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Abstract Background Solving the structure of mRNA transcripts is a major challenge for both research and molecular diagnostic purposes. Current approaches based on short-read RNA sequencing and RT-PCR techniques cannot fully explore the complexity of transcript structure. The emergence of third-generation long-read sequencing addresses this problem by solving this sequence directly. However, genes with low expression levels are difficult to study with the whole transcriptome sequencing approach. To fix this technical limitation, we propose a novel method to capture transcripts of a gene panel using a targeted enrichment approach suitable for Pacific Biosciences and Oxford Nanopore Technologies platforms. Results We designed a set of probes to capture transcripts of a panel of genes involved in hereditary breast and ovarian cancer syndrome. We present SOSTAR (iSofOrmS annoTAtoR), a versatile pipeline to assemble, quantify and annotate isoforms from long read sequencing using a new tool specially designed for this application. The significant enrichment of transcripts by our capture protocol, together with the SOSTAR annotation, allowed the identification of 1,231 unique transcripts within the gene panel from the eight patients sequenced. The structure of these transcripts was annotated with a resolution of one base relative to a reference transcript. All major alternative splicing events of the BRCA1 and BRCA2 genes described in the literature were found. Complex splicing events such as pseudoexons were correctly annotated. SOSTAR enabled the identification of abnormal transcripts in the positive controls. In addition, a case of unexplained inheritance in a family with a history of breast and ovarian cancer was solved by identifying an SVA retrotransposon in intron 13 of the BRCA1 gene. Conclusions We have validated a new protocol for the enrichment of transcripts of interest using probes adapted to the ONT and PacBio platforms. This protocol allows a complete description of the alternative structures of transcripts, the estimation of their expression and the identification of aberrant transcripts in a single experiment. This proof-of-concept opens new possibilities for RNA structure exploration in both research and molecular diagnostics.

Abstract The transition from a milk-based diet to exclusive solid feeding deeply modifies microbiota-host crosstalk. Specifically, early ingestion of plant polysaccharides would be one of the main nutritional components to drive host-microbiota-interaction. To capture the effects of polysaccharides early-life nutrition (starch vs rapidly fermentable fiber) on the holobiont development, we investigated on the one hand the gut bacteriome and metabolome and on the other hand the transcriptome of two host gut tissues. Rabbit model was used to study post-natal co-development of the gut microbiota and its host around weaning transition. The assessment of the microbial composition of the gut appendix together with the caecum was provided for the first time. Gene expression signatures were analyzed along the gut (ileum and caecum) through high-throughput qPCR. The data collected were completed by the analysis of animal growth changes and time-series assessment of blood biomarkers. Those accessible and reusable data could help highlight the gut development dynamics as well as biological adaptation processes at the onset of solid feeding.

ABSTRACT Agriculture intensification in Southern Brazil’s subtropical regions combined with the frequent occurrence of erosive rainfall has rendered the area a global water erosion hotspot. In this scenario, understanding and regulating erosion processes at the river catchment scale is critical for mitigating soil and water resource degradation. Traditional methods for tracing sediment sources are expensive and time-consuming and justify the development of alternative approaches. Therefore, in this study, we employed diffuse reflectance spectroscopy analyses in the ultraviolet-visible (UV-VIS), near-infrared (NIR), and mid-infrared (MIR) ranges, combined with multivariate models and spectral pre-processing techniques to estimate sediment source contributions in a homogeneous subtropical catchment (Conceição River, 804 km²). Soil samples (n = 181) were collected to characterize the four potential sediment sources, including: cropland (n = 78), stream bank (n = 36), unpaved road (n = 40) and pasture (n = 27). Moreover, 44 sediment samples were collected, including suspended sediment (n = 8), fine sediment deposited on the riverbed (n = 15), and suspended sediment samples collected in the water column during storm events (n = 21). Vector machine (SVM) model outperformed the others, with better accuracy and reliability. While UV-VIS spectra proved less effective due to soil homogeneity across the catchment, NIR and MIR spectra provided valuable information for discriminating sediment sources. Furthermore, reducing the number of potential sources (from four to three or two) improved model predictions, especially when distinguishing between surface sources (cropland and pasture) and subsurface sources (unpaved roads and stream banks). The study’s findings shed light on the power of efficient and cost-effective alternative methods for assessing sediment sources, which are vital for promoting effective erosion control and sustainable land management in similar regions.

Abstract Revealing how the mind represents information is a longstanding goal of cognitive science. However, there is currently no framework for reconstructing the broad range of mental representations that humans possess. Here, we ask participants to indicate what they perceive in images made of random visual features in a deep neural network. We then infer associations between the semantic features of their responses and the visual features of the images. This allows us to reconstruct the mental representations of multiple visual concepts, both those supplied by participants and other concepts extrapolated from the same semantic space. We validate these reconstructions in separate participants and further generalize our approach to predict behavior for new stimuli and in a new task. Finally, we reconstruct the mental representations of individual observers and of a neural network. This framework enables a large-scale investigation of conceptual representations.

Abstract DNA replication in bacteria takes place on highly compacted chromosomes, where segregation, transcription, and repair must occur simultaneously. Within this dynamic environment, colocalization of sister replisomes has been observed in many bacterial species, driving the hypothesis that a physical linker may tether them together. However, replisome splitting has also been reported in many of the same species, leaving the principles behind replisome organization a long-standing puzzle. Here, by tracking the replisome β-clamp subunit in live Caulobacter crescentus, we find that rapid DNA segregation can give rise to a second focus which resembles a replisome, but does not replicate DNA. Sister replisomes can remain colocalized, or split apart to travel along DNA separately upon disruption of chromosome inter-arm alignment. Furthermore, chromosome arm-specific replication-transcription conflicts differentially modify replication speed on the two arms, facilitate the decoupling of the two replisomes. With these observations, we conclude that the dynamic chromosome organization flexibly shapes the organization of sister replisomes, and we outline principles which can help to reconcile previously conflicting models of replisome architecture.

