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Abstract Citizen Science initiatives have a worldwide impact on environmental research by providing data at a global scale and high resolution. Mapping marine biodiversity remains a key challenge to which citizen initiatives can contribute. Here we describe a dataset made of both underwater and aerial imagery collected in shallow tropical coastal areas by using various low cost platforms operated either by citizens or researchers. This dataset is regularly updated and contains >1.6 M images from the Southwest Indian Ocean. Most of images are geolocated, and some are annotated with 51 distinct classes (e.g. fauna, and habitats) to train AI models. The quality of these photos taken by action cameras along the trajectories of different platforms, is highly heterogeneous (due to varying speed, depth, turbidity, and perspectives) and well reflects the challenges of underwater image recognition. Data discovery and access rely on DOI assignment while data interoperability and reuse is ensured by complying with widely used community standards. The open-source data workflow is provided to ease contributions from anyone collecting pictures.

Background: The importance of the subscapularis for reverse total shoulder arthroplasty has been demonstrated, especially for internal rotation and stability. In a deltopectoral approach, a detachment of the subscapularis is performed (tenotomy, tuberosity peeling, or osteotomy), but the tendon is not always repairable at the end. When it is repaired, healing is obtained in only 40%-76% of the cases, with potential consequences for the outcomes. The anterior muscle-sparing (AMS) approach is a deltopectoral approach with preservation of the subscapularis, providing a solution to these problems. We present the surgical technique and results. Methods: In a retrospective study, we included our first 45 cases of reverse total shoulder arthroplasty performed with the AMS approach for a degenerative affection of the shoulder (massive rotator cuff tear, cuff tear arthropathy, primary glenohumeral arthritis, or rheumatoid arthritis), excluding traumatic and revision cases. The subscapularis was intact in all the cases. The mean age at inclusion was 74.1 years. No patients were lost at the minimum 24-month follow-up. All the patients underwent a clinical evaluation preoperatively and at the last follow-up, including Constant score, simple shoulder value, pain scale, and range of motion. An X-ray evaluation was conducted postoperatively and at the last follow-up to assess implant positioning and evolution. Results: There was no intraoperative complication, and the mean operative time was 62 minutes. We observed a significant improvement in Constant score (from 36 to 70, P

Prison authorities around the world are already confronting the direct and indirect consequences of climate change. Heatwaves, coastal and inland floods, storms, droughts and swelling-shrinking of clay soils are the main climate hazards identified as posing risks to French prisons. After a brief overview of the possible impacts of climate change on prisons, this article presents actions taken by the prison administration’s laboratory to co-create a much-needed strategy for transformation that seeks to adapt to climate change as well as mitigate its impacts. The strategy, created by examining future environmental trends, aims to anticipate and suggest actions for different timescales: acquiring data and producing knowledge; visualizing what future prisons might look like and possible trajectories for their transformation; organizing collective discussions about prisons to establish a shared vision, and supporting appropriation of the results to assist in decision-making and action-taking.

Abstract Searching for similar genomic sequences is an essential and fundamental step in biomedical research. State-of-the-art computational methods performing such comparisons fail to cope with the exponential growth of genomic sequencing data. We introduce the concept of sparsified genomics where we systematically exclude a large number of bases from genomic sequences and enable faster and memory-efficient processing of the sparsified, shorter genomic sequences, while providing comparable accuracy to processing non-sparsified sequences. Sparsified genomics provides benefits to many genomic analyses and has broad applicability. Sparsifying genomic sequences accelerates the state-of-the-art read mapper (minimap2) by 2.57-5.38x, 1.13-2.78x, and 3.52-6.28x using real Illumina, HiFi, and ONT reads, respectively, while providing comparable memory footprint, 2x smaller index size, and more correctly detected variations compared to minimap2. Sparsifying genomic sequences makes containment search through very large genomes and large databases 72.7-75.88x (1.62-1.9x when indexing is preprocessed) faster and 723.3x more storage-efficient than searching through non-sparsified genomic sequences (with CMash and KMC3). Sparsifying genomic sequences enables robust microbiome discovery by providing 54.15-61.88x (1.58-1.71x when indexing is preprocessed) faster and 720x more storage-efficient taxonomic profiling of metagenomic samples over the state-of-the-art tool (Metalign).

Abstract Endosomal nucleic acid sensing by Toll-like receptors (TLRs) is central to antimicrobial immunity and several autoimmune conditions such as systemic lupus erythematosus (SLE). The innate immune adaptor TASL mediates, via the interaction with SLC15A4, the activation of IRF5 downstream of human TLR7, TLR8 and TLR9, but the pathophysiological functions of this axis remain unexplored. Here we show that SLC15A4 deficiency results in a selective block of TLR7/9-induced IRF5 activation, while loss of TASL leads to a strong but incomplete impairment, which depends on the cell type and TLR engaged. This residual IRF5 activity is ascribed to a previously uncharacterized paralogue, Gm6377, named here TASL2. Double knockout of TASL and TASL2 (TASLDKO) phenocopies SLC15A4-deficient feeble mice showing comparable impairment of innate and humoral responses. Consequently, TASLDKO mice fail to control chronic LCMV infection, while being protected in a pristane-induced SLE disease model. Our study thus demonstrates the critical pathophysiological role of SLC15A4 and TASL/TASL2 for TLR7/9-driven inflammatory responses, further supporting the therapeutic potential of targeting this complex in SLE and related diseases.

Abstract Background Pearl millet (Pennisetum glaucum (L.) R. Br.) production has decreased over the years due to several constraints, including insect pest attacks, which contribute to its status as neglected and underutilized species in Benin. In order to develop an integrated pest management strategy, we documented farmers’ post-harvest conservation practices, perceptions, and management of storage insect pests. Four hundred millet producers were surveyed using a semi-structured questionnaire in 76 villages in northern Benin. The entomofauna associated with stored pearl millet was identified by extracting samples from farmers’ storage structures and incubating them for a month in the laboratory. Results Our results showed that farmers perceived insect pests as the most important constraint to pearl millet storage. Vernacular taxonomy and local nomenclature of insect pests of stored pearl millet varied among sociolinguistic groups. Four species of insects were associated with stored millet with the weevils Sitophilus oryzae L. and Sitophilus zeamais L. as the most important ones. Three storage structures (attic, bedroom, and store) and a storage tool (polypropylene bags) were inventoried. Synthetic chemical insecticides were the most commonly used method for protecting stored millet. Also, farmers employed four plants that repel and kill insects to safeguard stored pearl millet. A differential sensitivity of pearl millet varieties to storage insect attacks was reported with four potential resistant varieties. Some factors that influence the use of a pest management method were determined. Conclusions The development of an integrated pest management needs to test the sensitivity of resistant varieties and the bioactivity of recorded insecticidal plants. The farmers’ perception suggests that the Souhoun n’nin gberenou landrace and the usage of bark of A. senegalensis and leaves of A. indica are the best ways to preserve millet for a long time. Raising awareness among pearl millet producers on good storage practices and the biological management of storage insect pests were recommended. Factors that influence the use of pest management methods must be integrated into the development of national strategies.

