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Abstract A recent study reported exaggerated false positives by popular differential expression methods when analyzing large population samples. We reproduce the differential expression analysis simulation results and identify a caveat in the data generation process. Data not truly generated under the null hypothesis led to incorrect comparisons of benchmark methods. We provide corrected simulation results that demonstrate the good performance of dearseq and argue against the superiority of the Wilcoxon rank-sum test as suggested in the previous study.

Abstract Background We assessed the prognostic value of serological humoral markers measured one month after the last dose of the primary COVID-19 vaccine course for predicting the risk of severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection over the following six months in specific populations. Methods ANRS0001SCOV-POPART is a French nationwide multicenter prospective observational cohort study assessing the immune response to Covid-19 vaccines routinely administered to 11 subgroups of patients with chronic disease and a control group. Participants from the ANRS0001S COV-POPART were included if they received at least two doses of Covid-19 vaccine for the primary vaccine course, had measurements of anti-Spike, anti-receptor binding domain (RBD) IgG-specific or neutralizing antibodies one month after the end of the primary vaccine course, without being infected by SARS-CoV-2 before the measurement. SARS-CoV-2 infections defined by a positive PCR/antigenic test or seroconversion to detectable anti nucleocapsid antibodies were evaluated until the first COVID-19 booster injection. Cox proportional hazards models taking into account interval-censored data were implemented to estimate the association between each antibody level and the risk of SARS-CoV-2 infection. Predictive performances were evaluated by the area under the receiving operating characteristic curve (AUROC). Results Two thousand five hundred seventy adults from a specific population and 1,123 from the control group were included. The cumulative probabilities of SARS-CoV-2 infections at five months after serological measurement were 6.0% 95% confidence interval: [5.0; 7.9] and 10.1% 95% confidence interval: [8.3; 11.9], respectively. Higher levels of anti-Spike IgG antibody were associated with a lower risk of SARS-CoV-2 infections in the control group, but not in the specific populations. Among the specific populations, AUROC were 74.5%, 74.9%, and 72.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. AUROC were superior in the specific populations, 82.0%, 81.2%, and 81.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. Conclusions Vaccine-induced antibody response after the primary course of Covid-19 infection only moderately discriminated between participants developing a SARS-CoV-2 infection during the Omicron wave. Trial registration NCT04824651 (first posted: 2021-04-01).

Abstract Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination.

In July 2023, the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic. This report summarizes the rich discussions that occurred during the workshop.The workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data, social media, and wastewater monitoring. Significant advancements were noted in the development of predictive models, with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease trends. The role of open collaboration between various stakeholders in modelling was stressed, advocating for the continuation of such partnerships beyond the pandemic. A major gap identified was the absence of a common international framework for data sharing, which is crucial for global pandemic preparedness.Overall, the workshop underscored the need for robust, adaptable modelling frameworks and the integration of different data sources and collaboration across sectors, as key elements in enhancing future pandemic response and preparedness.

rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo are WHO-prequalified vaccination regimens against Ebola virus disease (EVD). Challenges associated with measuring long-term clinical protection warrant the evaluation of immune response kinetics after vaccination.Data from a large phase 2 randomized double-blind clinical trial (PREVAC) were used to evaluate waning of anti-Ebola virus (EBOV) glycoprotein (GP1,2) antibody concentrations after rVSVΔG-ZEBOV-GP or Ad26.ZEBOV, MVA-BN-Filo vaccination with linear mixed-effect regression models.After a post-vaccination peak, each vaccination strategy was associated with a decrease of anti-EBOV GP1,2 antibody concentrations with distinct kinetics, highlighting a less-rapid decline in antibody levels after vaccination by rVSVΔG-ZEBOV-GP. One year after administration of the vaccine, antibody concentrations were higher in children compared to adults for both vaccines, although with different effect sizes: 1.74-fold higher concentrations (95% confidence interval [CI] [1.48; 2.02]) for children 12–17 years old to 3.10-fold higher concentrations (95% CI [2.58; 3.69]) for those 1–4 years old compared to adults for Ad26.ZEBOV, MVA-BN-Filo versus 1.36-fold (95% CI [1.12; 1.61]) to 1.41-fold (95% CI [1.21; 1.62]) higher at month 12 higher than these values for adults, with relatively small changes from one age category of children to another for rVSVΔG-ZEBOV-GP. Antibody concentrations also differed according to geographical location, pre-vaccination antibody concentration, and sex.In combination with knowledge on memory response, characterization of the major determinants of immune response durability of both vaccinations may guide future EVD control protocols.Trial registration: ClinicalTrials.gov identifier: NCT02876328..

Abstract Background Alveolar soft part sarcoma is a rare tumour of soft tissues, mostly localized in muscles or deep soft tissues of the extremities. In rare occasions, this tumour develops in deep tissues of the abdomen or pelvis. Case presentation In this case report, we described the case of a 46 year old man who developed a primary splenic alveolar soft part sarcoma. The tumour displayed typical morphological alveolar aspect, as well as immunohistochemical profile notably TFE3 nuclear staining. Detection of ASPSCR1 Exon 7::TFE3 Exon 6 fusion transcript in molecular biology and TFE3 rearrangement in FISH confirmed the diagnosis. Conclusion We described the first case of primary splenic alveolar soft part sarcoma, which questions once again the cell of origin of this rare tumour.

BackgroundThe exposure to parasites may influence the immune response to vaccines in endemic African countries. In this study, we aimed to assess the association between helminth exposure to the most prevalent parasitic infections, schistosomiasis, soil transmitted helminths infection and filariasis, and the Ebola virus glycoprotein (EBOV GP) antibody concentration in response to vaccination with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in African and European participants using samples obtained from three international clinical trials.Methods/principal findingsWe conducted a study in a subset of participants in the EBL2001, EBL2002 and EBL3001 clinical trials that evaluated the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against EVD in children, adolescents and adults from the United Kingdom, France, Burkina Faso, Cote d'Ivoire, Kenya, Uganda and Sierra Leone. Immune markers of helminth exposure at baseline were evaluated by ELISA with three commercial kits which detect IgG antibodies against schistosome, filarial and Strongyloides antigens. Luminex technology was used to measure inflammatory and activation markers, and Th1/Th2/Th17 cytokines at baseline. The association between binding IgG antibodies specific to EBOV GP (measured on day 21 post-dose 2 and on Day 365 after the first dose respectively), and helminth exposure at baseline was evaluated using a multivariable linear regression model adjusted for age and study group. Seventy-eight (21.3%) of the 367 participants included in the study had at least one helminth positive ELISA test at baseline, with differences of prevalence between studies and an increased prevalence with age. The most frequently detected antibodies were those to Schistosoma mansoni (10.9%), followed by Acanthocheilonema viteae (9%) and then Strongyloides ratti (7.9%). Among the 41 immunological analytes tested, five were significantly (p < .003) lower in participants with at least one positive helminth ELISA test result: CCL2/MCP1, FGFbasic, IL-7, IL-13 and CCL11/Eotaxin compared to participants with negative helminth ELISA tests. No significant association was found with EBOV-GP specific antibody concentration at 21 days post-dose 2, or at 365 days post-dose 1, adjusted for age group, study, and the presence of any helminth antibodies at baseline.Conclusions/significanceNo clear association was found between immune markers of helminth exposure as measured by ELISA and post-vaccination response to the Ebola Ad26.ZEBOV/ MVA-BN-Filo vaccine regimen.Trial registrationNCT02416453, NCT02564523, NCT02509494. ClinicalTrials.gov.

