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Lentic waters are biogeochemical reactors, producing and receiving carbon (C) originally fixed by the terrestrial and aquatic biosphere, which is then buried in sediments or respired back to the atmosphere in the forms of carbon dioxide (CO2) and one of the more potent greenhouse gas (GHG) methane (CH4). Additionally, lakes serve as archives of terrestrial and aquatic carbon processes within their sediments, enabling the reconstruction of historical changes spanning thousands of years. These changes encompass alterations in land cover, indicated by pollen records, soil carbon erosion and shifts in lake productivity resulting from changes in land use and climate. Both the burial of C in lakes and the emissions of GHGs are recognised as important components of Earth's climate system, yet they remain poorly understood and constrained due to inadequate quantities and qualities of observations. In the case of GHG emissions from lakes, observations are often sporadic, failing to capture the significant spatial and temporal variations in emissions across diverse lentic systems. To address this challenge, process-based models that incorporate the interconnected biogeochemical processes occurring within lakes and their watersheds would arguably be the best tool to extrapolate from site-level observations to regional and finally global scales, to quantify the anthropogenic impact on these fluxes and to reconstruct long-term shifts in emissions and burial due to changes in land cover and climate. However, the development and evaluation of such models is hampered by the lack of observations in sufficient quality. In this project, we bring together a unique consortium of specialists in aquatic ecology, biogeochemistry, palynology, sedimentology and modelling of terrestrial and aquatic biogeochemistry. This project will put forth a national programme of systematic, long-term observations of lake GHG and C cycling processes of unmet detail, consistency and quality. First, at 40 pilot sites spanning typological and environmental gradients, there will be a comprehensive data acquisition endeavour to evaluate biological processes and mesological factors influencing the sequestration or recycling of organic carbon. This effort will be complemented with a synthesis of existing data (WP1). Second, based on well-dated sediment records, which include both newly-acquired and synthesised existing data, variability of lake C burial and their climate and land-use controls will be reconstructed over the past 150 years (WP2). For 15 of these pilot sites, reconstruction will go back until the mid-Holocene (5,000 years BP), allowing us to shed light on the anthropogenic perturbation of the C cycle in this earlier part of human history, which is commonly excluded from this type of research due to lack of information. The activities of these first two WPs will result in an open-source national database, guaranteeing valorisation of our research far beyond this project. In WP3, we will use the land surface model (LSM) ORCHIDEE C-lateral to assess C cycling in the terrestrial biosphere and the mobilisation of biospheric C into lakes, which is possible due to an explicit representation of soil C leaching and erosion processes and a downscaling scheme permitting us to assess C exports from watersheds at sub-grid scale. While LSMs are used to assess evolution of biospheric C budgets from the beginning of the Industrial Period, we will use it to hindcast the evolution since the mid-Holocene, using lake sediment records for model validation. Moreover, we will develop a new process-based lake C model supported by the database established in WPs 1 and 2, which we will couple to ORCHIDEE C-lateral to simulate lake C burial and GHG emissions in response to climate and processes in the lake watershed. This model set-up will first be used to better constrain contemporary large-scale lake GHG emissions and to disentangle the anthropogenic perturbation of these fluxes from the natural background flux. These estimates will be revolutionary, as they will allow attributing part of lake GHG emissions to anthropogenic emissions for national GHG budget reporting. Then, these models will be emulated to reconstruct evolution of lake GHG budgets and C budgets of the whole lake watershed since the mid-Holocene. While simulations will first be performed at the scales of France and Europe, the development of international partnerships to implement observations from other biomes (WP4) will finally support simulations at the global scale.

Abstract Background The aging global population forecasts a significant rise in severe trauma cases among individuals aged 65 and above. Frailty emerges as a paramount predictor of post-traumatic outcomes, surpassing age and trauma severity indices. Despite this, scant attention is given to the trajectory of elderly patients post-intensive care unit (ICU) stay following severe trauma, justifying this study. The objective of this study was to analyze trajectories (frailty, place of residence) following a major trauma requiring an ICU stay. Materials and methods An observational cohort study was conducted, leveraging data from a level 1 trauma center spanning 2018 to 2023. Inclusion criteria included elderly patients aged 65 and above admitted to the ICU for severe trauma. Data encompassed demographic profiles, trauma severity scores, clinical parameters, and frailty assessments sourced from the Traumabase database. Results Among 293 patients included 190 were non-frail, frailty was correlated with elevated mortality rates (114 (38.9%) at 6 months), heightened incidence of traumatic brain injuries, and notable declines in post-traumatic autonomy. Only 39.2% of patients had resumed residence at home six months post-injury, with a conspicuous trend towards institutionalization, particularly among frail individuals. Conclusion This study highlights the role of frailty in determining the outcomes of elderly patients following severe trauma. Frailty is associated with higher mortality, increased rates of institutionalization, and a decline in functional status. These results highlight the importance of assessing frailty in the trajectory of severely injured patients over the age of 65 years-old.

Abstract Background Microsatellite instability (MSI) due to mismatch repair deficiency (dMMR) is common in colorectal cancer (CRC). These cancers are associated with somatic coding events, but the noncoding pathophysiological impact of this genomic instability is yet poorly understood. Here, we perform an analysis of coding and noncoding MSI events at the different steps of colorectal tumorigenesis using whole exome sequencing and search for associated splicing events via RNA sequencing at the bulk-tumor and single-cell levels. Results Our results demonstrate that MSI leads to hundreds of noncoding DNA mutations, notably at polypyrimidine U2AF RNA-binding sites which are endowed with cis-activity in splicing, while higher frequency of exon skipping events are observed in the mRNAs of MSI compared to non-MSI CRC. At the DNA level, these noncoding MSI mutations occur very early prior to cell transformation in the dMMR colonic crypt, accounting for only a fraction of the exon skipping in MSI CRC. At the RNA level, the aberrant exon skipping signature is likely to impair colonic cell differentiation in MSI CRC affecting the expression of alternative exons encoding protein isoforms governing cell fate, while also targeting constitutive exons, making dMMR cells immunogenic in early stage before the onset of coding mutations. This signature is characterized by its similarity to the oncogenic U2AF1-S34F splicing mutation observed in several other non-MSI cancer. Conclusions Overall, these findings provide evidence that a very early RNA splicing signature partly driven by MSI impairs cell differentiation and promotes MSI CRC initiation, far before coding mutations which accumulate later during MSI tumorigenesis.

Abstract Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets ( 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

Abstract Background Dihydrogen (H2) is produced endogenously by the intestinal microbiota through the fermentation of diet carbohydrates. Over the past few years, numerous studies have demonstrated the significant therapeutic potential of H2 in various pathophysiological contexts, making the characterization of its production in laboratory species of major preclinical importance. Methods This study proposes an innovative solution to accurately monitor H2 production in free‐moving rodents while respecting animal welfare standards. The developed device consisted of a wire rodent cage placed inside an airtight chamber in which the air quality was maintained, and the H2 concentration was continuously analyzed. After the airtightness and efficiency of the systems used to control and maintain air quality in the chamber were checked, tests were carried out on rats and mice with different metabolic phenotypes, over 12 min to 1‐h experiments and repeatedly. H2 production rates (HPR) were obtained using an easy calculation algorithm based on a first‐order moving average. Results HPR in hyperphagic Zucker rats was found to be twice as high as in control Wistar rats, respectively, 2.64 and 1.27 nmol.s−1 per animal. In addition, the ingestion of inulin, a dietary fiber, stimulated H2 production in mice. HPRs were 0.46 nmol.s−1 for animals under control diet and 1.99 nmol.s−1 for animals under inulin diet. Conclusions The proposed device coupled with our algorithm enables fine analysis of the metabolic phenotype of laboratory rats or mice with regard to their endogenous H2 production.