Abstract Background Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapidly evolving interstitial lung disease (ILD), driving its mortality. Specific imaging-based biomarkers associated with the evolution of lung disease are needed to help predict and quantify ILD. Methods We evaluated the potential of an automated ILD quantification system (icolung®) from chest CT scans, to help in quantification and prediction of ILD progression in SSc-ILD. We used a retrospective cohort of 75 SSc-ILD patients to evaluate the potential of the AI-based quantification tool and to correlate image-based quantification with pulmonary function tests and their evolution over time. Results We evaluated a group of 75 patients suffering from SSc-ILD, either limited or diffuse, of whom 30 presented progressive pulmonary fibrosis (PPF). The patients presenting PPF exhibited more extensive lesions (in % of total lung volume (TLV)) based on image analysis than those without PPF: 3.93 (0.36–8.12)* vs. 0.59 (0.09–3.53) respectively, whereas pulmonary functional test showed a reduction in Force Vital Capacity (FVC)(pred%) in patients with PPF compared to the others : 77 ± 20% vs. 87 ± 19% (p

Abstract Background The COVID-19 pandemic prompted significant shifts to teleworking, raising questions about potential impacts on employee wellbeing. This study examined the association between self-reported changes to teleworking frequency (relative to before the pandemic) and two indicators of occupational burnout: emotional exhaustion and professionally diagnosed burnout. Methods Data were derived from two samples from a digital cohort study based in Geneva, Switzerland: one population-based, and one from a sample of workers who were likely mobilized in the early stages of the COVID-19 pandemic. Emotional exhaustion was measured using the Maslach Burnout Inventory (EE-MBI), while self-reported diagnosed burnout was assessed by asking participants if they had received a professional diagnosis of occupational burnout within the previous 12 months. Participants were categorized based on self-reported telework frequency changes: “no change,” “increase,” “decrease,” “never telework,” and “not possible to telework.” Adjusted regression models for each of the study samples were used to estimate associations between telework changes and burnout outcomes, accounting for sociodemographic, household, and work-related factors. Results In the population-based sample of salaried employees (n = 1,332), the median EE-MBI score was 14 (interquartile range: 6–24), and 7.3% reported diagnosed burnout. Compared to those reporting no change in telework frequency (19% of the sample), those reporting a decrease (4%) and those reporting that teleworking was not possible (28.7%) had significantly higher emotional exhaustion scores (adjusted beta (aβ) 5.26 [95% confidence interval: 1.47, 9.04] and aβ 3.51 [0.44, 6.59], respectively) and additionally reported higher odds of diagnosed burnout (adjusted odds ratio (aOR) 10.59 [3.24, 34.57] and aOR 3.42 [1.22, 9.65], respectively). “Increased” (28.9%) and “never” (19.4%) telework statuses were not significantly associated with burnout outcomes. These trends were mirrored in the “mobilized-workers” sample, with the exception that those reporting that teleworking was not possible did not report significantly higher odds of diagnosed burnout compared to those reporting no change in telework frequency. Conclusions Decreased teleworking frequency and not having the possibility of telework were associated with higher emotional exhaustion and diagnosed burnout. As organizations reconsider their telework policies in a post-pandemic era, they should consider the impact of such organizational changes on employee wellbeing.

Purpose: To develop a controlled vocabulary of less than 30 terms that represents level 1 of a taxonomy for the field of operations management, integrating previous available work to improve efficiency in searching and retrieving scientific information in the area. Design/methodology/approach: A systematic review of encyclopedias and glossaries in the field was conducted, mainly based on Hill (2012, 2019). The three authors employed an iterative process to define and validate the first-level terms, contrasting them with sources such as Gass & Fu (2013), Helms (2006), and the APICS thesaurus. Affinity diagrams were used to structure and relate the identified terms. Findings: 20 top-level terms covering the main areas of operations management were identified and defined. The resulting taxonomy is available online (https://taxom.blogs.upv.es/). It provides a hierarchical structure that integrates the main concepts of the field, differentiating itself from previous work by focusing on relevance to research, education, and professional practice contexts. Research limitations/implications: The thematic coverage of the proposed taxonomy requires further verification to ensure its comprehensiveness. Future research should focus on validating the taxonomy by applying it to a representative sample of articles within the field of operations management. This validation process will help confirm whether the first-level terms are robust and precise for effective categorisation and usability in academic and professional contexts. Practical implications: The taxonomy facilitates scientific editorial management by providing a standardised list for selecting keywords in manuscripts and identifying reviewers' fields of expertise. It also improves the efficiency of mapping science studies and systematic reviews and enhances the visibility and accessibility of published research in operations management.

Abstract Hereditary spastic paraplegia (HSP) encompasses a group of rare genetic diseases primarily affecting motor neurons. Among these, spastic paraplegia type 11 (SPG11) represents a complex form of HSP caused by deleterious variants in the SPG11 gene, which encodes the spatacsin protein. Previous studies have described several potential roles for spatacsin, including its involvement in lysosome and autophagy mechanisms, neuronal and neurites development or mitochondria function. Despite these findings, the precise function of the spatacsin protein remains elusive. To elucidate its function, we conducted an extensive RNA sequencing (RNAseq) experiment and transcriptomic analysis in three distinct neural structures (cerebellum, cortex and hippocampus) and at three different ages (6 weeks, 4 months and 8 months) in both wild type and Spg11 −/− mice. Our functional analysis of differentially expressed genes (DEGs) and Gene Set Enrichment Analysis (GSEA) revealed dysregulation in pathways related to inflammation, RNA metabolism and neuronal and neurite development, factors frequently implicated in neurodegenerative disorders. Notably, we also observed early deregulation in cellular pathways related to cell proliferation. Our results represent a significant step towards a better understanding of the functions of spatacsin in the cell and the underlying cellular mechanisms disrupted by its absence.

Abstract Background Sepsis-associated encephalopathy (SAE) may be worsened by early systemic insults. We aimed to investigate the association of early systemic insults with outcomes of critically ill patients with severe SAE. Methods We performed a retrospective analysis using data from the French OUTCOMEREA prospective multicenter database. We included patients hospitalized in intensive care unit (ICU) for at least 48 h with severe SAE (defined by a score on the Glasgow Coma Scale (GCS) ≤ 13 and severe sepsis or septic shock (SEPSIS 2.0 criteria)) requiring invasive ventilation and who had no primary brain injury. We analyzed early systemic insults (abnormal glycemia ( 200 mmHg), carbon dioxide abnormalities ( 13. Results We included 995 patients with severe SAE, of whom 883 (89%) exhibited at least one early systemic insult that persisted through day 3. Compared to non-survivors, survivors had significantly less early systemic insults (hypoglycemia, hypotension, hypothermia, and anemia) within the first 48 h of ICU admission. The absence of correction of the following systemic insults at day 3 was independently associated with mortality: blood pressure (adjusted hazard ratio (aHR) = 1.77, 95% confidence interval (CI) 1.34–2.34), oxygenation (aHR = 1.78, 95% CI 1.20–2.63), temperature (aHR = 1.46, 95% CI 1.12–1.91) and glycemia (aHR = 1.41, 95% CI 1.10–1.80). Persistent abnormal blood pressure, temperature and glycemia at day 3 were associated with decreased chances of awakening. Conclusions In patients with severe SAE, the persistence of systemic insults within the first three days of ICU admission is associated with increased mortality and decreased chances of awakening.

