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Background and Purpose: Nonalcoholic fatty liver disease refers to liver pathologies, ranging from steatosis to steatohepatitis, with fibrosis ultimately leading to cirrhosis and hepatocellular carcinoma. Although several mechanisms have been suggested, including insulin resistance, oxidative stress, and inflammation, its pathophysiology remains imperfectly understood. Over the last decade, a dysfunctional unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress emerged as one of the multiple driving factors. In parallel, growing evidence suggests that insulin‐degrading enzyme (IDE), a highly conserved and ubiquitously expressed metallo‐endopeptidase originally discovered for its role in insulin decay, may regulate ER stress and UPR. Experimental Approach: We investigated, by genetic and pharmacological approaches, in vitro and in vivo, whether IDE modulates ER stress‐induced UPR and lipid accumulation in the liver. Key Results: We found that IDE‐deficient mice display higher hepatic triglyceride content along with higher inositol‐requiring enzyme 1 (IRE1) pathway activation. Upon induction of ER stress by tunicamycin or palmitate in vitro or in vivo, pharmacological inhibition of IDE, using its inhibitor BDM44768, mainly exacerbated ER stress‐induced IRE1 activation and promoted lipid accumulation in hepatocytes, effects that were abolished by the IRE1 inhibitors 4μ8c and KIRA6. Finally, we identified that IDE knockout promotes lipolysis in adipose tissue and increases hepatic CD36 expression, which may contribute to steatosis. Conclusion and Implications: These results unravel a novel role for IDE in the regulation of ER stress and development of hepatic steatosis. These findings pave the way to innovative strategies modulating IDE to treat metabolic diseases. [ABSTRACT FROM AUTHOR]

Background: In oncology, the suffering of patients and the burnout of health professionals are key issues. Mindfulness meditation is a holistic approach that can help to improve well-being. While numerous studies have shown the benefits of meditation for both patients and health professionals, the added value of offering shared meditation to groups of patients, health professionals and third persons has not been assessed. Beyond strengthening the relationship between carers and patients, opening up meditation sessions to third parties (neither carers nor patients) enables patients to escape the stigma of their illness. We previously conducted a pilot study that validated the feasibility and the relevance of shared meditation with a specifically designed programme. Methods/Design: IMPLIC-2 is a two-arm randomised study designed to assess the added value of this meditation programme (optimised following the pilot study), particularly for cancer patients (our target population). People motivated to follow the programme, without previous regular practice of meditation and able to participate in the sessions are eligible. The study will include 96 participants: 16 health professionals, 16 third persons and 64 patients. The latter will be randomized in two arms: the experimental arm ("Shared" meditation) consisting of 4 mixed groups of 8 patients, 4 health professionals and 4 third parties, and the control arm ("Patient" meditation) consisting of 2 groups of 16 patients. Validated questionnaires will be used to measure the effects of the programme, notably in terms of quality of life, perceived stress, feelings of self-efficacy, qualities of mindfulness and self-compassion, and carers' burn-out. Participants' perception of a change in their quality of life and satisfaction will be measured at the end of the programme. A complementary qualitative focus-group approach will be used to optimise implementation of the programme beyond the study. Discussion: The well-being of oncology patients would be improved. Dealing with overworked carers would have a beneficial impact on the way they interact with patients. In addition, encounters between the three types of population will allow otherness to be viewed differently and alleviate suffering by promoting collective humanity. Trial Registration: NCT06041607, registered: 09/18/2023. Protocol version: Version n°1.2 dated from 08/29/2023. [ABSTRACT FROM AUTHOR]

Traditional myoelectric controls of trans-humeral prostheses fail to provide intuitive coordination of the necessary degrees of freedom. We previously showed that by using artificial neural network predictions to reconstruct distal joints, based on the shoulder posture and movement goals (i.e., position and orientation of the targeted object), participants were able to position and orient an avatar hand to grasp objects with natural arm performances. However, this control involved rapid and unintended prosthesis movements at each modification of the movement goal, impractical for real-life scenarios. Here, we eliminate this abrupt change using novel methods based on an angular trajectory, determined from the speed of stump movement and the gap between the current and the 'goal' distal configurations. These new controls are tested offline and online (i.e., involving participants-in-the-loop) and compared to performances obtained with a natural control. Despite a slight increase in movement time, the new controls allowed twelve valid participants and six participants with trans-humeral limb loss to reach objects at various positions and orientations without prior training. Furthermore, no usability or workload degradation was perceived by participants with upper limb disabilities. The good performances achieved highlight the potential acceptability and effectiveness of those controls for our target population. [ABSTRACT FROM AUTHOR]