Abstract Background & aims Despite its high prevalence in the western world metabolic dysfunction-associated steatotic liver disease (MASLD) does not benefit from targeted pharmacological therapy. We measured healthcare utilisation and identified factors associated with high-cost MASLD patients in France. Methods The prevalent population with MASLD (including non-alcoholic steatohepatitis) in the CONSTANCES cohort, a nationally representative sample of 200,000 adults aged between 18 and 69, was linked to the French centralised national claims database (SNDS). Study participants were identified by the fatty liver index (FLI) over the period 2015–2019. MASLD individuals were classified according as “high-cost” (above 90th percentile) or “non-high cost” (below 90th percentile). Factors significantly associated with high costs were identified using a multivariate logistic regression model. Results A total of 14,437 predominantly male (69%) participants with an average age of 53 ± SD 12 years were included. They mainly belonged to socially deprived population groups with co-morbidities such as diabetes, high blood pressure, mental health disorders and cardiovascular complications. The average expenditure was €1860 ± SD 4634 per year. High-cost MASLD cost €10,863 ± SD 10,859 per year. Conditions associated with high-cost were mental health disorders OR 1.79 (1.44–2.22), cardiovascular diseases OR 1.54 (1.21–1.95), metabolic comorbidities OR 1.50 (1.25–1.81), and respiratory disease OR 1.50 (1.11–2.00). The 10% high-cost participants accounted for 58% of the total national health care expenditures for MASLD. Conclusion Our results emphasize the need for comprehensive management of the comorbid conditions which were the major cost drivers of MASLD. Graphical Abstract

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is preferentially treated by prompt endovascular coiling, which is not available in Guadeloupe. Subsequently, patients are transferred to Paris, France mainland, by commercial airplane (6751 km flight) after being managed according to guidelines. This study describes the characteristics, management and outcomes related to these patients. Methods Retrospective observational cohort study of 148 patients admitted in intensive care unit for a suspected aSAH and transferred by airplane over a 10-year period (2010–2019). Results The median [interquartile range] age was 53 [45–64] years and 61% were female. On admission, Glasgow coma scale was 15 [13–15], World Federation of Neurological Surgeons (WFNS) grading scale was 1 [1–3] and Fisher scale was 4 [2–4]. External ventricular drainage and mechanical ventilation were performed prior to the flight respectively in 42% and 47% of patients. One-year mortality was 16% over the study period. By COX logistic regression analysis, acute hydrocephalus (hazard ratio [HR] 2.34, 95% confidence interval [CI] 0.98–5.58) prior to airplane transfer, WFNS grading scale on admission (HR 1.53, 95% CI 1.16–2.02) and age (OR 1.03, 95% 1.00–1.07) were associated with one-year mortality. Conclusion When necessary, transatlantic air transfer of patients with suspected aSAH after management according to local guidelines seems feasible and safe.

Aim: High-density lipoprotein (HDL) particles in ST-segment elevation myocardial infarction (STEMI) are deficient in their anti-atherogenic function. Molecular determinants of such deficiency remain obscure. Methods: Five major HDL subpopulations were isolated using density-gradient ultracentrifugation from STEMI patients (n = 12) and healthy age- and sex-matched controls (n = 12), and 160 species of phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, phosphatidylserine, phosphatidic acid, sphingomyelin and ceramide were quantified by LC-MS/MS. Results: Multiple minor species of proinflammatory phosphatidic acid and lysophosphatidylcholine were enriched by 1.7–27.2-fold throughout the majority of HDL subpopulations in STEMI. In contrast, minor phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, sphingomyelin and ceramide species were typically depleted up to 3-fold in STEMI vs. control HDLs, while abundances of their major species did not differ between the groups. Intermediate-to-long-chain phosphatidylcholine, phosphatidylinositol and phosphatidylglycerol species were more affected by STEMI than their short-chain counterparts, resulting in positive correlations between their fold decrease and the carbon chain length. Additionally, fold decreases in the abundances of multiple lipid species were positively correlated with the double bond number in their carbon chains. Finally, abundances of several phospholipid and ceramide species were positively correlated with cholesterol efflux capacity and antioxidative activity of HDL subpopulations, both reduced in STEMI vs controls. KEGG pathway analysis tied these species to altered glycerophospholipid and linoleic acid metabolism. Conclusions: Minor unsaturated intermediate-to-long-chain phospholipid and sphingolipid species in HDL subpopulations are most affected by STEMI, reflecting alterations in glycerophospholipid and linoleic acid metabolism with the accumulation of proinflammatory lysolipids and maintenance of homeostasis of major phospholipid species.

This study analyzes the integration of the Arabic dialectal loan wesh into the French language and the language habits of the French. Through the suburban language commonly defined as "slang" and hip hop culture, particularly rap, this borrowing has undergone several important semantic shifts and numerous graphic variants. The various definitions of this term in the Petit Robert 2023 (paper version) and the Wiktionnaire (online), as well as statistical research in Internet corpora, reveal evolutions, linguistic variations and trends generated essentially by sociolinguistic functions.

OBJECTIVES:. To identify distinct phenotypes of critically ill leptospirosis patients upon ICU admission and their potential associations with outcome. DESIGN:. Retrospective observational study including all patients with biologically confirmed leptospirosis admitted to the ICU between January 2014 and December 2022. Subgroups of patients with similar clinical profiles were identified by unsupervised clustering (factor analysis for mixed data and hierarchical clustering on principal components). SETTING:. All patients admitted to the ICU of the University Hospital of Guadeloupe on the study period. PATIENTS:. One hundred thirty critically ill patients with confirmed leptospirosis were included. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. At ICU admission, 34% of the patients had acute respiratory failure, and 26% required invasive mechanical ventilation. Shock was observed in 52% of patients, myocarditis in 41%, and neurological involvement in 20%. Unsupervised clustering identified three clusters—“Weil’s Disease” (48%), “neurological leptospirosis” (20%), and “multiple organ failure” (32%)—with different ICU courses and outcomes. Myocarditis and neurological involvement were key components for cluster identification and were significantly associated with death in ICU. Other factors associated with mortality included shock, acute respiratory failure, and requiring renal replacement therapy. CONCLUSIONS AND RELEVANCE:. Unsupervised analysis of critically ill patients with leptospirosis revealed three patient clusters with distinct phenotypic characteristics and clinical outcomes. These patients should be carefully screened for neurological involvement and myocarditis at ICU admission.