Abstract Iminophosphoranes with the general formula (R3P═NR′) have great potential in synthetic chemistry as valuable precursors/intermediates in organic synthesis or as building blocks for various organic compounds. However, the synthetic approaches and conditions to prepare iminophosphoranes are still poorly understood, limiting the utility of this chemistry for organic materials. In this article, a simple and efficient synthesis of previously unattainable poly(arylene iminophosphoranes) is reported. The azide-phosphine Staudinger polycondensation is used, and the reaction conditions are carefully studied, including consideration of light and air, the influence of solvent and temperature, and investigation of the electronic and steric effects of multiazides. The newly defined reaction conditions appear to be highly versatile, allowing the use of both electron-rich and electron-deficient arylazides for reaction with phosphines to synthesize a library of poly(arylene iminophosphorane) networks that exhibit exceptional thermal and oxidative stability. Interestingly, despite the ylidic-form of the iminophosphorane linkage as shown by theoretical calculations, these newly developed poly(arylene-iminophosphorane) networks exhibit semiconducting properties, such as absorption band edges up to 800 nm and optical band gaps in the range of 1.70 to 2.40 eV. Finally, we demonstrate the broad applicability of these polymers by processing them into glassy films, creating foam-like structures and synthesizing metallo-polymer hybrids.

Abstract Diffuse coronary artery disease (CAD) impacts the immediate hemodynamic and clinical outcomes of percutaneous coronary intervention (PCI). We evaluated whether the diffuse pattern of CAD derived from angiographic Quantitative flow ratio (QFR) impacts the immediate hemodynamic outcome post-PCI and the medium term predicted vessel-oriented composite endpoint (VOCE). Paired pre-procedure QFRs were assessed in 503 patients and 1022 vessels in the Multivessel TALENT (MVT) trial. The pathophysiological pattern of CAD was defined as “predominantly diffuse” or “focal” according to a virtual QFR pullback pressure gradient (PPG) index

Abstract Background After cardiac arrest (CA), the European recommendations suggest to use a neuron-specific enolase (NSE) level > 60 µg/L at 48–72 h to predict poor outcome. However, the prognostic performance of NSE can vary depending on electroencephalogram (EEG). The objective was to determine whether the NSE threshold which predicts poor outcome varies according to EEG patterns and the effect of electrographic seizures on NSE level. Methods A retrospective study was conducted in a tertiary CA center, using a prospective registry of 155 adult patients comatose 72 h after CA. EEG patterns were classified according to the Westhall classification (benign, malignant or highly malignant). Neurological outcome was evaluated using the CPC scale at 3 months (CPC 3–5 defining a poor outcome). Results Participants were 64 years old (IQR [53; 72,5]), and 74% were male. 83% were out-of-hospital CA and 48% were initial shockable rhythm. Electrographic seizures were observed in 5% and 8% of good and poor outcome patients, respectively (p = 0.50). NSE blood levels were significantly lower in the good outcome (median 20 µg/L IQR [15; 30]) compared to poor outcome group (median 110 µg/l IQR [49;308], p 45.2 µg/L was predictive of unfavorable outcome with 100% specificity and a higher sensitivity (70.8%) compared to the recommended NSE cut-off of 60 µg/l (Se = 66%). Combined to electrographic seizures, a NSE > 53.5 µg/L predicts poor outcome with 100% specificity and a higher sensitivity (77.7%) compared to the recommended cut-off (Se = 66.6%). Combined to a benign EEG, a NSE level > 78.2 µg/L was highly predictive of a poor outcome with a higher specificity (Sp = 100%) compared to the recommended cut-off (Sp = 94%). Conclusion In comatose patients after AC, a personalized approach of NSE according to EEG pattern could improve the specificity and sensitivity of this biomarker for poor outcome prediction. Compared to others malignant EEG, no significant difference of NSE level was observed in case of electrographic seizures.

Abstract Questions about when early members of the genus Homo adapted to extreme environments like deserts and rainforests have traditionally focused on Homo sapiens. Here, we present multidisciplinary evidence from Engaji Nanyori in Tanzania’s Oldupai Gorge, revealing that Homo erectus thrived in hyperarid landscapes one million years ago. Using biogeochemical analyses, precise chronometric dating, palaeoclimate simulations, biome modeling, fire history reconstructions, palaeobotanical studies, faunal assemblages, and archeological evidence, we reconstruct an environment dominated by semidesert shrubland. Despite these challenges, Homo erectus repeatedly occupied fluvial landscapes, leveraging water sources and ecological focal points to mitigate risk. These findings suggest archaic humans possessed an ecological flexibility previously attributed only to later hominins. This adaptability likely facilitated the expansion of Homo erectus into the arid regions of Africa and Eurasia, redefining their role as ecological generalists thriving in some of the most challenging landscapes of the Middle Pleistocene.

Abstract Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson’s disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3−/− mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Expression of genes encoding anti-inflammatory proteins and neuroprotective factors was reduced in the striatum of MPTP-treated mGlu3−/− mice. We also examined polymorphic variants of GRM3 (the mGlu3 receptor encoding gene) in 723 PD patients and 826 healthy controls. Two GRM3 haplotypes were associated with PD, and gene variants correlated with motor and non-motor signs. Interestingly, PD patients carrying each of the two haplotypes showed an impaired cortical plasticity in the paired associated stimulation paradigm of magnetic transcranial stimulation. These findings suggest that mGlu3 receptors are neuroprotective in mouse models of parkinsonism and shape mechanisms of cortical plasticity in PD.

Abstract We aimed to identify and validate factors related to uncontrolled hypertension. Participants treated with at least one antihypertensive drug from the prospective contemporaneous CoLaus|PsyCoLaus study were enrolled. We investigated the association between hypertension status (uncontrolled, defined as systolic blood pressure [SBP] ≥ 140 mm Hg and/or diastolic blood pressure [DBP] ≥ 90 mm Hg, versus controlled hypertension [SBP/DBP

Abstract Bone marrow adipose tissue is a distinct adipose subtype comprising more than 10% of fat mass in healthy humans. However, the functions and pathophysiological correlates of this tissue are unclear, and its genetic determinants remain unknown. Here, we use deep learning to measure bone marrow adiposity in the femoral head, total hip, femoral diaphysis, and spine from MRI scans of approximately 47,000 UK Biobank participants, including over 41,000 white and over 6300 non-white participants. We then establish the heritability and genome-wide significant associations for bone marrow adiposity at each site. Our meta-GWAS in the white population finds 67, 147, 134, and 174 independent significant single nucleotide polymorphisms, which map to 54, 90, 43, and 100 genes for the femoral head, total hip, femoral diaphysis, and spine, respectively. Transcriptome-wide association studies, colocalization analyses, and sex-stratified meta-GWASes in the white participants further resolve functional and sex-specific genes associated with bone marrow adiposity at each site. Finally, we perform a multi-ancestry meta-GWAS to identify genes associated with bone marrow adiposity across the different bone regions and across ancestry groups. Our findings provide insights into BMAT formation and function and provide a basis to study the impact of BMAT on human health and disease.

