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Abstract It has been suggested that having a reputation for being prosocial is a critical part of social status across all human societies. It has also been argued that prosocial behavior confers benefits, whether physiological, such as stress reduction, or social, such as building allies or becoming more popular. Here, we investigate the relationship between helping reputation (being named as someone others would go to for help), and hair-derived chronic stress (hair cortisol concentration). In a sample of 77 women and 62 men, we found that perceived helping reputation was not related to chronic stress. Overall, the results of our study suggest that, in an egalitarian society with fluid camp membership and widely practiced generosity such as the Hadza, helping reputation does not necessarily boost stress-related health benefits through prestige-signaling mechanisms observed in hierarchical, large-scale societies.

Abstract There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21–28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P

Abstract The formulation of sustainable fish feeds based on plant ingredients supplemented by alternative ingredients to plant (insect, micro-algae, yeast) and genetic selection of fish for plant-based diets were tested on rainbow trout in two separate experiments. Plant-based diets and corresponding diets supplemented with an ingredient mix: insect, micro-algae and yeast in Experiment A, and insect and yeast in Experiment B were compared to commercial-like diets. In experiment A, the mix-supplemented diet was successful in compensating the altered growth performance of fish fed their respective plant-based diet compared to those fed the commercial diet, by restoring feed conversion. In experiment B, the selected line demonstrated improved growth performances of fish fed mix-supplemented and plant-based diets compared to the non-selected line. Metabolomics demonstrated a plasma compositional stability in fish fed mix-supplemented and basal plant-based diets comprising an amino acid accumulation and a glucose depletion, compared to those fed commercial diets. The selected line fed mix-supplemented and commercial diets showed changes in inositol, ethanol and methanol compared to the non-selected line, suggesting an involvement of microbiota. Changes in plasma glycine-betaine content in fish fed the mix-supplemented diet suggest the ability of the selected line to adapt to alternative ingredients.

Abstract The role of force application in immune cell recognition is now well established, the force being transmitted between the actin cytoskeleton to the anchoring ligands through receptors such as integrins. In this chain, the mechanics of the cytoskeleton to receptor link, though clearly crucial, remains poorly understood. To probe this link, we combine mechanical extraction of membrane tubes from T cells using optical tweezers, and fitting of the resulting force curves with a viscoelastic model taking into account the cell and relevant molecules. We solicit this link using four different antibodies against various membrane bound receptors: antiCD3 to target the T Cell Receptor (TCR) complex, antiCD45 for the long sugar CD45, and two clones of antiCD11 targeting open or closed conformation of LFA1 integrins. Upon disruption of the cytoskeleton, the stiffness of the link changes for two of the receptors, exposing the existence of a receptor to cytoskeleton link—namely TCR-complex and open LFA1, and does not change for the other two where a weaker link was expected. Our integrated approach allows us to probe, for the first time, the mechanics of the intracellular receptor–cytoskeleton link in immune cells.

Abstract Agriculture and forestry cover more than 75% of Europe, and invertebrate pests are a costly challenge for these two economic sectors. Landscape management is increasingly promoted as a solution to enhance biological pest control, but little is known on its effects on adjacent crop fields and woodlands. This study aims to explore the effect of the proportion of woodlands and permanent grasslands as well as crop diversity on biological pest control simultaneously in cereals fields and woodland patches, in south-western France. We used different types of sentinel prey as well as bird and carabid community metrics to assess biological pest control potential in these two ecosystems. We first show that land cover variables influence biological pest control both in cereal fields and woodland patches, but have antagonistic effects in the two ecosystems. Although results vary according to the biological control indicator considered, we show that increasing landscape heterogeneity represents a valuable solution to manage trade-offs and promote higher average predation rates across forests and cereal fields. Our study therefore calls for more integrative studies to identify landscape management strategies that enable nature-based solutions across ecosystems.

Abstract This paper presents a new strategy to generate synthetic samples containing casting defects. Four samples of Inconel 100 containing casting defects such as shrinkages and pores have been characterized using X-ray tomography and are used as reference for this application. Shrinkages are known to be tortuous in shape and more detrimental for the mechanical properties of materials, especially metal fatigue, whereas pores can be of two types: broken shrinkage pores with arbitrary shape and gaseous pores of spherical shape. For the generation of synthetic samples, an integrated module of Spatial Point Pattern (SPP) analysis and deep learning techniques such as Generative Adversarial Networks (GANs) and Convolutional Neural Networks (CNNs) are used. The SPP analysis describes the spatial distributions of casting defects in material space, whereas GANs and CNNs generate a defect of arbitrary morphology very close to real defects. SPP analysis reveals the existence of two different void nucleation mechanisms during metal solidification associated to shrinkages and pores. Our deep learning model successfully generates casting defects with defect size ranging from 100 µm to 1.5 mm and of very realistic shapes. The entire synthetic microstructure generation process respects the global defect statistics of reference samples and the generated samples are validated by statistically comparing with real samples.

Abstract Hydrogen sulfide (H2S) is a gaseous signaling molecule that participates in various signaling functions in health and diseases. The tetrameric cystathionine γ-lyase (CSE) contributes to H2S biogenesis and several investigations provide evidence on the pharmacological modulation of CSE as a potential target for the treatment of a multitude of conditions. D-penicillamine (D-pen) has recently been reported to selectively impede CSE-catalyzed H2S production but the molecular bases for such inhibitory effect have not been investigated. In this study, we report that D-pen follows a mixed-inhibition mechanism to inhibit both cystathionine (CST) cleavage and H2S biogenesis by human CSE. To decipher the molecular mechanisms underlying such a mixed inhibition, we performed docking and molecular dynamics (MD) simulations. Interestingly, MD analysis of CST binding reveals a likely active site configuration prior to gem-diamine intermediate formation, particularly H-bond formation between the amino group of the substrate and the O3′ of PLP. Similar analyses realized with both CST and D-pen identified three potent interfacial ligand-binding sites for D-pen and offered a rational for D-pen effect. Thus, inhibitor binding not only induces the creation of an entirely new interacting network at the vicinity of the interface between enzyme subunits, but it also exerts long range effects by propagating to the active site. Overall, our study paves the way for the design of new allosteric interfacial inhibitory compounds that will specifically modulate H2S biogenesis by cystathionine γ-lyase.

Abstract In recent years there has been much research regarding the extent to which social status is related to long-term indices of health. The majority of studies looking at the interplay between social status and health have been conducted in industrialized societies. However, it has been argued that most of human evolution took place in small, mobile and egalitarian hunter-gatherer groups where individuals exhibited very little variation in terms of material wealth or possessions. In this study, we looked at the extent to which two domains of social status, hunting reputation (being perceived as a good hunter) and popularity (being perceived as a friend), are related to physiological stress levels among Hadza men, hunter-gatherers living in Northern Tanzania. The results of our study show that neither hunting reputation nor popularity is associated with stress levels. Overall, our data suggest that, in at least some traditional small-scale societies exhibiting an egalitarian social model, such as the Hadza, the variation in social status measures based on both popularity and hunting reputation does not translate into one of the commonly used indices of wellbeing.