White-box cryptography aims at protecting implementations of cryptographic algorithms against a very powerful attacker who controls the execution environment. The first defensive brick traditionally embedded in such implementations consists of encodings, which are bijections supposed to conceal sensitive data manipulated by the white-box. Several previous works have sought to evaluate the relevance of encodings to protect white-box implementations against grey-box attacks such as Differential Computation Analysis (DCA). However, these works have been either probabilistic or partial in nature. In particular, while they showed that DCA succeeds with high probability against AES white-box implementations protected by random encodings, they did not refute the existence of a particular class of encodings that could prevent the attack. One could thus wonder if carefully crafting specific encodings instead of drawing random bijections could be a solution. This article bridges the gap between preceding research efforts and investigates this question. We first focus on the protection of the S-box output and we show that no 4-bit encoding can actually protect this sensitive value against side-channel attacks. We then argue that the use of random 8-bit encodings is both necessary and sufficient, but that this assertion holds exclusively for the S-box output. Indeed, while we define a class of 8-bit encodings that actually prevents a classical DCA targeting the MixColumns output, we also explain how to adapt this attack and exploit the correlation traces in order to defeat even these specific encodings. Our work thus rules out the existence of a set of practical encodings that could be used to protect an AES white-box implementation against DCA-like attacks.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p

Abstract Unraveling the effects of continuous dislocation interactions with interfaces, particularly at the nanometer length scales, is key to a broader understanding of plasticity, to material design and to material certification. To this end, this work proposes a novel discrete dislocation dynamics-based model for dislocation interface interactions tracking the fate of residual dislocation on interfaces. This new approach is used to predict the impact of dislocation/interface reactions on the overall mechanical behavior of accumulative roll bonded nanometallic laminates. The framework considers the dynamic evolution of the interface concurrent with a large network of dislocations, thus, accounting for the local short and long range effects of the dislocations under the external boundary conditions. Specifically, this study focuses on two-phase Fe/Cu nanometallic laminates, and investigates the role of the underlying elastic and plastic contrast of the Fe and the Cu layers on the composite response of the material. Moreover, the role of initial microstructures, resulting from processing is also investigated. Subsequently, the model is used to examine the effect of layer thickness and interface orientation relationship on the residual stresses of the relaxed microstructure. The associated mechanical response of these laminates are compared when loaded under normal direction compression, as well as shear compression. Finally, this work predicts a dominant effect of the layer thickness, as compared to the interface orientation relationship, on the macroscopic response and on the residual stresses of these nanolaminates, while the local dislocation transmission propensity through the interface is significantly influenced by the corresponding orientation relationship.

Abstract Background Improving pigs’ ability to digest diets with an increased dietary fiber content is a lever to improve feed efficiency and limit feed costs in pig production. The aim of this study was to determine whether information on the gut microbiota and host genetics can contribute to predict digestive efficiency (DE, i.e. digestibility coefficients of energy, organic matter, and nitrogen), feed efficiency (FE, i.e. feed conversion ratio and residual feed intake), average daily gain, and daily feed intake phenotypes. Data were available for 1082 pigs fed a conventional or high-fiber diet. Fecal samples were collected at 16 weeks, and DE was estimated using near‑infrared spectrometry. A cross-validation approach was used to predict traits within the same diet, for the opposite diet, and for a combination of both diets, by implementing three models, i.e. with only genomic (Gen), only microbiota (Micro), and both genomic and microbiota information (Micro+Gen). The predictive ability with and without sharing common sires and breeding environment was also evaluated. Prediction accuracy of the phenotypes was calculated as the correlation between model prediction and phenotype adjusted for fixed effects. Results Prediction accuracies of the three models were low to moderate ( 0.52). Prediction accuracies were not affected by the stratification of diets in the reference and validation sets and were in the same order of magnitude within the same diet, for the opposite diet, and for the combination of both diets. Prediction accuracies of the three models were significantly higher when pigs in the reference and validation populations shared common sires and breeding environment than when they did not (P

Precipitation strengthening is a key strategy for improving the overall mechanical properties of Mg alloys. In Mg-Al alloys, basal precipitates are known to strengthen against twinning, resulting in an increase in the critical resolved shear stress (CRSS) necessary for continued deformation. Although several models have been proposed to quantify the influence of precipitate shape, size, and distribution on the CRSS, the accuracy, scope, and applicability of these models has not been fully assessed. Accordingly, the objectives of this study are: (i) to analyze the accuracy of analytical models proposed in the literature for precipitation strengthening against twin thickening and propagation (in Mg-Al alloys) using phase-field (PF) simulations, (ii) to propose modifications to these model forms to better capture the observed trends in the PF data, and (iii) to subsequently test the predictiveness of the extended models in extrapolating to experimental strengthening data. First, using an atomistically-informed phase-field method, the interactions between migrating twin boundaries (during the propagation and thickening stages) and basal plates are simulated for different precipitate sizes and arrangements. In general, comparison of the increase in CRSS determined from the PF simulations and the predictions from four precipitation strengthening models reveals that modifications are necessary to the model forms to extend their applicability to precipitation strengthening against both twin thickening and propagation. A subsequent comparison between predictions from the extended models and experimental strengthening data for peak age-hardened samples reveals that the (extended) single dislocation and dislocation wall models provide reasonably accurate values of the increase in CRSS. Ultimately, the results presented here help elucidate the fidelity and applicability of the various hardening models in predicting precipitation strenghtening effects in technologically important alloys.

Nowadays, materials science is moving towards the understanding and control of materials in nonequilibrium states by making use of perturbative techniques to investigate their dynamical responses. From this perspective, the use of ultrashort light pulses seems to be a relevant approach as it can selectively address different degrees of freedom in solid-state systems and more particularly electrons. Such a method can help to decipher the physical phenomena arising from electronic correlations and complements a more conventional methodology where the phase diagrams of materials are investigated at thermodynamical equilibrium. Here, we combine femtosecond optical spectroscopy and a high-pressure setup to monitor the ultrafast out-of-equilibrium photo response of a V_{2}O_{3} thin film across the pressure driven insulator-to-metal transition. The experimental results demonstrate the possibility to use the spectroscopy of coherent phonons as a thermodynamical phase marker in V_{2}O_{3} thin films. In addition, the frequency behavior of the ultrafast coherent phonon mode (A_{1g} character) seems to reflect the manifestation of a strong coupling between the lattice and electronic degrees of freedom near first-order transition lines with a pronounced drop in frequency around the critical pressure.

Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids, in adjunct with saline solution rinses. Surgical management is proposed in patients who failed after medical treatment. In France, two biologics are reimbursed in case of severe uncontrolled CRSwNP despite medical treatment and endoscopic sinus surgery. Waiting for head-to-head biologics comparison, studies should report the efficacy and safety of biologics in large real-life cohorts. This study protocol describes the aims and methods of a prospective, observational, national, multicentric cohort of patients with CRSwNP treated with biologics.Methods and analysis The BIOlogics in severe nasal POlyposis SurvEy is a French multicentre prospective observational cohort study. The main aim is to assess the efficacy and tolerance of biologics in patients with CRSwNP, with or without association with other type 2 diseases, and to determine the strategies in case of uncontrolled disease under biologics. Patients over 18 years old requiring biologics for CRSwNP in accordance with its marketing approval in France (ie, severe nasal polyposis, with lack of control under nasal corticosteroid, systemic corticosteroids and surgery) are invited to participate. Collected data include topical history of surgical procedures and biologics, medication and use of systemic corticosteroids, visual analogical scales for specific symptoms, Sino-Nasal Outcome Test-22 questionnaire, nasal polyp score, asthma control test, Lund-Mackay score on CT scan and IgE concentration and eosinophilic count on blood sample.Trial registration NCT05228041/DRI_2021/0030.

The present work focuses on the manufacturing, mechanical characterization, and modeling of hybrid Flax/Hemp/Polypropylene (PP) composites under dry conditions. Geometric parameters of the fibers were measured both before and after the melt processing. The results indicated that the processed fibers, especially the hybrid ones, had a narrowed length distribution with an average fiber length of 0.48 mm for hybrids compared to 0.62 mm for non-hybrids. The hybrid composites were mechanically characterized using basic and loading-unloading tensile tests with various fiber combinations and weight percentages. The study also examined the effect of strain rate and cutting angle on the behaviors of the composites. The results demonstrated the significance of fiber orientation as the primary factor in explaining mechanical variations. The tensile strength and Young's Modulus of FH30 composites (PP + 15 wt% flax + 15 wt% hemp) increased by about 24.1 % and 10.9 %, respectively, when the plates were cut into dumbbell shapes at a 90° angle to the injection molding flow direction, compared to a cut at 0° The study also showed that the tensile strength is directly proportional to the mass fraction of reinforcements, with an increase in tensile strength by 7.9 % for 0° cut angle specimens between FH10 (PP + 5 wt% flax + 5 wt% hemp) and FH30 bio-composites, while the uniform strain is inversely proportional to the mass fraction of reinforcements, evidenced by a reduction in uniform strain of 30 % between FH10 and FH30 samples. Morphological observations revealed the presence of bands indicating the propagation of micro-cracks, as well as debonding or cohesive failure. Finally, a Perzyna-type elasto-viscoplastic constitutive model was applied to accurately predict the overall mechanical response of a hybrid composite material. Specifically, the model successfully captured the tension deformation behavior of hybrid natural short-fiber thermoplastic composites, including the elastic stage, yield stress, and nonlinear hardening.

Road traffic related death and injury continues to be a major challenge globally. Unsafe road use is particularly evident in low- and middle-income countries while also being a growing concern for private sector organisations. The Safe System approach is recognized internationally as the leading approach to improving road safety and previous work has codified the essential management functions and interventions evident in its successful implementation. Tracking the development of Safe System adoption within the public and private sectors is of interest for several reasons. This paper presents recent development and use of road safety maturity frameworks and discusses the utility of these approaches for road safety practitioners and researchers.

Impediments in replication fork progression cause genomic instability, mutagenesis, and severe pathologies. At stalled forks, RPA-coated single-stranded DNA (ssDNA) activates the ATR kinase and directs fork remodeling, 2 key early events of the replication stress response. RFWD3, a recently described Fanconi anemia (FA) ubiquitin ligase, associates with RPA and promotes its ubiquitylation, facilitating late steps of homologous recombination (HR). Intriguingly, RFWD3 also regulates fork progression, restart and stability via poorly understood mechanisms. Here, we used proteomics to identify putative RFWD3 substrates during replication stress in human cells. We show that RFWD3 interacts with and ubiquitylates the SMARCAL1 DNA translocase directly in vitro and following DNA damage in vivo. SMARCAL1 ubiquitylation does not trigger its subsequent proteasomal degradation but instead disengages it from RPA thereby regulating its function at replication forks. Proper regulation of SMARCAL1 by RFWD3 at stalled forks protects them from excessive MUS81-mediated cleavage in response to UV irradiation, thereby limiting DNA replication stress. Collectively, our results identify RFWD3-mediated SMARCAL1 ubiquitylation as a novel mechanism that modulates fork remodeling to avoid genome instability triggered by aberrant fork processing.

Abstract A 7‐year‐old neutered male Domestic shorthair cat, with a 1.5‐year history of left eye enucleation secondary to a diffuse iris malignant melanoma, was evaluated for progressive onset of pelvic limb paresis and ataxia with severe thoracolumbar hyperaesthesia and dysorexia. Neurological examination localised a lesion to the T3–L3 spinal cord segments. Magnetic resonance imaging of the thoracolumbar spine showed a well‐defined extradural T1‐weighted hyperintense non‐contrast‐enhancing mass, initially suggesting a potential haemorrhagic component. Exploratory surgery revealed a brownish extradural lumbar mass. Histologic examination concluded to a melanoma, most probably metastatic given the animal's previous medical history. This report highlights the importance of collecting a complete medical history, which can help in obtaining a preliminary differential diagnosis in cats with clinical signs of myelopathy. Although the location of this metastasis is particularly unusual both in human and veterinary medicine, making optimal treatment challenging for neurosurgeon, our increased understanding of immune and tumour cell biology during the past decade is likely to improve the future treatments of feline melanoma and its metastases.

Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction with surgery, but with a generally low efficiency. Ongoing researches are focused on understanding the genetic and molecular basis of chondrosarcoma following high linear energy transfer (LET) irradiation, which may lead to treatments that are more effective. The goal of this study is to evaluate the differential effects of DNA damage repair inhibitors and high LET irradiation on chondrosarcoma versus chondrocyte cells and the LET-dependency of the effects. Two chondrosarcoma cell lines with different IDH mutation status and one chondrocyte cell line were exposed to low LET (X-ray) and high LET (carbon ion) irradiation in combination with an Olaparib PARP inhibitor. Cell survival and DNA repair mechanisms were investigated. High LET irradiation drastically reduced cell survival, with a biological efficiency three times that of low LET. Olaparib significantly inhibited PARylation in all the tested cells. A significant reduction in cell survival of both chondrosarcoma and chondrocyte cells was observed following the treatment combining Olaparib and X-ray. PARP inhibition induced an increase in PARP-1 expression and a reduced effect on the cell survival of WT IDH chondrosarcoma cells. No radiosensitizing effect was observed in cells exposed to Olaparib paired with high LET irradiation. NHEJ was activated in response to high LET irradiation, neutralizing the PARP inhibition effect in both chondrosarcoma cell lines. When high LET irradiation is not available, PARP inhibition could be used in combination with low LET irradiation, with significant radiosensitizing effects on chondrosarcoma cells. Chondrocytes may be affected by the treatment combination too, showing the need to preserve normal tissues from radiation fields when this kind of treatment is suggested.