Abstract Prime Editing can rewrite genes in living cells by allowing point mutations, deletions, or insertion of small DNA sequences with high precision. However, its safe and efficient delivery into human stem cells remains a technical challenge. In this report, we engineer Nanoscribes, virus-like particles that encapsidate ribonucleoprotein complexes of the Prime Editing system and allow their delivery into recipient cells. We identify key features that unlock the potential of Nanoscribes, including the use of multiple fusogens, the improvement of pegRNAs structures, their encoding by a Pol II system and the optimization of Prime-Editors. Nanoscribes edit HEK293T with an efficiency of 68% at the HEK3 locus with increased fidelity over DNA-transfection and support pegRNA-multiplexing. Importantly, Nanoscribes permit editing of myoblasts, hiPSCs and hiPSCs-derived hematopoietic stem cells with an editing efficiency up to 25%. Nanoscribes is an asset for development of next generation genome editing approaches using VLPs.

Abstract Neuronal population activity in sensory cortices is the substrate for perceptual decisions. Yet, we still do not understand how neuronal information content in sensory cortices relates to behavioral reports. To reconcile neurometric and psychometric performance, we recorded the activity of V1 neurons in mice performing a Go/NoGo orientation discrimination task. We found that, around the discrimination threshold, V1 does not represent the orientation of the stimuli as canonically expected. Instead, it forms categorical representations characterized by a relocation of activity at task-relevant domains of the orientation representational space. The relative neuronal activity at those discrete domains accurately predicted the probabilities of the animals’ decisions. Our results thus suggest that the categorical integration of discretized feature representations from sensory cortices explains perceptual decisions.

Abstract Revealing the effects of multiple global change drivers on ecosystem dynamics and functioning is a crucial endeavour, which necessitates the use of appropriate tools. Here, we present the Aquatic Metatron, a unique mesocosm facility providing a large‐scale experimental resource to study the combined effects of global change components, in particular climate change and habitat fragmentation, on the ecological and evolutionary dynamics of aquatic ecosystems. The Aquatic Metatron consists of 144 mesocosms of 2 m3 each that can be connected to each other with aquatic corridors, and—for a subset of them—with aerial corridors. This enables effective control of dispersal across meta‐ecosystems. In addition, the temperature in each mesocosm is supervised and precisely controlled, either through a heating (all mesocosms) or a cooling (72 mesocosms) system. All mesocosms can be monitored automatically for abiotic and biotic factors (pH, dissolved oxygen, conductivity, turbidity and chlorophyll a) allowing for long‐term experimentation. We tested the platform by conducting three experiments involving the manipulation of various components of global change: climate warming, biodiversity loss, eutrophication and aquatic/aerial fragmentation. The technical innovations of the platform have been validated, in particular its capacity to accurately recreate multiple climatic scenarios (e.g. heatwaves, warming, cooling) and the possibility of using aerial and water corridors to simulate fragmented landscapes. The Aquatic Metatron is located in the south‐west of France (https://sete‐moulis‐cnrs.fr/fr) and is part of AnaEE France and AnaEE‐ERIC (https://www.anaee.eu/), which are large‐scale research infrastructures. The Aquatic Metatron is a research facility accessible to external researchers and projects.

The upgrade of the European Synchrotron Radiation Facility (ESRF) in Grenoble, France to an Extremely Brilliant Source (EBS) is expected to enable time-resolved synchrotron serial crystallography (SSX) experiments with sub-millisecond time resolution. ID29 is a new beamline dedicated to SSX experiments at ESRF–EBS. Here, we report experiments emerging from the initial phase of user operation at ID29. We first used microcrystals of photoactive yellow protein as a model system to exploit the potential of microsecond pulses for SSX. Subsequently, we investigated microcrystals of cytochrome c nitrite reductase (ccNiR) with microsecond X-ray pulses. CcNiR is a decaheme protein that is ideal for the investigation of radiation damage at the various heme-iron sites. Finally, we performed a proof-of-concept subsecond time-resolved SSX experiment by photoactivating microcrystals of a myxobacterial phytochrome.

Background: The significant rate of recurrent instability following arthroscopic stabilization surgery points to a need for an evidence-based treatment approach. The instability severity index Score (ISI score) is a point-based algorithm that may be used to assist clinicians in selecting the optimal treatment approach, but its efficacy compared with a traditional treatment algorithm has not been previously validated. The aim was to compare two surgical treatment algorithms: the ISI score and a conventional treatment algorithm (CTA). Methods: This was a prospective, randomized controlled trial involving participants who were randomized to either the ISI score or CTA and were followed for 24 months postrandomization. In the ISI score cohort, patients underwent a Latarjet procedure if they presented with a score >3 points. Those scoring ISI score ≦3 points underwent an arthroscopic Bankart repair. Patients randomized to the CTA group underwent a Latarjet procedure if the glenoid bone loss was > 25%. The primary outcome was the Western Ontario Shoulder Instability Index. Secondary outcomes included the American Shoulder and Elbow Surgeons score as well as recurrence rates between groups. Results: Sixty-three patients were randomized to ISI score (n = 31) or CTA (n = 32). At two years, the Western Ontario Shoulder Instability Index score was similar between groups (ISI score: 84.1 ± 16.9, CTA: 85.7 ± 12.5, P = .70). Similarly, no differences were detected in American Shoulder and Elbow Surgeons scores (ISI score: 93.2 ± 16.2, CTA: 92.6 ± 9.9, P = .89). Apprehension was reported in 18.5% for the ISI score group and 20% in the CTA group (P = 1.00). At a 24-month follow-up, there was no difference in redislocations: one in ISI score group and none in the CTA group (P = .48). There were two revision surgeries in the ISI score group and two in the CTA group. Conclusion: This study did not demonstrate any differences in functional outcomes, the incidence of apprehension, or failure rates between the two treatment algorithms at 24-month follow-up.

Abstract The influx of whole genome sequencing (WGS) data in the public health and clinical diagnostic sectors has created a need for data analysis methods and bioinformatics expertise, which can be a bottleneck for many laboratories. At Sciensano, the Belgian national public health institute, an intuitive and user-friendly bioinformatics tool portal was implemented using Galaxy, an open-source platform for data analysis and workflow creation. The Galaxy @Sciensano instance is available to both internal and external scientists and offers a wide range of tools provided by the community, complemented by over 50 custom tools and pipelines developed in-house. The tool selection is currently focused primarily on the analysis of WGS data generated using Illumina sequencing for microbial pathogen typing, characterization and outbreak detection, but it also addresses specific use cases for other data types. Our Galaxy instance includes several custom-developed 'push-button' pipelines, which are user-friendly and intuitive stand-alone tools that perform complete characterization of bacterial isolates based on WGS data and generate interactive HTML output reports with key findings. These pipelines include quality control, de novo assembly, sequence typing, antimicrobial resistance prediction and several relevant species-specific assays. They are tailored for pathogens with active genomic surveillance programs, and clinical relevance, such as Escherichia coli, Listeria monocytogenes, Salmonella spp. and Mycobacterium tuberculosis. These tools and pipelines utilize internationally recognized databases such as PubMLST, EnteroBase, and the NCBI National Database of Antibiotic Resistant Organisms, which are automatically synchronized on a regular basis to ensure up-to-date results. Many of these pipelines are part of the routine activities of Belgian national reference centers and laboratories, some of which use them under ISO accreditation. This resource is publicly available for noncommercial use at https://galaxy.sciensano.be/ and can help other laboratories establish reliable, traceable and reproducible bioinformatics analyses for pathogens encountered in public health settings.

