmetry, 78 patients did not have GERD and 166 patients had GERD [41 with and 125 without ARS performed]). The mean DeMeester score was higher in the GERD-ARS group than GERD-noARS group (p = 0.03). An increase in donor-specific antibodies' mean fluorescence intensity values was observed only in GERD after LTx (M6 vs day 0, p

Research Framework : Parents can use at least two strategies to limit the detrimental effects of their child’s use of digital technology. Active mediation refers to sharing, discussing and exchanging opinions with the child on the influences of technology. Restrictive mediation involves setting rules around its usage, as well as technical measures, such as installing parental controls.Objectives : The aim of this study is to examine some parent-specific (i.e., gender, education level, problematic social media use) and family specific (i.e., parental stress, number of siblings, shared responsibility for childcare, child age) determinants that may be associated with the use of these mediations.Methodology: A sample of 112 parents completed surveys (75% women; M age = 33.42; SD = 0.51) whose child (M age = 6.97; SD = 3.89; range = 1 to 16 years old) uses a tablet or mobile phone. Two hierarchical linear regression models with forms of mediation as dependent variables were each tested.Results: Active mediation is positively associated with problematic social media use, the number of siblings and shared responsibility for childcare, and negatively associated with parental stress. Restrictive mediation is not correlated to any of these variables.Conclusions : Since restrictive mediation includes stricter technical measures, it may be associated with circumstantial occurrences, such as a parent’s fear in response to a specific incident.Contribution : A better understanding of the factors and contexts influencing parental mediation behaviours enables us to offer a wider range of strategies adapted to each family’s unique situation. Parents can thus foster the development of safe behaviours their children, without causing unwanted negative effects from the use of digital technologies.

Selective rearranged during transfection (RET) tyrosine kinase inhibitor, pralsetinib, demonstrated clinical efficacy and was well tolerated in lung and thyroid cancers with RET gene mutations or fusions in clinical trials. While the latter focused on the risk of pneumonitis, there is a lack of data regarding other types of infectious risks associated with pralsetinib. Herein, we report the case of a 53-year-old patient with a CCDC6-RET fusion neuroendocrine tumor, who achieved a partial response with pralsetinib as the fifth-line therapy. Of particular note, during pralsetinib therapy, the clinical course was complicated by five severe infectious events, namely, two oxygen-requiring pneumonias, two distinct spondylodiscitis, and one pneumocystis. Our study highlights the increased risk of any type of opportunistic infectious event with pralsetinib, but not selpercatinib, which is probably caused by off-target JAK1/2 inhibition.

Background Pulmonary arterial hypertension (PAH) ultimately leads to right ventricular failure and premature death. The identification of circulating biomarkers with prognostic utility is considered a priority. As chronic inflammation is recognized as key pathogenic driver, we sought to identify inflammation‐related circulating proteins that add incremental value to current risk stratification models for long‐term survival in patients with PAH. Methods and Results Plasma levels of 384 inflammatory proteins were measured with the proximity extension assay technology in patients with PAH (n=60) and controls with normal hemodynamics (n=28). Among these, 51 analytes were significantly overexpressed in the plasma of patients with PAH compared with controls. Cox proportional hazard analyses and C‐statistics were performed to assess the prognostic value and the incremental prognostic value of differentially expressed proteins. A panel of 6 proteins (CRIM1 [cysteine rich transmembrane bone morphogenetic protein regulator 1], HGF [hepatocyte growth factor], FSTL3 [follistatin‐like 3], PLAUR [plasminogen activator, urokinase receptor], CLSTN2 [calsyntenin 2], SPON1 [spondin 1]) were independently associated with death/lung transplantation at the time of PAH diagnosis after adjustment for the 2015 European Society of Cardiology/European Respiratory Society guidelines, the REVEAL (Registry to Evaluate Early and Long‐Term PAH Disease Management) 2.0 risk scores, and the refined 4‐strata risk assessment. CRIM1, PLAUR, FSTL3, and SPON1 showed incremental prognostic value on top of the predictive models. As determined by Western blot, FSTL3 and SPON1 were significantly upregulated in the right ventricle of patients with PAH and animal models (monocrotaline‐injected and pulmonary artery banding‐subjected rats). Conclusions In addition to revealing new actors likely involved in cardiopulmonary remodeling in PAH, our screening identified promising circulating biomarkers to improve risk prediction in PAH, which should be externally confirmed.