Abstract The subtropical oceanic gyre in the North Pacific Ocean is currently covered with tens of thousands of tonnes of floating plastic debris, dispersed over millions of square kilometres. A large fraction is composed of fishing nets and ropes while the rest is mostly composed of hard plastic objects and fragments, sometimes carrying evidence on their origin. In 2019, an oceanographic mission conducted in the area, retrieved over 6000 hard plastic debris items > 5 cm. The debris was later sorted, counted, weighed, and analysed for evidence of origin and age. Our results, complemented with numerical model simulations and findings from a previous oceanographic mission, revealed that a majority of the floating material stems from fishing activities. While recent assessments for plastic inputs into the ocean point to coastal developing economies and rivers as major contributors into oceanic plastic pollution, here we show that most floating plastics in the North Pacific subtropical gyre can be traced back to five industrialised fishing nations, highlighting the important role the fishing industry plays in the solution to this global issue.

Abstract Occupational enrichment emerges as a promising strategy for improving the welfare of farmed animals. This form of enrichment aims to stimulate cognitive abilities of animals by providing them with more opportunities to interact with and control their environment. Predictability of salient daily events, and in particular predictability of feeding, is currently one of the most studied occupational enrichment strategies and can take several forms. In fish, while temporal predictability of feeding has been widely investigated, signalled predictability (based on a signal, such as light or sound) has received little attention. Depending on the type of predictability used and the ecology of the species, the effects on fish welfare often differ. The present study aimed to determine which feeding predictability would be most appropriate for rainbow trout, the main continental farmed fish in Europe, and what the consequences might be for their welfare. We tested four feeding predictability conditions: temporal (based on time of day), signalled (based on bubble diffusion), temporal + signalled (based on time and bubble diffusion), and unpredictable (random feeding times). Behavioural and zootechnical outcomes recorded were swimming activity, aggressive behaviours, burst of accelerations, and jumps, emotional reactivity, and growth. Our results showed that rainbow trout can predict daily feedings relying on time and/or bubbles as predictors as early as two weeks of conditioning, as evidenced by their increased swimming activity before feeding or during feed omission tests, which allowed to reinforce their conditioned response. Temporal predictability alone resulted in an increase in pre-feeding aggressive behaviours, burst of accelerations, and jumps, suggesting that the use of time as the sole predictor of feedings in husbandry practices may be detrimental to fish welfare. Signalled predictability with bubbles alone resulted in fewer pre-feeding agonistic behaviours, burst of accelerations, and jumps than in the temporal predictability condition. The combination of temporal and signalled predictability elicited the highest conditioned response and the level of pre-feeding aggression behaviours, burst of accelerations and jumps tended to be lower than for temporal predictability alone. Interestingly, fish swimming activity during bubble diffusion also revealed that bubbles were highly attractive regardless of the condition. Rainbow trout growth and emotional reactivity were not affected by the predictability condition. We conclude, therefore, that the use of bubbles as a feeding predictor could represent an interesting approach to improve rainbow trout welfare in farms, by acting as both an occupational and physical enrichment.

Abstract Between the Last Glacial Maximum and the mid-Holocene, the Mediterranean Sea experienced major hydrological changes. The deposition of the last sapropel, S1, during the Early Holocene is a consequence of these changes. In order to cause anoxia in the Eastern Mediterranean Sea (EMS) bottom water, a long preconditioning period of a few thousand years would need to occur throughout the deglaciation prior to S1. It is generally believed that this freshwater was of North Atlantic origin, later supplemented by the African Humid period (AHP). Here, we investigate another potentially important source of freshwater to the EMS: the Fennoscandian ice sheet (FIS) meltwater, running into the Caspian and Black Seas. A few scenarios of continental hydrologic perturbation have been developed to drive a high-resolution Mediterranean Sea general circulation model. We demonstrate that, during the last deglaciation, FIS meltwater flowing into the Black Sea reduced surface salinity and ventilation over the main convection areas in the EMS. By including continental hydrological changes, a more consistent framework is produced to characterize the hydrology of the Mediterranean Sea during the last deglaciation and the Early Holocene.

Abstract Fungal communities associated with roots play a key role in nutrient uptake and in mitigating the abiotic and biotic stress of their host. In this study, we characterized the roots mycobiome of wild and cultivated pearl millet [Pennisetum glaucum (L.) R. Br., synonym: Cenchrus americanus (L.) Morrone] in three agro-ecological areas of Senegal following a rainfall gradient. We hypothesized that wild pearl millet could serve as a reservoir of endophytes for cultivated pearl millet. We therefore analyzed the soil factors influencing fungal community structure and whether cultivated and wild millet shared the same fungal communities. The fungal communities associated with pearl millet were significantly structured according to sites and plant type (wild vs cultivated). Besides, soil pH and phosphorus were the main factors influencing the fungal community structure. We observed a higher fungal diversity in cultivated compared to wild pearl millet. Interestingly, we detected higher relative abundance of putative pathotrophs, especially plant pathogen, in cultivated than in wild millet in semi-arid and semi-humid zones, and higher relative abundance of saprotrophs in wild millet in arid and semi-humid zones. A network analysis based on taxa co-occurrence patterns in the core mycobiome revealed that cultivated millet and wild relatives had dissimilar groups of hub taxa. The identification of the core mycobiome and hub taxa of cultivated and wild pearl millet could be an important step in developing microbiome engineering approaches for more sustainable management practices in pearl millet agroecosystems.

Abstract Nanoshells made of a silica core and a gold shell possess an optical response that is sensitive to nanometer-scale variations in shell thickness. The exponential red shift of the plasmon resonance with decreasing shell thickness makes ultrathin nanoshells (less than 10 nm) particularly interesting for broad and tuneable ranges of optical properties. Nanoshells are generally synthesised by coating gold onto seed-covered silica particles, producing continuous shells with a lower limit of 15 nm, due to an inhomogeneous droplet formation on the silica surface during the seed regrowth. In this paper, we investigate the effects of three variations of the synthesis protocol to favour ultrathin nanoshells: seed density, polymer additives and microwave treatment. We first maximised gold seed density around the silica core, but surprisingly its effect is limited. However, we found that the addition of polyvinylpyrrolidone during the shell synthesis leads to higher homogeneity and a thinner shell and that a post-synthetic thermal treatment using microwaves can further smooth the particle surface. This study brings new insights into the synthesis of metallic nanoshells, pushing the limits of ultrathin shell synthesis.