This article presents an adaptive remeshing strategy between the finite element method (FEM) and the discrete element method (DEM). To achieve this strategy, an edge‐to‐edge coupling method based on Lagrange multipliers has been set‐up to ensure the continuity of velocities at the interface. To switch from a computation initially purely FEM to a FEM‐DEM one, a field transfer method was required. In particular, a displacement field transfer method has been set‐up. The switching from a FEM subdomain to a DEM one is activated by a transition criterion. Each time a FEM subdomain is substituted by a DEM one, the DEM subdomain microscopic properties are set‐up with respect to the subdomain geometry and desired particle refinement. This is performed thanks to the linking to the so‐called "Cooker," a tool distributed along with the GranOO Workbench. Two subdomain remeshing cases were dealt with: that of an initially FEM subdomain that is converted to DEM, and that of DEM subdomains which coalesce. A numerical test case shows that the dynamic remeshing method behaves as expected: FEM subdomains are substituted by DEM ones when the transition criterion is met, and DEM subdomains coalesce when required. The final numerical test case shows a good agreement with a crack propagation experiment of the literature, while a speedup of about 20 was observed when compared to pure DEM computation. [ABSTRACT FROM AUTHOR]

The haemoglobin content in meat is consistently associated with an increased risk of colorectal cancer, whereas calcium may play a role as a chemopreventive agent. Using rodent models, calcium salts have been shown to prevent the promotion of haem-induced and red meat-induced colorectal carcinogenesis by limiting the bioavailability of the gut luminal haem iron. Therefore, this study aimed to compare impacts of dietary calcium provided as calcium salts or dairy matrix on gut homoeostasis perturbations by high haeminic or non-haeminic iron intakes. A 3-week intervention study was conducted using Fischer 344 rats. Compared to the ferric citrate-enriched diet, the haemoglobin-enriched diet led to increased faecal, mucosal, and urinary lipoperoxidation-related biomarkers, resulting from higher gut luminal haem iron bioavailability. This redox imbalance was associated to a dysbiosis of faecal microbiota. The addition of calcium to haemoglobin-enriched diets limited haem iron bioavailability and counteracted redox imbalance, with improved preventive efficacy when calcium was provided in dairy matrix. Data integration revealed correlations between haem-induced lipoperoxidation products and bacterial communities belonging to Peptococcaceae, Eubacterium coprostanoligenes group, and Bifidobacteriaceae. This integrated approach provides evidence of the benefits of dairy matrix as a dietary calcium vehicle to counteract the deleterious side-effects of meat consumption. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the first cause of death from gynecological malignancies mainly due to development of chemoresistance. Despite the emergence of PARP inhibitors, which have revolutionized the therapeutic management of some of these ovarian cancers, the 5-year overall survival rate remains around 45%. Therefore, it is crucial to develop new therapeutic strategies, to identify predictive biomarkers and to predict the response to treatments. In this context, functional assays based on patient-derived tumor models could constitute helpful and relevant tools for identifying efficient therapies or to guide clinical decision making. Method: The OVAREX study is a single-center non-interventional study which aims at investigating the feasibility of establishing in vivo and ex vivo models and testing ex vivo models to predict clinical response of ovarian cancer patients. Patient-Derived Xenografts (PDX) will be established from tumor fragments engrafted subcutaneously into immunocompromised mice. Explants will be generated by slicing tumor tissues and Ascites-Derived Spheroids (ADS) will be isolated following filtration of ascites. Patient-derived tumor organoids (PDTO) will be established after dissociation of tumor tissues or ADS, cell embedding into extracellular matrix and culture in specific medium. Molecular and histological characterizations will be performed to compare tumor of origin and paired models. Response of ex vivo tumor-derived models to conventional chemotherapy and PARP inhibitors will be assessed and compared to results of companion diagnostic test and/or to the patient's response to evaluate their predictive value. Discussion: This clinical study aims at generating PDX and ex vivo models (PDTO, ADS, and explants) from tumors or ascites of ovarian cancer patients who will undergo surgical procedure or paracentesis. We aim at demonstrating the predictive value of ex vivo models for their potential use in routine clinical practice as part of precision medicine, as well as establishing a collection of relevant ovarian cancer models that will be useful for the evaluation of future innovative therapies. Trial registration: The clinical trial has been validated by local research ethic committee on January 25th 2019 and registered at ClinicalTrials.gov with the identifier NCT03831230 on January 28th 2019, last amendment v4 accepted on July 18, 2023. [ABSTRACT FROM AUTHOR]

Currently, collaborative robots (cobots) are mostly programmed to do one task repetitively. They can be programmed at different speeds and work near human operators. The goal of our research was to investigate the effect of robot speed on acceptance, subjective and objective stress, and cognitive workload of individuals. Therefore, we organized a repeated measures experiment in which participants (N = 25) conducted an assembly task with the YuMi cobot from ABB at a low and at a high speed. Subjective and physiological responses were collected, and participants were subjected to a standardized stress test. Our results indicate that when working with a cobot at a high speed, people believe they can work faster and be more productive but also experience a higher workload and higher perceived stress. We also found that tonic EDA is a significant physiological predictor for monitoring perceived stress in humans. We observed a greater relative increase in tonic EDA from baseline to task execution during high-speed mode compared to low-speed mode. Additionally, this increase in tonic EDA significantly correlated with participants' perceived stress levels. However, workload could not be predicted by any of the physiological measures. Future research should explore the effect of higher cobot working speeds and the use of physiological measures (such as stress) as input to guide the collaboration between individuals and cobots. [ABSTRACT FROM AUTHOR]