Occupational and environmental exposures, particularly those related to urban and suburban atmospheres, are increasingly linked to a range of pulmonary diseases. While diagnostic methods for these diseases are well established, analytical tools for assessing elemental contamination in lung tissue remain underutilized. This study introduces a novel framework based on laser‐induced breakdown spectroscopy (LIBS) for the in situ quantification of elemental titanium (Ti) in lung tissues from both animal models and human specimens. Rigorous validation is conducted using animal models exposed to TiO2 P25 nanoparticles and a comparative analysis with inductively coupled plasma mass spectrometry. The novel quantitative metric Svalue demonstrates robust correlation with elemental concentrations, expanding LIBS utility to volumetric organ analysis. This validated methodology is subsequently applied to human lung specimens preserved in paraffin. The research holds significant promise as a diagnostic tool for assessing exposure levels to environmental or occupational hazards, thereby offering valuable contributions to the fields of toxicology and respiratory medicine.

Interventricular septum pellet retention after air-gunshot injury in a persistently asymptomatic patient is a rare, clinically significant occurrence. Management involved monitoring, echocardiography, and computed tomography scans. After risk-benefit analysis, we favored a nonsurgical management without prophylactic antibiotics or colchicine. No post-traumatic pericarditis was observed. Patient remained asymptomatic and in excellent condition at 1-month follow-up.

ABSTRACTRecent advances in big and streaming data systems have enabled real-time analysis of data generated by Internet of Things (IoT) systems and sensors in various domains. In this context, many applications require integrating data from several heterogeneous sources, either stream or static sources. Frameworks such as Apache Spark are able to integrate and process large datasets from different sources. However, these frameworks are hard to use when the data sources are heterogeneous and numerous. To address this issue, we propose a system based on mediation techniques for integrating stream and static data sources. The integration process of our system consists of three main steps: configuration, query expression and query execution. In the configuration step, an administrator designs a mediated schema and defines mapping between the mediated schema and local data sources. In the query expression step, users express queries using customized SQL grammar on the mediated schema. Finally, our system rewrites the query into an optimized Spark application and submits the application to a Spark cluster. The results are continuously returned to users. Our experiments show that our optimizations can improve query execution time by up to one order of magnitude, making complex streaming and spatial data analysis more accessible.

Abstract Background Iron deficiency (ID) is often associated with other comorbidities in older patients and is a factor of morbimortality. However, the prevalence of ID remains poorly documented in this population. Methods The CARENFER PA study was a French multicenter cross-sectional study whose objective was to evaluate ID in patients (> 75 years) admitted to a geriatric unit. The primary endpoint was the ID prevalence defined as: serum ferritin

Abstract Aims From a patient and health system perspective, managing worsening heart failure (WHF) as an outpatient has become a priority. Remote management allows early detection of WHF, enabling timely intervention with the aim of preventing hospitalization. The objective of the study was to evaluate the feasibility and safety of remotely managing WHF events using a multiparametric platform. Methods and results All patients enrolled in the heart failure remote management programme of the Bordeaux University Hospital Telemedicine Center between 1 January and 31 December 2021 were included in the study. Follow‐up data were collected until 1 March 2022. Inclusion criteria were chronic heart failure (HF) with New York Heart Association ≥II symptoms and an elevated B‐type natriuretic peptide (BNP > 100 pg/mL or N‐terminal‐pro‐BNP > 1000 pg/mL). Patient assessments were performed remotely and included measurements of body weight, blood pressure, heart rate, symptoms, biochemical parameters, and data from cardiac implantable electronic devices when available. In total, 161 patients (71 ± 11 years old, 79% male) were followed for a mean of 291 ± 66 days with a mean adherence to the remote monitoring system of 80 ± 20%. Over this period, 52 (32.3%) patients had 105 WHF events, of which 66 (63%) were successfully managed remotely, the remaining requiring hospitalization. Freedom from WHF events and hospitalization at 300 days were 66% and 85%, respectively (P

Abstract Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms.