Abstract The L-band vegetation optical depth data garners significant interest for its ability to effectively monitor vegetation, thanks to minimal saturation within this frequency range. However, the existing datasets have limited temporal coverage, constrained by the start of the respective satellite missions. Global L-band equivalent AI-Based Vegetation Optical Depth or GLAB-VOD is a global long-term consistent microwave vegetation optical depth dataset created using machine learning to expand the SMAP-IB VOD dataset temporal coverage from 2015-2020 to 2002-2020. The GLAB-VOD dataset has an 18-day temporal resolution and 25 km spatial resolution on the EASE2 grid and covers 2002-2020. An auxiliary consistent daily brightness temperature product, called GLAB-TB, is developed in parallel and ensures the consistency of the VOD product across time periods with different microwave satellites. As a result of its temporal consistency, this dataset can be used to study long-term global and regional trends in vegetation biomass and utilized in any other applications where long-term consistency is necessary. The GLAB-VOD dataset shows excellent spatial correlation globally when compared with biomass (up to R = 0.92) and canopy height (R = 0.93), outperforming its target dataset, SMAP-IB VOD.

Abstract The demographical history of France remains largely understudied despite its central role toward understanding modern population structure across Western Europe. Here, by exploring publicly available Europe-wide genotype datasets together with the genomes of 3234 present-day and six newly sequenced medieval individuals from Northern France, we found extensive fine-scale population structure across Brittany and the downstream Loire basin and increased population differentiation between the northern and southern sides of the river Loire, associated with higher proportions of steppe vs. Neolithic-related ancestry. We also found increased allele sharing between individuals from Western Brittany and those associated with the Bell Beaker complex. Our results emphasise the need for investigating local populations to better understand the distribution of rare (putatively deleterious) variants across space and the importance of common genetic legacy in understanding the sharing of disease-related alleles between Brittany and people from western Britain and Ireland.

This paper is one of the first studies focusing on phase and microstructure formation mechanisms during reactive sintering of AlxCoCrFeNi (x = 0.3, 1) high entropy alloys (HEAs). The alloys have been prepared by mechanical activation followed by spark plasma sintering (SPS). Both powders are subjected to gluing to the milling vials and the phenomenon intensifies with Al content, resulting in a more important mechanical alloying delay for the equiatomic composition. The temperature influence on phase and microstructure formation was investigated by SPS from 550 to 1100 °C. Al0.3CoCrFeNi reactive sintering led to a face-centered cubic (FCC) solid solution with a grain size around hundreds of nanometers with nanometric intergranular B2 precipitates which content and size reduced with the temperature increase. Grain growth was observed at prior particle boundaries due to dynamic recrystallization, a phenomenon that can be controlled through modification of the milling and sintering steps, leading thus to tailored grain sizes. For the AlCoCrFeNi composition, temperature increase favors secondary FCC formation and leads to sigma phase precipitation. A dual homogeneous-heterogeneous microstructure is obtained due to the important gluing leading to insufficient milling. The dynamic recrystallization at prior particle boundaries promotes also body-centered cubic (BCC) to FCC phase transition. Therefore, the proposed reactive sintering route allows to obtain, for the equiatomic composition, alloys exhibiting very fine microstructures, with higher FCC fraction content than by conventional metallurgy processes.

RESUMO Hoje o nível de endividamento está elevado e a responsabilidade desta situação não recai sobre o Fundo Monetário Internacional ou sobre os bancos. O endividamento tem origem no funcionamento dos regimes de acumulação e na política econômica seguida na década de 70. A modificação da situação econômica mundial, a passagem de uma economia internacional endividada e com liquidez para uma economia sem liquidez contribuíram para que o endividamento se autonomize em relação ao sistema produtivo. A dolarização das economias e do passivo das empresas públicas, a queda dos salários reais, o empobrecimento crescente de novos estratos populacionais, o agravamento da miséria alimentar nas cidades, constituem as consequências desse endividamento.

Abstract Background Little is known about the trends in morbidity and mortality at the population level that followed the introduction of newer once-daily long-acting bronchodilators for COPD. The purpose of the study was to evaluate whether the availability of new bronchodilators was associated with changes in the temporal trends in severe COPD exacerbations and mortality between 2007 and 2018 in the older population with COPD; and whether this association was homogeneous across sex and socioeconomic status classes. Methods We used an interrupted time-series and three segments multivariate autoregressive models to evaluate the adjusted changes in slopes (i.e., trend effect) in monthly severe exacerbation and mortality rates after 03/2013 and 02/2015 compared to the tiotropium period (04/2007 to 02/2013). Cohorts of individuals > 65 years with COPD were created from the nationally representative database of the Quebec Integrated Chronic Disease Surveillance System in the province of Quebec, Canada. Whether these trends were similar for men and women and across different socioeconomic status classes was also assessed. Results There were 130,750 hospitalizations for severe exacerbation and 104,460 deaths, including 24,457 (23.4%) respiratory-related deaths, over the study period (928,934 person-years). Significant changes in trends were seen after 03/2013 for all-cause mortality (-1.14%/month;95%CI -1.90% to -0.38%), which further decreased after 02/2015 (-1.78%/month;95%CI -2.70% to -0.38%). Decreases in respiratory-related mortality (-2.45%/month;95%CI -4.38% to -0.47%) and severe exacerbation (-1,90%/month;95%CI -3.04% to -0.75%) rates were only observed after 02/2015. These observations tended to be more pronounced in women than in men and in higher socioeconomic status groups (less deprived) than in lower socioeconomic status groups (more deprived). Conclusions The arrival of newer bronchodilators was chronologically associated with reduced trends in severe exacerbation, all-cause and respiratory-related mortality rates among people with COPD > 65 years. Our findings document population benefits on key patient-relevant outcomes in the years following the introduction of newer once-daily long-acting bronchodilators and their combinations, which were likely multifactorial. Public health efforts should focus on closing the gap between lower and higher socioeconomic status groups.

Abstract Parkinson’s disease is characterized by the degeneration of substantia nigra pars compacta (SNc) dopaminergic neurons, leading to motor and cognitive symptoms. Numerous cellular and molecular adaptations following neurodegeneration or dopamine replacement therapy (DRT) have been described in motor networks but little is known regarding associative basal ganglia loops. This study investigated the contributions of nigrostriatal degeneration and pramipexole (PPX) on neuronal activity in the orbitofrontal cortex (OFC), frontostriatal plasticity, and markers of synaptic plasticity. Bilateral nigrostriatal degeneration was induced by viral-mediated expression of human mutated alpha-synuclein in the SNc. Juxtacellular recordings were performed in anesthetized rats to evaluate neuronal activity in the OFC. Recordings in the dorsomedial striatum (DMS) were performed, and spike probability in response to OFC stimulation was measured before and after high-frequency stimulation (HFS). Post-mortem analysis included stereological assessment of nigral neurodegeneration, BDNF and TrkB protein levels. Nigrostriatal neurodegeneration led to altered firing patterns of OFC neurons that were restored by PPX. HFS of the OFC led to an increased spike probability in the DMS, while dopaminergic loss had the opposite effect. PPX led to a decreased spike probability following HFS in control rats and failed to counteract the effect of dopaminergic neurodegeneration. These alterations were associated with decreased levels of BDNF and TrkB in the DMS. This study demonstrates that nigral dopaminergic loss and PPX both contribute to alter frontostriatal transmission, precluding adequate information processing in associative basal ganglia loops as a gateway for the development of non-motor symptoms or non-motor side effects of DRT.