Abstract A geomorphological survey immediately west of the Minoan town of Malia (Crete) shows that a tsunami resulting from the Bronze Age Santorini eruption reached the outskirts of the Palatial center. Sediment cores testify a unique erosional event during the Late Minoan period, followed locally by a high energy sand unit comprising marine fauna. This confirms that a tsunami impacted northern Crete and caused an inundation up to 400 m inland at Malia. We obtained a radiocarbon range of 1744–1544 BCE for the secure pre-tsunami context and an interval 1509–1430 BCE for the post-event layer. Examination of tsunami deposits was used to constrain run-up not exceeding 8 m asl. The results open the field for new research on the Bronze Age Santorini tsunami regarding both impact and consequences for the Minoan civilization.

Abstract Higher transmissibility of SARS-CoV-2 in cold and dry weather conditions has been hypothesized since the onset of the COVID-19 pandemic but the level of epidemiological evidence remains low. During the first wave of the pandemic, Spain, Italy, France, Portugal, Canada and USA presented an early spread, a heavy COVID-19 burden, and low initial public health response until lockdowns. In a context when testing was limited, we calculated the basic reproduction number (R0) in 63 regions from the growth in regional death counts. After adjusting for population density, early spread of the epidemic, and age structure, temperature and humidity were negatively associated with SARS-CoV-2 transmissibility. A reduction of mean absolute humidity by 1 g/m3 was associated with a 0.15-unit increase of R0. Below 10 °C, a temperature reduction of 1 °C was associated with a 0.16-unit increase of R0. Our results confirm a dependency of SARS-CoV-2 transmissibility to weather conditions in the absence of control measures during the first wave. The transition from summer to winter, corresponding to drop in temperature associated with an overall decrease in absolute humidity, likely contributed to the intensification of the second wave in north-west hemisphere countries. Non-pharmaceutical interventions must be adjusted to account for increased transmissibility in winter conditions.

Abstract Despite the key importance of the landscape matrix for bats, we still not fully understand how the effect of forest composition interacts at combined stand and landscape scales to shape bat communities. In addition, we lack detailed knowledge on the effects of local habitat structure on bat-prey relationships in forested landscapes. We tested the assumptions that (i) forest composition has interacting effects on bats between stand and landscape scales; and (ii) stand structure mediates prey abundance effects on bat activity. Our results indicated that in conifer-dominated landscapes (> 80% of coniferous forests) bat activity was higher in stands with a higher proportion of deciduous trees while bats were less active in stands with a higher proportion of deciduous trees in mixed forest landscapes (~ 50% of deciduous forests). Moth abundance was selected in the best models for six among nine bat species. The positive effect of moth abundance on Barbastella barbastellus was mediated by vegetation clutter, with dense understory cover likely reducing prey accessibility. Altogether, our findings deepen our understanding of the ecological processes affecting bats in forest landscapes and strengthen the need to consider both landscape context and trophic linkage when assessing the effects of stand-scale compositional and structural attributes on bats.

Abstract COVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological (including plasma cytokines) features were assessed. Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response but higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels. NEFAs and PUFAs concentrations were negatively correlated with the number of ventilator-free days. Among hospitalized patients with severe pneumonia, COVID-19 is independently associated with higher NEFAs (mainly linoleic and arachidonic acids) and lower apolipoprotein E and HDL concentrations. These features might act as mediators in COVID-19 pathogenesis and emerge as new therapeutic targets. Further investigations are required to define the role of NEFAs in the pathogenesis and the dysregulated immune response associated with COVID-19. Trial registration: NCT04435223.

Abstract A low-cost, compact, and high gain Fabry–Perot cavity (FPC) antenna which operates at 300 GHz is presented. The antenna is fabricated using laser-cutting brass technology. The proposed antenna consists of seven metallic layers; a ground layer, an integrated stepped horn element (three-layers), a coupling layer, a cavity layer, and an aperture-frequency selective surface (FSS) layer. The proposed aperture-FSS function acts as a partially reflective surface, contributing to a directive beam radiation. For verification, the proposed sub-terahertz (THz) FPC antenna prototype was developed, fabricated, and measured. The proposed antenna has a measured reflection coefficient below − 10 dB from 282 to 304 GHz with a bandwidth of 22 GHz. The maximum measured gain observed is 17.7 dBi at 289 GHz, and the gain is higher than 14.4 dBi from 285 to 310 GHz. The measured radiation pattern shows a highly directive pattern with a cross-polarization level below − 25 dB over the whole band in all cut planes, which confirms with the simulation results. The proposed antenna has a compact size, low fabrication cost, high gain, and wide operating bandwidth. The total height of the antenna is 1.24 $${\lambda }_{0}$$ λ 0 ( $${\lambda }_{0}$$ λ 0 at the design frequency, 300 GHz) , with a size of 2.6 mm × 2.6 mm. The proposed sub-THz waveguide-fed FPC antenna is suitable for 6G wireless communication systems.

Abstract We designed a strategy, based on a careful examination of the activation capabilities of proteins and antibodies used as substrates for adhering T cells, coupled to protein microstamping to control at the same time the position, shape, spreading, mechanics and activation state of T cells. Once adhered on patterns, we examined the capacities of T cells to be activated with soluble anti CD3, in comparison to T cells adhered to a continuously decorated substrate with the same density of ligands. We show that, in our hand, adhering onto an anti CD45 antibody decorated surface was not affecting T cell calcium fluxes, even adhered on variable size micro-patterns. Aside, we analyzed the T cell mechanics, when spread on pattern or not, using Atomic Force Microscopy indentation. By expressing MEGF10 as a non immune adhesion receptor in T cells we measured the very same spreading area on PLL substrates and Young modulus than non modified cells, immobilized on anti CD45 antibodies, while retaining similar activation capabilities using soluble anti CD3 antibodies or through model APC contacts. We propose that our system is a way to test activation or anergy of T cells with defined adhesion and mechanical characteristics, and may allow to dissect fine details of these mechanisms since it allows to observe homogenized populations in standardized T cell activation assays.

Abstract Electronic cigarette has the potential to serve as a tobacco cessation aid if the prerequisites which are safety and efficacy in term of nicotine delivery are achieved. The nicotine-based liquids are mainly composed by propylene glycol and glycerol playing the important role of airborne carriers. 1,3 propanediol is proposed as a propylene glycol substitute to potentially improve the thermal stability, nicotine delivery and to decrease inhaled flavors concentrations. We have implemented various thermal, physicochemical and computational methods to evaluate the use of 1,3 propanediol as a substitute (or additional ingredient) to propylene glycol in e-liquids compositions. Our results indicate that 1,3 propanediol is stable upon heating when electronic cigarette are used in recommended conditions. We demonstrate that 1,3 propanediol gave better thermic profile compared to propylene glycol and glycerol, showing less thermal decomposition by-products. In addition, 1,3 propanediol gives to nicotine a more basic environment ensuring a high level of free base nicotine form. We have also established a quantum mechanical based computational method to validate e-liquids as flavor enhancer. Our findings showed that globally 1,3 propanediol seems to have better flavoring properties than glycerol and propylene glycol. Finally, 1,3 propanediol seems to induce quite similar aerodynamic properties compared to propylene glycol and glycerol.