Measuring resistances at the nanoscale has attracted recent attention for developing microelectronic components, memory devices, molecular electronics, and two-dimensional materials. Despite the decisive contribution of scanning probe microscopy in imaging resistance and current variations, measurements have remained restricted to qualitative comparisons. Reference resistance calibration samples are key to advancing the research-to-manufacturing process of nanoscale devices and materials through calibrated, reliable, and comparable measurements. No such calibration reference samples have been proposed so far. In this work, we demonstrate the development of a multi-resistance reference sample for calibrating resistance measurements in conductive probe atomic force microscopy (C-AFM) covering the range from 100 Ω to 100 GΩ. We present a comprehensive protocol for in situ calibration of the whole measurement circuit encompassing the tip, the current sensing device, and the system controller. Furthermore, we show that our developed resistance reference enables the calibration of C-AFM with a combined relative uncertainty (given at one standard deviation) lower than 2.5% over an extended range from 10 kΩ to 100 GΩ and lower than 1% for a reduced range from 1 MΩ to 50 GΩ. Our findings break through the long-standing bottleneck in C-AFM measurements, providing a universal means for adopting calibrated resistance measurements at the nanoscale in the industrial and academic research and development sectors.

Background: Social Communication Disorder (SCD), introduced in the DSM-5, is distinguished from Autism Spectrum Disorder (ASD) by the absence of restricted and repetitive behaviors or interests (RRBIs). Aim: To compare the adaptive, sensory, communication, and cognitive profiles of children with ASD and SCD. Methods: The assessments of nine children with SCD and ten with ASD were compared with either Fisher’s Exact Test or the Mann–Whitney Test. Assessments included the Vineland Adaptive Behavior Scales, the Autism Diagnostic Observation Schedule (ADOS), the Short Sensory Profile, Bishop’s Children’s Communication Checklist, a pragmatics evaluation, and the Wechsler Intelligence Scale for Children IV. Results: The total ADOS score and the second subtotal “Restricted and Repetitive Behaviors” were significantly higher (p = 0.022) in the ASD group than in the SCD group. The Vineland standard score for the “Socialization” domain was significantly lower (p = 0.037) in the ASD group (mean: 51 +/− 19) than in the SCD group (mean: 80 +/− 28). The working memory index score was also significantly lower (p = 0.013) in the ASD group compared to the SCD group. Conclusions: While ASD and SCD share similarities in communication and pragmatic difficulties, some distinctions have been identified, e.g. in executive functioning and the impact on socialization, which may be linked to the absence of RRBIs in SCD. These findings highlight the challenges posed by this nosographic separation during diagnostic evaluations due to the scarcity of discriminative tools.

A 2.5-month-old girl admitted for failure to thrive and severe pancytopenia was diagnosed with methylmalonic acidemia (MMA) secondary to transcobalamin II deficiency, an inborn error of vitamin B12 metabolism. Opportunistic Cytomegalovirus and Pneumocystis jirovecii pneumonia led to severe acute respiratory distress syndrome (ARDS) and immune reconstitution inflammatory syndrome (IRIS) after treatment initiation with vitamin B12 supplementation. In children with interstitial pneumonia-related ARDS, normal lymphocyte count should not delay invasive procedures required to document opportunistic infections. MMA can be associated with underlying lymphocyte dysfunction and vitamin B12 supplementation can fully reverse the associated immunodeficiency. IRIS may appear in highly treatment-responsive forms of pancytopenia in children and prompt treatment of dysregulated inflammation with high-dose corticosteroids should be initiated.