Abstract The study of microorganism interactions is important for understanding the organization and functioning of microbial consortia. Additionally, the interaction between yeast and bacteria is of interest in the field of health and nutrition area for the development of probiotics. To investigate these microbial interactions at the cellular and molecular levels, a simple, reliable, and quantitative method is proposed. We demonstrated that flow cytometry enables the measurement of interactions at a single-cell level by detecting and counting yeast cells with bound fluorescent bacteria. Imaging flow cytometry revealed that the number of bacteria attached to yeast followed a Gaussian distribution whose maximum reached 14 bacterial cells using a clinical Escherichia coli strain E22 and the laboratory yeast strain BY4741. We found that the dynamics of adhesion resemble a Langmuir adsorption model, albeit it is a rapid and almost irreversible process. This adhesion is dependent on the mannose-specific type 1 fimbriae, as E. coli mutants lacking these appendages no longer adhere to yeast. However, this type 1 fimbriae-dependent adhesion could involve additional yeast cell wall factors, since the interaction between bacteria and yeast mutants with altered mannan content remained comparable to that of wild-type yeast. In summary, flow cytometry is an appropriate method for studying bacteria-yeast adhesion, as well as for the high-throughput screening of candidate molecules likely to promote or counteract this interaction.

Abstract The limited capabilities of current quantum hardware significantly constrain the scale of experimental demonstrations of most quantum algorithmic primitives. This makes it challenging to perform benchmarking of the current hardware using useful quantum algorithms, i.e., application-oriented benchmarking. In particular, the Harrow-Hassidim-Lloyd (HHL) algorithm is a critical quantum linear algebra primitive, but the majority of the components of HHL are far out of the reach of noisy intermediate-scale quantum devices, which has led to the proposal of hybrid classical-quantum variants. The goal of this work is to further bridge the gap between proposed near-term friendly implementations of HHL and the kinds of quantum circuits that can be executed on noisy hardware. Our proposal adds to the existing literature of hybrid quantum algorithms for linear algebra that are more compatible with the current scale of quantum devices. Specifically, we propose two modifications to the Hybrid HHL algorithm proposed by Lee et al., leading to our algorithm Hybrid $$\hbox {HHL}^{++}$$ HHL + + : (1) propose a novel algorithm for determining a scaling factor for the linear system matrix that maximizes the utility of the amount of ancillary qubits allocated to the phase estimation component of HHL, and (2) introduce a heuristic for compressing the HHL circuit. We demonstrate the efficacy of our work by running our modified Hybrid HHL on Quantinuum System Model H-series trapped-ion quantum computers to solve different problem instances of small-scale portfolio optimization problems, leading to the largest experimental demonstrations of HHL for an application to date.

Abstract Background Learning to interpret electrocardiograms (ECGs) is a crucial objective in medical education. Despite its importance, errors in ECGs interpretation are common, and the optimal teaching methods have not yet been clearly established. Objectives To evaluate students’ confidence in ECGs analysis and their opinion on current teaching methods, and to assess the effectiveness of a new ECG educational approach. Methods First, we conducted a survey on ECG learning among fourth to sixth-year medical students. Second, a 5-week multicenter comparative study was conducted with fourth-year medical students during their cardiology internship. Two different teaching methods were used, assigned by center. The first group participated in 5-minutes workshops 4 times a week using a “reversed classroom” method, supervised by a cardiologist, where students took turns selecting, presenting and discussing ECGs. The control group attended a single 2-hour face-to-face ECG course. All participants completed a 30-minute ECGs analysis test at baseline and after 5 weeks. Results Out of 401 survey respondents, the confidence levels in ECG interpretation were 3/5 (IQR 2–3) for routine situations and 2/5 (IQR 1–3) for emergency situations. Satisfaction with ECG teaching was low (2/5, IQR 1–3) and 96.3% of respondents favored more extensive ECG training. In the comparative study, 52 students from 3 medical schools were enrolled (control group: n = 27; workshop group: n = 25). Both groups showed significant improvement in exam scores from baseline to 5-week (33/100 ± 12/100 to 44/100 ± 12/100, p

Abstract Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27–176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax)

Abstract We report our 5-year experience in neurofibromatosis type 1 prenatal diagnosis (PND): 205 PNDs in 146 women (chorionic villus biopsies, 88% or amniocentesis, 12%). The NF1 variant was present in 85 (41%) and absent in 122 (59%) fetuses. Among 205 pregnancies (207 fetuses), 135 were carried to term (119 unaffected and 16 NF1 affected children), 69 pregnancy terminations (affected fetuses), 2 miscarriages, and 1 in utero death. The majority of PND requests came from parents with sporadic NF1. We describe two PNDs in women with mosaic NF1. In both families, direct PND showed the absence of the maternal NF1 variant in the fetus. However, microsatellite markers analysis showed that the risk haplotype had been transmitted. These rare cases of germline mosaicism illustrate the pitfall of indirect PND. Our study illustrates the crucial consequences of PND for medical and genetic counseling decisions. We also point to the challenges of germline mosaics.

Abstract A seed recovered during archaeological excavations of a cave in the Judean desert was germinated, with radiocarbon analysis indicating an age of 993 CE– 1202 calCE. DNA sequencing and phylogenetic analysis identified the seedling as belonging to the angiosperm genus Commiphora Jacq., sister to three Southern African Commiphora species, but unique from all other species sampled to date. The germinated seedling was not closely related to Commiphora species commonly harvested for their fragrant oleoresins including Commiphora gileadensis (L.) C.Chr., candidate for the locally extinct “Judean Balsam” or “Balm of Gilead” of antiquity. GC-MS analysis revealed minimal fragrant compounds but abundance of those associated with multi-target bioactivity and a previously undescribed glycolipid compound series. Several hypotheses are offered to explain the origins, implications and ethnobotanical significance of this unknown Commiphora sp., to the best of our knowledge the first identified from an archaeological site in this region, including identification with a resin producing tree mentioned in Biblical sources and possible agricultural relationship with the historic Judean Balsam.