Abstract Serial macromolecular crystallography has become a powerful method to reveal room temperature structures of biological macromolecules and perform time-resolved studies. ID29, a flagship beamline of the ESRF 4th generation synchrotron, is the first synchrotron beamline in the world capable of delivering high brilliance microsecond X-ray pulses at high repetition rate for the structure determination of biological macromolecules at room temperature. The cardinal combination of microsecond exposure times, innovative beam characteristics and adaptable sample environment provides high quality complete data, even from an exceptionally small amount of crystalline material, enabling what we collectively term serial microsecond crystallography (SµX). After validating the use of different sample delivery methods with various model systems, we applied SµX to an integral membrane receptor, where only a few thousands diffraction images were sufficient to obtain a fully interpretable electron density map for the antagonist istradefylline-bound A2A receptor conformation, providing access to the antagonist binding mode. SµX, as demonstrated at ID29, will quickly find its broad applicability at upcoming 4th generation synchrotron sources worldwide and opens a new frontier in time-resolved SµX.

Abstract Background To reduce the number of deaths caused by exsanguination, the initial management of severe trauma aims to prevent, if not limit, the lethal triad, which consists of acidosis, coagulopathy, and hypothermia. Recently, several studies have suggested adding hypocalcemia to the lethal triad to form the lethal diamond, but the evidence supporting this change is limited. Therefore, the aim of this study was to compare the lethal triad and lethal diamond for their respective associations with 24-h mortality in severe trauma patients receiving transfusion. Methods We performed a multicenter retrospective analysis of patients in TraumaBase®, a French database (2011–2023). The patients included in this study were all trauma patients who had received transfusions of at least 1 unit of red blood cells (RBCs) within the first 6 h of hospital admission and for whom ionized calcium measurements were available. Hypocalcemia was defined as an ionized calcium level

Abstract Mitochondria are crucial for cellular metabolism and signalling. Mitochondrial activity is modulated by mitochondrial fission and fusion, which are required to properly balance metabolic functions, transfer material between mitochondria, and remove defective mitochondria. Mitochondrial fission occurs at mitochondria-endoplasmic reticulum (ER) contact sites, and requires the formation of actin filaments that drive mitochondrial constriction and the recruitment of the fission protein DRP1. The role of actin in mitochondrial fusion remains entirely unexplored. Here we show that preventing actin polymerisation on either mitochondria or the ER disrupts both fission and fusion. We show that fusion but not fission is dependent on Arp2/3, whereas both fission and fusion require INF2 formin-dependent actin polymerization. We also show that mitochondria-associated actin marks fusion sites prior to the fusion protein MFN2. Together, our work introduces a method for perturbing organelle-associated actin and demonstrates a previously unknown role for actin in mitochondrial fusion.

Abstract AI techniques are increasingly being used to identify individuals both offline and online. However, quantifying their effectiveness at scale and, by extension, the risks they pose remains a significant challenge. Here, we propose a two-parameter Bayesian model for exact matching techniques and derive an analytical expression for correctness (κ), the fraction of people accurately identified in a population. We then generalize the model to forecast how κ scales from small-scale experiments to the real world, for exact, sparse, and machine learning-based robust identification techniques. Despite having only two degrees of freedom, our method closely fits 476 correctness curves and strongly outperforms curve-fitting methods and entropy-based rules of thumb. Our work provides a principled framework for forecasting the privacy risks posed by identification techniques, while also supporting independent accountability efforts for AI-based biometric systems.

Abstract Background and methods E-health solutions are a promising tool to assist patients in self-managing symptoms for various diseases. This study aimed to assess the feasibility, reliability, usability, and satisfaction of a digital medical device (ZEMY) for patients’ self-monitoring of symptoms commonly experienced during breast cancer treatment and to enhance interaction with healthcare professionals. In this open-label, interventional, multicentre, single-arm clinical trial (NCT03558490), patients at all stages of breast cancer initiating oral and/or parenteral treatment were recruited at initiation of therapy and followed for 3 months. During treatment, the patients reported 9 symptoms (diarrhoea, nausea/vomiting, fever/febrile neutropenia, fatigue, pain, cutaneous and mucosal toxicities, hypertension, anxiety/depression) through the ZEMY application, which provided self-management recommendations and sent message alerts to healthcare professionals. To reach the primary feasibility endpoint, more than 50% of patients with one-sided 95% confidence interval (exact CI computed using Clopper-Pearson method) had to complete at least 3 symptoms entries, of which more than 60% complete until receiving a recommendation. Results Out of the 56 screened patients, 54 were included in the analysis between June 12th 2018 and January 11th 2019, and 52 completed the study. Over half of patients (31/54 [57.4%]) were feasibility responders, but this percentage was not significantly higher than the predefined minimum feasibility cut-off of 50%, as the lower limit of the one-sided 95% exact CI was 45.3%. Nonetheless, 87.0% of patients reported at least 3 symptoms with ZEMY and 66.0% had an entry completion rate ≥ 60%. Six of the 9 symptoms were reported at least once by more than 30% of the patients. The recommendations were considered relevant at least once for more than 80% of cases for each symptom. Patients were more satisfied (mean 10-point visual analogue scale score: 6.3 ± 2.9) with ZEMY than healthcare professionals (4.4 ± 1.5). The global patients’ quality of life remained stable during the study. Conclusions ZEMY provided satisfactory recommendations for the self-management of selected symptoms occurring during anti-cancer treatment and demonstrated good usability, but its feasibility was indemonstrable. Trail registration The trial was registered on June 14th 2018 at ClinicalTrails.gov (Trial Registration Number: NCT03558490).

Abstract Background In holobiont, microbiota is known to play a central role on the health and immunity of its host. Then, understanding the microbiota, its dynamic according to the environmental conditions and its link to the immunity would help to react to potential dysbiosis of aquacultured species. While the gut microbiota is highly studied, in marine invertebrates the hemolymph microbiota is often set aside even if it remains an important actor of the hemolymph homeostasis. Indeed, the hemolymph harbors the factors involved in the animal homeostasis that interacts with the microbiota, the immunity. In the Southwest Pacific, the high economical valued shrimp Penaeus stylirostris is reared in two contrasted sites, in New Caledonia (NC) and in French Polynesia (FP). Results We characterized the active microbiota inhabiting the hemolymph of shrimps while considering its stability during two seasons and at a one-month interval and evidenced an important microbial variability between the shrimps according to the rearing conditions and the sites. We highlighted specific biomarkers along with a common core microbiota composed of 6 ASVs. Putative microbial functions were mostly associated with bacterial competition, infections and metabolism in NC, while they were highly associated with the cell metabolism in FP suggesting a rearing site discrimination. Differential relative expression of immune effectors measured in the hemolymph of two shrimp populations from NC and FP, exhibited higher level of expression in NC compared to FP. In addition, differential relative expression of immune effectors was correlated to bacterial biomarkers based on their geographical location. Conclusions Our data suggest that, in Pacific shrimps, both the microbiota and the expression of the immune effectors could have undergone differential immunostimulation according to the rearing site as well as a geographical adaptative divergence of the shrimps as an holobiont, to their rearing sites. Further, the identification of proxies such as the core microbiota and site biomarkers, could be used to guide future actions to monitor the bacterial microbiota and thus preserve the productions.