Abstract Some obese subjects overeat lipid-rich foods. The origin of this eating behavior is unknown. We have here tested the hypothesis that these subjects could be characterized by an impaired fatty taste sensitivity linked to a change in the gustatory papillae microbial and salivary environment. The composition of microbiota and saliva surrounding the circumvallate papillae was analyzed in combination with the orosensory lipid detection threshold in normal weight (NW) and obese (O) adults. Microbial architecture was similar to what was known in feces, but with an increased frequency of Proteobacteria. No difference in the orosensory sensitivity to lipids and composition of oral microbiota and saliva was observed between NW and O subjects. By contrast, specific bacterial and salivary signatures were found in lipid non-tasters, irrespectively of BMI. A multivariate approach highlighted that the salivary flow, lysozyme activity, total antioxidant capacity and TM7 bacterial family discriminated between tasters and non-tasters. Subgroup analysis of obese tasters (OT) versus obese non-tasters (ONT) identified specific bacterial metabolic pathways (i.e. phosphotransferase and simple sugar transport systems) as being higher in ONT. Altogether with the identification of a set of significant salivary variables, our study suggests that an “obese tongue” phenotype is associated with decreased orosensory sensitivity to lipids in some obese subjects.

Abstract Groundwater is a vital freshwater resource for both humans and ecosystems. Achieving sustainable management requires a detailed knowledge of the aquifer structure and of its behavior in response to climatic and anthropogenic forcing. Traditional monitoring is carried out using piezometer networks, and recently complemented with new geophysical or satellite-based observations. These techniques survey either local (small-scale) water systems or regional areas (large scale) but, to date, adequate observation tools are lacking at the water management scale (i.e. several tens of kms), which is generally explored by modeling. Using 30 years of continuous recording by four seismic stations of the Gräfenberg Array (Germany), we demonstrate that long-term observations of velocity variations (approximately 0.01%) of surface waves can be extracted from such recordings of ocean-generated seismic noise. These small variations can be explained by changes to mechanical properties of the complex aquifer system in the top few hundred meters of the crust. The velocity changes can be interpreted as effects of temperature diffusion and water storage changes. Seismic noise recordings may become a new and valuable tool to monitor heterogeneous groundwater systems at mesoscale, in addition to existing observation methods.

Abstract Plant Growth-Promoting Bacteria (PGPB) of the genus Azospirillum are known to enhance root growth and yield in many plant species including cereals. To probe the underlying mechanisms, correlations between modifications of yield and 6-leaf plantlet characteristics were estimated on maize in four fields with contrasting soil properties over two consecutive years using the commercial isolate A. lipoferum CRT1. In both years, plantlet metabolome, photosynthetic potential and organ morphology were found to display field- and inoculation-specific signatures. Metabolomic analyses revealed that A. lipoferum CRT1 mostly affected sugar metabolism with no suggested impact on N and P assimilation. Mineral nitrogen feeding increased yield but did not affect yield enhancement by the bacterial partner. However, greater improvements of leaf photosynthetic potential correlated with yield diminutions and larger plantlets in all of their proportions correlated with yield enhancements. Bacterial inoculation restored proper seed-to-adult plant ratio when it accidentally dropped below 80%. Only in these cases did it raise yield. All in all, securing mature plant density is hypothesized as being the primary driver of A. lipoferum CRT1-mediated yield enhancement in maize fields.

Abstract Although plasma phospholipid transfer protein (PLTP) has been mainly studied in the context of atherosclerosis, it shares homology with proteins involved in innate immunity. Here, we produced active recombinant human PLTP (rhPLTP) in the milk of new lines of transgenic rabbits. We successfully used rhPLTP as an exogenous therapeutic protein to treat endotoxemia and sepsis. In mouse models with injections of purified lipopolysaccharides or with polymicrobial infection, we demonstrated that rhPLTP prevented bacterial growth and detoxified LPS. In further support of the antimicrobial effect of PLTP, PLTP-knocked out mice were found to be less able than wild-type mice to fight against sepsis. To our knowledge, the production of rhPLTP to counter infection and to reduce endotoxemia and its harmful consequences is reported here for the first time. This paves the way for a novel strategy to satisfy long-felt, but unmet needs to prevent and treat sepsis.

