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Every fungal cell is encapsulated in a cell wall, essential for cell viability, morphogenesis, and pathogenesis. Most knowledge of the cell wall composition in fungi has focused on ascomycetes, especially human pathogens, but considerably less is known about early divergent fungal groups, such as species in the Zoopagomycota and Mucoromycota phyla. To shed light on evolutionary changes in the fungal cell wall, we studied the monosaccharide composition of the cell wall of 18 species including early diverging fungi and species in the Basidiomycota and Ascomycota phyla with a focus on those with pathogenic lifestyles and interactions with plants. Our data revealed that chitin is the most characteristic component of the fungal cell wall, and was found to be in a higher proportion in the early divergent groups. The Mucoromycota species possess few glucans, but instead have other monosaccharides such as fucose and glucuronic acid that are almost exclusively found in their cell walls. Additionally, we observed that hexoses (glucose, mannose and galactose) accumulate in much higher proportions in species belonging to Dikarya. Our data demonstrate a clear relationship between phylogenetic position and fungal cell wall carbohydrate composition and lay the foundation for a better understanding of their evolution and their role in plant interactions.

In the context of urban 3D mapping, the 3D modelling step is a crucial operation, which can be very error prone, particularly when high fidelity and accuracy are required. While automatic reconstruction tools are way faster and less expensive than manual ones, these last are less sensible to the data defects.To combine all this complementary advantages, we propose a semi-automatic approach, where human operators will manually correct the result of an automatic reconstruction tool.While the automated reconstruction tool will be taken on the shelf, we have developed our own polyhedral modeler tool to make the correction step. In this article, we present this polyhedral modeler, which is based on face shifting, edge flipping and automatic topological events resolution.

Recent advancements in 3D data acquisition and processing have enabled high-fidelity urban modeling. Yet, production of structured 3D models in standards like CityGML remain complex, resource-intensive, and difficult to automate. This paper introduces a low-cost alternative that we call “structured mesh model” designed to cover many applications of structured 3D models at a lower cost. It relies on integrating geometric simplification with segmentation alignment to produce a lightweight, unified mesh representation. Using an edge-collapse algorithm, our method combines geometry from an existing mesh with labeled point cloud data to create a continuous mesh with edges aligned to segmentation boundaries, preserving both geometric fidelity and semantic clarity. The resulting structured mesh efficiently reduces memory requirements while maintaining accuracy, offering a practical solution for simulations and urban analyses that require structured 3D data.

BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Abstract Background Few data are available on the long-term mortality and functional status of geriatric patients surviving after hospitalization for COVID-19. We compared the mortality and functional status 18 months after hospitalization for geriatric patients who were hospitalized for COVID-19 or another diagnosis. Methods This was a multicentric cohort study in Paris from January to June 2021. We included patients aged 75 years and over who were hospitalized with COVID-19 or not during this period and compared their vital and functional status 18 months after hospitalization. Results We included 254 patients (63 hospitalized for COVID-19). As compared with patients hospitalized for other reasons, those hospitalized for COVID-19 were younger (mean [SD] age 86 [6.47] vs. 88 [6.41] years, p = 0.03), less frail (median Clinical Frailty Scale score 5 [4–6] vs. 6 [4–6], p 0.007) and more independent at baseline (median activities of daily living score 5.5 [4–6] vs. 5 [3.5–6], p 0.03; instrumental activities of daily living score 3 [1–4] vs. 2 [0–3], p 0.04). At 18 months, 50.8% (n = 32/63) of COVID-19 patients had died versus 66% (n = 126/191) of non-COVID-19 patients (p 0.03). On multivariate analysis, COVID-19 positivity was not significantly associated with 18-month mortality (adjusted hazard ratio 0.67, 95% confidence interval 0.40 to 1.13). At 18 months, the two groups did not differ in activities of daily living or frailty scores. Conclusions In this multicenter study of long-term mortality in geriatric patients discharged alive after hospitalization, positive COVID-19 status was not associated with excess mortality.