Abstract Background Acute respiratory distress syndrome (ARDS) occurring in patients with hematological malignancies (HM) is a life-threatening condition with specific features. Mortality rate remains high but improvement has been described over the past several years. We aimed to describe characteristics and outcomes of ARDS in HM patients admitted in French ICUs (Intensive Care Units) during a one year-period. Data for this nationwide cohort study were collected from the French national hospital database (Programme de Médicalisation des Systèmes d’Information (PMSI)). All patients (18 years or older) admitted to French ICUs in 2017 and with a diagnosis of ARDS were included. Three groups were compared according to the presence of an HM, a solid cancer or no cancer. The primary endpoint was 90-day mortality. Secondary endpoints were the description of ICU management, etiologies of ARDS and mortality risk factors. Results A total of 12 846 patients with ARDS were included. Among them, 990 had HM and 2744 had a solid cancer. The main malignancies were non-Hodgkin lymphoma (NHL) (28.5%), acute myeloid leukemia (AML) (20.4%) and multiple myeloma (19.7%). Day-90 mortality in patients with HM was higher than in patients with no cancer (64.4% vs. 46.6% p = 0.01) but was not different from that of patients with solid cancer (64.4% vs. 61.4%,p = 0.09). Intubation rate was lower in patients with HM in comparison with both groups (87.7% vs. 90.4% p = 0.02 for patients with solid cancer and 87.7% vs. 91.3%; p

Abstract Current adeno-associated virus (AAV) gene therapy using nature-derived AAVs is limited by non-optimal tissue targeting. In the treatment of muscular diseases (MD), high doses are often required but can lead to severe adverse effects. Here, we rationally design an AAV capsid that specifically targets skeletal muscle to lower treatment doses. We computationally integrate binding motifs of human integrin alphaV beta6, a skeletal muscle receptor, into a liver-detargeting capsid. Designed AAVs show higher productivity and superior muscle transduction compared to their parent. One variant, LICA1, demonstrates comparable muscle transduction to other myotropic AAVs with reduced liver targeting. LICA1’s myotropic properties are observed across species, including non-human primate. Consequently, LICA1, but not AAV9, effectively delivers therapeutic transgenes and improved muscle functionality in two mouse MD models (male mice) at a low dose (5E12 vg/kg). These results underline the potential of our design method for AAV engineering and LICA1 variant for MD gene therapy.

Abstract Microbial carbon use efficiency (CUE) affects the fate and storage of carbon in terrestrial ecosystems, but its global importance remains uncertain. Accurately modeling and predicting CUE on a global scale is challenging due to inconsistencies in measurement techniques and the complex interactions of climatic, edaphic, and biological factors across scales. The link between microbial CUE and soil organic carbon relies on the stabilization of microbial necromass within soil aggregates or its association with minerals, necessitating an integration of microbial and stabilization processes in modeling approaches. In this perspective, we propose a comprehensive framework that integrates diverse data sources, ranging from genomic information to traditional soil carbon assessments, to refine carbon cycle models by incorporating variations in CUE, thereby enhancing our understanding of the microbial contribution to carbon cycling.

Avidin-biotin binding, the most robust non-covalent protein-ligand interaction occurring in nature, has wide-ranging applications in biotechnology. A frequent challenge in these applications is accurately determining the number of unoccupied biotin binding sites in avidin-containing fusion proteins. We delineate a novel assay protocol in miniaturized format to quantify available biotin binding sites based on the affinity of the anionic dye 4′-hydroxyazobenzene-2-carboxylic acid for biotin binding sites within avidin. We apply this assay as a quality control assay to evaluate the number of available biotin binding sites in different fusion protein production batches. This method offers a streamlined alternative to fluorescence-based assays commonly employed to assess biotin binding, is less time-consuming than other methods and is applicable to diverse fusion proteins.

ABSTRACT Purpose: To compare transperineal (TP) vs transrectal (TR) magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) fusion-guided prostate biopsy (PBx) in a large, ethnically diverse and multiracial cohort. Materials and Methods: Consecutive patients who underwent multiparametric (mp) MRI followed by TP or TR TRUS-fusion guided PBx, were identified from a prospective database (IRB #HS-13-00663). All patients underwent mpMRI followed by 12-14 core systematic PBx. A minimum of two additional target-biopsy cores were taken per PIRADS≥3 lesion. The endpoint was the detection of clinically significant prostate cancer (CSPCa; Grade Group, GG≥2). Statistical significance was defined as p

Abstract Background The aim of this study (EPIDIAB) was to assess the relationship between epicardial adipose tissue (EAT) and the micro and macrovascular complications (MVC) of type 2 diabetes (T2D). Methods EPIDIAB is a post hoc analysis from the AngioSafe T2D study, which is a multicentric study aimed at determining the safety of antihyperglycemic drugs on retina and including patients with T2D screened for diabetic retinopathy (DR) (n = 7200) and deeply phenotyped for MVC. Patients included who had undergone cardiac CT for CAC (Coronary Artery Calcium) scoring after inclusion (n = 1253) were tested with a validated deep learning segmentation pipeline for EAT volume quantification. Results Median age of the study population was 61 [54;67], with a majority of men (57%) a median duration of the disease 11 years [5;18] and a mean HbA1c of7.8 ± 1.4%. EAT was significantly associated with all traditional CV risk factors. EAT volume significantly increased with chronic kidney disease (CKD vs no CKD: 87.8 [63.5;118.6] vs 82.7 mL [58.8;110.8], p = 0.008), coronary artery disease (CAD vs no CAD: 112.2 [82.7;133.3] vs 83.8 mL [59.4;112.1], p = 0.0004, peripheral arterial disease (PAD vs no PAD: 107 [76.2;141] vs 84.6 mL[59.2; 114], p = 0.0005 and elevated CAC score (> 100 vs

Abstract Background Early pregnancy Zika virus (ZIKV) infection is associated with major brain damage in fetuses, leading to microcephaly in 0.6–5.0% of cases, but the underlying mechanisms remain largely unknown. Methods To understand the kinetics of ZIKV infection during fetal development in a nonhuman primate model, four cynomolgus macaque fetuses were exposed in utero through echo-guided intramuscular inoculation with 103 PFU of ZIKV at 70–80 days of gestation, 2 controls were mock inoculated. Clinical, immuno-virological and ultrasound imaging follow-ups of the mother/fetus pairs were performed until autopsy after cesarean section 1 or 2 months after exposure (n = 3 per group). Results ZIKV was transmitted from the fetus to the mother and then replicate in the peripheral blood of the mother from week 1 to 4 postexposure. Infected fetal brains tended to be smaller than those of controls, but not the femur lengths. High level of viral RNA ws found after the first month in brain tissues and placenta. Thereafter, there was partial control of the virus in the fetus, resulting in a decreased number of infected tissue sections and a decreased viral load. Immune cellular and humoral responses were effectively induced. Conclusions ZIKV infection during the second trimester of gestation induces short-term brain injury, and although viral genomes persist in tissues, most of the virus is cleared before delivery.

Abstract Background The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. Methods We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. Results Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. Conclusion These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.

Abstract Background The Clinical Dementia Rating (CDR) scale allows to detect the presence of dementia and to assess its severity, however its evaluation requires a significant time (45 min). We evaluated the agreement between two methods of collection of the CDR: face-to-face interview or based on the information available in the patient’s medical record. Methods The CLIMER study was conducted among patients attending a memory center. The CDR scale was evaluated during face-to-face interviews between neuropsychologists and patients and their caregivers and based on blind analysis of the information of the patients’ medical record by neuropsychologists. The agreement of the CDR sum of boxes (CDR-SB), the 5-point scale CDR and the different domains of the CDR evaluated between the different methods was measured using intraclass correlation (ICC) coefficient, Bland and Altman method, and linearly weighted Kappa. Results The study included 139 patients (means ± SD age 80.1 ± 6, 58.3% women, 71.9% with dementia). The ICC for the CDR-SB score assessed by face-to-face and with all the information available in the patient’s medical record was 0.95 (95% CI: 0.93–0.97). The mean difference between the CDR-SB score assessed by face-to-face and with the medical record was 0.098 ± 1.036, and 92.4% of the patients lay within the 95% limits of agreement. The ICC for the 5-point scale CDR assessed by face-to-face and with the patient’s medical record was 0.92 (95% CI: 0.88–0.95) when all the available information of the patient’s medical record was used. The linear weighted Kappa coefficients was 0.79 (95% CI: 0.68–0.91) for the 5-point scale CDR comparison between the two evaluation methods. The analysis by domain of the CDR showed ICC ranging from 0.65 to 0.91 depending of the domains and the methods of evaluation. Conclusion This study showed an excellent level of agreement of the evaluation of the CDR- SB and the 5-point scale CDR when using all the information of the patient’s medical record compared to the face-to-face interview. Trial registration https//clinicaltrials.gov/ct2/show/NCT04763941 Registration Date 02/17/2021.