The issue of adolescent secondhand smoke (SHS) is globally significant, given that it serves as a preventable risk factor for disease prevalence and mortality rates among youth. This study evaluates trends in adolescent SHS across 27 countries from 2003 to 2021, aiming to identify global variations and sex-specific differences, providing insights for future policy recommendations. The data for this study were collected from the Global School-based Student Health Survey conducted by the World Health Organization, 2003-2021. The term SHS in this context denoted how many days people smoked in their presence for at least one day within the past 7 days. Linear regression models were employed to examine the trends of SHS exposure by country. In the present analysis based on 175,370 adolescents (male, 46.69%) aged between 13 and 15 years from 27 countries across the five continents, SHS decreased in 14 countries but exhibited an increasing trend in 3 countries (Benin [β, 3.20; 95% CI, 2.50-3.91]; Maldives [β, 0.93; 0.21-1.65]; Myanmar [β, 0.62; 0.29-0.95]). Significant increasing trends in females were observed in the Maldives (β, 1.18; 0.25-2.11) and Thailand (β, 0.36; 0.04-0.69) while males showed increasing trends in Kuwait (β, 1.90; 0.79-3.00) and Vanuatu (β, 1.95; 0.35-3.54). Our analysis of adolescents from 27 countries indicates that the majority of nations exhibited decreasing trends in SHS. This suggests that global efforts to prevent SHS are achievable through individual initiatives and international monitoring. However, the presence of increasing trends in certain countries underscores the need for stronger regulations and policies to address this issue., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Stride velocity 95th centile (SV95C) is a wearable-derived endpoint representing the 5% fastest strides taken during everyday living. In July 2023, SV95C received European Medicines Agency (EMA) qualification for use as a primary endpoint in trials of patients with Duchenne muscular dystrophy (DMD) aged ≥ 4 years-becoming the first digital endpoint to receive such qualification. We present the data supporting this qualification, providing insights into the evidentiary basis of qualification as a digital clinical outcome assessment. Clinical trials, natural history studies, and patient surveys (ages 5 - 14 years) showed that SV95C is accurate, valid, reliable, sensitive, and clinically meaningful. SV95C significantly correlated with traditional DMD assessments, increased rapidly after steroid initiation (0.090 m/s 3 months post-treatment), and declined steadily in patients on stable steroid regimens. Compared with traditional assessments, SV95C demonstrated earlier sensitivity to disease progression (3 vs 9 months) and greater sensitivity at 12 months. Distribution- and anchor-based approaches revealed a change of - 0.10 to - 0.20 m/s as clinically meaningful. The EMA qualification of SV95C illustrates the willingness of regulators to accept novel digital endpoints for drug approval, setting an important precedent for the evidentiary basis of regulatory digital endpoint qualification that could transform clinical development in disorders affecting movement., Competing Interests: Declarations. Competing interests: L.S. is a member of scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, Biophytis, Cytokinetics, Dynacure, F. Hoffmann-La Roche Ltd, GeneTx Biotherapeutics, REGENXBIO, Santhera Pharmaceuticals, and Sarepta Therapeutics, Inc., has consulted for Pfizer and Affinia, conducts research funded by Novartis Gene Therapies (formerly AveXis), Biogen, and F. Hoffmann-La Roche Ltd, holds part of the patent WO2017129890A1 with no financial interest, and has provided consultancy services to SYSNAV. P.S. is an employee of and hold stocks in F. Hoffmann-La Roche Ltd. M.P. reports no disclosures relevant to the manuscript. A.M. reports no disclosures relevant to the manuscript. N.B. reports no disclosures relevant to the manuscript. V.A.S. provides intellectual consultancies and teaching activities for Biogen, F. Hoffmann-La Roche Ltd, Novartis, Lupin, Dyne Therapeutics, and PTC Therapeutics. C.V. reports participation in scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, PTC Therapeutics, F. Hoffmann-La Roche Ltd, Italfarmaco, and Sarepta Therapeutics, Inc., and is involved in research funded by Novartis Gene Therapies (formerly AveXis), Biogen, Sarepta Therapeutics, Inc., and F. Hoffmann-La Roche Ltd. U.S.S. is a member of scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, F. Hoffmann-La Roche Ltd, Pfizer, Santhera Pharmaceuticals, Sarepta Therapeutics, Inc., Italfarmaco, and PTC Therapeutics, and has received honoraria for invited talks or chair positions in scientific symposia from Novartis Gene Therapies (formerly AveXis), Biogen, F. Hoffmann-La Roche Ltd, Pfizer, Santhera Pharmaceuticals, Sarepta Therapeutics, Inc., Italfarmaco, and PTC Therapeutics. M.S. has provided consultancy services for and received honoraria (as a member of scientific advisory boards) from Biogen, F. Hoffmann-La Roche Ltd, and Novartis Gene Therapies (formerly AveXis). A.M.S. reports no disclosures relevant to the manuscript. S.C.P. reports participation in scientific advisory boards for EspeRare Foundation, Wave Life Sciences Ltd, Argenx, and Sarepta Therapeutics, Inc., and has provided consultancy service for Alia Therapeutics and LSC Lifesciences. M.T. has participated in scientific advisory boards for Biogen, PTC Therapeutics, F. Hoffmann-La Roche Ltd, and Sarepta Therapeutics, Inc., and has received honoraria for invited lectures from Biogen, Sarepta Therapeutics, Inc., and PTC Therapeutics. A.N. reports participation in scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, PTC Therapeutics, F. Hoffmann-La Roche Ltd, Italfarmaco, Pfizer, Dyne Therapeutics, and Sarepta Therapeutics, Inc., and is involved in research funded by Novartis Gene Therapies (formerly AveXis) and Biogen. P.F. reports no disclosures relevant to the manuscript. T. S. is an employee of Sarepta Therapeutics, Inc. and has stock and stock options. R.D.D. is Head of Clinical Development at Solid Biosciences, was previously employed at F. Hoffmann-La Roche Ltd, Santhera Pharmaceuticals, and Novartis, and has stock in Solid Biosciences and F. Hoffmann-La Roche Ltd. N.G. reports activities as a Data and Safety Monitoring Board member for Pfizer, Antisense Therapeutics, Wave Life Sciences Ltd, and Genethon. E.M. has served on clinical steering committees and/or as a consultant and received compensation from Italfarmaco, PTC Therapeutics, Sarepta Therapeutics, Inc., Santhera Pharmaceuticals, Pfizer Inc., F. Hoffmann-La Roche Ltd, Wave Life Sciences, NS Pharma, and Dyne Therapeutics, and is involved in research funded by Novartis Gene Therapies (formerly AveXis), Biogen, Sarepta Therapeutics, Inc., and F. Hoffmann-La Roche Ltd. V.S. has served on scientific advisory boards for Astellas Gene Therapies, Biogen, Edgewise Therapeutics, Ipsen, Kate Therapeutics, ML Bio Solutions, Novartis Gene Therapies, PepGen, F. Hoffmann-La Roche Ltd, Sanofi, Sarepta Therapeutics, Inc., Vertex Pharmaceuticals, and Wave Therapeutics, has received speaker honoraria from Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, and Sarepta Therapeutics, Inc., has received grants for clinical research from Sarepta Therapeutics, Inc. and Sanofi, and has received support from the NIHR Newcastle Biomedical Research Centre. M.G.O. is an employee of and hold stocks in F. Hoffmann-La Roche Ltd. J.B. is an employee of and hold stocks in F. Hoffmann-La Roche Ltd. F.M. reports participation in scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, F. Hoffmann-La Roche Ltd, Italfarmaco, Pfizer, Dyne Therapeutics, and Sarepta Therapeutics, Inc., and is involved in research funded by Novartis Gene Therapies (formerly AveXis), Biogen, Sarepta Therapeutics, Inc., and F. Hoffmann-La Roche Ltd. A.T. has nothing to disclose other than his employment at SYSNAV, a company that collaborated with the Institute of Myology to create ActiMyo®. M.A. was an employee of SYSNAV at the time that this manuscript was developed. D.E. has nothing to disclose other than his employment at SYSNAV, a company that collaborated with the Institute of Myology to create ActiMyo®., (© 2024. The Author(s).)

The triple combination elexacaftor-tezacaftor-ivacaftor (ETI) has provided unprecedented clinical benefits for people with cystic fibrosis (pwCF) and drastically transformed the outcome of this disease. We aimed to describe the evolution of lung bacterial colonization in 198 French adult pwCF taking into account the use of concomitantly respiratory treatment. We collected sputum cultures produced during the entire follow-up period starting 3 years before and ending 1 year after ETI initiation. All sputum cultures were centralized and analyzed at our bacteriological laboratory. Clinical data included pulmonary function, respiratory treatments, physiotherapy, number of IV antibiotics treatment, as well as inpatient stays. We observed a significant decrease in colonization prevalence by any CF pathogen after one year of treatment with ETI (p < 0.001). This decrease was confirmed for Pseudomonas aeruginosa, MRSA and MSSA, Stenotrophomonas maltophilia, Achromobacter spp. and nontuberculous mycobacteria (NTM). The maximal density of bacteria documented in sputum cultures decreased from 2.10 7 CFU/ml to 1.10 6 CFU/ml after one year of ETI. We also found a decrease in prevalence of Pseudomonas aeruginosa chronic colonization and in the density of Pseudomonas aeruginosa after one year of ETI. These results confirm the decrease in prevalence and bacterial density of lung colonisation for most of the CF pathogens, including Achromobacter spp, Stenotrophomonas maltophilia concomitantly to the clinical improvement. Further studies are needed to better understand the underlying mechanisms of these microbiological changes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Influenza vaccine effectiveness (VE) varies seasonally due to host, virus and vaccine characteristics. To investigate how antigenic matching and dosage impact VE, we developed a mechanistic knowledge-based mathematical model. Immunization with a split vaccine is modeled for exposure to A/H1N1 or A/H3N2 virus strains. The model accounts for cross-reactivity of immune cells elicited during previous immunizations with new antigens. We simulated vaccine effectiveness (sVE) of high dose (HD) versus standard dose (SD) vaccines in the older population, from 2011 to 2022. We find that sVE is highly dependent on antigenic matching and that higher dosage improves immunogenicity, activation and memory formation of immune cells. In alignment with clinical observations, the HD vaccine performs better than the SD vaccine in all simulations, supporting the use of the HD vaccine in the older population. This model could be adapted to predict the impact of alternative virus strain selection on clinical outcomes in future influenza seasons., (© 2024. The Author(s).)