Introduction Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control ‘on-demand’ arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental ‘systematic’ arm, VA-ECMO will be pre-emptively initiated. We hypothesise a ‘systematic’ strategy will increase the number of ventilatory-free days at day 28.Methods and analysis We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events.Ethics and dissemination The sponsor is the Assistance Publique–Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals.Trial registration number NCT05664204.

Background. The benefit of extracorporeal photopheresis on the course of kidney transplant rejection is unknown. The aim of our study was to investigate the variations in transcriptomics on graft biopsies when extracorporeal photopheresis was used to treat chronic humoral rejection after kidney transplantation. Methods. We retrospectively analyzed the mRNA expression of 770 genes of interest in graft biopsies performed before and after treatment. Eight patients received an average of 23 extracorporeal photopheresis sessions over 4 mo between the 2 biopsies. Results. Transcriptomic analysis of the graft biopsies identified a significant (adjusted P

RÉSUMÉLa plateforme nationale collaborative des repères de crues, réalisée par le réseau Vigicrues, est destinée à collecter, partager des marques d’inondation de tous types et à en faciliter l’exploitation. Ces marques, qu’elles soient des repères physiques d’événements anciens ou des laisses éphémères relevées suite à des inondations récentes, constituent un patrimoine collectif précieux et indispensable, d’une part pour entretenir la culture du risque, d’autre part pour réaliser les études et modélisations visant à prévenir et prévoir les inondations.Dans cet article, nous présentons différentes analyses du patrimoine, constitué mi-2023 d’environ 75 000 repères, et un recensement, non exhaustif, d’usages pour la collecte et la gestion des repères de crues sur les territoires.Après 7 années d’existence, la plateforme des repères de crues ainsi que son référentiel de données sont adoptés comme la référence nationale en matière de recensement de marques d’inondations et l’enrichissement de la base de données est continu. Le recensement des repères historiques reste à compléter sur certains secteurs, cependant, grâce à l’amélioration des organisations régionales, au développement d’outils facilitant la collecte et au support mutualisé offert par la plateforme, les nouveaux repères sont plus systématiquement relevés et valorisés suite aux événements d’inondation majeurs.

Reducing contributions from non-neuronal sources is a crucial step in functional magnetic resonance imaging (fMRI) connectivity analyses. Many viable strategies for denoising fMRI are used in the literature, and practitioners rely on denoising benchmarks for guidance in the selection of an appropriate choice for their study. However, fMRI denoising software is an ever-evolving field, and the benchmarks can quickly become obsolete as the techniques or implementations change. In this work, we present a denoising benchmark featuring a range of denoising strategies, datasets and evaluation metrics for connectivity analyses, based on the popular fMRIprep software. The benchmark prototypes an implementation of a reproducible framework, where the provided Jupyter Book enables readers to reproduce or modify the figures on the Neurolibre reproducible preprint server (https://neurolibre.org/). We demonstrate how such a reproducible benchmark can be used for continuous evaluation of research software, by comparing two versions of the fMRIprep. Most of the benchmark results were consistent with prior literature. Scrubbing, a technique which excludes time points with excessive motion, combined with global signal regression, is generally effective at noise removal. Scrubbing was generally effective, but is incompatible with statistical analyses requiring the continuous sampling of brain signal, for which a simpler strategy, using motion parameters, average activity in select brain compartments, and global signal regression, is preferred. Importantly, we found that certain denoising strategies behave inconsistently across datasets and/or versions of fMRIPrep, or had a different behavior than in previously published benchmarks. This work will hopefully provide useful guidelines for the fMRIprep users community, and highlight the importance of continuous evaluation of research methods.