Abstract A multi-phase field model is employed to study the microstructural evolution of an alloy undergoing liquid dealloying, specifically considering the role of grain boundaries. A semi-implicit time-stepping algorithm using spectral methods is implemented, which enables simulating large 2D and 3D domains over long time scales while still maintaining a realistic interfacial thickness. Simulations reveal a mechanism of coupled grain–boundary migration to maintain equilibrium contact angles with the topologically complex solid–liquid interface, which locally accelerates diffusion-coupled growth of a liquid channel into the precursor. This mechanism asymmetrically disrupts the ligament connectivity of the dealloyed structure in qualitative agreement with published experimental observations. The grain boundary migration-assisted corrosion channels form even for precursors with small amounts of the dissolving alloy species, below the parting limit. The activation of this grain boundary dealloying mechanism depends strongly on grain boundary mobility.

Topological states have been receiving a great deal of interest in various wave problems, such as photonic, acoustic, and elastic waves. However, few studies of topological elastic waves in non-periodic systems have been reported. Recently, hyperuniform systems suppressing long-range order while partly maintaining short-range order have provided new opportunities to control waves. In this work, we study the elastic topological interface states appearing between two Su–Schrieffer–Heeger (SSH)-like pillared metabeams where each metabeam, is constituted by a mirror symmetric hyperuniform structure. The SSH-like model is constructed by combining two hyperuniform metabeams with inverted configurations. We demonstrate that this structure could open new bandgaps at low frequencies, of which some are nontrivial and can support topological interface modes. We further show that the number of low-frequency bandgaps supporting the topological modes increases with the level of randomness, hence providing a high number of interface modes in the same structure. The robustness of the topological interface states against random perturbations in the pillars’ positions is further verified. Our work offers a reliable platform for studying topological properties and hyperuniform metamaterials and designing wave control devices for low-frequency wave attenuation and robust energy localization.

The Al2O3-SiC-C or ASC castables are used in the main runners of blast furnaces. Most of the papers published to date focus on laboratory corrosion tests because access to the post-mortem samples of ASC castables is difficult. However, investigation of post-mortem samples is crucial in reducing the wear of ASC castables. The main runner is divided into the turbulence, middle, and non-turbulence zones. The microstructures of post-mortem samples located in working linings of different zones were investigated by SEM/EDS technique. The thermodynamic simulations were carried out in different systems, such as slag/refractory and iron/refractory, using the FactSage software. The SEM/EDS results showed the formation of phases with low melting points, such as gehlenite and anorthite, together with spinel solid solutions in the matrix and calcium dialuminate near the alumina aggregates. The thermodynamic simulations showed that slag and iron tend to react with alumina and silicon carbide, respectively.

Abstract Purpose To describe clinical and biological features and the outcomes of patients admitted for histoplasmosis in two intensive care units (ICU) in French Guyana and in the French West Indies (Guadeloupe). Methods All patients admitted to these two ICUs for culture-proven histoplasmosis between January 2014 to August 2022 were included in the study. Using univariate and multivariate analysis, we assessed risk factors at ICU admission that were associated with death. Results Forty patients were included (65% men). Median age was 56 years and simplified acute physiologic score (SAPS) II was 65. HIV was found in 58%, another immunodeficiency was identified in 28%, and no underlying immunodeficiency could be identified in 14% of patients. Within the first 24 h of ICU admission, 85% of patients had acute respiratory failure, 78% had shock, 30% had coma, and 48% had hemophagocytic lymphohistiocytosis. Mechanical ventilation was instituted in 78% of patients and renal replacement therapy in 55%. The 30-day mortality was 53%. By multivariate analysis, factors independently associated with 30-day mortality were SOFA score (odds ratio [OR] 1.5, 95% confidence interval [CI] [1.1–2.1]), time between symptom onset and treatment per day (OR 1.1, 95% CI 1.0–1.1), and hemophagocytic lymphohistiocytosis (OR 6.4, 95% CI 1.1–47.5). Conclusion Histoplasmosis requiring ICU admission is a protean disease with multiple and severe organ involvement. Immunodeficiency is found in most patients. The prognosis remains severe despite appropriate treatment and is worsened by late treatment initiation.

Abstract Zirconium alloys are widely used in harsh environments characterized by high temperatures, corrosivity, and radiation exposure. These alloys, which have a hexagonal closed packed (h.c.p.) structure thermo-mechanically degrade, when exposed to severe operating environments due to hydride formation. These hydrides have a different crystalline structure, than the matrix, which results in a multiphase alloy. To accurately model these materials at the relevant physical scale, it is necessary to fully characterize them based on a microstructural fingerprint, which is defined here as a combination of features that include hydride geometry, parent and hydride texture and crystalline structure of these multiphase alloys. Hence, this investigation will develop a reduced order modeling approach, where this microstructural fingerprint is used to predict critical fracture stress levels that are physically consistent with microstructural deformation and fracture modes. Machine Learning (ML) methodologies based on Gaussian Process Regression, random forests, and multilayer perceptrons (MLP) were used to predict material fracture critical stress states. MLPs, or neural networks, had the highest accuracy on held-out test sets across three predetermined strain levels of interest. Hydride orientation, grain orientation or texture, and hydride volume fraction had the greatest effect on critical fracture stress levels and had partial dependencies that were highly significant, and in comparison hydride length and hydride spacing have less effects on fracture stresses. Furthermore, these models were also used accurately predicted material response to nominal applied strains as a function of the microstructural fingerprint.

Abstract Hydride precipitation within zirconium alloys affects ductility and fracture behavior. The complex distribution of hydrides and their interaction with defects, such as dislocations, have a significant role in crack nucleation and failure. Hence, there is substantial variability in the microstructural behavior of hydrided zirconium. A deterministic fracture model coupled to a dislocation-density based crystalline plasticity approach was used to predict failure. Deterministic simulations were used to develop a database of crack initiation for representative microstructural characteristics, such as texture, crystalline structure, hydride orientations and spacing, and hydride geometry. The machine learning (ML) analysis is based on Extreme Value Theory (EVT) and a Bayesian based Gaussian Process Regression (GPR). Fracture probability is significantly influenced by hydride orientation and dislocation-density interactions. Furthermore, surrogate reduced order models (ROM) models were used to predict the likelihood of failure. This approach provides a ML framework to predict failure at different physical scales.