With the new generation of space telescopes such as the James Webb Space Telescope (JWST), it is possible to better characterize the atmospheres of exoplanets. The atmospheres of Hot and ultra-hot Jupiters are highly heterogeneous and asymmetrical. The difference between the temperatures on the day and night sides is especially extreme in the case of ultra-hot Jupiters. We introduce a new tool to compute synthetic light curves from 3D general circulation model (GCM) simulations, developed in the Pytmosph3R framework. We show how rotation induces a variation in the flux during the transit that is a source of information on the chemical and thermal distribution of the atmosphere. We find that the day–night gradient linked to ultra-hot Jupiters has an effect close to stellar limb darkening, but opposite to tidal deformation. We confirm the impact of the atmospheric and chemical distribution on variations in the central transit time, though the variations found are smaller than those in available observational data, which could indicate that the east–west asymmetries are underestimated, due to the chemistry or clouds. [ABSTRACT FROM AUTHOR]

In the context of global warming, it is crucial to focus on the effects of temperature on the emergence of new lineages of endemic pathogen species, such as Puccinia striiformis f. sp. tritici (Pst) the causal agent of yellow rust on wheat. We characterized the thermal aptitude of representative isolates from the most recent common European Pst races. We assessed two key aggressiveness components—infection efficiency (IE) and latency period (LP)—under warm and cold thermal regimes, comparing 10 Pst isolates collected from 2010 to 2020 with three "old" reference isolates. The significant differences observed suggest that this species has the potential to adapt to temperature changes, but that such adaptation probably did not drive the establishment of neither the previously dominant races 'Warrior' and 'Warrior(-)', nor the following most recent races. These races display "generalist" behavior with respect to temperature, with 'Warrior(-)' showing no more aggressiveness than the races replaced since the 1990s. The differences in competitive success between emerging Pst lineages are probably due to the deployment of resistance genes in wheat and the advantages of new forms of virulence emerging independently of thermal adaptability. However, variations in thermal adaptability for both aggressiveness components suggested an impact of geographic origin within the 'Warrior' and 'Warrior(-)' races, as previously reported for the "old" reference isolates. Furthermore, the independence of thermal adaptability established for IE and LP implies that the effects of temperature may depend on the stage of the epidemic (early or late), potentially modifying seasonal dynamics. [ABSTRACT FROM AUTHOR]

Understanding the potato tuber development and effects of drought at key stages of sensitivity on yield is crucial, particularly when considering the increasing incidence of drought due to climate change. So far, few studies addressed the time course of tuber growth in soil, mainly due to difficulties in accessing underground plant organs in a non‐destructive manner. This study aims to understand the tuber growth and quality and the complex long‐term effects of realistic water stress on potato tuber yield. MRI was used to monitor the growth kinetics and spatialization of individual tubers in situ and the evolution of internal defects throughout the development period. The intermittent drought applied to plants reduced tuber yield by reducing tuber growth and increasing the number of aborted tubers. The reduction in the size of tubers depended on the vertical position of the tubers in the soil, indicating water exchanges between tubers and the mother plant during leaf dehydration events. The final size of tubers was linked with the growth rate at specific developmental periods. For plants experiencing stress, this corresponded to the days following rewatering, suggesting tuber growth plasticity. All internal defects occurred in large tubers and within a short time span immediately following a period of rapid growth of perimedullary tissues, probably due to high nutrient requirements. To conclude, the non‐destructive 3D imaging by MRI allowed us to quantify and better understand the kinetics and spatialization of tuber growth and the appearance of internal defects under different soil water conditions. [ABSTRACT FROM AUTHOR]

Geographical features may have a considerable effect on local climate. The local climate zone (LCZ) system proposed by is nowadays seen as a standard approach for classifying any zone according to a set of urban canopy parameters. While many methods already exist to map the LCZ, only few tools are openly and freely available. This paper presents the algorithm implemented in the GeoClimate software to identify the LCZ of any place in the world based on vector data. Six types of information are needed as input: the building footprint, road and rail networks, water, vegetation, and impervious surfaces. First, the territory is partitioned into reference spatial units (RSUs) using the road and rail network, as well as the boundaries of large vegetation and water patches. Then 14 urban canopy parameters are calculated for each RSU. Their values are used to classify each unit to a given LCZ type according to a set of rules. GeoClimate can automatically prepare the inputs and calculate the LCZ for two datasets, namely OpenStreetMap (OSM, available worldwide) and the BD TOPO® v2.2 (BDT, a French dataset produced by the national mapping agency). The LCZ are calculated for 22 French communes using these two datasets in order to evaluate the effect of the dataset on the results. About 55 % of all areas have obtained the same LCZ type, with large differences when differentiating this result by city (from 30 % to 82 %). The agreement is good for large patches of forest and water, as well as for compact mid-rise and open low-rise LCZ types. It is lower for open mid-rise and open high-rise, mainly due to the height underestimation of OSM buildings located in open areas. Through its simplicity of use, GeoClimate has great potential for new collaboration in the LCZ field. The software (and its source code) used to produce the LCZ data is freely available at 10.5281/zenodo.6372337 ; the scripts and data used for the purpose of this article can be freely accessed at 10.5281/zenodo.7687911 and are based on the R package available at 10.5281/zenodo.7646866. [ABSTRACT FROM AUTHOR]