Introduction and aimsThe organization of healthcare pathways for neurodevelopmental disorders (NDD) relies on different levels of expertise depending on the complexity of these disorders. NDDs affect between 8% and 15% of children. Historically, national recommendations and healthcare planning measures were initially devoted to autism spectrum disorders and were gradually extended to Attention deficit hyperactivity disorder (ADHD) and specific learning and development disorders. Private doctors play an increasing role in these pathways at different levels of care due to difficulties in organization, particularly in the health and social sector. The aim of this work was to evaluate the contribution of second-line private doctors in the diagnosis and care of children affected by NDD.MethodsA first series of surveys in 2016 evaluated the level of commitment of primary care pediatricians; this online national survey was repeated in 2023 among 1,430 members of the French Association of Ambulatory Pediatrics (Association Française de Pédiatrie Ambulatoire: AFPA) to assess their training, current and future involvement, and activity in NDD care. Analysis was performed by the main author using Epi-Info software.ResultsThe study identified in 2023 214 second-line private doctors (14% of all pediatricians in activity), of which 185 agreed to appear in a directory published the same year by the AFPA to facilitate referrals from other professionals. Sex ratio of responders is usual for paediatricians: 79.5%/20.5% (F/M), with a distribution among ages showing a slight increase of the age range between age 51–60 (30.5%). Our data indicate that in France in 2022, second-line private doctors made 48%–53% of NDD diagnoses, 24%–26.4% of follow-up consultations and declare to be accountable for 21% of initial prescriptions for Methylphenidate. Among these second-line doctors, 40% had completed a post-university degree on NDD, 74.3% had completed professional development training (PDT) and 85.2% had completed either or both types of training. Most doctors participating in the survey wanted to improve their level of practice, suggesting that in five years, the number of second-line private doctors will increase by 20% to 244 despite 24 planned retirements within the same period. This data probably underestimates the role of private doctors in NDD diagnosis, follow-up, and initial Methylphenidate prescriptions given the unfavourable working conditions (no financial compensation for long appointments, difficulty accessing paramedical and psychological assessments).ConclusionsOur data confirms that diagnosis and care coordination in the various presentations of NDD may rely on different types of practices and specializations: medical and social professionals, mental health professionals, but also a growing body of medical doctors involved in developmental and behavioural pediatrics. This data and reflection will be helpful for organizing healthcare in France or in other countries. Main study limitation relies in the self-declaration of MD's involvement in NDD and could not evaluate the activity of employed MD's from the social and medico social sector, nor be based on the national databases for prescription. It remains however the first attempt of characterization of medical activity at the national level in France for NDD.

Background: Non-pharmaceutical interventions (NPIs) and vaccines have been widely used to manage the COVID-19 pandemic. However, uncertainty persists regarding the effectiveness of these interventions due to data quality issues, methodological challenges, and differing contextual factors. Accurate estimation of their effects is crucial for future epidemic preparedness. Methods: To address this, we developed a population-based mechanistic model that includes the impact of NPIs and vaccines on SARS-CoV-2 transmission and hospitalization rates. Our statistical approach estimated all parameters in one step, accurately propagating uncertainty. We fitted the model to comprehensive epidemiological data in France from March 2020 to October 2021. With the same model, we simulated scenarios of vaccine rollout. Results: The first lockdown was the most effective, reducing transmission by 84 % (95 % confidence interval (CI) 83–85). Subsequent lockdowns had diminished effectiveness (reduction of 74 % (69–77) and 11 % (9–18), respectively). A 6 pm curfew was more effective than one at 8 pm (68 % (66–69) vs. 48 % (45–49) reduction), while school closures reduced transmission by 15 % (12–18). In a scenario without vaccines before November 2021, we predicted 159,000 or 168 % (95 % prediction interval (PI) 70-315) more deaths and 1,488,000 or 300 % (133-492) more hospitalizations. If a vaccine had been available after 100 days, over 71,000 deaths (16,507–204,249) and 384,000 (88,579–1,020,386) hospitalizations could have been averted. Conclusion: Our results highlight the substantial impact of NPIs, including lockdowns and curfews, in controlling the COVID-19 pandemic. We also demonstrate the value of the 100 days objective of the Coalition for Epidemic Preparedness Innovations (CEPI) initiative for vaccine availability.

Abstract The persistence of the long-term immune response induced by the heterologous Ad26.ZEBOV, MVA-BN-Filo two-dose vaccination regimen against Ebola has been investigated in several clinical trials. Longitudinal data on IgG-binding antibody concentrations were analyzed from 487 participants enrolled in six Phase I and Phase II clinical trials conducted by the EBOVAC1 and EBOVAC2 consortia. A model based on ordinary differential equations describing the dynamics of antibodies and short- and long-lived antibody-secreting cells (ASCs) was used to model the humoral response from 7 days after the second vaccination to a follow-up period of 2 years. Using a population-based approach, we first assessed the robustness of the model, which was originally estimated based on Phase I data, against all data. Then we assessed the longevity of the humoral response and identified factors that influence these dynamics. We estimated a half-life of the long-lived ASC of at least 15 years and found an influence of geographic region, sex, and age on the humoral response dynamics, with longer antibody persistence in Europeans and women and higher production of antibodies in younger participants.

Abstract Background Effectiveness of actions to reduce sugar-sweetened beverage (SB) consumption in children still needs to be improved. Furthermore, the growing concern about sustainable food systems encourages to develop sustainability-based interventions. The objective of this cluster randomised controlled trial is to evaluate the long-term effectiveness of nutrition- and environmental sustainability-based interventions on the reduction in SB intake and on the increase in tap water consumption in 3rd to 6th grade primary school children (8 to 11 years of age). Methods Forty-eight French-speaking Belgian primary schools (equivalent to around 3500 pupils involved in the evaluation) are randomised using a factorial plan: (i) control, (ii) nutrition-based intervention, (iii) sustainability-based intervention, and (iv) both. The interventions (encouragement of water breaks; provision of posters, leaflets, reusable cups, and glass bottles; website; meetings at school) were undertaken from February 2022 to June 2023. Evaluation includes questionnaires for the children and their parents on various determinants of dietary behaviour, a 4-day diary to collect information on the child’s beverage consumption, and audits at schools. The first evaluation was conducted in Spring 2021 before any intervention, with the two post-intervention evaluations being held in 2022 and 2023. The main quantitative judgement criterion will be the change over time in the mean SB consumption (in ml/day) in the intervention groups compared with the control group. Given the context of the research (school), the safety of the intervention, and the content of data collection, a consent was acknowledged as unnecessary by the Ethical Committee of the Faculty of Psychology (ULB; n°073/2021), but children and parents are explicitly informed of their right to refuse to fill in the questionnaires. Discussion Multicomponent interventions based on nutrition and on environmental sustainability, alone or mixed, will provide an original and topical insight into health promotion at school around dietary behaviours. The dissemination plan will enable to widely inform stakeholders, school staff, and families, in addition to the scientific community through the usual medium (articles, conferences), about the research findings in 2024–2025. Trial registration ISRCTN Registry ISRCTN99843102. Retrospectively registered on 25 May 2021