The increase in marine diseases, particularly in economically important mollusks, is a growing concern. Among them, the Pacific oyster (Crassostrea gigas) production faces challenges from several diseases, such as the Pacific Oyster Mortality Syndrome (POMS) or vibriosis. The microbial education, which consists of exposing the host immune system to beneficial microorganisms during early life stages is a promising approach against diseases. This study explores the concept of microbial education using controlled and pathogen-free bacterial communities and assesses its protective effects against POMS and Vibrio aestuarianus infections, highlighting potential applications in oyster production. We demonstrate that it is possible to educate the oyster immune system by adding microorganisms during the larval stage. Adding culture based bacterial mixes to larvae protects only against the POMS disease while adding whole microbial communities from oyster donors protects against both POMS and vibriosis. The efficiency of immune protection depends both on oyster origin and on the composition of the bacterial mixes used for exposure. No preferential protection was observed when the oysters were stimulated with their sympatric strains. Furthermore, the added bacteria were not maintained into the oyster microbiota, but this bacterial addition induced long term changes in the microbiota composition and oyster immune gene expression. Our study reveals successful immune system education of oysters by introducing beneficial microorganisms during the larval stage. We improved the long-term resistance of oysters against critical diseases (POMS disease and Vibrio aestuarianus infections) highlighting the potential of microbial education in aquaculture., (© 2024. The Author(s).)

Ultra-high dose rate FLASH radiotherapy, a promising cancer treatment approach, offers the potential to reduce healthy tissue damage during radiotherapy. As the mechanisms underlying this process remain unknown, several hypotheses have been proposed, including the altered production of radio-induced species under ultra-high dose rate (UHDR) conditions. This study explores realistic irradiation scenarios with various dose-per-pulse and investigates the role of pulse temporal structure. Using the Geant4 toolkit and its Geant4-DNA extension, we modeled the Oriatron eRT6 linac, a FLASH-validated electron beam, and conducted simulations covering four distinct dose-per-pulse scenarios - 0.17 Gy, 1 Gy, 5 Gy, and 10 Gy - all featuring a 1.8 µs pulse duration. Results show close agreement between simulated and experimental dose profiles in water, validating the eRT6 model for Geant4-DNA simulations. We observed important changes in the temporal evolution of certain species, such as the earlier fall in hydroxyl radicals ([Formula: see text]) and reduced production and lifetime of superoxide ([Formula: see text]) with higher dose-per-pulse levels. The pulse temporal structure did not influence the long-term evolution of species. Our findings encourage further investigation into different irradiation types, such as multi-pulse configurations, and emphasize the need to add components in water to account for relevant cellular processes., (© 2024. The Author(s).)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in individuals with obesity. Sexual dimorphism is present in MASLD. A noninvasive test to diagnose the severity of the disease, in particular the presence of Metabolic dysfunction-associated steatohepatitis (MASH), is lacking. This European multicenter prospective study uses a blood test based on mid-infrared (MIR) metabolic fingerprinting of individuals with severe or morbid obesity to diagnose MASH. Three hundred eighty-two individuals with severe or morbid obesity undergoing bariatric surgery were enrolled prospectively. Liver biopsies were obtained during surgery and assessed centrally. An algorithm was defined to calculate a score from the recorded MIR spectrum and to establish a diagnostic threshold to classify patients with MASH. Among the women (n = 217), MASH was diagnosed in 14.3% of cases. For women, the performance in terms of AUC were 0.83 and 0.82 in the calibration and validation groups, respectively. For a threshold of 0.1817, sensitivities were 86% and 70%, specificities were 81% and 75%, PPV were 43% and 32%, NPV were 97% and 94% and ACC were 82% and 74% for the calibration and validation groups, respectively. For men (n = 78; MASH: 33.3%), the performance of the spectral model was poor. The metabolic fingerprint obtained by MIR spectroscopy can rule out MASH in women with severe or morbid obesity. Its value in men needs new studies.Trial registration: ClinicalTrials.gov identifier: ClinicalTrials.gov identifier: NCT03978247 (04/06/2019)., (© 2024. The Author(s).)

To investigate intestinal health and its potential disruptors in vitro, representative models are required. Human induced pluripotent stem cell (hiPSC)-derived intestinal epithelial cells (IECs) more closely resemble the in vivo intestinal tissue than conventional in vitro models like human colonic adenocarcinoma Caco-2 cells. However, the potential of IECs to study immune-related responses upon external stimuli has not been investigated in detail yet. The aim of the current study was to evaluate immune-related effects of IECs by challenging them with a pro-inflammatory cytokine cocktail. Subsequently, the effects of Lactiplantibacillus plantarum WCFS1 were investigated in unchallenged and challenged IECs. All exposures were compared to Caco-2 cells and in vivo data where possible. Upon the inflammatory challenge, IECs and Caco-2 cells induced a pro-inflammatory response which was strongest in IECs. Heat-killed L. plantarum exerted the strongest effect on immune parameters in the IEC model, while L. plantarum in the stationary growth phase had most pronounced effects on immune-related gene expression in Caco-2 cells. Unfortunately, comparison to in vivo transcriptomics data showed limited similarities, which could be explained by essential differences in the study setups. Altogether, hiPSC-derived IECs show a high potential as a model to study immune-related responses in the intestinal epithelium in vitro., (© 2024. The Author(s).)