In northern cold-temperate countries, a large portion of annual streamflow is produced by spring snowmelt, which often triggers floods. It is important to have spatial information about snow variables such as snow water equivalent (SWE), which can be incorporated into hydrological models, making them more efficient tools for improved decision-making. The present research implements a unique spatial pattern metric in a multi-objective framework for calibration of hydrological models and attempts to determine whether raw SNODAS (SNOw Data Assimilation System) data can be utilized for hydrological model calibration. The spatial efficiency (SPAEF) metric is explored for spatially calibrating SWE. Different calibration experiments are performed combining Nash–Sutcliffe efficiency (NSE) for streamflow and root-mean-square error (RMSE) and SPAEF for SWE, using the Dynamically Dimensioned Search (DDS) and Pareto Archived Dynamically Dimensioned Search multi-objective optimization (PADDS) algorithms. Results of the study demonstrate that multi-objective calibration outperforms sequential calibration in terms of model performance (SWE and discharge simulations). Traditional model calibration involving only streamflow produced slightly higher NSE values; however, the spatial distribution of SWE could not be adequately maintained. This study indicates that utilizing SPAEF for spatial calibration of snow parameters improved streamflow prediction compared to the conventional practice of using RMSE for calibration. SPAEF is further implied to be a more effective metric than RMSE for both sequential and multi-objective calibration. During validation, the calibration experiment incorporating multi-objective SPAEF exhibits enhanced performance in terms of NSE and Kling–Gupta efficiency (KGE) compared to calibration experiment solely based on NSE. This observation supports the notion that incorporating SPAEF computed on raw SNODAS data within the calibration framework results in a more robust hydrological model. The novelty of this study is the implementation of SPAEF with respect to spatially distributed SWE for calibrating a distributed hydrological model. [ABSTRACT FROM AUTHOR]

Women undergoing controlled ovarian hyperstimulation prior to in vitro fertilization (IVF) are treated using various protocols to induce multiple follicular growths. Complete failure of all oocytes to mature during IVF cycles is rare; however, it is a known cause of primary female infertility. Recently, pathogenic variations in a few genes have been identified in women with oocyte maturation defects; however, the underlying genetic causes remain largely unknown. This study included a Turkish family comprising three sisters with recurring oocyte maturation arrest at the germinal vesicle stage after multiple ovarian stimulations. Exome sequencing revealed a homozygous missense variant (c.1037C>T, p.Ala346Val) in the EPAB gene (also known as PABPC1L) in all three affected sisters, which was either absent or heterozygous in the unaffected family members. Functional experiments confirming the pathogenicity of the variant were performed by transfecting HEK293T cells and demonstrated the instability and increased rate of proteolysis of the mutated PABPC1L/EPAB protein. The identified variant, located in the well-conserved fourth RNA recognition motif (RRM4), in silico 3D modelling suggested changes in the physical properties of the pathogenic variant of PABPC1L/EPAB. Our findings validate PABPC1L/EPAB as an essential genetic contributor to the oocyte maturation process in humans and have direct implications for the genetic counselling of patients and their family members. [ABSTRACT FROM AUTHOR]

Collisionless trapped-electron mode (CTEM) turbulence is an important contributor to heat and particle transport in fusion devices. The ion-temperature gradient (ITG)/trapped-electron mode (TEM) fluid models are rarely treated analytically, due to the large number of transport channels involved, e.g., particle and ion/electron heat transport. The CTEM fluid model [Anderson et al., Plasma Phys. Controlled Fusion 48, 651 (2006)] provides a simplified model, in the regime where the density gradient drive (∇ n) is negligible compared to the electron temperature gradient drive (∇ T e ). This provides a starting point to study mechanisms associated with linear waves, such as crossphase dynamics, and its possible role in the formation of E × B staircase. Here, an extended CTEM fluid model (with both ∇ n and ∇ T e drive) is derived from the more general ITG/TEM model, using a simplified ion density response, and its linear dynamics is first analyzed and compared with CTEM gyrokinetic simulations with bounce-averaged kinetic electrons, while nonlinear analysis is left for future work. The wave action density is derived for this CTEM model. Comparisons of linear ITG spectrum are also made with other analytical models. [ABSTRACT FROM AUTHOR]