Abstract Background The current biodiversity crisis underscores the urgent need for sustainable management of the human uses of nature. In the context of sustainability management, adopting the ecosystem service (ES) concept, i.e., the benefits humans obtain from nature, can support decisions aimed at benefiting both nature and people. However, marine ecosystems in particular endure numerous direct drivers of change (i.e., habitat loss and degradation, overexploitation, pollution, climate change, and introduction of non-indigenous species) all of which threaten ecosystem structure, functioning, and the provision of ES. Marine ecosystems have received less attention than terrestrial ecosystems in ES literature, and knowledge on marine ES is hindered by the highly heterogeneous scientific literature with regard to the different types of marine ecosystem, ES, and their correlates. Here, we constructed a systematic map of the existing literature to highlight knowledge clusters and knowledge gaps on how changes in marine ecosystems influence the provision of marine ES. Method We searched for all evidence documenting how changes in structure and functioning of marine ecosystems affect the delivery of ES in academic and grey literature sources. In addition to Scopus, Web of Science, and Google Scholar, we searched 6 online databases from intergovernmental agencies, supranational or national organizations, and NGOs. We screened English-language documents using predefined inclusion criteria on titles, abstracts, and then full texts, without any geographic or temporal limitations. All qualifying literature was coded and metadata were extracted. No formal validity appraisal was undertaken. We identified knowledge clusters and gaps in terms of which ecosystem types, biodiversity components, or ES types have been studied and how these categories are linked. Review findings Our searches identified 41 884 articles published since 1968 of which 12 140 were duplicates; 25 747 articles were excluded at the title-screening stage, then 2774 at the abstract stage. After full-text screening, a total of 653 articles—having met the eligibility criteria—were included in the final database, spanning from 1977 to July 2021. The number of studies was unevenly distributed across geographic boundaries, ecosystem types, ES, and types of pressure. The most studied ecosystems were pelagic ecosystems on continental shelves and intertidal ecosystems, and deep-sea habitats and ice-associated ecosystems were the least studied. Food provision was the major focus of ES articles across all types of marine ecosystem (67%), followed by climate regulation (28%), and recreation (14%). Biophysical values were assessed in 91% of the analysed articles, 30% assessed economic values, but only 3% assessed socio-cultural values. Regarding the type of impact on ecosystems, management effects were the most studied, followed by overexploitation and climate change (with increase in seawater temperature being the most commonly assessed climate change pressure). Lastly, the introduction of non-indigenous species and deoxygenation were the least studied. Conclusions This systematic map provides, in addition to a database, knowledge gaps and clusters on how marine ecosystem changes impact ES provision. The current lack of knowledge is a threat to the sustainability of human actions and knowledge-based nature conservation. The knowledge gaps and clusters highlighted here could guide future research and impact the beneficial development of policy and management practices.

Understanding the dynamics of citizens' opinions, preferences, perceptions, and attitudes is pivotal in political science and essential for informed policymaking. Although highly sophisticated tools have been developed for analyzing these dynamics through surveys, outside the field of polarization, these analyses often focus on average responses, thereby missing important information embedded in other parameters of data distribution. Our study aims to fill this gap by illustrating how analyzing the evolution of both the mean and the distribution shape of responses can offer complementary insights into opinion dynamics. Specifically, we explore this through the French public's perception of defense issues, both before and after the onset of the war in Ukraine. Our findings underscore how routinely combining classical approaches with the use of existing tools for measuring distribution shapes can provide valuable perspectives for researchers and policymakers alike, by highlighting the nuanced shifts in public opinion that traditional methods might overlook.

Background Comparative genomic analyses to delineate gene evolutionary histories inform the understanding of organismal biology by characterising gene and gene family origins, trajectories, and dynamics, as well as enabling the tracing of speciation, duplication, and loss events, and facilitating the transfer of gene functional information across species. Genomic data are available for an increasing number of species from the genus Drosophila, however, a dedicated resource exploiting these data to provide the research community with browsable results from genus-wide orthology delineation has been lacking. Methods Using the OMA Orthologous Matrix orthology inference approach and browser deployment framework, we catalogued orthologues across a selected set of Drosophila species with high-quality annotated genomes. We developed and deployed a dedicated instance of the OMA browser to facilitate intuitive exploration, visualisation, and downloading of the genus-wide orthology delineation results. Results DrosOMA - the Drosophila Orthologous Matrix browser, accessible from https://drosoma.dcsr.unil.ch/ - presents the results of orthology delineation for 36 drosophilids from across the genus and four outgroup dipterans. It enables querying and browsing of the orthology data through a feature-rich web interface, with gene-view, orthologous group-view, and genome-view pages, including comprehensive gene name and identifier cross-references together with available functional annotations and protein domain architectures, as well as tools to visualise local and global synteny conservation. Conclusions The DrosOMA browser demonstrates the deployability of the OMA browser framework for building user-friendly orthology databases with dense sampling of a selected taxonomic group. It provides the Drosophila research community with a tailored resource of browsable results from genus-wide orthology delineation.

Wind resource assessment is a crucial step for the development of offshore wind energy. It relies on the installation of measurement devices, whose placement is an open challenge for developers. Indeed, the optimal sensor placement for field reconstruction is an open challenge in the field of sparse sampling. As for the application to offshore wind field reconstruction, no similar study was found, and standard strategies are based on semi-empirical choices. In this paper, a sparse sampling method using a Gaussian mixture model on numerical weather prediction data is developed for offshore wind reconstruction. It is applied to France's main offshore wind energy development areas: Normandy, southern Brittany and the Mediterranean Sea. The study is based on 3 years of Météo-France AROME's data, available through the MeteoNet data set. Using a Gaussian mixture model for data clustering, it leads to optimal sensor locations with regards to wind field reconstruction error. The proposed workflow is described and compared to state-of-the-art methods for sparse sampling. It constitutes a robust yet simple method for the definition of optimal sensor siting for offshore wind field reconstruction. The described method applied to the study area output sensor arrays of respectively seven, four and four sensors for Normandy, southern Brittany and the Mediterranean Sea. Those sensor arrays perform approximately 20 % better than the median Monte Carlo case and more than 30 % better than state-of-the-art methods with regards to wind field reconstruction error.

Vehicle interior air quality is an issue of growing interest among car manufacturers and customers. GC-MS is the benchmark method for the analysis of indoor air or material emissions. It is suitable for the quantification of target pollutants and the most abundant compounds. It fails, however, to uncover the true molecular complexity of these samples. In the present study, we describe the development of a TD-GC × GC-TOFMS method designed to detect polar and potentially odorous molecules in car material emissions. Attention is paid to the hyphenation of the thermodesorber and the gas chromatograph, both at software and hardware levels, and the constraints due to pressure limitations on the thermodesorber (evaluated at 414 kPa/60 psi at the end of the temperature ramp and at 138 kPa/20 psi at rest). A compromise was made for the 2D column length and diameter to balance separation and pressure (50 × 0.18 × 0.18 cm × mm × µm + 60 cm transfer line selected). On various materials, we were able to observe several hundreds of polar molecules, among them were between 75 and 150 odorants per material. This work lays the foundation for the widespread screening of potential odorants in car material emissions.