Pregnancy and the postpartum period represent phases of heightened vulnerability to thrombotic microangiopathies (TMAs), as evidenced by distinct patterns of pregnancy-specific TMAs (e.g., preeclampsia, HELLP syndrome), as well as a higher incidence of nonspecific TMAs, such as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome, during pregnancy. Significant strides have been taken in understanding the underlying mechanisms of these disorders in the past 40 years. This progress has involved the identification of pivotal factors contributing to TMAs, such as the complement system, ADAMTS13, and the soluble VEGF receptor Flt1. Regardless of the specific causal factor (which is not generally unique in relation to the usual multifactorial origin of TMAs), the endothelial cell stands as a central player in the pathophysiology of TMAs. Pregnancy has a major impact on the physiology of the endothelium. Besides to the development of placenta and its vascular consequences, pregnancy modifies the characteristics of the women’s microvascular endothelium and tends to render it more prone to thrombosis. This review aims to delineate the distinct features of pregnancy-related TMAs and explore the contributing mechanisms that lead to this increased susceptibility, particularly influenced by the “gravid endothelium.” Furthermore, we will discuss the potential contribution of histopathological studies in facilitating the etiological diagnosis of pregnancy-related TMAs.

The theme of “Power and Letters” can hardly be dissociated from its counterpoint “Letters and Power”. In a state where there was no institutionalised censorship, but where the power of the emperor increased markedly after the crisis of the 3rd century, we will begin by looking at the main means that the sovereigns and their entourage had at their disposal to control literary production. This will be followed by an overview of courtly production, in particular panegyric literature, its codification and the significant changes it underwent throughout the period under consideration. Finally, we will look at the political function of literature, particularly in its parenetic dimension. Without excluding the eastern part of the empire and Greek literature, the focus will be on the western and Latin-speaking world.

Abstract In patients with type 2 diabetes, pancreatic beta cells progressively degenerate and gradually lose their ability to produce insulin and regulate blood glucose. Beta cell dysfunction and loss is associated with an accumulation of aggregated forms of islet amyloid polypeptide (IAPP) consisting of soluble prefibrillar IAPP oligomers as well as insoluble IAPP fibrils in pancreatic islets. Here, we describe a human monoclonal antibody selectively targeting IAPP oligomers and neutralizing IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro. Antibody treatment in male rats and mice transgenic for human IAPP, and human islet-engrafted mouse models of type 2 diabetes triggers clearance of IAPP oligomers resulting in beta cell protection and improved glucose control. These results provide new evidence for the pathological role of IAPP oligomers and suggest that antibody-mediated removal of IAPP oligomers could be a pharmaceutical strategy to support beta cell function in type 2 diabetes.

The Amazonian region covers a significant part of the South American continent and harbors outstanding biodiversity. However, much of its history is still unknown. This situation has begun to change with paleontological field efforts over the last decades, which have been proving that fossils can be common in this region. Despite their great current species richness and abundance in the area today, marsupials have a sparse fossil record, restricted to a few specimens from handful Cenozoic Amazonian localities. Here we present new records of fossil marsupial teeth from the Solimões Formation (lower Eocene–Pliocene), on the Juruá and Envira riverbanks (Acre, Northwestern Brazil). The localities investigated yield at least four distinct didelphid didelphimorphians at PRE 06 (Ponto Rio Envira: Marmosini ?Marmosa sp., Didelphis cf. D. solimoensis, Thylamys? colombianus, plus unidentified didelphids), and two paucituberculatans from the Juruá River localities (Ponto Rio Juruá: the palaeothentid Palaeothentinae indet. at PRJ 25 and PRJ 33’, and Abderitidae indet. from PRJ 33). In agreement with the associated mammalian faunas, most of the didelphids, except for Thylamys? colombianus from PRE 06, indicate a (?early) Late Miocene age for this locality. Conversely, the abderitid specimens found in situ at PRJ 33 would match a Middle Miocene age. The palaeothentids found at PRJ 25 and PRJ 33’ localities cannot be considered for biostratigraphic inferences, since they were found outside a stratigraphic context. Nevertheless, these paucituberculatans considerably add to our knowledge, as they are the first ever recorded in Brazilian Amazonia.