Reelin, a large extracellular glycoprotein, plays critical roles in neuronal development and synaptic plasticity in the central nervous system (CNS). Recent studies have revealed non-neuronal functions of plasma Reelin in inflammation by promoting endothelial–leukocyte adhesion through its canonical pathway in endothelial cells (via ApoER2 acting on NF-κB), as well as in vascular tone regulation and thrombosis. In this study, we have investigated the safety and efficacy of selectively depleting plasma Reelin as a potential therapeutic strategy for chronic inflammatory diseases. We found that Reelin expression remains stable throughout adulthood and that peripheral anti-Reelin antibody treatment with CR-50 efficiently depletes plasma Reelin without affecting its levels or functionality within the CNS. Notably, this approach preserves essential neuronal functions and synaptic plasticity. Furthermore, in mice induced with experimental autoimmune encephalomyelitis (EAE), selective modulation of endothelial responses by anti-Reelin antibodies reduces pathological leukocyte infiltration without completely abolishing diapedesis. Finally, long-term Reelin depletion under metabolic stress induced by a Western diet did not negatively impact the heart, kidney, or liver, suggesting a favorable safety profile. These findings underscore the promising role of peripheral anti-Reelin therapeutic strategies for autoimmune diseases and conditions where endothelial function is compromised, offering a novel approach that may avoid the immunosuppressive side effects associated with conventional anti-inflammatory therapies.

Abstract Local waterlogging often occurs on the steep slopes of clayey–calcareous soils in southwestern France, causing nutrients and pollutants transfer to the river bodies and reduced ecosystems services. These soils developed in the Miocene molassic hill formation and are generally impermeable with abundant traces of hydromorphy and heterogenous spatial distribution. This article aims to describe the hydrological functioning of these soils, based on a cross analysis of pedological, hydrological, and geophysical characterizations. Our experimental site is the catchment area located in Auradé (southwestern France). Here, we analyze the flows at the outlet of the studied watershed together with piezometric and climatic monitoring from September 2020 to September 2021. We show that the hydrological year is divided into three phases: first, a soil recharge phase with an effective rainfall of about 100 mm; second, a saturation phase, when 80% of the effective precipitation is drained mostly by runoff and hypodermic flows; third, a drying phase. Soil waterlogging events usually occur during the saturation phase. They are due to several forms of flow: surface runoff associated with return flow, hypodermic flow caused by the presence of soil layers with lower hydraulic conductivity in the subsurface (swelling clays and plowing sole) and groundwater flow with intermittent connection of the soil water table in the hillside to the alluvial groundwater table. We also conducted independent seismic refraction tomography analyses that validate localized waterlogging patterns along the catchment and open the way to spatializing areas with high waterlogging potential at the scale of the study plot.

Summary: Chronic infection with hepatitis delta virus (HDV) affects between 12-20 million people worldwide and represents the most severe form of viral hepatitis, leading to accelerated liver disease progression, cirrhosis and its complications, such as end-stage-liver disease and hepatocellular carcinoma. From the discovery of HDV in 1977 by Prof. Mario Rizzetto, knowledge on the HDV life cycle and mechanisms of viral spread has expanded. However, little is still known about the natural history of the disease, host-viral interactions, and the role of the immune system in HDV persistence. Diagnosis of HDV is still challenging due to a lack of standardised assays, while accurate viral load quantification is needed to assess response and endpoints of antiviral treatment. Until recently, interferon has represented the only treatment option in patients with chronic hepatitis delta; however, it is associated with low efficacy and a high burden of side effects. The discovery of the entry inhibitor bulevirtide has represented a breakthrough in HDV treatment, by demonstrating high rates of viral suppression in phase II and III trials, results which have been confirmed in real-world settings and in patients with compensated advanced liver disease. In the meantime, other compounds (i.e. lonafarnib, new anti-hepatitis B virus drugs) are under development to provide alternative or combined strategies for HDV cure. The first international Delta Cure meeting was organised in Milan in October 2022 with the aim of sharing and disseminating the latest data; this review summarises key takeaway messages from state-of-the-art lectures and research data on HDV.

Abstract Background and study aims Egypt has been a pioneer in implementing a nationwide HCV screening and treatment program. Assessment of liver fibrosis after HCV eradication is important. The value of liver stiffness measurement (LSM) for this purpose is still debated. The aim of this prospective longitudinal study was to assess LSM evolution after HCV eradication. Patients and methods One-hundred and three HCV patients, treated with a standard DAA regimen (sofosbuvir/daclatasvir for 3 months), underwent LSM before and 24 weeks after the end of treatment. Patients were classified into 3 groups according to baseline LSM (Baveno VI): group 1: patients without compensated advanced chronic liver disease (cACLD) (LSM 15 kPa). Results The characteristics of patients were as follows: mean age 55 ± 10 years, males 48.5%, and BMI 26.31 ± 3.33 kg/m2. All patients were Child–Pugh score A and achieved SVR at W24. A significant LSM decrease was observed at W24 compared to baseline: all patients: 5.8 vs. 8.8 kPa, p = 0.002; group 1: 4.75 vs. 6.0 kPa, p = 0.0001; group 2 11.9 vs. 12.6 kPa, p = 0.042; and group 3: 24.2 vs. 28.3 kPa, p = 0.0001. Group 1 had the highest LSM decline (23.83%), followed by group 3 (14.3%) and group 2 (8.4%). Conclusion HCV eradication was associated with a significant LSM decrease in all groups of patients. This is likely related to improvement of fibrosis, but its relation to improvement of necro-inflammation cannot be excluded. Longer follow-up of fibrosis in these patients is needed.

Senescence can have beneficial and detrimental impact on cancer progression depending on the cellular context. Here the authors show that NRF2 regulates the senescence phenotype in malignant cells which consequently contribute to glioblastoma progression.

Feeding an increasing world population in the context of climate change is one of the grand challenges faced by our generation. Here, the authors show that external application of synthetic complementary peptides can increase the abundance of target proteins to modulate plant growth or stress resistance.