Abstract With the ever-growing reliance on polymeric materials for numerous applications, new avenues to induce, design and control degradation are clearly important. Here, we describe a previously unreported approach to controlling enzymatic hydrolysis of high molecular weight branched polymers formed from the new free-radical polymer synthesis strategy transfer-dominated branching radical telomerisation (TBRT). Modifying the chemical nature of TBRT polymers may be accomplished through telogen selection and multi-vinyl taxogen (MVT) design, and we show telogen-driven control of enzyme-catalysed hydrolysis and the impact of careful placement of hydrolytically susceptible groups within readily synthesised MVTs. Our results indicate that utilising conventional free-radical chemistries and unsaturated monomers as feedstocks for highly branched polymer architectures has considerable potential for the design of future materials that degrade into very low molecular weight byproducts at variable and controllable rates.

Abstract Bio-based carbon dioxide removal encompasses a range of (1) natural sink enhancement concepts in agriculture and on organic soils including peatlands, and in forestry, (2) bio-based building materials, and (3) bioenergy production with CO2 capture and storage (BECCS). A common database on these concepts is crucial for their consideration in strategies and implementation. In this study, we analyse standardised factsheets on these concepts. We find different dynamics of deployment until 2045: for CO2 removal rates from the atmosphere, natural sink enhancement concepts are characterised by gradually increasing rates, followed by a saturation and potentially a decrease after few decades; forest-related measures ramp up slowly and for construction projects and bioenergy plants, annually constant removal rates are assumed during operation which drop to zero afterwards. The expenses for removing 1 t CO2 from the atmosphere were found to be between 8 and 520 € t CO2 −1, which arises from high divergence both in capital and operational expenditures among the concepts. This high variability of expenses seems to suggest the more cost-effective concepts should be implemented first. However, aspects from economics, resource base and environmental impacts to social and political implications for Germany need to be considered for developing implementation strategies. All concepts investigated could be deployed on scales to significantly contribute to the German climate neutrality target.

Abstract Corn snakes are emerging models for animal colouration studies. Here, we focus on the Terrazzo morph, whose skin pattern is characterized by stripes rather than blotches. Using genome mapping, we discover a disruptive mutation in the coding region of the Premelanosome protein (PMEL) gene. Our transcriptomic analyses reveal that PMEL expression is significantly downregulated in Terrazzo embryonic tissues. We produce corn snake PMEL knockouts, which present a comparable colouration phenotype to Terrazzo and the subcellular structure of their melanosomes and xanthosomes is also similarly impacted. Our single-cell expression analyses of wild-type embryonic dorsal skin demonstrate that all chromatophore progenitors express PMEL at varying levels. Finally, we show that in wild-type embryos PMEL-expressing cells are initially uniformly spread before forming aggregates and eventually blotches, as seen in the adults. In Terrazzo embryos, the aggregates fail to form. Our results provide insights into the mechanisms governing colouration patterning in reptiles.

Abstract The inhibitor of κB (IκB) kinase (IKK) is a central regulator of NF-κB signaling. All IKK complexes contain hetero- or homodimers of the catalytic IKKβ and/or IKKα subunits. Here, we identify a YDDΦxΦ motif, which is conserved in substrates of canonical (IκBα, IκBβ) and alternative (p100) NF-κB pathways, and which mediates docking to catalytic IKK dimers. We demonstrate a quantitative correlation between docking affinity and IKK activity related to IκBα phosphorylation/degradation. Furthermore, we show that phosphorylation of the motif’s conserved tyrosine, an event previously reported to promote IκBα accumulation and inhibition of NF-κB gene expression, suppresses the docking interaction. Results from integrated structural analyzes indicate that the motif binds to a groove at the IKK dimer interface. Consistently, suppression of IKK dimerization also abolishes IκBα substrate binding. Finally, we show that an optimized bivalent motif peptide inhibits NF-κB signaling. This work unveils a function for IKKα/β dimerization in substrate motif recognition.

Abstract Nucleotidyltransferases (NTases) control diverse physiological processes, including RNA modification, DNA replication and repair, and antibiotic resistance. The Mycobacterium tuberculosis NTase toxin family, MenT, modifies tRNAs to block translation. MenT toxin activity can be stringently regulated by diverse MenA antitoxins. There has been no unifying mechanism linking antitoxicity across MenT homologues. Here we demonstrate through structural, biochemical, biophysical and computational studies that despite lacking kinase motifs, antitoxin MenA1 induces auto-phosphorylation of MenT1 by repositioning the MenT1 phosphoacceptor T39 active site residue towards bound nucleotide. Finally, we expand this predictive model to explain how unrelated antitoxin MenA3 is similarly able to induce auto-phosphorylation of cognate toxin MenT3. Our study reveals a conserved mechanism for the control of tuberculosis toxins, and demonstrates how active site auto-phosphorylation can regulate the activity of widespread NTases.

Abstract The continued advancement of electrochemical technologies requires an increasingly detailed understanding of the microscopic processes that control their performance, inspiring the development of new multi-modal diagnostic techniques. Here, we introduce a neutron imaging approach to enable the quantification of spatial and temporal variations in species concentrations within an operating redox flow cell. Specifically, we leverage the high attenuation of redox-active organic materials (high hydrogen content) and supporting electrolytes (boron-containing) in solution and perform subtractive neutron imaging of active species and supporting electrolyte. To resolve the concentration profiles across the electrodes, we employ an in-plane imaging configuration and correlate the concentration profiles to cell performance with polarization experiments under different operating conditions. Finally, we use time-of-flight neutron imaging to deconvolute concentrations of active species and supporting electrolyte during operation. Using this approach, we evaluate the influence of cell polarity, voltage bias and flow rate on the concentration distribution within the flow cell and correlate these with the macroscopic performance, thus obtaining an unprecedented level of insight into reactive mass transport. Ultimately, this diagnostic technique can be applied to a range of (electro)chemical technologies and may accelerate the development of new materials and reactor designs.

Abstract The MOS model (acronym coming from the French MOdèle Simplifié) was born from the desire to have a simple tool that can quantify the contribution of the diffusive reactive environment to the alteration of a vitrified nuclear waste package in deep geological disposal conditions. In the model, this environmental contribution consists partly of the ability of iron, metallic casing corrosion products, and argillite to consume silicon, and partly of the brake on diffusive transport provided by silicon through the successive layers of environmental material. It is a modeling tool serving as an intermediary between operational modeling for the calculation of the source term from the glass, mathematically more simple and giving higher upper margins, and models that use geochemistry and transport, giving greater accuracy for the interactions between glass and its environment. The goal of the MOS model is to calculate the possible impact of silicon reactive diffusion on the alteration rate within the different layers of material surrounding nuclear glass. This article lists the simplifying hypotheses on which the MOS is based, presents the digital resolution method for an environment consisting of several successive layers with different reactivity and transport properties, and explains the model’s implementation.