BackgroundIntensive care units (ICUs) handle the most critical patients with a high risk of mortality. Due to those conditions, close monitoring is necessary and therefore, a large volume of data is collected. Collaborative ventures have enabled the emergence of large open access databases, leading to numerous publications in the field. ObjectiveThe aim of this scoping review is to identify the characteristics of studies using open access intensive care databases and to describe the contribution of these studies to intensive care research. MethodsThe research was conducted using 3 databases (PubMed–MEDLINE, Embase, and Web of Science) from the inception of each database to August 1, 2022. We included original articles based on 4 open databases of patients admitted to ICUs: Amsterdam University Medical Centers Database, eICU Collaborative Research Database, High time resolution ICU dataset, Medical Information Mart for Intensive Care (II to IV). A double-blinded screening for eligibility was performed, first on the title and abstract and subsequently on the full-text articles. Characteristics relating to publication journals, study design, and statistical analyses were extracted and analyzed. ResultsWe observed a consistent increase in the number of publications from these databases since 2016. The Medical Information Mart for Intensive Care databases were the most frequently used. The highest contributions came from China and the United States, with 689 (52.7%) and 370 (28.3%) publications respectively. The median impact factor of publications was 3.8 (IQR 2.8-5.8). Topics related to cardiovascular and infectious diseases were predominant, accounting for 333 (25.5%) and 324 (24.8%) articles, respectively. Logistic regression emerged as the most commonly used statistical model for both inference and prediction questions, featuring in 396 (55.5%) and 281 (47.5%) studies, respectively. A majority of the inference studies yielded statistically significant results (84.0%). In prediction studies, area under the curve was the most frequent performance measure, with a median value of 0.840 (IQR 0.780-0.890). ConclusionsThe abundance of scientific outputs resulting from these databases, coupled with the diversity of topics addressed, highlight the importance of these databases as valuable resources for clinical research. This suggests their potential impact on clinical practice within intensive care settings. However, the quality and clinical relevance of these studies remains highly heterogeneous, with a majority of articles being published in low–impact factor journals.

Abstract Ultrawide bandgap (UWBG) semiconductors offer new possibilities to develop power electronics. High voltage operation for the off‐state as well as high temperature stability of the devices in on‐state are required. More than AlGaN/GaN heterostructures, AlGaN/AlGaN heterostructures are promising candidates to meet these criteria. Furthermore, the possibility to choose the Al molar fraction of AlGaN paves the way to more tunable heterostructures. In this study, the electronic transport properties of AlGaN channel heterostructures grown on silicon substrates with various aluminum contents, focusing on the temperature dependence of the electron mobility, is investigated. Experimental results from Hall effect measurements are confronted with carrier scattering models and deep level transient spectroscopy analysis to quantify limiting effects. These results demonstrated the significant potential of Al‐rich AlGaN channel heterostructures grown on silicon substrates for high power and high temperature applications.

This work investigates the possibility of predicting the remaining lifetime of a power plant by making accelerated aging testing on monocrystalline silicon cells modules working on a photovoltaic plant for eleven years in France and compares the results with the same testing done on modules from the same batch eleven years ago when they were new. The paper focuses on damp heat results. It is found that the degradation behaviour of the modules exposed outdoor has a similar trend compared to the modules tested eleven years ago when they were new but with a two-to-three-times quicker degradation. Moreover, electroluminescence characterization highlights some degradation differences, especially at the edges of the solar cells. Modelling the lifetime through empirical damp heat model on the used modules predict that degradation may accelerate after 3 to 4 years contrary to what was concluded based on the initial modules testing results eleven years ago: no degradation linked to heat and humidity conditions should have happened before 30 years.

This work aims to perform an assessment of cell cracks impact on PV module’s performances. Cracks can occur during transportation, severe weather conditions such as hailstorms [1], poor installation practices and manufacturing [2]. Even with multiwire interconnection technologies, the impact of such defects can affect PV module’s performances as well as the energy yield and lifetime of a photovoltaic installation [3]. Moreover, cracks will leave the silicon edge unpassivated with a risk of being more sensitive to external stresses, especially on highly efficient technologies like TOPCon. The main objective of this work is studying the cracks impact on new module’s technology performance to quantify its impact on the production yield and forecast power plant performance. A laboratory testing sequence was performed on two different Glass/backsheet PV technologies: PERC and TOPCon. First, a cracking procedure was conducted to generate several cracks patterns on two batches of PV modules similar to the patterns observed on powerplants sites. An electrical characterization was then performed to carry out a first evaluation of power losses after the cracks. Moreover, several accelerated aging sequences were conducted on the cracked and reference modules to quantify the average losses after each accelerated aging test.

Background & Aims: Selective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide observational cohort ACABi-GERCOR-PRONOBIL. Methods: Inclusion criteria were advanced iCCA with limited or no extrahepatic disease, treated with first-line gemcitabine plus platinum chemotherapy +/- concurrent SIRT. All patients treated with chemotherapy and concurrent SIRT were included. To ensure groups’ similarity, a rigorous selection was applied to the chemo-only group, with exclusion of patients with liver involvement >50% and extrahepatic metastases. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR) and tumor resection rate. Propensity score and inverse probability of treatment weighting (IPTW) propensity approaches were used to address confounding factors between groups. Results: Between July 2007 and December 2023, 277 patients met the Real-SIRTCCA inclusion criteria, with 88 in the chemo-SIRT group and 189 in chemo-only group. Chemo-SIRT was associated with longer PFS (median = 10.8 vs. 5.5 months, hazard ratio [HR] 0.54, 95% CI 0.41-0.71, p

Burkholderia cepacia complex (Bcc) is an important group of opportunistic pathogens most frequently affecting patients with cystic fibrosis and responsible for life-threatening infections. Therapeutic options are limited owing to high levels of resistance of the organism, either intrinsic or acquired, to many antimicrobial agents. We describe here the successful treatment of a patient with cystic fibrosis who developed post-transplant lung abscesses and sternal osteitis caused by pan-resistant Burkholderia cenocepacia. He was treated with a combination of ceftazidime-avibactam, ciprofloxacin, meropenem, minocycline, sulfadiazine, and tobramycin. Repurposing multitarget drugs including old and new antibiotics, and their combinations with synergistic effects is a promising strategy to overcome clinical therapeutic impasses with difficult-to-treat-resistance (DTR) bacteria.

Aim: The aim of the present study was to define whether cardiac myosin contributes to energy conservation in the heart of hibernating mammals. Methods: Thin cardiac strips were isolated from the left ventricles of active and hibernating grizzly bears; and subjected to loaded Mant-ATP chase assays, X-ray diffraction and proteomics. Main findings: Hibernating grizzly bears displayed an unusually high proportion of ATP-conserving super-relaxed cardiac myosin molecules that are likely due to altered levels of phosphorylation and rod region stability. Conclusions: Cardiac myosin depresses the heart's energetic demand during hibernation by modulating its function.