Balance involves several sensory modalities including vision, proprioception and the vestibular system. This study aims to investigate vestibulospinal activation elicited by tone burst stimulation in various muscles and how head position influences these responses. We recorded electromyogram (EMG) responses in different muscles (sternocleidomastoid-SCM, cervical erector spinae-ES-C, lumbar erector spinae-ES-L, gastrocnemius-G, and tibialis anterior-TA) of healthy participants using tone burst stimulation applied to the vestibular system. We also evaluated how head position affected the responses. Tone burst stimulation elicited reproducible vestibulospinal reflexes in the SCM and ES-C muscles, while responses in the distal muscles (ES-L, G, and TA) were less consistent among participants. The magnitude and polarity of the responses were influenced by the head position relative to the cervical spine. When the head was rotated or tilted, the polarity of the vestibulospinal responses changed, indicating the integration of vestibular and proprioceptive inputs in generating these reflexes. Overall, our study provides valuable insights into the complexity of vestibulospinal reflexes and their modulation by head position. However, the high variability in responses in some muscles limits their clinical application. These findings may have implications for future research in understanding vestibular function and its role in posture and movement control. [ABSTRACT FROM AUTHOR]

This study investigates the impact of gravity on lower limb muscle coordination during pedaling. It explores how pedaling behaviors, kinematics, and muscle activation patterns dynamically adapts to changes in gravity and resistance levels. The experiment was conducted in parabolic flights, simulating microgravity, hypergravity (1.8 g), and normogravity conditions. Participants pedaled on an ergometer with varying resistances. The goal was to identify potential changes in muscle synergies and activation strategies under different gravitational contexts. Results indicate that pedaling cadence adjusted naturally in response to both gravity and resistance changes. Cadence increased with higher gravity and decreased with higher resistance levels. Muscular activities were characterized by two synergies representing pull and push phases of pedaling. The timing of synergy activation was influenced by gravity, with a delay in activation observed in microgravity compared to other conditions. Despite these changes, the velocity profile of pedaling remained stable across gravity conditions. The findings strongly suggest that the CNS dynamically manages the shift in body weight by finely tuning muscular coordination, thereby ensuring the maintenance of a stable motor output. Furthermore, electromyography analysis suggest that neuromuscular discharge frequencies were not affected by gravity changes. This implies that the types of muscle fibers recruited during exercise in modified gravity are similar to those used in normogravity. This research has contributed to a better understanding of how the human locomotor system responds to varying gravitational conditions, shedding light on the potential mechanisms underlying astronauts' gait changes upon returning from space missions. [ABSTRACT FROM AUTHOR]

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In a companion paper, we introduced a publicly available pipeline to characterize exoplanet atmospheres through high-resolution spectroscopy. In this paper, we use this pipeline to study the biases and degeneracies that arise in atmospheric characterization of exoplanets in near-infrared ground-based transmission spectroscopy. We inject synthetic planetary transits into sequences of SPIRou spectra of the well known M dwarf star Gl 15 A, and study the effects of different assumptions on the retrieval. We focus on (i) mass and radius uncertainties, (ii) non-isothermal vertical profiles, and (iii) identification and retrieval of multiple species. We show that the uncertainties on mass and radius should be accounted for in retrievals and that depth-dependent temperature information can be derived from high-resolution transmission spectroscopy data. Finally, we discuss the impact of selecting wavelength orders in the retrieval and the issues that arise when trying to identify a single species in a multispecies atmospheric model. This analysis allows us to understand better the results obtained through transmission spectroscopy and their limitations in preparation to the analysis of actual SPIRou data. [ABSTRACT FROM AUTHOR]

Objective: To examine the characteristics and the effectiveness of virtual reality systems on upper limb impairments in children and young adults with cerebral palsy. Data sources: An electronic search was conducted on PubMed, PEDro, Web of Science, Central, and EMBASE. Methods: The protocol of this review was prospectively registered in the PROSPERO database (CRD42022302271). Randomized controlled trials that tested the effects of virtual reality-based interventions on the upper limb of participants with cerebral palsy were included. The methodological quality of the studies was measured by the PEDro scale. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. The data of the studies were analyzed in meta-analysis and presented in forest plots and narrative synthesis. Results: Twenty-two studies involving 746 participants were included. Ten different virtual reality systems were used in the interventions, of which six were designed specifically for rehabilitation and four commercial video games. We found an effect in favor of virtual reality when it was used in combination with conventional therapy for upper limb activity (SMD = 0.65; 95% CI (0.19 to 1.11)). However, the certainty of the evidence of the comparisons ranged from very low to low. Conclusion: Virtual reality seems to be an effective tool for upper limb activity in children and young adults with cerebral palsy. Nevertheless, future studies should present a better methodological quality, a larger sample size, and well-defined rehabilitation programs to reduce the inconsistency of the evidence in this domain. [ABSTRACT FROM AUTHOR]

