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A DNA barcode library for Culex mosquitoes (Diptera: Culicidae) of South America with the description of two cryptic species of subgenus Melanoconion
No full textInternational audienceAmong mosquitoes (Diptera: Culicidae), the genus Culex Linnaeus is one of the most diverse in the world and includes numerous known vector species of parasites and viruses to humans. Morphological identification of Culex species is notoriously difficult and relies mostly on the examination of properly dissected male genitalia which largely prevents female and immature identification during entomological, ecological or arboviral surveys. The aims of this study were (i) to establish a DNA barcode library for Culex mosquitoes of French Guiana based on the mitochondrial gene cytochrome c oxidase I (COI) marker, (ii) to compare three approaches of molecular delimitation of species to morphological identification, (iii) to test the effectiveness of the COI marker at a broader geographical scale across South America, and (iv) to discuss the internal classification of the genus Culex as regard to our phylogenetic analysis. Mosquitoes used in this study were sampled in French Guiana between 2013 and 2023. We provide 246 COI sequences for 90 morphologically identified species of Culex , including five new country records and two newly described species. Overall, congruence between morphological identification and molecular delimitations using the COI barcode was high. The Barcode of Life Data clustering approach into Barcode Index Numbers gives the best result in terms of species delimitation. Inconsistencies between morphological identification and molecular delimitation can be explained by introgression, incomplete lineage sorting, imperfect taxonomy or the effect of geographical gap in sampling. This increases by almost two-fold the number of mosquito species for which a DNA barcode is available in French Guiana, including 75% of the Culex species currently known in the territory. Finally, this study confirms the usefulness of the COI barcode in identifying Culex of South America, but also points the limits of this marker for some groups of species within the subgenera Culex and Melanoconion
Étude de l'hétérogénéité des clones mutés FLT3 dans la leucémie aiguë myéloïde et implication dans la réponse au traitement
No full textNPM1 and FLT3-ITD mutations are the most commonly detected at acute myeloid leukemia (AML) diagnosis.NPM1-mutated AMLs have a favorable outcome. However, they display highly heterogeneous co-mutations and phenotypes, which can influence both prognosis and response to treatment. To explore the link between somatic mutations and phenotypic differentiation, we used a multi-omics single-cell sequencing platform on 11 NPM1-mutated AML diagnostic samples. Our analysis revealed unique associations between co-mutations and surface protein expression. Although these associations were patient-specific, they allowed the enrichment of genetic subclones by cell sorting,paving the way for the functional characterization of minority genetic clones.Since 2017, FLT3-mutated patients have been treated in the first-line setting with a combination of intensive chemotherapy (ICT) and the FLT3-inhibitor midostaurin (MIDO). Although the addition of MIDO has improved overall survival, complete remission rates remain close to 60-70%, and relapses still occur in over 40% of cases.To identify the underlying mechanisms of resistance, we conducted a retrospective,multicenter study including 150 relapsed or refractory (R/R) patients harboring FLT3-ITD (n = 130) and/or FLT3-TKD (n = 26) at diagnosis as assessed by fragment analysis. Patients were treated in front-line with either ICT and MIDO (n = 54) or ICT alone (n = 96). For the first time, we examined the evolution of FLT3-ITD clones between diagnosis and R/R disease with a high-throughput sequencing approach allowing the detection of FLT3-ITD microclones (allelic ratio < 0.05). We demonstrated that the addition of MIDO to ICT reduced the FLT3-ITD persistence rate at R/R disease.In patients receiving ICT and MIDO, the presence of several FLT3-ITD clones at diagnosis was associated with a higher probability of retaining a positive FLT3-ITDstatus at R/R disease. Considering both treatment groups, if only 24% of FLT3-ITDmicroclones were retained at relapse, 43% of these became macroclones. Together,these results identify some parameters influencing the fitness of FLT3-ITD clones and highlight the importance of using sensitive techniques for FLT3-ITD screening inclinical practice.Les mutations de NPM1 et les mutations FLT3-ITD sont les plus fréquemment mises en évidence au diagnostic de leucémie aiguë myéloïde (LAM). Les LAM mutées NPM1 ont un pronostic globalement favorable. Toutefois, elles présentent des co-mutations et des phénotypes très hétérogènes, susceptibles d’influencer le pronostic ainsi que la réponse au traitement. Afin d’explorer le lien entre les mutations somatiques et la différenciation phénotypique, nous avons utilisé une plateforme de séquençage unicellulaire multi-omique chez 11 échantillons diagnostiques de LAM mutées NPM1. Notre analyse a mis en évidence des associations spécifiques entre les co-mutations et l’expression de protéines de surface. Même si ces associations étaient propres à chaque patient, elles ont permis l'enrichissement en sous-clones génétiques spécifiques par tri cellulaire et ouvrent ainsi la voie à la caractérisation fonctionnelle des clones génétiques minoritaires.Depuis 2017, les patients mutés FLT3 sont traités en première ligne par une association de chimiothérapie intensive (CTI) et de midostaurine (MIDO), un inhibiteur de FLT3. Bien que l’ajout de la MIDO ait permis d’améliorer la survie des patients, lestaux de rémission complète obtenus demeurent proches de 60-70% et les rechutes surviennent encore dans plus de 40% des cas. Afin d’identifier les mécanismes de résistance à l’oeuvre, nous avons réalisé une étude rétrospective et multicentrique incluant 150 patients en rechute ou réfractaires (R/R) présentant une mutation FLT3-ITD (n = 130) et/ou FLT3-TKD (n = 26) au diagnostic en analyse de fragments. Les patients ont été traités en première ligne soit par l’association CTI et MIDO (n = 54)soit uniquement par CTI (n = 96). Pour la première fois, nous avons étudié l’évolution des clones FLT3-ITD entre le diagnostic et le stade R/R à l’aide d’une approche de séquençage à haut débit permettant d’identifier les microclones FLT3-ITD (ratioallélique < 0,05). Nous avons démontré que l’ajout de MIDO à la CTI diminue le taux de persistance de la mutation FLT3-ITD au stade R/R. Chez les patients traités par CTI et MIDO, la présence de plusieurs clones FLT3-ITD au diagnostic était associée à une probabilité plus importante de conserver un statut FLT3-ITD positif au stade R/R.Au sein des deux groupes de traitement combinés, bien que seulement 24% des microclones FLT3-ITD aient été conservés à la rechute, 43% d’entre eux sont devenus des macroclones. Au total, ces résultats identifient des paramètres influençant l’évolution des clones FLT3-ITD et soulignent l’importance d’utiliser des techniques sensibles pour rechercher les mutations FLT3-ITD en pratique clinique
Should We Transplant Candidates With a Positive SARS-CoV-2 RT-PCR Test?