Abstract Background Headache disorders are the most common neurological disorders worldwide. Despite their widespread prevalence and importance, the topic of headache is inconsistently taught at both the undergraduate and postgraduate levels. The goal of this study is to establish a better picture of the current state of Headache Medicine (HM) training in Neurology postgraduate programs in Canada and describe the impact of the current pandemic on training in this domain. Methods Online surveys were sent to senior residents of adult Neurology programs in Canada. We also conducted telephone interviews with Neurology Program Directors. Descriptive statistics were analyzed, and thematic analysis was used to review free text. Results A total of 36 residents, and 3 Program Directors participated in the study. Most of the teaching in HM is done by headache specialists and general neurology faculty. Formal teaching is mainly given during academic half day. Most of the programs expose their residents to Onabotulinum toxin A injections and peripheral nerve blocks, but they don’t offer much formal teaching regarding these procedures. Residents consider HM teaching important and they would like to have more. They don’t feel comfortable performing interventional headache treatments, despite feeling this should be part of the skillset of a general neurologist. Conclusion Our study is the first to establish the current state of headache teaching in post-graduate neurology programs as perceived by trainees and program directors in Canada. The current educational offerings leave residents feeling poorly prepared to manage headaches, including procedural interventions. There is a need to diversify the source of teaching, so the educational burden doesn’t lie mostly upon Headache specialists who are already in short supply. Neurology Residency programs need to adapt their curriculum to face the current need in HM.

Abstract The aim of the Protocole National De Diagnostic et de Soins/French National Protocol for Diagnosis and Healthcare (PNDS) is to provide advice for health professionals on the optimum care provision and pathway for patients with glycogen storage disease type III (GSD III).The protocol aims at providing tools that make the diagnosis, defining the severity and different damages of the disease by detailing tests and explorations required for monitoring and diagnosis, better understanding the different aspects of the treatment, defining the modalities and organisation of the monitoring. This is a practical tool, to which health care professionals can refer. PNDS cannot, however, predict all specific cases, comorbidities, therapeutic particularities or hospital care protocols, and does not seek to serve as a substitute for the individual responsibility of the physician in front of his/her patient.

Abstract Background The prevalence of post-surgical lumbar neuropathic radiculopathy is approximately 30%. Poor response to the recommended treatments for neuropathic pain, namely antidepressants and/or gabapentinoids, requires the development of new techniques to prevent chronic pain. One such well-tolerated technique is the administration of autologous plasma enriched in platelets and fibrin (PRF). This approach is largely used in regenerative medicine owing to the anti-inflammatory and analgesic properties of PRF. It could also be an interesting adjuvant to surgery, as it reduces neurogenic inflammation and promotes nerve recovery, thereby reducing the incidence of residual postoperative chronic pain. The aim of the present study is to evaluate the benefit of periradicular intraoperative application of PRF on the residual postsurgical neuropathic pain after disc herniation surgery. Methods A randomized, prospective, interventional, controlled, single-blind study with evaluation by a blind outcome assessor will be performed in Strasbourg University Hospital. We will compare a control group undergoing conventional surgery to an experimental group undergoing surgery and periradicular administration of PRF (30 patients in each arm). The primary outcome is the intensity of postoperative neuropathic radicular pain, measured by a visual analog scale (VAS) at 6 months post-surgery. The secondary outcomes are the characteristics of neuropathic pain (NPSI), the quality of life (SF-12 and PGIC), the presence of anxiety/depression symptoms (HAD), and the consumption of analgesics. We will also carry out transcriptomic analysis of a panel of pro- and anti-inflammatory cytokines in blood samples, before surgery and at 6 months follow-up. These gene expression results will be correlated with clinical data, in particular, with the apparition of postoperative neuropathic pain. Discussion This study is the first randomized controlled trial to assess the efficacy of PRF in the prevention of neuropathic pain following surgery for herniated disc. This study addresses not only a clinical question but will also provide information on the physiopathological mechanisms of neuropathic pain. Trial registration This study is registered at ClinicalTrials.gov: NCT05196503 , February 24, 2022.