Background & Aims: Biliary abnormalities in autoimmune hepatitis (AIH) and interface hepatitis in primary biliary cholangitis (PBC) occur frequently, and misinterpretation may lead to therapeutic mistakes with a negative impact on patients. This study investigates the use of a deep learning (DL)-based pipeline for the diagnosis of AIH and PBC to aid differential diagnosis. Methods: We conducted a multicenter study across six European referral centers, and built a library of digitized liver biopsy slides dating from 1997 to 2023. A training set of 354 cases (266 AIH and 102 PBC) and an external validation set of 92 cases (62 AIH and 30 PBC) were available for analysis. A novel DL model, the autoimmune liver neural estimator (ALNE), was trained on whole-slide images (WSIs) with H&E staining, without human annotations. The ALNE model was evaluated against clinico-pathological diagnoses and tested for interobserver variability among general pathologists. Results: The ALNE model demonstrated high accuracy in differentiating AIH from PBC, achieving an area under the receiver operating characteristic curve of 0.81 in external validation. Attention heatmaps showed that ALNE tends to focus more on areas with increased inflammation, associating such patterns predominantly with AIH. A multivariate explainable ML model revealed that PBC cases misclassified as AIH more often had ALP values between 1 × upper limit of normal (ULN) and 2 × ULN, coupled with AST values above 1 × ULN. Inconsistency among general pathologists was noticed when evaluating a random sample of the same cases (Fleiss’s kappa value 0.09). Conclusions: The ALNE model is the first system generating a quantitative and accurate differential diagnosis between cases with AIH or PBC. Impact and implications: This study demonstrates the significant potential of the autoimmune liver neural estimator model, a transformer-based deep learning system, in accurately distinguishing between autoimmune hepatitis and primary biliary cholangitis using digitized liver biopsy slides without human annotation. The scientific justification for this work lies in addressing the challenge of differentiating these conditions, which often present with overlapping features and can lead to therapeutic mistakes. In addition, there is need for quantitative assessment of information embedded in liver biopsies, which are currently evaluated on qualitative or semi-quantitative methods. The results of this study are crucial for pathologists, researchers, and clinicians, providing a reliable diagnostic tool that reduces interobserver variability and improves diagnostic accuracy of these conditions. Potential methodological limitations, such as the diversity in scanning techniques and slide colorations, were considered, ensuring the robustness and generalizability of the findings.

Summary: Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are extensively evaluated for the risk of suicidal behaviors or ideation; the influence of psychiatric history or obesity on this potential effect remains to be investigated. Therefore, we aimed to assess the association between GLP-1 RA and suicide or suicide attempt, considering these factors. Methods: Patients ≥18 y who died by suicide or were hospitalized for suicide attempt (2013–2021) with at least one GLP-1 RA dispensing within the 180 preceding days were selected from the French National Health Data System (SNDS). A case-time-control design compared, for each patient, GLP-1 RA exposure in the 30 days preceding the outcome (composite of suicide or suicide attempt) to three earlier 30-day reference periods. Potential exposure trend bias was controlled using up to five time-controls matched on age, sex, psychiatric history, obesity, calendar time. Analyses were adjusted for time-varying confounders. Finally dipeptidyl peptidase-4 (DPP-4) inhibitors were studied as negative controls for potential biases. Findings: This study included 1102 cases and 5494 controls. Mean case age was 57.4 years (SD 11.4); 44.6% were male, 67.6% had a recent psychiatric history and 51.3% had obesity. GLP-1 RA use was not associated with an increased risk of suicide or suicide attempt (OR, 0.62; 95% CI, 0.51–0.75), with consistent results for DPP-4 inhibitors (0.75; 0.67–0.84). Results obtained according to recent psychiatric history and obesity were comparable. Interpretation: This large nationwide case-time-control study provides reassurance about the short-term psychiatric safety of GLP-1 RA, showing no specific risk for patients with psychiatric disorders or obesity. Funding: French Medicines Agency.

Staphylococcus aureus is a pathogenic microorganism often found in animal-derived foods and is known for its ability to readily develop resistance to antibiotic treatments. This study was designed to determine the prevalence of S. aureus strains in raw milk and meat in Italy and to evaluate their antibiotic resistance profiles and biofilm production. Among the meat isolates, 41.67% were resistant to ampicillin, and 25% were methicillin-resistant S. aureus (MRSA). In milk, 20% of the isolates were resistant to gentamycin, while 5.71% were MRSA. The prevalence of multidrug-resistant strains was higher in meat (16.67%) compared to milk (5.71%). The biofilm formation capability was assessed in most of the isolates (80% in milk and 100% in meat). Representative strains exhibiting different antibiotic resistance profiles were all negative for the enterotoxin genes sea, seb, sec, sed, and see, but harbored potential virulence factors such as hemolytic activity, high pigmentation, low cell envelop permeability, charged and hydrophobicity. Finally, the interaction of representative strains with human Caco-2 intestinal cell line showed that most strains had an adhesion capacity. Our findings reveal that foodborne isolates of S. aureus present a considerable threat to consumers due to their production of virulence factors, which enhance their pathogenicity and increase the likelihood of antibiotic treatment failures.

Summary: Background: mRNA-based cancer vaccines show promise in triggering antitumour immune responses. To combine them with existing immunotherapies, the intratumoral immune microenvironment needs to be deeply characterised. Here, we test nanostructured lipid carriers (NLCs), the so-called Lipidots®, for delivering unmodified mRNA encoding Ovalbumin (OVA) antigen to elicit specific antitumour responses. Methods: We evaluated whether NLC OVA mRNA complexes activate dendritic cells (DCs) in vitro and identified the involved signalling pathways using specific inhibitors. We tested the anti-tumoral impact of Ova mRNA vaccine in B16-OVA and E.G7-OVA cold tumour-bearing C57Bl6 female mice as well as its synergy effect with an anti-PD-1 therapy by following the tumour growth and performing immunophenotyping of innate and adaptive immune cells. The intratumoral vaccine-related gene signature was assessed by RNA-sequencing. The immune memory response was assessed by re-challenging surviving treated mice with tumour cells. Findings: Our vaccine activates DCs in vitro through the TLR4/8 and ROS signalling pathways and induces specific T cell activation while exhibits significant preventive and therapeutic antitumour efficacy in vivo. A profound intratumoral remodelling of the innate and adaptive immunity in association with an increase in the gene expression of chemokines (Cxcl10, Cxcl11, Cxcl9) involved in CD8+ T cell attraction were observed in immunised mice. The combination of vaccine and anti-PD-1 therapy improves the rates of complete responses and memory immune responses compared to monotherapies. Interpretation: Lipidots® are effective platform for the development of vaccines against cancer based on mRNA delivery. Their combination with immune checkpoint blockers could counter tumour resistance and promote long-term antitumour immunity. Funding: This work was supported by Inserm Transfert, la Région Auvergne Rhône Alpes, FINOVI, and the French Ministry of Higher Education, research and innovation (LipiVAC, COROL project, funding reference N° 2102992411).