Abstract Background Primaquine (PQ) has activity against mature P. falciparum gametocytes and proven transmission blocking efficacy (TBE) between humans and mosquitoes. WHO formerly recommended a single transmission blocking dose of 0.75 mg/kg but this was little used. Then in 2012, faced with the emergence of artemisinin-resistant P. falciparum (ARPf) in SE Asia, the WHO recommended a lower dose of 0.25 mg/kg to be added to artemisinin-based combination therapy in falciparum-infected patients in low transmission areas. This dose was considered safe in glucose-6-phosphate dehydrogenase deficiency (G6PDd) and not requiring G6PD testing. Subsequent single low-dose primaquine (SLDPQ) studies have demonstrated safety in different G6PD variants. Dosing remains challenging in children under the age of 5 because of the paucity of PQ pharmacokinetic (PK) data. We plan to assess the anti-infectivity efficacy of SLDPQ using an allometrically scaled, weight-based regimen, with a target dose of 0.25 mg/kg, in children with acute uncomplicated falciparum malaria. Methods This study is an open label, randomised 1:1, phase IIb study to assess TBE, tolerability, pharmacokinetics and acceptability of artesunate pyronaridine (ASPYR) administered alone or combined with SLDPQ in 56 Burkinabe children aged ≥ 6 months–

Abstract Background Activation of innate immunity is a first line of host defense during acute critical illness (ACI) that aims to contain injury and avoid tissue damages. Aberrant activation of innate immunity may also participate in the occurrence of organ failures during critical illness. This review aims to provide a narrative overview of recent advances in the field of innate immunity in critical illness, and to consider future potential therapeutic strategies. Main text Understanding the underlying biological concepts supporting therapeutic strategies modulating immune response is essential in decision-making. We will develop the multiple facets of innate immune response, especially its cellular aspects, and its interaction with other defense mechanisms. We will first describe the pathophysiological mechanisms of initiation of innate immune response and its implication during ACI. We will then develop the amplification of innate immunity mediated by multiple effectors. Our review will mainly focus on myeloid and lymphoid cellular effectors, the major actors involved in innate immune-mediated organ failure. We will third discuss the interaction and integration of innate immune response in a global view of host defense, thus considering interaction with non-immune cells through immunothrombosis, immunometabolism and long-term reprogramming via trained immunity. The last part of this review will focus on the specificities of the immune response in children and the older population. Conclusions Recent understanding of the innate immune response integrates immunity in a highly dynamic global vision of host response. A better knowledge of the implicated mechanisms and their tissue-compartmentalization allows to characterize the individual immune profile, and one day eventually, to develop individualized bench-to-bedside immunomodulation approaches as an adjuvant resuscitation strategy.

Abstract Land Use and Land Cover (LULC) maps are important tools for environmental planning and social-ecological modeling, as they provide critical information for evaluating risks, managing natural resources, and facilitating effective decision-making. This study aimed to generate a very high spatial resolution (0.5 m) and detailed (21 classes) LULC map for the greater Mariño watershed (Peru) in 2019, using the MORINGA processing chain. This new method for LULC mapping consisted in a supervised object-based LULC classification, using the random forest algorithm along with multi-sensor satellite imagery from which spectral and textural predictors were derived (a very high spatial resolution Pléiades image and a time serie of high spatial resolution Sentinel-2 images). The random forest classifier showed a very good performance and the LULC map was further improved through additional post-treatment steps that included cross-checking with external GIS data sources and manual correction using photointerpretation, resulting in a more accurate and reliable map. The final LULC provides new information for environmental management and monitoring in the greater Mariño watershed. With this study we contribute to the efforts to develop standardized and replicable methodologies for high-resolution and high-accuracy LULC mapping, which is crucial for informed decision-making and conservation strategies.