Convincing evidence of domain growth in the heating of ultrastable glasses suggests that the equilibration dynamics of supercooled liquids could be driven by a nucleation and growth mechanism. We investigate this possibility by simulating the equilibration dynamics of a model glass during both heating and cooling between poorly and well-annealed states. Though we do observe the growth of domains during heating, we find that domains are absent during cooling. This absence is inconsistent with classical nucleation theory. By comparing the equilibration dynamics of our glass with that of two models with kinetic constraints, we demonstrate that dynamical facilitation generically leads to heating driven by domain growth and cooling without domains. Our results provide strong evidence that dynamical facilitation, not nucleation and interfacial-tension-driven domain growth, is the driving mechanism for the equilibration dynamics of glass formers.

Selenium is an essential trace element in our diet, crucial for the composition of human selenoproteins, which include 25 genes such as glutathione peroxidases and thioredoxin reductases. The regulation of the selenoproteome primarily hinges on the bioavailability of selenium, either from dietary sources or cell culture media. This selenium-dependent control follows a specific hierarchy, with “housekeeping” selenoproteins maintaining constant expression while “stress-regulated” counterparts respond to selenium level fluctuations. This study investigates the variability in fetal bovine serum (FBS) selenium concentrations among commercial batches and its effects on the expression of specific stress-related cellular selenoproteins. Despite the limitations of our study, which exclusively used HEK293 cells and focused on a subset of selenoproteins, our findings highlight the substantial impact of serum selenium levels on selenoprotein expression, particularly for GPX1 and GPX4. The luciferase reporter assay emerged as a sensitive and precise method for evaluating selenium levels in cell culture environments. While not exhaustive, this analysis provides valuable insights into selenium-mediated selenoprotein regulation, emphasizing the importance of serum composition in cellular responses and offering guidance for researchers in the selenoprotein field.

The cardiac response to physical exertion is linked to factors such as age, work intensity, and fitness levels. The primary objective of this study was to characterize within-session changes in cardiac response to running in Canadian football athletes, which may indicate physical fatigue. Performance profiles were collected from GPS and heart rate (HR) sensors worn by 30 male Canadian varsity football players (20–26 years old) over 28 games and practices. Running efforts with 60–180 s of rest were detected, and the maximum HR (HRmax) and peak HR recovery (HRRpk) during rest were extracted. Additionally, a new metric of cardiovascular cost (CVC) was developed to reflect the efficiency of the HR response to physical workload. HRmax was higher in games (p < 0.001) and in linemen (p < 0.001), and it increased over time (p < 0.001). HRRpk was higher in skilled players (p < 0.001) and changed over time (p < 0.001) depending on the rest period. CVC was higher in linemen (p < 0.001) and increased over time (p < 0.001). This study demonstrated the utility of HR response metrics to quantify ongoing fatigue experienced by Canadian football athletes and proposed a novel fatigue metric capable of monitoring an athlete’s fatigue state in real time.

Pelagic stingray (Pteroplatytrygon violacea) is the only species of stingray (Dasyatidae) that utilizes both pelagic and demersal habitats. It is the main bycatch species in pelagic longline fisheries targeting bluefin tuna (Thunnus thynnus) in the Gulf of Lions. In the Mediterranean Sea, their stock structure, behavioural ecology and movements are unknown. For the first time in the Mediterranean, 17 individuals (39–60 cm disc width) were tagged with pop-up satellite archival transmitting tags using a novel method of tag attachment to investigate horizontal and vertical movements. The tags were attached for between two and 60 days. Between the months of July and October, pelagic stingray occupied a temperature range of 12.5–26.6 °C, and a depth range extending from the surface to 480 m. Monthly trends in catch-per-unit-effort (CPUE) of pelagic stingray peaked in August and decreased by late autumn. Pelagic stingray may aggregate on the continental shelf during summer and move southwards in early autumn, and this movement pattern is considered in relation to the reproductive cycle and overwintering. At-vessel mortality was low, but there was varying evidence of post-release mortality, indicating the need for further work. Future work and options for bycatch mitigation are also discussed.