This study examines how motion influences turbulent velocity fluctuations utilizing measurements obtained from a wind lidar profiler. Onshore tests were performed using a WindCube v2.1 lidar, which was mobile and mounted on a hexapod to simulate buoy motion. Additionally, a fixed WindCube v2.1 lidar was used as a reference during these tests. To assess the motion-induced effects on velocity fluctuations measured by floating lidar systems, the root-mean-square error (RMSE) of velocity fluctuations obtained from the fixed and mobile lidars was calculated. A comprehensive wind dataset spanning 22.5 h was analyzed, with a focus on regular motions involving single-axis rotations and combinations of rotations around multiple axes. The investigation of single-axis rotations revealed that the primary influencing factor on the results was the alignment between the tilt direction of the mobile lidar and the wind direction. The highest RMSE values occurred when the tilt of the mobile lidar leans in the wind direction, resulting in pitch motion, whereas the lowest RMSE values were observed when the tilt of the mobile lidar leans perpendicular to the wind direction, resulting in roll motion. Moreover, the addition of motion around extra axes of rotation was found to increase RMSE.

Benedetti G. M., et al. (2022). Pioneras en geografía. Mujeres en la docencia e investigación en las carreras de Geografía de Universidades Argentinas. Editorial de la Facultad de Filosofía y Letras, Universidad de Buenos Aires. 88 p. ISBN: 978-987-8927-35-0

Multiple myeloma (MM) is associated with a wide variety of recurrent genomic alterations. The most common translocation in MM is t(11;14). In this retrospective, single-center, non-interventional study, patients’ bone marrow samples were examined at diagnosis and at relapse(s) following treatment with anti-myeloma regimens to determine whether t(11;14) status was stable over time. This stability cohort consisted of 272 patients, of whom 118 were t(11;14)-positive at diagnosis and 154 were negative. All patients in the stability cohort retained the same t(11;14) status at relapse that they had at diagnosis of MM. Sixteen patients who had t(11;14)-positive MM at diagnosis had multiple longitudinal assessments by fluorescence in situ hybridization (FISH) at relapse events and remained t(11;14)-positive across all timepoints. Patients who had t(11;14)-positive disease at diagnosis of monoclonal gammopathy of unknown significance or smoldering MM also retained t(11;14) positivity through MM diagnosis and relapse. The t(11;14) fusion patterns also remained constant for 90% of patients. For detection of t(11;14), results from FISH and next-generation sequencing (NGS) were compared to determine the rate of concordance between these two methods. This concordance cohort contained 130 patients, of whom 66 had t(11;14)-positive disease and 64 were t(11;14)-negative. In this sample set, the concordance between FISH- and NGS-based detection of t(11;14) was 100%. These results strongly suggest that the t(11;14) rearrangement remains stable during the full disease course in patients with MM and can be detected by FISH- and NGS-based methodologies.

Introduction: Although the physiological role of the C-terminal hydrolase domain of the soluble epoxide hydrolase (sEH-H) is well investigated, the function of its N-terminal phosphatase activity (sEH-P) remains unknown. Objectives: This study aimed to assess in vivo the physiological role of sEH-P. Methods: CRISPR/Cas9 was used to generate a novel knock-in (KI) rat line lacking the sEH-P activity. Results: The sEH-P KI rats has a decreased metabolism of lysophosphatidic acids to monoacyglycerols. KI rats grew almost normally but with less weight and fat mass gain while insulin sensitivity was increased compared to wild-type rats. This lean phenotype was more marked in males than in female KI rats and mainly due to decreased food consumption and enhanced energy expenditure. In fact, sEH-P KI rats had an increased lipolysis allowing to supply fatty acids as fuel to potentiate brown adipose thermogenesis under resting condition and upon cold exposure. The potentiation of thermogenesis was abolished when blocking PPARγ, a nuclear receptor activated by intracellular lysophosphatidic acids, but also when inhibiting simultaneously sEH-H, showing a functional interaction between the two domains. Furthermore, sEH-P KI rats fed a high-fat diet did not gain as much weight as the wild-type rats, did not have increased fat mass and did not develop insulin resistance or hepatic steatosis. In addition, sEH-P KI rats exhibited enhanced basal cardiac mitochondrial activity associated with an enhanced left ventricular contractility and were protected against cardiac ischemia–reperfusion injury. Conclusion: Our study reveals that sEH-P is a key player in energy and fat metabolism and contributes together with sEH-H to the regulation of cardiometabolic homeostasis. The development of pharmacological inhibitors of sEH-P appears of crucial importance to evaluate the interest of this promising therapeutic strategy in the management of obesity and cardiac ischemic complications.

In highly fragmented and relatively stable cold-seep ecosystems, species are expected to exhibit high migration rates and long-distance dispersal of long-lived pelagic larvae to maintain genetic integrity over their range. Accordingly, several species inhabiting cold seeps are widely distributed across the whole Atlantic Ocean, with low genetic divergence between metapopulations on both sides of the Atlantic Equatorial Belt (AEB, i.e. Barbados and African/European margins). Two hypotheses may explain such patterns: (i) the occurrence of present-day gene flow or (ii) incomplete lineage sorting due to large population sizes and low mutation rates. Here, we evaluated the first hypothesis using the cold seep mussels Gigantidas childressi, G. mauritanicus, Bathymodiolus heckerae and B. boomerang. We combined COI barcoding of 763 individuals with VIKING20X larval dispersal modelling at a large spatial scale not previously investigated. Population genetics supported the parallel evolution of Gigantidas and Bathymodiolus genera in the Atlantic Ocean and the occurrence of a 1-3 Million-year-old vicariance effect that isolated populations across the Caribbean Sea. Both population genetics and larval dispersal modelling suggested that contemporary gene flow and larval exchanges are possible across the AEB and the Caribbean Sea, although probably rare. When occurring, larval flow was eastward (AEB - only for B. boomerang) or northward (Caribbean Sea - only for G. mauritanicus). Caution is nevertheless required since we focused on only one mitochondrial gene, which may underestimate gene flow if a genetic barrier exists. Non-negligible genetic differentiation occurred between Barbados and African populations, so we could not discount the incomplete lineage sorting hypothesis. Larval dispersal modelling simulations supported the genetic findings along the American coast with high amounts of larval flow between the Gulf of Mexico (GoM) and the US Atlantic Margin, although the Blake Ridge population of B. heckerae appeared genetically differentiated. Overall, our results suggest that additional studies using nuclear genetic markers and population genomics approaches are needed to clarify the evolutionary history of the Atlantic bathymodioline mussels and to distinguish between ongoing and past processes.

En este libro, se considera la raza como la esencialización de un grupo humano en función de criterios biológicos y culturales; la raza es una categoría política, una construcción social fundada, en este caso, para justificar la esclavitud de los siglos XVI al XIX en tres regiones de plantaciones: los actuales estados de Virginia y Luisiana en el sur de Estados Unidos, y Cuba. El vínculo de la negritud con la esclavitud constituye el eje central de la investigación; justificó la sistematización de la esclavitud de las personas de color, así como la permanencia de este estatus y de la institución esclavista a lo largo de los siglos.