Abstract Deregulation of transcription factors (TFs) leading to uncontrolled proliferation of tumor cells within the microenvironment represents a hallmark of cancer. However, the biological and clinical impact of transcriptional interference, particularly in multiple myeloma (MM) cells, remains poorly understood. The present study shows for the first time that MYC and JUNB, two crucial TFs implicated in MM pathogenesis, orchestrate distinct transcriptional programs. Specifically, our data revealed that expression levels of MYC, JUNB, and their respective downstream targets do not correlate and that their global chromatin-binding patterns are not significantly overlapping. Mechanistically, MYC expression was not affected by JUNB knockdown, and conversely, JUNB expression and transcriptional activity were not affected by MYC knockdown. Moreover, suppression of MYC levels in MM cells via targeting the master regulator BRD4 by either siRNA-mediated knockdown or treatment with the novel proteolysis targeting chimera (PROTAC) MZ-1 overcame bone marrow (BM) stroma cell/IL-6-induced MYC- but not MEK-dependent JUNB-upregulation and transcriptional activity. Consequently, targeting of the two non-overlapping MYC- and JUNB-transcriptoms by MZ-1 in combination with genetic or pharmacological JUNB-targeting approaches synergistically enhanced MM cell death, both in 2D and our novel dynamic 3D models of the BM milieu as well as in murine xenografts. In summary, our data emphasize the opportunity to employ MYC and JUNB dual-targeting treatment strategies in MM as another exciting approach to further improve patient outcomes.

Abstract Background Septoria tritici blotch (STB), caused by the foliar fungus Zymoseptoria tritici, is one of the most damaging disease of wheat in Europe. Genetic resistance against this fungus relies on different types of resistance from non-host resistance (NHR) and host species specific resistance (HSSR) to host resistance mediated by quantitative trait loci (QTLs) or major resistance genes (Stb). Characterizing the diversity of theses resistances is of great importance for breeding wheat cultivars with efficient and durable resistance. While the functional mechanisms underlying these resistance types are not well understood, increasing piece of evidence suggest that fungus stomatal penetration and early establishment in the apoplast are both crucial for the outcome of some interactions between Z. tritici and plants. To validate and extend these previous observations, we conducted quantitative comparative phenotypical and cytological analyses of the infection process corresponding to 22 different interactions between plant species and Z. tritici isolates. These interactions included four major bread wheat Stb genes, four bread wheat accessions with contrasting quantitative resistance, two species resistant to Z. tritici isolates from bread wheat (HSSR) and four plant species resistant to all Z. tritici isolates (NHR). Results Infiltration of Z. tritici spores into plant leaves allowed the partial bypass of all bread wheat resistances and durum wheat resistance, but not resistances from other plants species. Quantitative comparative cytological analysis showed that in the non-grass plant Nicotiana benthamiana, Z. tritici was stopped before stomatal penetration. By contrast, in all resistant grass plants, Z. tritici was stopped, at least partly, during stomatal penetration. The intensity of this early plant control process varied depending on resistance types, quantitative resistances being the least effective. These analyses also demonstrated that Stb-mediated resistances, HSSR and NHR, but not quantitative resistances, relied on the strong growth inhibition of the few Z. tritici penetrating hyphae at their entry point in the sub-stomatal cavity. Conclusions In addition to furnishing a robust quantitative cytological assessment system, our study uncovered three stopping patterns of Z. tritici by plant resistances. Stomatal resistance was found important for most resistances to Z. tritici, independently of its type (Stb, HSSR, NHR). These results provided a basis for the functional analysis of wheat resistance to Z. tritici and its improvement.

By 2040, more than one in four Europeans is expected to be over 65. Despite improvements in older patients' care, oral healthcare is still neglected. One of the major obstacles could be the negative representations associated with aging: ageism. The present study aims to quantify and qualify ageism for general and specific representations of aging associated with the mouth of an older patient compared to a young patient in dental students. Undergraduate students at the French dental school of Clermont-Ferrand were invited to participate in the study. Ageism was quantified by asking the students to estimate how many older adults have some negative conditions, which were then compared to real data. Representations of the mouth of a young vs. an older adult were collected by asking each student to write the first five words that came to their mind when they thought about the mouth of a young person and then the mouth of an older person. The students exhibited a large overestimation of health problems in the older adult population. The words given for a young adult were positive 49% of the time (vs. 23% negative), whereas 69% of the words were negative for an older adult (vs. 8% positive). The students in the second year were less negative than students in higher years. Our study contributes to assessing how dental students could exhibit implicit ageism. They show very negative representations of aging from the beginning of their training, which get even worse after they are exposed to clinical training with older patients.