Abstract Background Dupuytren’s contracture is a hereditary disorder which causes progressive fibrosis of the palmar aponeurosis of the hand, resulting in digital flexion contractures of the affected rays. Limited fasciectomy is a standard surgical treatment for Dupuytren’s, and the one with the lowest recurrence rate; however, the recurrence is still relatively high (2–39%). Adipose-derived stem cells have been shown to inhibit Dupuytren’s myofibroblasts proliferation and contractility in vitro, as well as to improve scar quality and skin regeneration in different types of surgeries. Autologous adipose tissue grafting has already been investigated as an adjuvant treatment to percutaneous needle fasciotomy for Dupuytren’s contracture with good results, but it was only recently associated with limited fasciectomy. The purpose of REMEDY trial is to investigate if limited fasciectomy with autologous adipose tissue grafting would decrease recurrence compared to limited fasciectomy alone. Methods The REMEDY trial is a multi-centre open-label randomised controlled trial (RCT) with 1:1 allocation ratio. Participants (n = 150) will be randomised into two groups, limited fasciectomy with autologous adipose tissue grafting versus limited fasciectomy alone. The primary outcome is the recurrence of Dupuytren’s contracture on any of the treated rays at 2 years postoperatively. The secondary outcomes are recurrence at 3 and 5 years, scar quality, complications, occurrence of algodystrophy (complex regional pain syndrome), patient-reported hand function, and hypodermal adipose tissue loss at 1 year postoperatively in a small subset of patients. Discussion The REMEDY trial is one of the first studies investigating limited fasciectomy associated with autologous adipose tissue grafting for Dupuytren’s contracture, and, to our knowledge, the first one investigating long-term outcomes of this treatment. It will provide insight into possible benefits of combining adipose tissue grafting with limited fasciectomy, such as lower recurrence rate and improvement of scar quality. Trial registration ClinicalTrials.gov NCT05067764, June 13, 2022.

Abstract Background Postoperative pain delays ambulation, extends hospital stay, reduces the probability of recovery, and increases risk of long-term functional impairment. Pain management in hip fractured patients poses a challenge to the healthcare teams. Older adults are more vulnerable to opioid-associated side effect and it is primordial to minimize their exposure to opioids. Acetaminophen is associated with reduced opioid use so we need to focus on acetaminophen use in first-line analgesia. Methods We conducted a controlled before/after study to assess the ability of an audit and feedback (A&F) intervention built with nurses to improve the quality of perioperative pain management in older patients hospitalized for hip fracture in an orthogeriatric unit (experimental group) versus a conventional orthopedic unit (no A&F intervention). The primary endpoint was the percentage of patients who received 3 g/day of acetaminophen during the three postoperative days, before and after the A&F intervention. Secondary endpoints included nurses’ adherence to medical prescriptions, clinical data associated with patients and finally factors associated with intervention. The significative level was set at 0.05 for statistical analysis. Results We studied data from 397 patients (mean age 89 years, 75% female). During the postoperative period, 16% of patients from the experimental group received 3 g/day of acetaminophen before the A&F intervention; the percentage reached 60% after the intervention. The likelihood of receiving 3 g/day of acetaminophen during the postoperative period and adhering to the medical prescription of acetaminophen were significantly increased in the experimental group as compared with the control group. The patient’s functional status at discharge (assessed by Activities of Daily Living scores) was significantly better and the length of hospital stay significantly reduced after the A&F intervention. Conclusion Our controlled before/after study showed that an A&F intervention significantly improved perioperative pain management in older adults hospitalized for hip fracture. Involving teams in continuous education programs appears crucial to improve the quality of pain management and ensure nurses’ adherence to medical prescriptions.

Abstract Background Type A acute aortic dissection (TAAAD) is a deadly condition that demands immediate surgery, because it involves a critically. The mortality and morbidity associated with it are significant, and it is vital that the patient’s conditions and treatment strategies are fully understood to ensure the appropriate management of TAAAD. This study aims to ascertain whether hemiarch repair (HAR) versus extended arch repair (EAR) with or without descending aortic intervention results in better perioperative and late outcomes for patients with TAAAD. Methods Four leading centers of cardiac surgery from two European countries have joined forces to create a groundbreaking multicenter observational registry (AoArch). This study was approved by the institutional review board (IRB 202201173). We conducted a retrospective review (NCT 0591263) of our prospectively maintained database for patients who underwent operative repair of DeBakey type I or type II dissection from January 1, 2005 to March 2024 (NCT 05927090). We will analyze how patient co-morbidities, referral conditions, and surgical strategies involving hemi-arch repair (HAR) and extended arch repair (EAR) impact early and late adverse events. We have developed a procedure urgency algorithm based on the severity of preoperative hemodynamic conditions and malperfusion due to TAAAD, and we will use it to assess the primary clinical outcomes: in-hospital mortality, late mortality, and reoperations on the aorta. We will define secondary outcomes as permanent neurologic deficit, the need for new dialysis, respiratory failure, a composite of major adverse events (myocardial infarction, cerebrovascular accidents, the need for dialysis, or the need for tracheostomy), and a composite of major adverse pulmonary events (intubation over 48 h, pneumonia, reintubation, tracheostomy), and reoperation due to bleeding. Discussion This multicenter registry will definitively determine the prognostic significance of critical preoperative conditions and the efficacy of extended arch interventions and hemiarch repair in reducing the risk of early adverse events after surgery for TAAAD. This registry will provide insights into the long-term durability of different strategies of surgical repair for TAAAD.

Abstract Introduction Although largely used, the place of oxygen therapy and its devices in patients with acute hypoxemic respiratory failure (ARF) deserves to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Emergency Medicine Society (Société Française de Médecine d’Urgence, SFMU) organized a consensus conference on oxygen therapy in ARF (excluding acute cardiogenic pulmonary oedema and hypercapnic exacerbation of chronic obstructive diseases) in December 2023. Methods A committee without any conflict of interest (CoI) with the subject defined 7 generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model. An independent work group reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Fifteen experts in the field from both societies proposed their own answers in a public session and answered questions from the jury (a panel of 16 critical-care and emergency medicine physicians, nurses and physiotherapists without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. Results The jury provided 22 statements answering 11 questions: in patients with ARF (1) What are the criteria for initiating oxygen therapy? (2) What are the targets of oxygen saturation? (3) What is the role of blood gas analysis? (4) When should an arterial catheter be inserted? (5) Should standard oxygen therapy, high-flow nasal cannula oxygen therapy (HFNC) or continuous positive airway pressure (CPAP) be preferred? (6) What are the indications for non-invasive ventilation (NIV)? (7) What are the indications for invasive mechanical ventilation? (8) Should awake prone position be used? (9) What is the role of physiotherapy? (10) Which criteria necessarily lead to ICU admission? (11) Which oxygenation device should be preferred for patients for whom a do-not-intubate decision has been made? Conclusion These recommendations should optimize the use of oxygen during ARF.