Because SARS-CoV-2 constantly mutates to escape from the immune response, there is a reduction of neutralizing capacity of antibodies initially targeting the historical strain against emerging Variants of Concern (VoC)s. That is why the measure of the protection conferred by vaccination cannot solely rely on the antibody levels, but also requires to measure their neutralization capacity. Here we used a mathematical model to follow the humoral response in 26 individuals that received up to three vaccination doses of Bnt162b2 vaccine, and for whom both anti-S IgG and neutralization capacity was measured longitudinally against all main VoCs. Our model could identify two independent mechanisms that led to a marked increase in measured humoral response over the successive vaccination doses. In addition to the already known increase in IgG levels after each dose, we identified that the neutralization capacity was significantly increased after the third vaccine administration against all VoCs, despite large inter-individual variability. Consequently, the model projects that the mean duration of detectable neutralizing capacity against non-Omicron VoC is between 348 days (Beta variant, 95% Prediction Intervals PI [307; 389]) and 587 days (Alpha variant, 95% PI [537; 636]). Despite the low neutralization levels after three doses, the mean duration of detectable neutralizing capacity against Omicron variants varies between 173 days (BA.5 variant, 95% PI [142; 200]) and 256 days (BA.1 variant, 95% PI [227; 286]). Our model shows the benefit of incorporating the neutralization capacity in the follow-up of patients to better inform on their level of protection against the different SARS-CoV-2 variants. Trial registration: This clinical trial is registered with ClinicalTrials.gov, Trial IDs NCT04750720 and NCT05315583.

Batteries of electric vehicles require appropriate cooling to allow for increased performances such as high energy density and fast charging capabilities. Immersion of the cells in a dielectric fluid provides substantial benefits in terms of safety and performance, but the selection of a relevant coolant remains a complex task and guidance to engineers in the field of vehicle electrification is sparce. This paper reviews the fluid properties which are considered most significant for this application, and provides an experimental comparison of the key properties of one candidate fluid under various aging conditions devised to reproduce several years of operation in a vehicle.

Abstract Background While there seems to be a consensus that a decrease in gut microbiome diversity is related to a decline in health status, the associations between respiratory microbiome diversity and chronic lung disease remain a matter of debate. We provide a systematic review and meta-analysis of studies examining lung microbiota alpha-diversity in patients with asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) or bronchiectasis (NCFB), in which a control group based on disease status or healthy subjects is provided for comparison. Results We reviewed 351 articles on title and abstract, of which 27 met our inclusion criteria for systematic review. Data from 24 of these studies were used in the meta-analysis. We observed a trend that CF patients have a less diverse respiratory microbiota than healthy individuals. However, substantial heterogeneity was present and detailed using random-effects models, which limits the comparison between studies. Conclusions Knowledge on respiratory microbiota is under construction, and for the moment, it seems that alpha-diversity measurements are not enough documented to fully understand the link between microbiota and health, excepted in CF context which represents the most studied chronic respiratory disease with consistent published data to link alpha-diversity and lung function. Whether differences in respiratory microbiota profiles have an impact on chronic respiratory disease symptoms and/or evolution deserves further exploration.

Summary: Background: This analysis evaluated the immune response to the two-dose, heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccine regimen, administered 56-days apart, from multiple African sites based on results from one analytic laboratory. Methods: Immunogenicity across three trials (EBL2002, EBL2004/PREVAC, EBL3001) conducted in East and West Africa is summarised. Vaccine-induced Ebola glycoprotein-binding antibody concentrations were analysed by Q2 Solutions laboratory at baseline, 21 days (EBL2002 and EBL3001) or 28 days (EBL2004) post-dose 2 (regimen completion), and 12 months post-dose 1 using the validated Filovirus Animal Nonclinical Group Ebola glycoprotein enzyme-linked immunosorbent assay (ELISA). Responders were defined as those with a >2.5-fold increase from baseline or the lower limit of quantification (LLOQ) if

La Scala Vent Field, near the Solomon Islands in the Pacific Ocean, comprises diffuse vents and vigorous black smokers and hosts large beds of stalked barnacles and bacterial mats at vent peripheries, according to ship-borne multi-beam echo sounding and remotely operated vehicle surveys.

The development of aquatic plant beds can obstruct boat traffic, hinder the practice of water activities, and impact the functioning of freshwaters. In order to mitigate their effects, mechanical removal is often the preferred management solution. The objective of this study was to test, in mesocosms, the effect of frequency (none, one, and two cuts) and cutting dates (May and/or July) on the regeneration and colonization capabilities of the aquatic plant Egeria densa, an invasive alien species in France. The cutting date had no effect on the capabilities of E. densa, but the two cuts significantly reduced the plant’s biomass. Removal produced numerous fragments, which exhibited very high survival and anchoring rates. However, summer removal produced fragments with lower regeneration and colonization abilities compared to fragments from spring cutting. Mechanical removal only temporarily reduced the biomass of the aquatic plant beds and could promote the formation of new beds from the fragments generated by management and dispersed by water flow.

Abstract Background The capacity to use data linkage and artificial intelligence to estimate and predict health indicators varies across European countries. However, the estimation of health indicators from linked administrative data is challenging due to several reasons such as variability in data sources and data collection methods resulting in reduced interoperability at various levels and timeliness, availability of a large number of variables, lack of skills and capacity to link and analyze big data. The main objective of this study is to develop the methodological guidelines calculating population-based health indicators to guide European countries using linked data and/or machine learning (ML) techniques with new methods. Method We have performed the following step-wise approach systematically to develop the methodological guidelines: i. Scientific literature review, ii. Identification of inspiring examples from European countries, and iii. Developing the checklist of guidelines contents. Results We have developed the methodological guidelines, which provide a systematic approach for studies using linked data and/or ML-techniques to produce population-based health indicators. These guidelines include a detailed checklist of the following items: rationale and objective of the study (i.e., research question), study design, linked data sources, study population/sample size, study outcomes, data preparation, data analysis (i.e., statistical techniques, sensitivity analysis and potential issues during data analysis) and study limitations. Conclusions This is the first study to develop the methodological guidelines for studies focused on population health using linked data and/or machine learning techniques. These guidelines would support researchers to adopt and develop a systematic approach for high-quality research methods. There is a need for high-quality research methodologies using more linked data and ML-techniques to develop a structured cross-disciplinary approach for improving the population health information and thereby the population health.

The nomenclature of 14 taxa from Central and Southern Europe within the Dianthus virgineus group is discussed. Dianthus aggericola Jord., D. collivagus Jord., D. consimilis Jord., D. orophilus Jord., D. saxicola Jord., D. juratensis Jord. are here lectotypified by specimens from the Jordan herbarium in LY, while D. godronianus Jord. by a specimen in P. Dianthus subacaulis Vill. is neotypified by a specimen collected on Mont Ventoux (S. France) and housed in MPU. For D. sylvestris Wulfen, a lectotype is here designated and its previous neotypification is discussed. Dianthus caryophyllus var. tenuifolius Moris, D. caryophyllus f. minor Moris and D. sylvestris var. garganicus Ten. are lectotypified by specimens housed in herbarium Moris (TO) and herbarium Tenore (K). Dianthus virgineus var. tergestinus Rchb. is lectotypified by a drawing from the Icones florae Germanicae & Helveticae, while D. contractus var. evolutus Lojac. is neotypified by a specimen in P. For each taxon the currently accepted name is provided including new synonymies. The type indication is followed by nomenclatural and taxonomic notes, in which the original material found is commented and the reasons for the identification of the types are discussed.