Purpose: Acute radiodermatitis (ARD) is a frequent side effect of radiotherapy, a therapeutic option for head and neck squamous cell carcinoma (HNSCC). It is responsible for pain, quality of life (QoL) impairment, and increased risk of treatment discontinuation, which may compromise the prognosis for patients. Local therapies to prevent or alleviate ARD have been proposed without providing any high level of evidence to establish recommendations. Methods: We implemented a prospective multicenter randomized study on patients with HNSCC treated with definitive radiotherapy to assess the impact on ear, nose, and throat (ENT) pain of the application of a hydrogel-based skin dressing (HydroTac®) compared with the application of hyaluronic acid (Ialuset®) during radiotherapy. Results: Out of 130 enrolled patients, 48 patients per group were assessable for the main endpoint. No difference between groups was found: a worsening of ENT pain of 3 points or more on a visual analog scale from the initiation to 1 month after the end of the radiotherapy was observed for 8 patients (16.7%) who received HydroTac® compared to 13 patients (27%) who received Ialuset® (p = 0.342). The proportion of patients who experienced ARD and grades of ARD (CTCAE v4.0 criteria) were similar between groups. Patient compliance with radiodermatitis treatment was poor, with 56.1% of patients in the HydroTac® group having their treatment temporarily stopped. Conclusion: The application of a hydrogel dressing to prevent ARD during radiotherapy for HNSCC patients has failed to demonstrate a benefit. These results may be limited by the difficulties of applying the dressing. [ABSTRACT FROM AUTHOR]

Purpose: Food and Alcohol Disturbance (FAD) is characterized by the combination of problematic alcohol use and eating disorder symptoms to offset caloric intake associated with alcohol drinking and/or to enhance intoxication. The Compensatory Eating and Behaviors in Response to Alcohol Consumption Scale (CEBRACS) is a proven tool for measuring FAD, validated in English and Italian populations but never in the French population. The present study aims at validating a French version of the CEBRACS in a representative sample of university students and to determine its validity and reliability. Methods: 2267 university students completed the CEBRACS and measures of eating disorders, alcohol consumption and exercise. Results: An exploratory factor analysis revealed a 4-factor structure: enhancement of the effects of alcohol, dietary restraint and exercise, purging and vomiting and extreme fasting. The internal consistency for these subscales ranged from good to excellent. Correlations between the CEBRACS and eating disorders, alcohol and exercise measures revealed a good concurrent validity. No gender differences were found in the CEBRACS scores. Participants with a CEBRACS total score > 21 points were at higher risk for developing eating disorders and alcohol-related problems. Conclusions: These findings highlight the reliability and validity of the French version of the CEBRACS. The distinct factors identified in the CEBRACS allow to distinguish between participants with different motives for engaging FAD behaviour and thus to prevent future development of eating and/or alcohol use disorders. The CEBRACS seems to be a relevant scale to capture FAD behaviors and thus to prevent negative and deleterious consequences. Level of evidence: Level III, evidence obtained from well-designed cohort or case–control analytic studies. [ABSTRACT FROM AUTHOR]

Robust clinical activity has been observed with the immune checkpoint inhibitor pembrolizumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). However, given the response rate of 45% and a median progression-free survival of 16.5 months with first-line pembrolizumab demonstrated in KEYNOTE-177, there is room for improvement. Targeting a second immune receptor, such as CTLA-4, LAG-3, TIGIT, or ILT-4 may improve efficacy of PD-1 inhibition. Here we describe the design and rationale for the open-label, randomized, phase II KEYSTEP-008 trial, which will evaluate the efficacy and safety of pembrolizumab-based combination therapy compared with pembrolizumab monotherapy in chemotherapy-refractory (cohort A) or previously untreated (cohort B) MSI-H/dMMR mCRC. Clinical Trial Registration:NCT04895722 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA), depression, and substance abuse problems share similar symptomatology and have significant interplay. An underlying diagnosis of OSA can often be overlooked in patients with significant psychiatric illness and polysubstance use. Pediatric OSA is often associated with adenotonsillar hypertrophy and frequently requires surgical intervention for resolution of symptoms. Untreated OSA can worsen mental status and encourage polysubstance abuse as a form of self-medication. Proper identification and management of OSA plays an important role in treating psychiatric conditions. We report a 16-year-old with major depressive disorder (MDD), suicide attempts, polysubstance use disorder, and severe OSA admitted to an inpatient psychiatric facility. History included sleep and mood disturbances started at age 12. Patient presented with apnea–hypopnea index greater than 50 and started on bilevel-positive airway pressure (BiPAP) prior to admission. Management of OSA led to significant improvement of MDD, insomnia, and polysubstance abuse. OSA can often be overlooked in patients with MDD or substance abuse. Among adolescent patients with poorly managed psychiatric conditions, significant sleep disturbances, and polysubstance abuse, providers should maintain a high degree of suspicion for OSA, as its proper management will aid in the management of the other conditions. [ABSTRACT FROM AUTHOR]

Background/Aims Achalasia and hiatal hernia are rarely associated. The aim of the current study is to explore the clinical and manometric findings in patients with achalasia and hiatal hernia, and to determine if the presence of a hiatal hernia should influence therapeutic management in patients with achalasia. Methods This retrospective single center analysis included a group of patients with achalasia and hiatal hernia (study group) and a group of matched patients with achalasia but no hiatal hernia (control group). We recorded demographic, clinical, endoscopic, and manometric parameters and compared initial presentation and treatment outcomes between the groups. Results Between 2015 and 2022, achalasia was diagnosed in 294/1513 (19.4%) patients. Concomitant hiatal hernia was identified in 13/294 (4.4%) patients. Compared to patients with achalasia and no hiatal hernia, patients in the study group had lower Eckardt scores at baseline (5.4 ± 2.0 vs 7.8 ± 2.4; P = 0.005) but similar integrated relaxation pressure. Following treatment, patients in the study and control group had similar clinical success and prevalence of gastroesophageal reflux symptoms. Conclusions Hiatal hernia is rarely associated with achalasia. The presence of a hiatal hernia should not influence treatment decisions in patients with achalasia. [ABSTRACT FROM AUTHOR]