Abstract Background Severe trauma is the leading cause of disability and mortality in the patients under 35 years of age. Surgical site infections (SSI) represent a significant complication in this patient population. However, they are often inadequately investigated, potentially impacting the quality of patient outcomes. The aim of this study was to investigate the epidemiology of SSI and risk factors in severe trauma patients. Methods We conducted a multicenter retrospective cohort study screening the severe trauma patients (STP) admitted to two intensive care units of an academic institution in Marseille between years2018 and 2019. Those who underwent orthopedic or spinal surgery within 5 days after admission were included and classified into two groups according to the occurrence of SSI (defined by the Centers for Disease Control (CDC) international diagnostic criteria) or not. Our secondary goal was to evaluate STP survival at 48 months, risk factors for SSI and microbiological features of SSI. Results Forty-seven (23%) out of 207 STP developed an SSI. Mortality at 48-months did not differ between SSI and non-SSI patients (12.7% vs. 10.0%; p = 0.59). The fractures of 22 (47%) severe trauma patients with SSI were classified as Cauchoix 3 grade and 18 (38%) SSI were associated with the need for external fixators. Thirty (64%) severe trauma patients with SSI had polymicrobial infection, including 34 (72%) due to Gram-positive cocci. Empirical antibiotic therapy was effective in 31 (66%) cases. Multivariate analysis revealed that risk factors such as low hemoglobin, arterial oxygenation levels, hyperlactatemia, high serum creatinine and glycemia, and Cauchoix 3 grade on the day of surgery were associated with SSI in severe trauma patients. The generated predictive model showed a good prognosis performance with an AUC of 0.80 [0.73–0.88] and a high NPV of 95.9 [88.6–98.5] %. Conclusions Our study found a high rate of SSI in severe trauma patients, although SSI was not associated with 48-month mortality. Several modifiable risk factors for SSI may be effectively managed through enhanced perioperative monitoring and the implementation of a patient blood management strategy.

Abstract New, first-in-class oral antibiotics like zoliflodacin, developed in a public–private partnership, require an optimal introduction strategy while ensuring antibiotic stewardship. Zoliflodacin, given as a single dose for uncomplicated urogenital gonorrhoea, recently demonstrated non-inferiority to ceftriaxone plus azithromycin and safety in a phase 3 randomised controlled trial. Following regulatory approval, zoliflodacin could improve sexually transmitted infection (STI) management and help address the threat of untreatable gonorrhoea, as levels of resistance to current first-line treatments increase. The Global Antibiotic Research & Development Partnership (GARDP) convened an expert meeting during the 2023 STI and HIV World Congress to discuss key questions about the introduction of zoliflodacin in low- and middle-income countries (LMICs). The questions included: which patients to treat in which situations, the timing of introduction, and what additional evidence is needed to change policy for the use of new antibiotics for gonorrhoea. Recommendations from the expert group included: the generation of evidence for the role of a drug like zoliflodacin in clinical treatment failures; the need for additional antimicrobial resistance surveillance; investigation of the role of novel diagnostic approaches, such as point-of-care tests, to improve stewardship; study of preferences and values among the population in need; and modelling of the emergence of N. gonorrhoeae resistance and transmission in different scenarios. Forthcoming World Health Organization (WHO) global guidelines could outline recommendations for a new oral antibiotic like zoliflodacin based on existing evidence, and rational approaches for certain populations or use cases, while the evidence base is further strengthened.

The ID10 beamline of the SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East) synchrotron light source in Jordan was inaugurated in June 2023 and is now open to scientific users. The beamline, which was designed and installed within the European Horizon 2020 project BEAmline for Tomography at SESAME (BEATS), provides full-field X-ray radiography and microtomography imaging with monochromatic or polychromatic X-rays up to photon energies of 100 keV. The photon source generated by a 2.9 T wavelength shifter with variable gap, and a double-multilayer monochromator system allow versatile application for experiments requiring either an X-ray beam with high intensity and flux, and/or a partially spatial coherent beam for phase-contrast applications. Sample manipulation and X-ray detection systems are designed to allow scanning samples with different size, weight and material, providing image voxel sizes from 13 µm down to 0.33 µm. A state-of-the-art computing infrastructure for data collection, three-dimensional (3D) image reconstruction and data analysis allows the visualization and exploration of results online within a few seconds from the completion of a scan. Insights from 3D X-ray imaging are key to the investigation of specimens from archaeology and cultural heritage, biology and health sciences, materials science and engineering, earth, environmental sciences and more. Microtomography scans and preliminary results obtained at the beamline demonstrate that the new beamline ID10-BEATS expands significantly the range of scientific applications that can be targeted at SESAME.

The genus Coleus is revised for DR. Congo, Rwanda, Burundi, based on herbarium taxonomy. Ninety-five taxa are reported (89 species, 1 subspecies, 5 varieties). Fifteen new species and one new variety are described (Coleus duvigneaudii, C. esculentus var. kolweziensis, C. hildei, C. kaminaensis, C. kundelunguensis, C. linarioides, C. lisowskii, C. marunguensis, C. minusculus, C. mitwabaensis, C. mystax, C. pengbelensis, C. piscatorum, C. pseudoschizophyllus, C. ruziziensis and C. zigzag). Fourteen species are newly recorded in DR. Congo and two species are newly recorded in Burundi. Four new combinations are made (Coleus betonicifolius var. kasomenensis, C. esculentus var. densus, C. esculentus var. primulinus and C. parvifolius). Ten names are lectotypified. One name is neotypified. Thirteen new synonyms are reported. Particular attention is paid to the Coleus bojeri complex. Three names are resurrected to accommodate the extensive variation patterns in Central Africa (C. chevalieri, C. collinus and C. heterotrichus); their distribution in Africa is outlined and the circumscription of C. bojeri is amended accordingly. Fifteen taxa are endemic to the study region. A determination key is provided.

During the fieldworks conducted within the CaBOL project in 2020–2023, 14 new species of Heteroptera belonging to seven families, and a new species of Auchenorrhyncha were collected in Georgia for the first time: Trypetimorpha occidentalis Huang & Bourgoin, 1993 (Tropiduchidae), Dimorphopterus blissoides (Baerensprung, 1859) (Blissidae), Europiella decolor (Uhler, 1893), Tuponia mixticolor (A. Costa, 1862), Deraeocoris ventralis Reuter, 1904, Orthocephalus brevis (Panzer, 1798) (Miridae), Alloeorhynchus flavipes (Fieber, 1836) (Nabidae), Holcogaster fibulata (Germar, 1831), Vilpianus galii Wolff, 1802 (Pentatomidae), Holotrichius bergrothi Reuter, 1891, Reduvius ciliatus Jakovlev, 1879, Oncocephalus squalidus (Rossi, 1790) (Reduviidae), Pterotmetus staphyliniformis (Germar, 1831), Diomphalus hispidulus Fieber, 1864 (Rhyparochromidae), and Psacasta neglecta (Herrich-Schäffer, 1837) (Scutellaridae). The present study provides distributional, genetic, and collecting information on the newly recorded species followed by remarks.