Abstract Background The current biodiversity crisis calls for an urgent need to sustainably manage human uses of nature. The Ecosystem Services (ES) concept defined as « the benefits humans obtain from nature » support decisions aimed at promoting nature conservation. However, marine ecosystems, in particular, endure numerous direct pressures (e.g., habitat loss and degradation, overexploitation, pollution, climate change, and the introduction of non-indigenous species) all of which threaten ecosystem structure, functioning, and the very provision of ES. While marine ecosystems often receive less attention than terrestrial ecosystems in ES literature, it would also appear that there is a heterogeneity of knowledge within marine ecosystems and within the different ES provided. Hence, a systematic map on the existing literature will aim to highlight knowledge clusters and knowledge gaps on how changes in marine ecosystems influence the provision of marine ecosystem services. This will provide an evidence base for possible future reviews, and may help to inform eventual management and policy decision-making. Methods We will search for all evidence documenting how changes in structure and functioning of marine ecosystems affect the delivery of ES, across scientific and grey literature sources. Two bibliographic databases, Scopus and Web of Science Core Collection, will be used with a supplementary search undertaken in Google scholar. Multiple organisational websites related to intergovernmental agencies, supra-national or national structures, and NGOs will also be searched. Searches will be performed with English terms only without any geographic or temporal limitations. Literature screening, against predefined inclusion criteria, will be undertaken on title, abstract, and then full texts. All qualifying literature will be subjected to coding and meta-data extraction. No formal validity appraisal will be undertaken. Indeed, the map will highlight how marine ecosystem changes impact the ES provided. Knowledge gaps will be identified in terms of which ecosystem types, biodiversity components, or ES types are most or least studied and how these categories are correlated. Finally, a database will be provided, we will narratively describe this evidence base with summary figures and tables of pertinent study characteristics.

En México, existió un sinnúmero de maneras de entender y aplicar la legislación agraria, de desviarse de ella o ignorarla, de un ejido a otro; las prácticas han podido ser ilegales, lo que no significa que no contaban con legitimidad social. Las reformas de 1992 al artículo 27 constitucional, que tenían como objetivos la aparición de una nueva forma de propiedad privada y la integración de las tierras al mercado, buscaron también normar estas prácticas y homogeneizar las relaciones de los ejidatarios con el territorio. En este trabajo, estudiaremos la historia de dos ejidos del centro del estado de Veracruz, mediante la revisión de los archivos agrarios y la realización de trabajo de campo. Ambos ejidos presentaron grandes diferencias a lo largo del tiempo en sus prácticas y su “manera de ser ejido”. Buscaremos entender si la reforma de 1992 ha cumplido con su papel de normalización y homogeneización, si ha sido un parteaguas en las prácticas relacionadas con las tierras ejidales y si ha acabado, no solamente con la propiedad social, sino también con la idea de comunidad.

In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.

BackgroundRobust and flexible infectious disease surveillance is crucial for public health. Event-based surveillance (EBS) was developed to allow timely detection of infectious disease outbreaks by using mostly web-based data. Despite its widespread use, EBS has not been evaluated systematically on a global scale in terms of outbreak detection performance. ObjectiveThe aim of this study was to assess the variation in the timing and frequency of EBS reports compared to true outbreaks and to identify the determinants of variability by using the example of seasonal influenza epidemic in 24 countries. MethodsWe obtained influenza-related reports between January 2013 and December 2019 from 2 EBS systems, that is, HealthMap and the World Health Organization Epidemic Intelligence from Open Sources (EIOS), and weekly virological influenza counts for the same period from FluNet as the gold standard. Influenza epidemic periods were detected based on report frequency by using Bayesian change point analysis. Timely sensitivity, that is, outbreak detection within the first 2 weeks before or after an outbreak onset was calculated along with sensitivity, specificity, positive predictive value, and timeliness of detection. Linear regressions were performed to assess the influence of country-specific factors on EBS performance. ResultsOverall, while monitoring the frequency of EBS reports over 7 years in 24 countries, we detected 175 out of 238 outbreaks (73.5%) but only 22 out of 238 (9.2%) within 2 weeks before or after an outbreak onset; in the best case, while monitoring the frequency of health-related reports, we identified 2 out of 6 outbreaks (33%) within 2 weeks of onset. The positive predictive value varied between 9% and 100% for HealthMap and from 0 to 100% for EIOS, and timeliness of detection ranged from 13% to 94% for HealthMap and from 0% to 92% for EIOS, whereas system specificity was generally high (59%-100%). The number of EBS reports available within a country, the human development index, and the country’s geographical location partially explained the high variability in system performance across countries. ConclusionsWe documented the global variation of EBS performance and demonstrated that monitoring the report frequency alone in EBS may be insufficient for the timely detection of outbreaks. In particular, in low- and middle-income countries, low data quality and report frequency impair the sensitivity and timeliness of disease surveillance through EBS. Therefore, advances in the development and evaluation and EBS are needed, particularly in low-resource settings.

This study proposes to examine, through the analysis of comic strips illustrating Antiquity, the stakes and the integration of different regimes of historicity, such as the Resistance or the struggle against the colonizer, which are carried by the comic imagery of magazines of communist obedience from Vaillant at the end of the 1940s to Pif Gadget at the end of the 1970s and the beginning of the 1980s. How do the related artistic influences inherent to the stories and fictions deployed around Spartacus permeate the hero and how, conversely, does the ideological marking of the newspaper cross over to colour these ancient representations? In the end, this work shows that if the communist magazine is committed, at the turn of the 1960s-1970s, it does not seem to deliberately insert Marxist markings or opinions into the heart of the historical comics dealing with Antiquity, following the example of Spartacus or Taranis.

Fishing is a risky activity that has been mainly studied in ergonomics in order to optimize safety on board. The current ecological situation has led us to take an interest in a new way of fishing in order, among other things, to design more environmentally friendly fishing gear. Until now, no study has focused on how fishermen use fishing gear. Based on in situ observations on board two fishing boats and on explicitating self-confrontation interviews with four sailors, this study describes the use of fishing nets at different levels of the fishing activity: macro, meso and micro. It highlights the mechanical stress suffered by fishing nets and the patterns of use mobilized by the deckhands during the unmeshing of the catch. The results help to enrich the specifications for the design of biodegradable fishing gear, to enlighten the design teams on real fishing activity, and to build an environment facilitating the transition from current fishing practices to more sustainable ones.

Understanding drivers of biodiversity patterns is essential to evaluate the potential impact of deep-sea mining on ecosystems resilience. While the South West Pacific forms an independent biogeographic province for hydrothermal vent fauna, different degrees of connectivity among basins were previously reported for a variety of species depending on their ability to disperse. In this study, we compared phylogeographic patterns of several vent gastropods across South West Pacific back-arc basins and the newly-discovered La Scala site on the Woodlark Ridge by analysing their genetic divergence using a barcoding approach. We focused on six genera of vent gastropods widely distributed in the region: Lepetodrilus, Symmetromphalus, Lamellomphalus, Shinkailepas, Desbruyeresia and Provanna. A wide-range sampling was conducted at different vent fields across the Futuna Volcanic Arc, the Manus, Woodlark, North Fiji, and Lau Basins, during the CHUBACARC cruise in 2019. The Cox1-based genetic structure of geographic populations was examined for each taxon to delineate putative cryptic species and assess potential barriers or contact zones between basins. Results showed contrasted phylogeographic patterns among species, even between closely related species. While some species are widely distributed across basins (i.e. Shinkailepas tollmanni, Desbruyeresia melanioides and Lamellomphalus) without evidence of strong barriers to gene flow, others are restricted to one (i.e. Shinkailepas tufari complex of cryptic species, Desbruyeresia cancellata and D. costata). Other species showed intermediate patterns of isolation with different lineages separating the Manus Basin from the Lau/North Fiji Basins (i.e. Lepetodrilus schrolli, Provanna and Symmetromphalus spp.). Individuals from the Woodlark Basin were either endemic to this area (though possibly representing intermediate OTUs between the Manus Basin and the other eastern basins populations) or, coming into contact from these basins, highlighting the stepping-stone role of the Woodlark Basin in the dispersal of the South West Pacific vent fauna. Results are discussed according to the dispersal ability of species and the geological history of the South West Pacific.