This article presents the current state of bibliographic transition in France, the approach and the organization that were applied to make library catalogues compatible with semantic web technologies and bibliographic data on the web. In order to achieve this goal, it is necessary to move to entity-based cataloguing built on the IFLA LRM model. After a thorough study of the RDA standard, which was the first step to take, France has chosen to keep some autonomy and create a national cataloguing standard, RDA-FR, which is an Anglo-American standard adapted to the French context. In order to implement this change, the Bibliographic Transition programme has been assigned to two national bibliographic agencies with three operational pillars representing the three facets of the program: standardisation, training and support for the evolution of systems and data. The choices and the issues are given in details, as well as the missions and achievements of the groups. This organisation has been established to ensure a regular flow of information between the operational and strategic levels on one side and between different groups on the other side. Overall consistency is one of the key features of the programme whose role is to bring together and represent all French libraries and French cultural institutions while taking into account their needs and the needs of their users.

Abstract EPAC1, a cAMP-activated GEF for Rap GTPases, is a major transducer of cAMP signaling and a therapeutic target in cardiac diseases. The recent discovery that cAMP is compartmentalized in membrane-proximal nanodomains challenged the current model of EPAC1 activation in the cytosol. Here, we discover that anionic membranes are a major component of EPAC1 activation. We find that anionic membranes activate EPAC1 independently of cAMP, increase its affinity for cAMP by two orders of magnitude, and synergize with cAMP to yield maximal GEF activity. In the cell cytosol, where cAMP concentration is low, EPAC1 must thus be primed by membranes to bind cAMP. Examination of the cell-active chemical CE3F4 in this framework further reveals that it targets only fully activated EPAC1. Together, our findings reformulate previous concepts of cAMP signaling through EPAC proteins, with important implications for drug discovery.

Differential deposition by DC magnetron sputtering was applied to correct for figure errors of X-ray mirrors to be deployed on low-emittance synchrotron beamlines. During the deposition process, the mirrors were moved in front of a beam-defining aperture and the required velocity profile was calculated using a deconvolution algorithm. The surface figure was characterized using conventional off-line visible-light metrology instrumentation (long trace profiler and Fizeau interferometer) before and after the deposition. WSi2 was revealed to be a promising candidate material since it conserves the initial substrate surface roughness and limits the film stress to acceptable levels. On a 300 mm-long flat Si mirror the average height errors were reduced by a factor of 20 down to 0.2 nm root mean square. This result shows the suitability of WSi2 for differential deposition. Potential promising applications include the upgrade of affordable, average-quality substrates to the standards of modern synchrotron beamlines.

Background/Objectives: Physical Literacy (PL) is increasingly recognized as a key element in studies aimed at promoting Physical Activity (PA), but measurement tools for emerging adults and evidence for assessing and using this concept is lacking in a wide range of contexts. We aimed to validate the French version of the Perceived Physical Literacy Instrument (PPLI): a scale for investigating PL in young French adults. Methods: After PL and PA data collection (n = 2,248, agemean = 19 ± 1.53 yrs), exploratory and confirmatory factor analyses, Cronbach's α and Omega's ω and an Intraclass-Correlation analysis were undertaken. Spearman's rank correlation and the Boruta algorithm were used to investigate the association between PL and PA. Boruta's algorithm examined deeper external validation by analyzing the strength of an overall PL score in explaining PA, compared with separate dimensions of PL and individual characteristics (BMI, sex). Results: Results showed an acceptable level of reliability (ICC = 0.91), internal validity (α = 0.88; ω = 0.77), and external validity (Rhô >0.18, p