Introduction: COVID‐19 outbreak rapidly spread since early 2020 leading to the implementation of nationwide lockdowns. To cope with this sudden change, management guidelines were quickly published to adapt oncological care, with potential impact on cancer outcomes. Methods: We conducted a retrospective comparative cohort study to assess the impact of the COVID‐19 outbreak in 2020 on cancer outcomes in metastatic patients. Two cohorts of metastatic patients receiving intravenous (iv) therapy in a French oncological day care hospital were assessed: a 2020 cohort during the first French lockdown, and a 2018 historical cohort before the COVID‐19 pandemic. We performed a propensity score analysis to match patients from the two cohorts. After one‐year follow‐up, we compared progression‐free survival (PFS) and overall survival (OS) between cohorts. Adaptations of medical oncological treatments in 2020 were also analysed. Results: The 376 patients of the 2020 cohort were matched with 376 of the 2018 cohort. No SARS‐CoV‐2 infection was observed in the 2020 cohort. The adjusted PFS was significantly shorter in 2020 compared to 2018 (HR = 1.23; 95% CI: 1.03–1.46), as well as among patients without treatment adaptation compared to matched patients of the 2018 cohort (HR = 1.33; 95% CI: 1.10–1.61). We did not observe any significant difference of PFS among the group with treatment adaptations. OS was not significantly different. Conclusion: Metastatic cancer patients treated during the first lockdown had a higher risk of disease progression 1 year after COVID‐19 outbreak. However, oncological treatment adaptations or SARS‐CoV‐2 infections do not explain these results. A longer follow‐up is needed to observe the impact on OS. [ABSTRACT FROM AUTHOR]

Water vapour atmospheres with content equivalent to the Earth’s oceans, resulting from impacts1 or a high insolation2,3, were found to yield a surface magma ocean4,5. This was, however, a consequence of assuming a fully convective structure2–11. Here, we report using a consistent climate model that pure steam atmospheres are commonly shaped by radiative layers, making their thermal structure strongly dependent on the stellar spectrum and internal heat flow. The surface is cooler when an adiabatic profile is not imposed; melting Earth’s crust requires an insolation several times higher than today, which will not happen during the main sequence of the Sun. Venus’s surface can solidify before the steam atmosphere escapes, which is the opposite of previous works4,5. Around the reddest stars (Teff < 3,000 K), surface magma oceans cannot form by stellar forcing alone, whatever the water content. These findings affect observable signatures of steam atmospheres and exoplanet mass–radius relationships, drastically changing current constraints on the water content of TRAPPIST-1 planets. Unlike adiabatic structures, radiative–convective profiles are sensitive to opacities. New measurements of poorly constrained high-pressure opacities, in particular far from the H2O absorption bands, are thus necessary to refine models of steam atmospheres, which are important stages in terrestrial planet evolution.It is reported using a consistent climate model that pure steam atmospheres are commonly shaped by radiative layers, making their thermal structure strongly dependent on the stellar spectrum and internal heat flow. [ABSTRACT FROM AUTHOR]

In northern cold-temperate countries, a large portion of annual streamflow is produced by spring snowmelt, which often triggers floods. It is important to have spatial information about snow parameters such as snow water equivalent (SWE), which can be incorporated into hydrological models, making them more efficient tools for improved decision-making. The future Terrestrial Snow Mass Mission (TSMM) aims to provide high-resolution spatially distributed SWE information; thus, 5 spatial SWE calibration should be considered along with conventional streamflow calibration for model optimization since the overall water balance is often a key objective in the hydrological modelling. The present research implements a unique spatial pattern metric in a multi-objective framework for calibration approach of hydrological models and attempts to determine whether raw SNODAS data can be utilized for hydrological model calibration. The SPAtial Efficiency (SPAEF) metric is explored for spatially calibrating SWE. The HYDROTEL hydrological model is applied to the Au Saumon River Watershed (∽1120 km² 10 ) in Eastern Canada using MSWEP precipitation data and ERA-5 land reanalysis temperature data as input to generate high-resolution SWE and streamflow. Different calibration experiments are performed combining Nash-Sutcliffe efficiency (NSE) for streamflow and root-mean-square error (RMSE), and SPAEF for SWE, using the Dynamically Dimensioned Search (DDS) and Pareto Archived multi-objective optimization (PADDS) algorithms. Results of the study demonstrate that multi-objective calibration outperforms sequential calibration in terms of model performance. Traditional model calibration in15 volving only streamflow produced slightly higher NSE values; however, the spatial distribution of SWE could not be adequately maintained. This study indicates that utilizing SPAEF for spatial calibration of snow parameters improved streamflow prediction compared to the conventional practice of using RMSE for calibration. SPAEF is further implied to be a more effective metric than RMSE for both sequential and multi-objective calibration. During validation, the calibration experiment incorporating multi-objective SPAEF exhibits enhanced performance in terms of NSE and Kling-Gupta Efficiency (KGE) compared 20 to calibration experiment solely based on NSE. This observation supports the notion that incorporating SPAEF computed on raw SNODAS data within the calibration framework results in a more robust hydrological model. [ABSTRACT FROM AUTHOR]