Using the example of the traditional recycling of lead batteries in “backyard” workshops in India, this article demonstrates the value of an interdisciplinary approach to ascertain the many political, technical and environmental dimensions of the operation of urban mines. The use of human and social sciences (anthropology of techniques, social geography), engineering sciences (process engineering) and geosciences (geophysics, geochemistry) makes it possible to track reverse logistics chains by following the material flow of lead from one step to the next; operations chains by breaking down all the effective operations on the material in workshops and factories; and contamination chains by taking soil samples in the vicinity of production sites. This epistemic contrast between the physical sciences and the humanities and social sciences enables us to better understand the issues involved in the circulation and transformation of recovered materials, and to examine the possibilities of doing science differently.

Under pathological conditions such as multiple sclerosis (MS), leukocytes infiltrate the central nervous system where they, in concert with activated microglia, promote inflammatory demyelination resulting in a broad spectrum of symptoms, including paralysis. Therefore, all current therapeutic approaches to MS target the immune system, blocking inflammation and paralysis progression, but may compromise the immune system. In this focused review, we present an underestimated compartment, the blood–brain barrier, which is compromised during MS and becomes permeable to leukocytes infiltrating the central nervous system. This barrier has the potential to offer new therapeutic strategies and is easily accessible for drugs. We highlight this paradigm using the example of the therapeutic anti-Reelin strategy we have developed. Reelin is a plasma protein that regulates the expression of adhesion markers on the endothelial surface, thus promoting the infiltration of inflammatory cells and propagating inflammation. Building Back a Better Blood–Brain Barrier (the “6B” strategy) may have advantages compared to actual immunosuppressive drugs because it restores a physiological function rather than suppressing the immune system.

Objective: In adults with sleep complaints, we assessed the software of automatic analysis of mandibular movements to identify sleep and wake states by confrontation with the polysomnography (PSG) and the actigraphy (ACTG). Material and Methods: Simultaneous and synchronized in-lab PSG, ACTG, and JAWAC were carried out in 100 patients with a sleep complaint. Epoch by epoch analysis was realized to assess the ability to sleep-wake distinction. Sleep parameters as measured by the three devices were compared. These included three regularly reported parameters: total sleep time (TST), sleep onset latency (SOL), and wake after sleep onset (WASO). Also, two supplementary parameters, wake during sleep period (WDSP) and latency to arising (LTA) were added to measure separately the quiet wakefulness states. Results: The epoch by epoch analysis showed that the JAWAC, as compared to ACTG, classified sleep and wake states with greater specificity, while the overall accuracy and sensitivity of the two devices were comparable. The sleep parameters analysis showed that for the JAWAC estimates, the differences in TST, SOL, and LTA values were not statistically significant. However, WDSP and subsequently WASO were slightly underestimated. In contrast, the dissimilarities between ACTG estimates and PSG measurements of all the above sleep parameters were statistically significant; TST was overestimated whilst SOL, LTA, WDSP, and WASO were underestimated. Conclusion: This study indicated that, besides its ability to reliably estimate TST, the JAWAC based on mandibular movements’ analysis was able, in adults with sleep complaints, to overcome the important problem of the recognition of the state of quiet wakefulness.

Abstract The receptor-binding domain (RBD) in S1 subunit and heptad repeat 1 (HR1) domain in S2 subunit of SARS-CoV-2 spike (S) protein are the targets of neutralizing antibodies (nAbs) and pan-coronavirus (CoV) fusion inhibitory peptides, respectively. However, neither nAb- nor peptide-based drugs can be used orally. In this study, we screened a one-bead-two-compound (OBTC) cyclic γ-AApeptide library against SARS-CoV-2 S protein and identified a hit: S-20 with potent membrane fusion inhibitory activity, but moderate selectivity index (SI). After modification, one derivative, S-20-1, exhibited improved fusion inhibitory activity and SI (>1000). S-20-1 could effectively inhibit infection by pseudotyped and authentic SARS-CoV-2 and pseudotyped variants of concern (VOCs), including B.1.617.2 (Delta) and B.1.1.529 (Omicron), as well as MERS-CoV, SARS-CoV, HCoV-OC43, HCoV-229E, and HCoV-NL63. It could also inhibit infection of a pseudotyped SARS-related coronavirus WIV1 (SARSr-CoV-WIV1) from bats. Intranasal application of S-20-1 to mice before or after challenge with HCoV-OC43 or SARS-CoV-2 provided significant protection from infection. Importantly, S-20-1 was highly resistant to proteolytic degradation, had long half-life, and possessed favorable oral bioavailability. Mechanistic studies suggest that S-20-1 binds with high affinity to RBD in S1 and HR1 domain in S2 of SARS-CoV-2 S protein. Thus, with its pan-CoV fusion and entry inhibitory activity by targeting two sites in S protein, desirable half-life, and promising oral bioavailability, S-20-1 is a potential candidate for further development as a novel therapeutic and prophylactic drug against infection by SARS-CoV-2 and its variants, as well as future emerging and reemerging CoVs.

ABSTRACT Postweaning diarrhea (PWD) in piglets impair welfare, induce economic losses and lead to overuse of antibiotics. The early life gut microbiota was proposed to contribute to the susceptibility to PWD. The objective of our study was to evaluate in a large cohort of 116 piglets raised in 2 separate farms whether the gut microbiota composition and functions during the suckling period were associated with the later development of PWD. The fecal microbiota and metabolome were analyzed by 16S rRNA gene amplicon sequencing and nuclear magnetic based resonance at postnatal day 13 in male and female piglets. The later development of PWD was recorded for the same animals from weaning (day 21) to day 54. The gut microbiota structure and α-diversity during the suckling period were not associated with the later development of PWD. There was no significant difference in the relative abundances of bacterial taxa in suckling piglets that later developed PWD. The predicted functionality of the gut microbiota and the fecal metabolome signature during the suckling period were not linked to the later development of PWD. Trimethylamine was the bacterial metabolite which fecal concentration during the suckling period was the most strongly associated with the later development of PWD. However, experiments in piglet colon organoids showed that trimethylamine did not disrupt epithelial homeostasis and is thus not likely to predispose to PWD through this mechanism. In conclusion, our data suggest that the early life microbiota is not a major factor underlying the susceptibility to PWD in piglets. IMPORTANCE This study shows that the fecal microbiota composition and metabolic activity are similar in suckling piglets (13 days after birth) that either later develop post-weaning diarrhea (PWD) or not, which is a major threat for animal welfare that also causes important economic losses and antibiotic treatments in pig production. The aim of this work was to study a large cohort of piglets raised in separates environments, which is a major factor influencing the early life microbiota. One of the main findings is that, although the fecal concentration of trimethylamine in suckling piglets was associated with the later development of PWD, this gut microbiota-derived metabolite did not disrupt the epithelial homeostasis in organoids derived from the pig colon. Overall, this study suggests that the gut microbiota during the suckling period is not a major factor underlying the susceptibility of piglets to PWD.