The communication between intestinal Glucagon like peptide 1 (GLP-1)-producing cells and the peripheral nervous system has garnered renewed interest considering the availability of anti-obesity and anti-diabetic approaches targeting GLP-1 signaling. While it is well-established that intestinal GLP-1 cells can exert influence through paracrine mechanisms, recent evidence suggests the possible existence of synaptic-like connections between GLP-1 cells and peripheral neurons, including those of the vagus nerve. In this study, using a reporter Phox2b-Cre-Tomato mouse model and super-resolution confocal microscopy, we demonstrated that vagal axons made apparent contacts with less than 0.5% of GLP-1 cells. Moreover, immunohistochemistry combined with super-resolution confocal microscopy revealed abundant post-synaptic density 95 (PSD-95) immunoreactivity within the enteric plexus of the lower intestines of C57/BL6 mice, with virtually none in its mucosa. Lastly, utilizing RNAScope in situ hybridization in the lower intestines of mice, we observed that GLP-1 cells expressed generic markers of secretory cells such as Snap25 and Nefm, but neither synaptic markers such as Syn1 and Nrxn2, nor glutamatergic markers such as Slc17a7. Through theoretical considerations and a critical review of the literature, we concluded that intestinal GLP-1 cells primarily communicate with vagal neurons through paracrine mechanisms, rather than synaptic-like contacts., (© 2024. The Author(s).)

Intransitive gestures are expressive and symbolic, whereas pantomimes are object-related actions. These gestures convey different meanings depending on whether they are directed toward (TB) or away from the body (AB). TB gestures express mental states (intransitive) or hygiene/nutritional activities (pantomime), while AB gestures modify the behaviour of the observer (intransitive) or demonstrate tool use with an object (pantomime). A substantial body of literature suggests that females exhibit stronger social cue processing compared to males. Considering the social significance of gestures, this study aimed to explore the physiological gender differences in the observation of AB and TB gestures. Pupil dilation and High Frequency Heart Rate Variability (HF-HRV) were measured in 54 participants (27 female) while observing TB and AB gestures. The Interpersonal Reactivity Index (IRI) and the Vicarious Distress Questionnaire (VDQ) were used to assess social-emotional processes. Results showed greater pupil dilation in females for TB gestures, but no significant gender differences for HF-HRV. Males showed a significant correlation between increased pupil dilation to both TB and AB gestures and empathy levels (IRI). The support scale of the VDQ correlated significantly with TB gestures in males. These findings provide insight into the neurobiological basis of gender differences in perceiving social gestures., (© 2024. The Author(s).)

Antibiotic resistance in bacterial pathogens is a major threat to global health, exacerbated by the misuse of antibiotics. In hospital practice, results of bacterial cultures and antibiograms can take several days. Meanwhile, prescribing an empirical antimicrobial treatment is challenging, as clinicians must balance the antibiotic spectrum against the expected probability of susceptibility. We present here a proof of concept study of a machine learning-based system that predicts the probability of antimicrobial susceptibility and explains the contribution of the different cofactors in hospitalized patients, at four different stages prior to the antibiogram (sampling, direct examination, positive culture, and species identification), using only historical bacterial ecology data that can be easily collected from any laboratory information system (LIS) without GDPR restrictions once the data have been anonymised. A comparative analysis of different state-of-the-art machine learning and probabilistic methods was performed using 44,026 instances over 7 years from the Hôpital Européen Marseille, France. Our results show that multilayer dense neural networks and Bayesian models are suitable for early prediction of antibiotic susceptibility, with AUROCs reaching 0.88 at the positive culture stage and 0.92 at the species identification stage, and even 0.82 and 0.92, respectively, for the least frequent situations. Perspectives and potential clinical applications of the system are discussed., (© 2024. The Author(s).)

T-cell-based adoptive immunotherapy is a new pillar of cancer care. Tumor-redirected B cells could also contribute to therapy if their manipulation to rewire immunoglobulin (Ig) genes is mastered. We designed a single-chain Ig-encoding cassette ("scFull-Ig") that redirects antigen specificity when inserted at a single position of the IgH locus. This design, which places combined IgH and IgL variable genes downstream of a pVH promoter, nevertheless preserves all Ig functional domains and the intrinsic mechanisms that regulate expression from the IgM B cell receptor (BCR) expression to Ig secretion, somatic hypermutation and class switching. This single-locus editing provides an efficient and safe strategy to both disrupt endogenous Ig expression and encode a new Ig paratope. As a proof of concept, the functionality of scFull BCR and/or secreted Ig was validated against two different classical human tumor antigens, HER2 and hCD20. Once validated in cell lines, the strategy was extended to primary B cells, confirming the successful engineering of BCR and Ig expression and the ability of scFull-Ig to undergo further class switching. These results further pave the way for future B cell-based adoptive immunotherapy and strategies to express a therapeutic mAb with a variety of switched H-chains that provide complementary functions., (© 2024. The Author(s).)

Improving vaccine coverage among children is crucial to prevent the long-term consequences of COVID-19 infections and the emergence of resistant COVID-19 variants, especially in resource-scarce settings. This study determined factors influencing the willingness to take and pay for COVID-19 vaccine for children among Vietnamese healthcare professionals and the public. A Theory-Based discrete-choice experiment was focused on a different topic related to vaccines, including the COVID-19 vaccine for children, Monkeypox, the adult COVID-19 booster, the HIV vaccine, and a potential future pandemic. The recruitment period was from April to August 2022, and a total of 5700 Vietnamese individuals aged 16 and above from various regions of the country participated in the study. The data for the sub-study on the COVID-19 vaccination for children was completed by 891 of these participants. Most participants agreed on vaccination for all children. Among healthcare professionals it was 76.2% and 69.3% for the general population. Healthcare professionals were the main source of vaccine information (70.7%). Payment options of 50%, 100%, and full subsidy were the most popular. Concerns about vaccine characteristics were associated with lower acceptance among healthcare professionals and the general public. The burden of historical medical expenses negatively correlated with willingness to pay for vaccination, while service satisfaction positively correlated with willingness to pay. To develop an effective vaccination program among children in Vietnam, providing accurate information and satisfying vaccine services, primarily through knowledgeable and professional healthcare providers, can improve the willingness to vaccinate and pay for the COVID-19 vaccine., (© 2024. The Author(s).)

It has been suggested that having a reputation for being prosocial is a critical part of social status across all human societies. It has also been argued that prosocial behavior confers benefits, whether physiological, such as stress reduction, or social, such as building allies or becoming more popular. Here, we investigate the relationship between helping reputation (being named as someone others would go to for help), and hair-derived chronic stress (hair cortisol concentration). In a sample of 77 women and 62 men, we found that perceived helping reputation was not related to chronic stress. Overall, the results of our study suggest that, in an egalitarian society with fluid camp membership and widely practiced generosity such as the Hadza, helping reputation does not necessarily boost stress-related health benefits through prestige-signaling mechanisms observed in hierarchical, large-scale societies., (© 2024. The Author(s).)