Understanding drivers of biodiversity patterns is essential to evaluate the potential impact of deep-sea mining on ecosystems resilience. While the South West Pacific forms an independent biogeographic province for hydrothermal vent fauna, different degrees of connectivity among basins were previously reported for a variety of species depending on their ability to disperse. In this study, we compared phylogeographic patterns of several vent gastropods across South West Pacific back-arc basins and the newly-discovered La Scala site on the Woodlark Ridge by analysing their genetic divergence using a barcoding approach. We focused on six genera of vent gastropods widely distributed in the region: Lepetodrilus, Symmetromphalus, Lamellomphalus, Shinkailepas, Desbruyeresia and Provanna. A wide-range sampling was conducted at different vent fields across the Futuna Volcanic Arc, the Manus, Woodlark, North Fiji, and Lau Basins, during the CHUBACARC cruise in 2019. The Cox1-based genetic structure of geographic populations was examined for each taxon to delineate putative cryptic species and assess potential barriers or contact zones between basins. Results showed contrasted phylogeographic patterns among species, even between closely related species. While some species are widely distributed across basins (i.e. Shinkailepas tollmanni, Desbruyeresia melanioides and Lamellomphalus) without evidence of strong barriers to gene flow, others are restricted to one (i.e. Shinkailepas tufari complex of cryptic species, Desbruyeresia cancellata and D. costata). Other species showed intermediate patterns of isolation with different lineages separating the Manus Basin from the Lau/North Fiji Basins (i.e. Lepetodrilus schrolli, Provanna and Symmetromphalus spp.). Individuals from the Woodlark Basin were either endemic to this area (though possibly representing intermediate OTUs between the Manus Basin and the other eastern basins populations) or, coming into contact from these basins, highlighting the stepping-stone role of the Woodlark Basin in the dispersal of the South West Pacific vent fauna. Results are discussed according to the dispersal ability of species and the geological history of the South West Pacific.

Abstract Suicidal thoughts and behaviours are prevalent among college students. Yet little is known about screening tools to identify students at higher risk. We aimed to develop a risk algorithm to identify the main predictors of suicidal thoughts and behaviours among college students within one-year of baseline assessment. We used data collected in 2013–2019 from the French i-Share cohort, a longitudinal population-based study including 5066 volunteer students. To predict suicidal thoughts and behaviours at follow-up, we used random forests models with 70 potential predictors measured at baseline, including sociodemographic and familial characteristics, mental health and substance use. Model performance was measured using the area under the receiver operating curve (AUC), sensitivity, and positive predictive value. At follow-up, 17.4% of girls and 16.8% of boys reported suicidal thoughts and behaviours. The models achieved good predictive performance: AUC, 0.8; sensitivity, 79% for girls, 81% for boys; and positive predictive value, 40% for girls and 36% for boys. Among the 70 potential predictors, four showed the highest predictive power: 12-month suicidal thoughts, trait anxiety, depression symptoms, and self-esteem. We identified a parsimonious set of mental health indicators that accurately predicted one-year suicidal thoughts and behaviours in a community sample of college students.

ABSTRACT Cellulose being the most abundant polysaccharide on earth, beta-glucosidases hydrolyzing cello-oligosaccharides are key enzymes to fuel glycolysis in microorganisms developing on plant material. In Streptomyces scabiei, the causative agent of common scab in root and tuber crops, a genetic compensation phenomenon safeguards the loss of the gene encoding the cello-oligosaccharide hydrolase BglC by awakening the expression of alternative beta-glucosidases. Here, we revealed that the BglC compensating enzyme BcpE2 was the GH3-family beta-glucosidase that displayed the highest reported substrate promiscuity and was able to release the glucose moiety of all tested types of plant-derived heterosides (aryl β-glucosides, monolignol glucosides, cyanogenic glucosides, anthocyanosides, and coumarin heterosides). BcpE2 structure analysis highlighted a large cavity in the PA14 domain that covered the active site, and the high flexibility of this domain would allow proper adjustment of this cavity for disparate heterosides. The exceptional substrate promiscuity of BcpE2 provides microorganisms a versatile tool for scavenging glucose from plant-derived nutrients that widely vary in size and structure. Importantly, scopolin was the only substrate commonly hydrolyzed by both BglC and BcpE2, thereby generating the potent virulence inhibitor scopoletin. Next to fueling glycolysis, both enzymes would also fine-tune the strength of virulence. IMPORTANCE Plant decaying biomass is the most abundant provider of carbon sources for soil-dwelling microorganisms. To optimally evolve in such environmental niches, microorganisms possess an arsenal of hydrolytic enzymatic complexes to feed on the various types of polysaccharides, oligosaccharides, and monosaccharides. In this work, structural, enzymatic, and expression studies revealed the existence of a “swiss-army knife” enzyme, BcpE2, that was able to retrieve the glucose moiety of a multitude of plant-derived substrates that vary in size, structure, and origin. This enzyme would provide the microorganisms with a tool that would allow them to find nutrients from any type of plant-derived material.

En este trabajo se estudian varios expedientes de la Comisión Agraria Mixta del Archivo General del Estado de Veracruz para conseguir información sobre la aplicación de la reforma agraria y la creación de ejidos (propiedad social) en el centro y el sureste del estado, durante las décadas veinte, treinta y cuarenta del siglo XX. Se busca en especial entender el papel que tuvieron los diferentes actores en el proceso de reparto: lo que representó la expropiación de sus propiedades para los hacendados y las distintas estrategias que adoptaron para quedarse con sus tierras; y por otra parte, lo que significó la atribución de una parcela para los ejidatarios, que hasta entonces siempre habían trabajado en tierras ajenas. Se estudia también la reconfiguración que se dio en los territorios después de la dotación, como resultado de la apropiación campesina y de los procesos físicos y simbólicos de cambio.

The definition of correlates of protection is critical for the development of next-generation SARS-CoV-2 vaccine platforms. Here, we propose a model-based approach for identifying mechanistic correlates of protection based on mathematical modelling of viral dynamics and data mining of immunological markers. The application to three different studies in non-human primates evaluating SARS-CoV-2 vaccines based on CD40-targeting, two-component spike nanoparticle and mRNA 1273 identifies and quantifies two main mechanisms that are a decrease of rate of cell infection and an increase in clearance of infected cells. Inhibition of RBD binding to ACE2 appears to be a robust mechanistic correlate of protection across the three vaccine platforms although not capturing the whole biological vaccine effect. The model shows that RBD/ACE2 binding inhibition represents a strong mechanism of protection which required significant reduction in blocking potency to effectively compromise the control of viral replication.