Summary: Background: Systemic mastocytosis (SM) diagnosis requires the presence of 3 minor criteria or 1 major and 1 minor criterion according to the WHO 2016 classification. The aim of this study was to characterize patients with 1 or 2 minor SM criteria including KIT 816 mutation and/or aberrant expression of CD2 and/or CD25 on bone marrow (BM) mast cells (MCs), but without MC activation syndrome (MCAS) criteria. Methods: We included eligible patients from two countries diagnosed between 2011 and 2021. These patients are reported herein as monoclonal MC with clinical significance (MMCS). MMCS patients were compared with 432 patients with indolent SM (ISM) and 51 with BM mastocytosis (BMM) from the CEREMAST database. Findings: Overall, 51 patients with MMCS were included. MMCS patients with (n = 29) or without (n = 22) KIT 816 mutation did not differ significantly with regard to the prevalence of anaphylaxis and basal tryptase level. Anaphylaxis, often in the context of hymenoptera venom allergy, was more frequent in MMCS than in ISM (78% vs 35%, respectively; p

Cefiderocol, a siderophore-conjugated cephalosporine, is a promising drug used to treat infection with carbapenem-resistant gram-negative bacteria. Here, we report a case of pneumonia induced by multiple gram-negative pathogens, including a carbapenem-resistant Klebsiella pneumoniae developing cefiderocol resistance within 32 days of cefiderocol therapy. Whole genome sequencing of three consecutive K. pneumoniae isolates revealed that the bacteria were isogenic and were carrying several broad-spectrum β-lactamases (blaNDM5 and blaCTX-M-15). Two isolates with elevated minimum inhibitory concentration against cefiderocol harbored mutations in genes encoding siderophore: one in the cirA gene and one in both the cirA and the fiu genes. The combination of a metallo-β-lactamase background and mutations in siderophore receptors was associated with phenotypic resistance to cefiderocol.

Understanding the interplay between biology and mechanics in tissue architecture is challenging, particularly in terms of 3D tissue organization. Addressing this challenge requires a biological model enabling observations at multiple levels from cell to tissue, as well as theoretical and computational approaches enabling the generation of a synthetic model that is relevant to the biological model and allowing for investigation of the mechanical stresses experienced by the tissue. Using a monolayer human colon epithelium organoid as a biological model, freely available tools (Fiji, Cellpose, Napari, Morphonet, or Tyssue library), and the commercially available Abaqus FEM solver, we combined vertex and FEM approaches to generate a comprehensive viscoelastic finite element model of the human colon organoid and demonstrated its flexibility. We imaged human colon organoid development for 120 hours, following the evolution of the organoids from an immature to a mature morphology. According to the extracted architectural/geometric parameters of human colon organoids at various stages of tissue architecture establishment, we generated organoid active vertex models. However, this approach did not consider the mechanical aspects involved in the organoids' morphological evolution. Therefore, we applied a finite element method considering mechanical loads mimicking osmotic pressure, external solicitation, or active contraction in the vertex model by using the Abaqus FEM solver. Integration of finite element analysis (FEA) into the vertex model achieved a better fit with the biological model. Therefore, the FEM model provides a basis for depicting cell shape, tissue deformation, and cellular-level strain due to imposed stresses. In conclusion, we demonstrated that a combination of vertex and FEM approaches, combining geometrical and mechanical parameters, improves modeling of alterations in organoid morphology over time and enables better assessment of the mechanical cues involved in establishing the architecture of the human colon epithelium.

Soil health and One Health are global concerns, necessitating the development of refined indicators for effective monitoring. In response, we present the Anaconda R Package, a novel tool designed to enhance the analysis of eDNA data for biomonitoring purposes. Employing a combination of different approaches, this package allows for a comprehensive investigation of species abundance and community composition under diverse conditions. This study applied the Anaconda package to examine the impact of two types of duration fire-fallow cropping systems, using natural forests as a reference, on soil fungal and bacterial communities in Maré Island (New Caledonia). Condition-specific taxa were identified, particularly pathogenic fungi and bacteria, demonstrating the importance of long-term fallowing efforts. Notably, this package also revealed the potential contributions of beneficial soil microbes, including saprophytes and plant-endophyte fungi, in suppressing soil-borne pathogens. Over-represented microbial ASVs associated with both plant and animal pathogens, including those of potential concern for human health, were identified. This underscores the importance of maintaining intrinsic balance for effective disease suppression. Importantly, the advanced analytical and statistical methods offered by this package should be harnessed to comprehensively investigate the effects of agricultural practice changes on soil health within the One Health framework. Looking ahead, the application of this method extends beyond the realm of One Health, offering valuable insights into various ecological scenarios. Its versatility holds promise for elucidating complex interactions and dynamics within ecosystems. By leveraging this tool, researchers can explore the broader implications of agricultural practice modifications, facilitating informed decisions and sustainable environmental management.

Abstract The boreal summer Atlantic Niño, the dominant mode of interannual climate variability in the equatorial Atlantic, exerts profound effects on local ecosystems and broader climate patterns, yet its prediction remains a long‐standing challenge. The short lifecycle of the Atlantic Niño and the lack of precursor signals beyond about one season lead time have hindered the development of forecasts with useful accuracy and lead time. In this study, we propose a new approach to Atlantic Niño forecasting that extends beyond the Atlantic region by incorporating longer‐lasting precursors in the Pacific associated with El Niño‐Southern Oscillation events. Using this prediction framework, we can hindcast the Atlantic Niño with skill up to three seasons in advance. Our results highlight the critical role of inter‐basin interactions in shaping regional and global climate patterns, and provide new hope for improving seasonal climate prediction capabilities in the tropical Atlantic. Plain Summary Despite extensive efforts made by the climate research community, the equatorial Atlantic region, in particular the Atlantic Niño phenomenon, consistently demonstrates poor seasonal forecasting capabilities. In this study, we propose a new approach to Atlantic Niño forecasting by using longer‐lasting precursors in the Pacific. The new prediction framework enables skillful prediction of the boreal summer Atlantic Niño events up to three seasons in advance. The results of our study have the possibility to reduce the existing gap in seasonal prediction for the equatorial Atlantic region by leveraging inter‐basin information, particularly benefitting vulnerable communities in the tropical Atlantic basin.

Introduction Surgical site infections (SSIs) are the second leading cause of healthcare-associated infections in Europe with the highest rates being reported in colorectal surgery (ranging from 9% to 30%). Surgical antibiotic prophylaxis (SAP) is one of the most efficient measures for SSI prevention and should be started before surgical incision. Cefoxitin is an antibiotic widely used as SAP for colorectal surgery, but its continuous administration is currently the subject of debate due to its potential pharmacokinetic advantages. Therefore, the aim of the PROPHYLOXITIN study is to demonstrate that a loading dose followed by continuous infusion of cefoxitin during colorectal surgery (intervention group) decreases the rate of SSI compared to an intermittent bolus administration (control group).Methods and analysis The PROPHYLOXITIN study is a superiority, prospective, double-blind, randomised and multicentre study of 2000 patients undergoing colorectal surgery. The primary objective is to demonstrate the superiority of a loading dose of cefoxitin followed by continuous infusion over intermittent bolus administration in reducing the proportion of SSIs within 30 days after colorectal surgery. Subjects will be randomised 1:1 using a secure web-based random-number generator to one of two study groups. Randomised allocation of treatment will be done by minimisation and stratified according to the centre, the localisation of surgery (colon or rectum) and the type of surgical procedure (laparoscopy or laparotomy).Ethics and dissemination This research has been approved by an independent ethics committee and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.Trial registration number EudraCT 2022-003262-20 and Clinical trial NCT05755789.