Partial remission (PR) occurs in only half of people with new-onset type 1 diabetes (T1D) and corresponds to a transient period characterized by low daily insulin needs, low glycemic fluctuations and increased endogenous insulin secretion. While identification of people with newly-onset T1D and significant residual beta-cell function may foster patient-specific interventions, reliable predictive biomarkers of PR occurrence currently lack. We analyzed the plasma of children with new-onset T1D to identify biomarkers present at diagnosis that predicted PR at 3 months post-diagnosis. We first performed an extensive shotgun proteomic analysis using Liquid Chromatography-Tandem-Mass-Spectrometry (LCMS/MS) on the plasma of 16 children with new-onset T1D and quantified 98 proteins significantly correlating with Insulin-Dose Adjusted glycated hemoglobin A1c score (IDAA 1C ). We next applied a series of both qualitative and statistical filters and selected protein candidates that were associated to pathophysiological mechanisms related to T1D. Finally, we translationally verified several of the candidates using single-shot targeted proteomic (PRM method) on raw plasma. Taken together, we identified plasma biomarkers present at diagnosis that may predict the occurrence of PR in a single mass-spectrometry run. We believe that the identification of new predictive biomarkers of PR and β-cell function is key to stratify people with new-onset T1D for β-cell preservation therapies., (© 2024. The Author(s).)

This study examines tuberculosis (TB) incidence among students in Jilin Province, China, focusing on spatial, temporal, and demographic dynamics in areas of social inequality. Variation in incidence rate of TB was analyzed using the joinpoint regression method. Spatial analyses techniques included the global and local Moran indices and Getis-Ord Gi* analysis. Demographic changes in new cases were analyzed descriptively, and the Geodetector method measured the influence of risk factors on student TB incidence. The analysis revealed a declining trend in TB cases, particularly among male students. TB incidence showed geographical heterogeneity, with lower rates in underdeveloped rural areas compared to urban regions. Significant spatial correlations were observed, with high-high clusters forming in central Jilin Province. Hotspots of student TB transmission were primarily concentrated in the southwestern and central regions from 2008 to 2018. Socio-economic factors exhibited nonlinear enhancement effects on incidence rates, with a dominant bifactor effect. High-risk zones were predominantly located in urban centers, with university and high school students showing higher incidences than other educational stages. The study revealed economic determinants as being especially important in affecting TB incidence among students, with these factors having nonlinear interacting effects on student TB incidence., (© 2024. The Author(s).)

Imaging the internal architecture of fast-vibrating structures at micrometer scale and kilohertz frequencies poses great challenges for numerous applications, including the study of biological oscillators, mechanical testing of materials, and process engineering. Over the past decade, X-ray microtomography with retrospective gating has shown very promising advances in meeting these challenges. However, breakthroughs are still expected in acquisition and reconstruction procedures to keep improving the spatiotemporal resolution, and study the mechanics of fast-vibrating multiscale structures. Thereby, this works aims to improve this imaging technique by minimising streaking and motion blur artefacts through the optimisation of experimental parameters. For that purpose, we have coupled a numerical approach relying on tomography simulation with vibrating particles with known and ideal 3D geometry (micro-spheres or fibres) with experimental campaigns. These were carried out on soft composites, imaged in synchrotron X-ray beamlines while oscillating up to 400 Hz, thanks to a custom-developed vibromechanical device. This approach yields homogeneous angular sampling of projections and gives reliable predictions of image quality degradation due to motion blur. By overcoming several technical and scientific barriers limiting the feasibility and reproducibility of such investigations, we provide guidelines to enhance gated-CT 4D imaging for the analysis of heterogeneous, high-frequency oscillating materials., (© 2024. The Author(s).)

Vitamin D deficiency is a common deficiency worldwide, particularly among women of reproductive age. During pregnancy, it increases the risk of immune-related diseases in offspring later in life. However, how the body remembers exposure to an adverse environment during development is poorly understood. Herein, we explore the effects of prenatal vitamin D deficiency on immune cell proportions in offspring using vitamin D deficient mice established by dietary manipulation. We found that prenatal vitamin D deficiency alters immune cell proportions in offspring by changing the transcriptional properties of genes downstream of vitamin D receptor signaling in hematopoietic stem and progenitor cells of both the fetus and adults. Moreover, further investigations of the associations between maternal vitamin D levels and cord blood immune cell profiles from 75 healthy pregnant women and their term offspring also confirm that maternal vitamin D levels in the second trimester significantly affect immune cell proportions in the offspring. These findings imply that the differentiation properties of hematopoiesis act as long-term memories of prenatal vitamin D deficiency exposure in later life., (© 2024. The Author(s).)

Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use., (© 2024. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by the death of motoneurons. Several mutations in the KIF5A gene have been identified in patients with ALS. Some mutations affect the splicing sites of exon 27 leading to its deletion (Δ27 mutation). KIF5A Δ27 is aggregation-prone and pathogenic for motoneurons due to a toxic gain of function. Another mutation found to be enriched in ALS patients is a proline/leucine substitution at position 986 (P986L mutation). Bioinformatic analyses strongly suggest that this variant is benign. Our study aims to conduct functional studies in Drosophila to classify the KIF5A P986L variant. When expressed in motoneurons, KIF5A P986L does not modify the morphology of larval NMJ or the synaptic transmission. In addition, KIF5A P986L is uniformly distributed in axons and does not disturb mitochondria distribution. Locomotion at larval and adult stages is not affected by KIF5A P986L. Finally, both KIF5A WT and P986L expression in adult motoneurons extend median lifespan compared to control flies. Altogether, our data show that the KIF5A P986L variant is not pathogenic for motoneurons and may represent a hypomorphic allele, although it is not causative for ALS., (© 2024. The Author(s).)

Carbon dioxide rebreathing (CO 2 rebreathing) significantly influences respiratory drive and the work of breathing during BiPAP ventilation. We analyzed CO 2 movement during BiPAP ventilation to find a method of real time detection of CO 2 rebreathing without the need of CO 2 concentration measurement sampled from the circuit (method expensive and not routinely used). Observational study during routine care in 15 bed university hospital ICU. At 18 patients who required BiPAP ventilation, intubated or during noninvasive ventilation, during weaning period airflow, pressure and CO 2 concentration signals were registered on both sides of venting port and 17 respiratory parameters were measured or calculated for each of 4747 respiratory cycles analyzed. Based on CO 2 movement (expiration-inspiration sequences) 3 types of cycle were identified, type I and II do not induce rebreathing but type III does. To test differences between the 3 types ANOVA, t-tests, and canonical discriminant analysis (CDA) were used. Then a multilayer perceptron (MLP) network, a type of artificial neural network, using the above parameters (excluding CO 2 concentration) was applied to automatically identify the three types of respiratory cycles. Of the 4747 respiratory cycles, 1849 were type I, 1545 type II, and 1353 type III. ANOVA and t-tests showed significant differences between the types of respiratory cycles. CDA confirmed a correct apportionment of 93.9% of the cycles; notably, of 97.9% of type III. MLP automatically classified the respiratory cycles into the three types with 98.8% accuracy. Three types of respiratory cycles could be distinguished based on CO 2 movement during BiPAP ventilation. Artificial neural networks can be used to automatically detect respiratory cycle type III, the only inducing CO 2 rebreathing., (© 2024. The Author(s).)