Hydrogels, that are crosslinked polymer networks, can absorb huge quantities of water and/or biological fluids. Their physical properties, such as elasticity and soft tissue, together with their biocompatibility and biodegradability, closely resemble living tissues. The versatility of hydrogels has fuelled their application in various fields, such as agriculture, biomaterials, the food industry, drug delivery, tissue engineering, and regenerative medicine. Their combination with nanoparticles, specifically with Mesoporous Silica Nanoparticles (MSNs), have elevated these composites to the next level, since MSNs could improve the hydrogel mechanical properties, their ability to encapsulate and controlled release great amounts of different therapeutic agents, and their responsiveness to a variety of external and internal stimuli. In this review, the main features of both MSNs and hydrogels are introduced, followed by the discussion of different hydrogels-MSNs structures and an overview of their use in different applications, such as drug delivery technologies and tissue engineering.

Classic McEliece is one of the three code-based candidates in the fourth round of the NIST post-quantum cryptography standardization process in the Key Encapsulation Mechanism category. As such, its decapsulation algorithm is used to recover the session key associated with a ciphertext using the private key. In this article, we propose a new side-channel attack on the syndrome computation in the decapsulation algorithm that recovers the private key, which consists of the private Goppa polynomial g and the permuted support L. The attack relies on both practical aspects and theoretical contributions, namely that the side-channel distinguisher can accurately discriminate elements of the permuted support L, while relying only on a standard noisy Hamming weight leakage assumption and that there exists a cubic-time algorithm that uses this information to recover the private Goppa polynomial g. Compared with previous work targeting the Classic McEliece private key, this drastically improves both on the assumptions made in the attacker model and on the overall efficiency of the key-recovery algorithm. We have carried out the attack in practice on a microcontroller target running the reference implementation of Classic McEliece, and make the full attack source code available.

Study region: The study was conducted in an alluvial plain between the Rhône and the Ouvèze Rivers (in the southeast of France) extensively exploited for drinking water. The research area is characterized by significant groundwater-surface interactions influenced by groundwater pumping activities. Study focus: The aim of this study is to enhance the understanding of interactions between rivers and alluvial aquifers by combined multi-tracer and numerical modeling approaches. Over an 18-month period, groundwater temperature, piezometric levels, and river surface water levels were continuously monitored. Field campaigns focused on conductivity, stable isotopes of water, and radon-222 activity concentration in both groundwater and surface water. Radon-222 was used to quantify water exchanges between the river and the aquifer. A MODFLOW model, calibrated using piezometric data and PEST, was employed to simulate groundwater flow and reactive transport of radon-222 using MT3DMS. New hydrological insights for the region: The study reveals that river water recharges the aquifer, with radon-222 data delineating this recharge zone. The methodology extended the interpretation of periodic groundwater temperature signals to isotopic signals, allowing the identification of dispersivity and Darcy's velocity. The Ouvèze River was found to contribute approximately 55 % of the pumping water supply, alongside the Rhône. These findings provide valuable insights for sustainable water resource management, demonstrating the relevance of using natural tracers in scenarios where artificial tracers are impractical.

AbstractWe developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections.

Abstract Frailty, a condition that was first defined 20 years ago, is now assessed via multiple different tools. The Frailty Phenotype was initially used to identify a population of “pre-frail” and “frail” older adults, so as to prevent falls, loss of mobility, and hospitalizations. A different definition of frailty, via the Clinical Frailty Scale, is now actively used in critical care situations to evaluate over 65 year-old patients, whether it be for Intensive Care Unit (ICU) admissions, limitation of life-sustaining treatments or prognostication. Confusion remains when mentioning “frailty” in older adults, as to which tools are used, and what the impact or the bias of using these tools might be. In addition, it is essential to clarify which tools are appropriate in medical emergencies. In this review, we clarify various concepts and differences between frailty, functional autonomy and comorbidities; then focus on the current use of frailty scales in critically ill older adults. Finally, we discuss the benefits and risks of using standardized scales to describe patients, and suggest ways to maintain a complex, three-dimensional, patient evaluation, despite time constraints. Frailty in the ICU is common, involving around 40% of patients over 75. The most commonly used scale is the Clinical Frailty Scale (CFS), a rapid substitute for Comprehensive Geriatric Assessment (CGA). Significant associations exist between the CFS-scale and both short and long-term mortality, as well as long-term outcomes, such as loss of functional ability and being discharged home. The CFS became a mainstream tool newly used for triage during the Covid-19 pandemic, in response to the pressure on healthcare systems. It was found to be significantly associated with in-hospital mortality. The improper use of scales may lead to hastened decision-making, especially when there are strains on healthcare resources or time-constraints. Being aware of theses biases is essential to facilitate older adults’ access to equitable decision-making regarding critical care. The aim is to help counteract assessments which may be abridged by time and organisational constraints.