Benzodiazepines (BZDs) are the first‐line treatment of alcohol withdrawal. Comorbidity between benzodiazepine use disorder (BUD) and alcohol use disorders (AUD) is common. However, the risk factors are poorly characterized due to the paucity of available BUD screening tools. The present study aimed to rectify this by conducting an observational screening investigation for BUD in patients hospitalized for alcohol detoxification in a specialized unit. During a face‐to‐face interview, a short BUD screening tool, Echelle Cognitive d'Attachement aux benzodiazépines (ECAB), was administered to record recent patterns of BZD use, thereby allowing categorization of AUD patients as follows: non‐BZD users, BZD users without BUD, and BUD (ECAB ≥6). Clinical and sociodemographic risk factors were identified and recorded during clinical assessment and were analyzed using nonparametric bivariate tests and multinomial regression for association with BUD, with p < 0.05 for significance. Of the 150 AUD patients, 23 (15%) had comorbid BUD. Several variables were associated with ECAB score, with their independence being verified using multinomial regression, with lower risk of BUD versus BZD use, when the initial prescriber was an addiction specialist compared with a psychiatrist or a general practitioner [odds ratio (OR) = 0.12, 95% confidence interval (CI) = 0.14–0.75]. A higher risk of BZD use versus no use was evident when comorbid psychiatric disorders were present (OR = 9.2, 95%CI = 1.3–65). Our findings raise clinicians' awareness that in patients hospitalized for alcohol detoxification, BUD is highly prevalent but not specifically related to psychiatric disorders. BUD can be effectively screened by utilization of the ECAB. [ABSTRACT FROM AUTHOR]

This article analyzes Patrick Imbert's The Summit of the Gods (2021), which functions as a noteworthy example of animated sports film. As a result, the study of this animated film on climbing and of the authorial decisions made by Patrick Imbert and his collaborators is located at the intersection of several fields, which include the history of sport manga, the sociology of extreme sports, the philosophy of self-transcendence, as well as the literary (de)construction of transmedia storytelling. Consequently, the need to employ various sources becomes manifest in order to aptly frame the multiple significations present in both the form and the content of the film: the historical account of George Mallory's and Andrew Irvine's ascent, the playful comparisons between manga and animation, the director's personal commentaries as well as the film's reception and critique. [ABSTRACT FROM AUTHOR]

The recently discovered super-Earth LP 890-9 c is an intriguing target for atmospheric studies as it transits a nearby, low-activity late-type M-dwarf star at the inner edge of the Habitable Zone. Its position at the runaway greenhouse limit makes it a natural laboratory to study the climate evolution of hot rocky planets. We present the first 3D-Global Climate Model exo-Venus model for a modern Venus-like atmosphere (92 bar surface pressure, realistic composition, and H2SO4 radiatively-active clouds), applied to the tidally-locked LP 890-9 c to inform observations by JWST and future instruments. If LP 890-9 c has developed into a modern exo-Venus, then the modelled temperatures suggest that H2SO4 clouds are possible even in the substellar region. Like on modern Venus, clouds on LP 890-9 c would create a flat spectrum. The strongest CO2 bands in transmission predicted by our model for LP 890-9 c are about 10 ppm, challenging detection, given JWST estimated noise floor. Estimated phase curve amplitudes are 0.9 and 2.4 ppm for continuum and CO2 bands, respectively. While pointing out the challenge to characterise modern exo-Venus analogues, these results provide new insights for JWST proposals and highlight the influence of clouds in the spectrum of hot rocky exoplanet spectra. [ABSTRACT FROM AUTHOR]

We present the simulation, fabrication, and characterization of large area microstructured fiber tapers which enables broadband phasematching conditions of the four wave-mixing process. These silica-based tapers are intended to serve as a nonlinear gain medium for intense and high average power Fiber Optical Parametric Chirped Pulse Amplifier emitting at 2 μ m and strongly pumped at Yb wavelength. Different geometries (tapered/untapered, aspect ratio, etc.) are fabricated, analyzed and their broadening properties—key for supporting ultrashort pulses amplification—are compared and discussed. The characterization of nonlinear gain bandwidth of the tapers relies on a tunable source of stochastic pulses based on tunable amplified spontaneous emission in Yb-doped amplifiers. The strong overshoots of this source allows degenerate four-wave mixing process to occur thus generating broadband incoherent visible signal and mid-infrared idler waves at much lower average power than usually needed with coherent pumping. The idler centered around 1.85 μ m is broadened due to zero-dispersion wavelength shift along the taper. [ABSTRACT FROM AUTHOR]