OBJECTIVES: This study examined the associations between implemented disability-related policies and practices (DPP) and sustained employment among partially disabled employees in The Netherlands. METHODS: Employer survey data on implemented DPP were linked to register data on employment outcomes of partially disabled employees (N=6103 employees from N=366 employers). DPP included six domains based on 48 elements: sick leave policy, occupational health and safety services (OHS), prevention policy, reintegration policy, reintegration practices within the current employer and reintegration practices towards another employer. DPP domains were standardized on a 0–1 scale. Separate logistic regression models were estimated for DDP domains on one-year sustained employment adjusted for employee characteristics, firm size, and sector. RESULTS: Almost all organizations implemented at least one element of DPP on prevention policy, OHS, sick leave policy, and reintegration practices within the current employer, and two-thirds on reintegration policy and reintegration practices towards another employer. Implemented DPP on prevention policy [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.3–4.0], OHS (OR 1.9, 95% CI 1.1–3.2), and sick leave policy (OR 1.8, 95% CI 1.0–3.3) were positively associated with sustained employment. No significant results were found for reintegration policy and both reintegration practices domains. Stratified analysis showed that DDP domains were particularly associated with sustained employment in larger organizations and in the private sector. CONCLUSIONS: Implemented DPP related to sick leave policy, OHS and prevention policy are associated with sustained employment among partially disabled employees, in particular in larger organizations and in the private sector.

Aims: Precise implant positioning, tailored to individual spinopelvic biomechanics and phenotype, is paramount for stability in total hip arthroplasty (THA). Despite a few studies on instability prediction, there is a notable gap in research utilizing artificial intelligence (AI). The objective of our pilot study was to evaluate the feasibility of developing an AI algorithm tailored to individual spinopelvic mechanics and patient phenotype for predicting impingement. Methods: This international, multicentre prospective cohort study across two centres encompassed 157 adults undergoing primary robotic arm-assisted THA. Impingement during specific flexion and extension stances was identified using the virtual range of motion (ROM) tool of the robotic software. The primary AI model, the Light Gradient-Boosting Machine (LGBM), used tabular data to predict impingement presence, direction (flexion or extension), and type. A secondary model integrating tabular data with plain anteroposterior pelvis radiographs was evaluated to assess for any potential enhancement in prediction accuracy. Results: We identified nine predictors from an analysis of baseline spinopelvic characteristics and surgical planning parameters. Using fivefold cross-validation, the LGBM achieved 70.2% impingement prediction accuracy. With impingement data, the LGBM estimated direction with 85% accuracy, while the support vector machine (SVM) determined impingement type with 72.9% accuracy. After integrating imaging data with a multilayer perceptron (tabular) and a convolutional neural network (radiograph), the LGBM’s prediction was 68.1%. Both combined and LGBM-only had similar impingement direction prediction rates (around 84.5%). Conclusion: This study is a pioneering effort in leveraging AI for impingement prediction in THA, utilizing a comprehensive, real-world clinical dataset. Our machine-learning algorithm demonstrated promising accuracy in predicting impingement, its type, and direction. While the addition of imaging data to our deep-learning algorithm did not boost accuracy, the potential for refined annotations, such as landmark markings, offers avenues for future enhancement. Prior to clinical integration, external validation and larger-scale testing of this algorithm are essential. Cite this article: Bone Jt Open 2024;5(8):671–680.

Abstract Hypophosphatemia (serum phosphate

Abstract This study presents a detailed psychometric evaluation of a novel high-resolution electrotactile interface, which is developed to provide users with 3D spatial information and facilitate enhanced interaction with a Supernumerary Robotic Limb (SRL). The research introduces a novel electrotactile system that employs a multi-pad electrode configuration on the thigh, aimed at delivering intuitive feedback to users about the position of the SRL in a three-dimensional space. The interface's effectiveness was assessed through a series of psychometric tests, including static spatial discrimination, target-reaching with spatial feedback, frequency discrimination, and combined spatial/frequency modulation. The key findings demonstrate that participants could differentiate between 30 electrode pads with an average success rate of 62.7% when they were activated statically, while in the dynamic target-reaching task, the success rate increased to 88.1%. Frequency discrimination tests further revealed that four frequency levels could be distinguished with 86.0% success rate in single-pad feedback while the performance decreased to 74.3% in multi-pad distributed feedback. Finaly, in the closed-loop test with mixed spatial and frequency modulation, participants achieved an overall success rate of 78.8% in target reaching across 10 × 4 discrete 2D space. These results highlight the interface’s capability to transmit high-resolution spatial information through electrotactile feedback, offering a foundation for future applications in tactile-based navigation and control systems.

Abstract Obesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. We aimed to characterize in mice the sex-dependent effects of a high fat diet on these parameters. Male and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota, plasma adipokines and white adipose tissue response have been assessed. Both male and female HFD mice exhibited an increase of body weight and fat mass gain and glucose intolerance compared to SD mice. However, only male HFD mice tended to develop insulin resistance associated to increased Tnfα and Ccl2 mRNA expression in perigonadal adipose tissue. By contrast, only female HFD mice showed significant intestinal hyperpermeability that was associated with more markedly altered colonic inflammatory response. Cecal microbiota richness was markedly reduced in both sexes (Observed species) with sex-dependent modifications at the phyla or family level, e.g. decreased relative abundance of Bacillota and Lachnospiraceae in females, increased of Bacteroidaceae in males. Interestingly, some of these microbiota alterations were correlated with peripheral metabolic and inflammatory markers. In conclusions, male and female mice exhibit different responses to a high fat diet with specific changes of gut microbiota, intestinal barrier function, colonic and white adipose tissue inflammation, metabolic markers and body weight gain. The underlying mechanisms should be deciphered in further investigations.

Abstract Introduction Attacks on healthcare have further weakened the already fragile health system in the Central African Republic. We investigated attacks on healthcare in three conflict-affected prefectures—Ouaka, Haute-Kotto, and Vakaga—from 2016 to 2020. The study aim was to gain an in-depth understanding of the immediate and long-term effects of attacks on healthcare workers, facilities, supply chain, quality of care, and other components of the health system. We provide a qualitative description of the incidents, assess their impacts, identify mitigation efforts, and discuss challenges to recovery. Methods We used purposive and snowball sampling to identify participants in the study. Semi-structured key informant interviews were conducted with administrative and health authorities, front-line personnel, and staff of non-governmental organizations. Interviews were done in Sango, French, or English. Recorded interviews were transcribed and notes taken for non-recorded interviews. Transcripts and notes were analyzed using inductive coding, allowing participant responses to guide findings. Results Of 126 attacks identified over the study period, 36 key informants discussed 39 attacks. Attacks included killings, physical and sexual assault, abductions, arson, shelling with grenades, pillage, occupations, and verbal threats. The violence led to extended closures and debilitating shortages in healthcare services, disproportionately affecting vulnerable populations, such as children under five, or people who are elderly, chronically ill, or displaced. Healthcare workers faced psychological trauma and moral injury from repeated attacks and the inability to provide adequate care. Personnel and communities made enormous efforts to mitigate impacts, and advocate for assistance. They were limited by failed reporting mechanisms, ongoing insecurity, persistent lack of resources and external support. Conclusion Effective strategies to safeguard healthcare from violence exist but better support for communities and health workers is essential, including measures to assess needs, enhance security, and facilitate recovery by quickly rebuilding, resupplying, and re-staffing facilities. CAR’s government, international organizations, and donors should make concerted efforts to improve reporting mechanisms and end impunity for perpetrators. Their investment in community organizations and long-term health system support, especially for health worker training, salaries, and psychosocial care, are vital steps towards building resilience against and mitigating the impacts of attacks on healthcare.