Abstract The Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging pathogen of the Orthonairovirus genus that can cause severe and often lethal hemorrhagic diseases in humans. CCHFV has a broad tropism and can infect a variety of species and tissues. Here, by using gene silencing, blocking antibodies or soluble receptor fragments, we identify the low-density lipoprotein receptor (LDL-R) as a CCHFV entry factor. The LDL-R facilitates binding of CCHFV particles but does not allow entry of Hazara virus (HAZV), another member of the genus. In addition, we show that apolipoprotein E (apoE), an exchangeable protein that mediates LDL/LDL-R interaction, is incorporated on CCHFV particles, though not on HAZV particles, and enhances their specific infectivity by promoting an LDL-R dependent entry. Finally, we show that molecules that decrease LDL-R from the surface of target cells could inhibit CCHFV infection. Our study highlights that CCHFV takes advantage of a lipoprotein receptor and recruits its natural ligand to promote entry into cells.

Zymoseptoria tritici, the causal agent of Septoria tritici blotch, is one of Europe's most damaging wheat pathogens, causing significant economic losses. Genetic resistance is a common strategy to control the disease, Stb6 being a resistance gene used for more than 100 years in Europe. This study investigates the molecular mechanisms underlying Stb6-mediated resistance. Utilizing confocal microscopy imaging, we determined that Z. tritici epiphytic hyphae mainly accumulate the corresponding avirulence factor AvrStb6 in close proximity to stomata. Consequently, the progression of AvrStb6-expressing avirulent strains is hampered during penetration. The fungal growth inhibition co-occurs with a transcriptional reprogramming in wheat characterized by an induction of immune responses, genes involved in stomatal regulation, and cell wall-related genes. Overall, we shed light on the gene-for-gene resistance mechanisms in the wheat–Z. tritici pathosystem at the cytological and transcriptomic level, and our results highlight that stomatal penetration is a critical process for pathogenicity and resistance. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract In a retrospective study, 54 patients with treatment-resistant major depressive disorder (TRD) completed a free-viewing task in which they had to freely explore pairs of faces (an emotional face (happy or sad) opposite to a neutral face). Attentional bias to emotional faces was calculated for early and sustained attention. We observed a significant negative correlation between depression severity as measured by the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) and sustained attention to happy faces. In addition, we observed a positive correlation between depression severity and sustained attention to sad faces. No significant correlation between depression severity and early attention was found for either happy or sad faces. Although conclusions from the current study are limited by the lack of comparison with a control group, the eye-tracking free-viewing task appears to be a relevant, accessible and easy-to-use tool for measuring depression severity through emotional attentional biases in TRD.

Abstract Growth at the shoot apical meristem (SAM) is essential for shoot architecture construction. The phytohormones gibberellins (GA) play a pivotal role in coordinating plant growth, but their role in the SAM remains mostly unknown. Here, we developed a ratiometric GA signaling biosensor by engineering one of the DELLA proteins, to suppress its master regulatory function in GA transcriptional responses while preserving its degradation upon GA sensing. We demonstrate that this degradation-based biosensor accurately reports on cellular changes in GA levels and perception during development. We used this biosensor to map GA signaling activity in the SAM. We show that high GA signaling is found primarily in cells located between organ primordia that are the precursors of internodes. By gain- and loss-of-function approaches, we further demonstrate that GAs regulate cell division plane orientation to establish the typical cellular organization of internodes, thus contributing to internode specification in the SAM.