Summary: Background: There is an urgent need of a new generation of vaccine that are able to enhance protection against SARS-CoV-2 and related variants of concern (VOC) and emerging coronaviruses. Methods: We identified conserved T- and B-cell epitopes from Spike (S) and Nucleocapsid (N) highly homologous to 38 sarbecoviruses, including SARS-CoV-2 VOCs, to design a protein subunit vaccine targeting antigens to Dendritic Cells (DC) via CD40 surface receptor (CD40.CoV2). Findings: CD40.CoV2 immunization elicited high levels of cross-neutralizing antibodies against SARS-CoV-2, VOCs, and SARS-CoV-1 in K18-hACE2 transgenic mice, associated with viral control and survival after SARS-CoV-2 challenge. A direct comparison of CD40.CoV2 with the mRNA BNT162b2 vaccine showed that the two vaccines were equally immunogenic in mice. We demonstrated the potency of CD40.CoV2 to recall in vitro human multi-epitope, functional, and cytotoxic SARS-CoV-2 S- and N-specific T-cell responses that are unaffected by VOC mutations and cross-reactive with SARS-CoV-1 and, to a lesser extent, MERS epitopes. Interpretation: We report the immunogenicity and antiviral efficacy of the CD40.CoV2 vaccine in a preclinical model providing a framework for a pan-sarbecovirus vaccine. Fundings: This work was supported by INSERM and the Investissements d'Avenir program, Vaccine Research Institute (VRI), managed by the ANR and the CARE project funded from the Innovative Medicines Initiative 2 Joint Undertaking (JU).

Human papillomaviruses are common sexually transmitted infections, caused by a large diversity of genotypes. In the context of vaccination against a subgroup of genotypes, better understanding the role of genotype interactions and human sexual behavior on genotype dynamics is essential. Herein, we present an individual-based model that integrates realistic heterosexual partnership behaviors and simulates interactions between vaccine and non-vaccine genotypes. Genotype interactions were considered, assuming a previous vaccine-genotype infection shortened (competition) or extended (synergy) the duration of a secondary non-vaccine-genotype infection. Sexual behavior determined papillomavirus acquisition and transmission: only 19.5% of active individuals at most 1 partner r during the year, but > 80% of those with ≥ 2 partners, were infected before vaccine introduction. The pre-vaccination situation was consistent with all genotype interaction scenarios. These genotype interactions, despite being undetectable during the pre-vaccination era, markedly impacted genotype prevalence after vaccination started, with a significant increase/decrease of non-vaccine genotypes prevalence for respectively competitive/synergistic interactions. These prevalence changes were more pronounced in individuals with ≤ 3 partners per year (up to 30% of prevalence modification assuming 65% vaccine coverage) but barely visible for individuals with > 3 partners per year (at most 0.30%). Results suggest the presence of genotype interaction, which is consistent with the pre-vaccine situation, may impact the dynamics of non-vaccine genotypes, particularly in less active individuals.

Abstract High‐throughput sequencing of amplicons (HTSA) has been proposed as an effective approach to evaluate taxonomic and genetic diversity at the same time. However, there are still uncertainties as to how the results produced by different bioinformatics treatments impact the conclusions drawn on biodiversity and population genetics indices. We evaluated the ability of six bioinformatics pipelines to recover taxonomic and genetic diversity from HTSA data obtained from controlled assemblages. To that end, 20 assemblages were produced using 354 colonies of Botrylloides spp., sampled in the wild in ten marinas around Brittany (France). We used DNA extracted from preservative ethanol (ebDNA) after various time of storage (3, 6, and 12 months), and from a bulk of preserved specimens (bulkDNA). DNA was amplified with primers designed for targeting this ascidian genus. Results obtained from HTSA data were compared with Sanger sequencing on individual zooids (i.e., individual barcoding). Species identification and relative abundance determined with HTSA data from either ebDNA or bulkDNA were similar to those obtained with traditional individual barcoding. However, after 12 months of storage, the correlation between HTSA and individual‐based data was lower than after shorter durations. The six bioinformatics pipelines were able to depict accurately the genetic diversity using standard population genetics indices (HS and FST), despite producing false positives and missing rare haplotypes. However, they did not perform equally and dada2 was the only pipeline able to retrieve all expected haplotypes. This study showed that ebDNA is a nondestructive alternative for both species identification and haplotype recovery, providing storage does not last more than 6 months before DNA extraction. Choosing the bioinformatics pipeline is a matter of compromise, aiming to retrieve all true haplotypes while avoiding false positives. We here recommend to process HTSA data using dada2, including a chimera‐removal step. Even if the possibility to use multiplexed primer sets deserves further investigation to expand the taxonomic coverage in future similar studies, we showed that primers targeting a particular genus allowed to reliably analyze this genus within a complex community.

Abstract Background Weight gain (mainly gain of fat mass) occurs quickly after successful kidney transplantation and is associated with metabolic complications (alterations of glycaemic control, hyperlipidaemia). Determinants of weight gain are multifactorial and are mainly related to the transplant procedure itself (glucocorticoid use, increased appetite). In the modern era of transplantation, one challenge is to limit these metabolic alterations by promoting gain of muscle mass rather than fat mass. This prospective study was performed to assess determinants of fat mass, fat-free mass and body cell mass changes after kidney transplantation with a focus on physical activity and nutritional behaviour before and after transplantation. Methods Patients were included at the time of listing for deceased donor kidney transplantation. Body composition was determined using dual X-ray absorptiometry and bioimpedance spectroscopy to assess fat mass, fat-free mass and body cell mass (= fat-free mass − extracellular water) at the time of inclusion, 12 months later, and 1, 6, 12 and 24 months after transplantation. Recall dietary data and physical activity level were also collected. Results Eighty patients were included between 2007 and 2010. Sixty-five had a complete 24-month follow-up after kidney transplantation. Fat mass, fat-free mass and body cell mass decreased during the waiting period and early after kidney transplantation. The nadirs of body cell mass and fat-free mass occurred at 1 month and the nadir for fat mass occurred at 6 months. Maximum levels of all parameters of body composition were seen at 12 months, after which body cell mass and fat-free mass decreased, while fat mass remained stable. In multivariate analysis, male recipients, higher physical activity level and lower corticosteroid dose were significantly associated with better body cell mass recovery after kidney transplantation. Conclusions Lifestyle factors, such as physical activity level, together with low dose of corticosteroids seem to influence body composition evolution following kidney transplantation with recovery of body cell mass. Specific strategies to promote physical activity in kidney transplant recipients should be provided before and after kidney transplantation.

Abstract Natural killer (NK) cells are implicated among immune effectors after vaccination against viral pathogens, including Ebola virus. The two-dose heterologous Ebola virus vaccine regimen, adenovirus type 26.ZEBOV followed by modified vaccinia Ankara-BN-Filo (EBOVAC2 consortium, EU Innovative Medicines Initiative), induces NK cell activation and anti-Ebola glycoprotein (GP) antibody-dependent NK cell activation post-dose 1, which is further elevated post-dose 2. Here, in a multicentre, phase 2 clinical trial (EBL2001), we demonstrate durable ex vivo NK cell activation 180 days after dose 2, with responses enriched in CD56bright NK cells. In vitro antibody-dependent responses to immobilised Ebola GP increased after dose 1, and remained elevated compared to pre-vaccination levels in serum collected 180 days later. Peak NK cell responses were observed post-dose 2 and NK cell IFN-γ responses remained significantly elevated at 180 days post-dose 2. Individual variation in NK cell responses were influenced by both anti-Ebola GP antibody concentrations and intrinsic interindividual differences in NK cell functional capacity. In summary, this study demonstrates durable NK cell responses after Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccination and could inform the immunological evaluation of future iterations of the vaccine regimen and vaccination schedules.