Thromboembolic complications and excessive inflammation are frequent in severe COVID-19, potentially leading to long COVID. In non-COVID studies, we and others demonstrated that circulating Reelin promotes leukocyte infiltration and thrombosis. Thus, we hypothesized that Reelin participates in endothelial dysfunction and hyperinflammation during COVID-19. We showed that Reelin was increased in COVID-19 patients and correlated with the disease activity. In the severe COVID-19 group, we observed a hyperinflammatory state, as judged by increased concentration of cytokines (IL-1α, IL-4, IL-6, IL-10 and IL-17A), chemokines (IP-10 and MIP-1β), and adhesion markers (E-selectin and ICAM-1). Reelin level was correlated with IL-1α, IL-4, IP-10, MIP-1β, and ICAM-1, suggesting a specific role for Reelin in COVID-19 progression. Furthermore, Reelin and all of the inflammatory markers aforementioned returned to normal in a long COVID cohort, showing that the hyperinflammatory state was resolved. Finally, we tested Reelin inhibition with the anti-Reelin antibody CR-50 in hACE2 transgenic mice infected with SARS-CoV-2. CR-50 prophylactic treatment decreased mortality and disease severity in this model. These results demonstrate a direct proinflammatory function for Reelin in COVID-19 and identify it as a drug target. This work opens translational clinical applications in severe SARS-CoV-2 infection and beyond in auto-inflammatory diseases.

Summary: Reelin was originally identified as a regulator of neuronal migration and synaptic function, but its non-neuronal functions have received far less attention. Reelin participates in organ development and physiological functions in various tissues, but it is also dysregulated in some diseases. In the cardiovascular system, Reelin is abundant in the blood, where it contributes to platelet adhesion and coagulation, as well as vascular adhesion and permeability of leukocytes. It is a pro-inflammatory and pro-thrombotic factor with important implications for autoinflammatory and autoimmune diseases such as multiple sclerosis, Alzheimer’s disease, arthritis, atherosclerosis, or cancer. Mechanistically, Reelin is a large secreted glycoprotein that binds to several membrane receptors, including ApoER2, VLDLR, integrins, and ephrins. Reelin signaling depends on the cell type but mostly involves phosphorylation of NF-κB, PI3K, AKT, or JAK/STAT. This review focuses on non-neuronal functions and the therapeutic potential of Reelin, while highlighting secretion, signaling, and functional similarities between cell types.

Background: Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient’s medical management (outpa-tient care, standard hospital admission, and ICU admission). Methods: A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease. Results: Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.

The integration of photovoltaic (PV) systems into the global energy landscape has been boosted in recent years, driven by environmental concerns and research into renewable energy sources. The accurate prediction of temperature and solar irradiance is essential for optimizing the performance and grid integration of PV systems. Machine learning (ML) has become an effective tool for improving the accuracy of these predictions. This comprehensive review explores the pioneer techniques and methodologies employed in the field of ML-based forecasting of temperature and solar irradiance for PV systems. This article presents a comparative study between various algorithms and techniques commonly used for temperature and solar radiation forecasting. These include regression models such as decision trees, random forest, XGBoost, and support vector machines (SVM). The beginning of this article highlights the importance of accurate weather forecasts for the operation of PV systems and the challenges associated with traditional meteorological models. Next, fundamental concepts of machine learning are explored, highlighting the benefits of improved accuracy in estimating the PV power generation for grid integration.

Abstract This report describes a spinal cord epidural and synovial lipomatosis in a 3‐year‐old neutered male Eurasian dog. This dog presented for ambulatory paraparesis and was previously treated with immunosuppressive dosages of prednisolone for 2 years. Computed tomography (CT) myelography and magnetic resonnance imaging (MRI) images identified dorsal compression of the thoraco‐lumbar spinal cord by hypertrophic epidural fat. Histological examination identified extensive well‐differentiated mature adipose tissue in the subepithelial area of the tarsal synovium. Prednisolone is a reported predisposing factor in humans with lipomatosis.

Abstract Background The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Methods This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. Trial registration This study is registered on Clinicaltrials.gov ( NCT03789825 ).

Abstract Purpose Assess whether full-scale simulation exercises improved hospital pharmacies’ disaster preparedness. Methods Swiss hospital pharmacies performed successive full-scale simulation exercises at least four months apart. An interprofessional team created two scenarios, each representing credible regional-scale disasters involving approximately fifty casualties (a major road accident and a terrorist attack). Four exercise assessors used appraisal forms to evaluate participants’ actions and responses during the simulation (rating them using five-point Likert scales). Results Four hospital pharmacies performed two full-scale simulation exercises each. Differences between exercises one and two were observed. On average, the four hospitals accomplished 69% ± 6% of the actions expected of them during exercise one. The mean rate of expected actions accomplished increased to 84% ± 7% (p

Abstract Background Breeding pigs that can efficiently digest alternative diets with increased fiber content is a viable strategy to mitigate the feed cost in pig production. This study aimed at determining the contribution of the gut microbiota and host genetics to the phenotypic variability of digestive efficiency (DE) traits, such as digestibility coefficients of energy, organic matter and nitrogen, feed efficiency (FE) traits (feed conversion ratio and residual feed intake) and growth traits (average daily gain and daily feed intake). Data were available for 791 pigs fed a conventional diet and 735 of their full-sibs fed a high-fiber diet. Fecal samples were collected at 16 weeks of age to sequence the V3–V4 regions of the 16S ribosomal RNA gene and predict DE with near-infrared spectrometry. The proportions of phenotypic variance explained by the microbiota (microbiability) were estimated under three OTU filtering scenarios. Then, microbiability and heritability were estimated independently (models Micro and Gen) and jointly (model Micro+Gen) using a Bayesian approach for all traits. Breeding values were estimated in models Gen and Micro+Gen. Results Differences in microbiability estimates were significant between the two extreme filtering scenarios (14,366 and 803 OTU) within diets, but only for all DE. With the intermediate filtering scenario (2399 OTU) and for DE, microbiability was higher (> 0.44) than heritability (