Abstract Very old critically ill patients pose a growing challenge for intensive care. Critical illness and the burden of treatment in the intensive care unit (ICU) can lead to a long-lasting decline of functional and cognitive abilities, especially in very old patients. Multi-complexity and increased vulnerability to stress in these patients may lead to new and worsening disabilities, requiring careful assessment, prevention and rehabilitation. The potential for rehabilitation, which is crucial for optimal functional outcomes, requires a systematic, multi-disciplinary approach and careful long-term planning during and following ICU care. We describe this process and provide recommendations and checklists for comprehensive and timely assessments in the context of transitioning patients from ICU to post-ICU and acute hospital care, and review the barriers to the provision of good functional outcomes.

The database contains detailed statistics of compressible turbulent plane channel (TPC) flow, obtained from direct numerical simulation (DNS), with a very-high-order massively parallel solver of the compressible Navier-Stokes equations. It contains datasets for 25 different flow conditions determined by the corresponding HCB friction Reynolds number and centerline Mach number, covering the ranges 100⪅Reτ★⪅1000 and 0.3⪅M¯CLx⪅2.5. All calculations are for strictly isothermal wall conditions at temperature Tw=298K in a medium-size (MB) computational box (8πδ×2δ×4πδ where 2δ is the channel-height). Statistics (moments and pdfs) were collected after the elimination of the transient, and post-processed to create the dataset, which contains only plain text (.txt) space-separated multicolumn files for ease of use. The dataset for each flow-condition is tagged by the values of (Reτ★,M¯CLx) and is organized in 4 directories: (0) global data files, (1) profiles and budgets (meanflow profiles, velocity-moments up to 6-order, budgets of Reynolds-stresses transport, turbulent fluxes appearing in transport equations for velocity-moments and thermodynamic quantities, correlation coefficients between thermodynamic variables, and skewness and flatness profiles) as a function of the wall-distance, (2) single-variable probability density functions (pdfs) for numerous flow quantities at selected wall-normal distances, and (3) two-variable joint pdfs for numerous couples of flow-quantities at the same selected wall-normal distances.

Background: A new monoclonal antibody (nirsevimab; Beyfortus®) and a bivalent prefusion RSV vaccine (Abrysvo®) for maternal immunization have been approved recently. This is a modelling study to estimate the potential impact of different immunization programs with these products on RSV-bronchiolitis. Methods: Population-based real-world data from primary care and hospitalizations were considered. RSV bronchiolitis dynamics in absence of these immunization scenarios were explained by a multivariate age-structured Bayesian model. Then, the potential impact was simulated under different assumptions including the most recent clinical trial data. Differences in endpoints, populations, and timeframes between trials make the two products’ efficacy difficult to compare. Results: A seasonal with catch-up program, assuming a constant effectiveness of 79.5 % during the first 5 months followed by a linear decay to 0 by month 10 with nirsevimab, would prevent between 5121 and 8846 RSV bronchiolitis per 100,000 infants-years. Assuming 77.3 % effectiveness with the same decay, between 976 and 1686 RSV-hospitalizations per 100,000 infants-years could be prevented depending on the uptake. A year-round maternal immunization program, with 51 % of effectiveness during the first 6 months followed by a linear decay to 0 by month 10 would prevent between 3246 and 5606 RSV bronchiolitis cases per 100,000 infants-years. Assuming 56.9 % effectiveness with the same decay, between 713 and 1231 RSV-hospitalizations per 100,000 infants-years could be prevented. Conclusions: Our results suggest that each strategy would effectively reduce RSV-bronchiolitis.

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 In recent decades, detailed country-level estimates of income and wealth have become widely available and inform us about the evolution of inequality between and within countries. But a substantial portion of these available datasets lack sub-national geographical information, precluding the exploration of the spatial distribution and evolution of inequalities within countries. We present here a new dataset of disposable income for Europe at the subnational level. It has been compiled from existing income data (gross income, gross earnings, equivalised income, etc.) published by national statistical institutes at different geographical levels. We used linear regressions and numerical operations to estimate disposable income from other available socio-economic statistics (e.g. household size, tax rates). We developed a harmonization and adjustment procedures to ensure of the consistency of statistical units, income indicators, costs of living and inflation. The dataset covers 42 European countries distributed over more than 120,000 geographical entities on the 1995 to 2021 period (most of the data being available for the 2010–2020 decade). This new dataset opens avenues for investigating the links between income inequality and other socio-economic or ecological processes.