No full textInternational audienceBackground. It remains unclear whether physicians should accept transplantation offers for candidates with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test due to the potential risk of severe infection after initiating immunosuppressive therapy. Methods. A multicenter observational study was conducted in 19 French solid organ transplantation units. Patients on the waiting list for liver or kidney transplants who had a positive SARS-CoV-2 reverse transcription polymerase chain reaction nasopharyngeal swab at the time of transplantation were recorded. Results. Sixty-five patients were included. The recipients were predominantly men (n = 40; 62%) with a mean age of 55.4 y (SD = 16.5). On the day of transplantation, 2 patients exhibited symptoms compatible with COVID-19. The majority of patients (n = 55; 85%) underwent thoracic imaging, with only 3 patients showing imaging results compatible with COVID-19. Ten patients (28%) had a cycle threshold value <30. Anti–SARS-CoV-2 spike protein serology within 3 mo before transplantation was available for 36 patients; only 2 patients were seronegative. Due to COVID-19, physicians adapted the immunosuppressive therapy for 16 patients (25%). Specific antiviral therapy was used for 15 patients (23%), primarily remdesivir (n = 12). Overall, the majority of patients did not receive any adjustment of immunosuppressive therapy or antiviral treatment (n = 36; 55%). The outcomes were generally favorable even for patients with the lowest cycle threshold values, indicating a high viral load. Four patients died during follow-up, although none of these deaths were attributable to COVID-19. Conclusions. Transplantation appears to be safe for patients who are asymptomatic or have mild symptoms, reassuring thoracic imaging, and a history of anti–SARS-CoV-2 infection and/or immunization
Whole-genome sequencing revealed a novel structural variant in COL4A4 causing autosomal dominant Alport syndrome: A case report
No full textInternational audienceNext-generation sequencing has substantially transformed the genomic diagnosis of individuals affected by inherited renal disorders. Indeed, accurate and rapid diagnostic for patients with suspected genetic kidney diseases is not only important for prognosis and patient management but also for family counseling. Alport syndrome, a genetic disease primarily affecting the basement membrane, is characterized by hematuria, progressive kidney failure, hearing impairment, as well as ocular abnormalities and stems from mutations in genes encoding type IV collagen. In this study, we show the benefit of whole-genome sequencing for the molecular diagnosis of a dominant form of Alport syndrome by identifying a novel heterozygous pathogenic structural variant in a family with three affected members. This case underscores the potential of whole-genome sequencing as a frontline diagnostic approach for inherited kidney diseases and further indicates that structural variations represent an important cause of monogenic disorders
Role of Genomic, Economic, and Demographic Disparities in Mpox Epidemic in Africa: A Retrospective Cross-Country Analysis
No full textInternational audienceTo investigate the role of epidemic predictors in the mpox outbreak in Africa. This was a retrospective analysis of national-level mpox surveillance data from 20 mpox-affected African countries from January through December 2024. Predictors included viral clades, gross domestic product (GDP) per capita, and population density. A negative binomial regression model estimated the incidence rates ratio (IRR) [95% confidence interval] for mpox incidence and mortality. Random forest models assessed the influence of each predictor in the epidemic dynamic. Clade II was associated with lower mpox incidence (IRR = 0.15 [0.02-0.97]) and mortality (IRR = 0.09 [0.01-1.72]) compared to Clade I. GDP per capita was associated with a 95% reduction in cases count per US $1000 (IRR = 0.05 [0.38-0.74]). Population density was not significantly associated with mpox incidence or mortality. Random forest analysis confirmed GDP per capita as the strongest predictor of mpox burden. The 2024 mpox epidemic highlights how countries with low GDP per capita and Clade I face greater outbreak burdens. Strengthening health systems and addressing poverty as a key social determinant of health through a multisectoral approach are essential to ensure equitable outbreak prevention, control, and long-term resilience.</div
Background-invariant re-identification of dogs from camera-trap videos in non-controlled environments
No full textSource Agritrop Cirad (https://agritrop.cirad.fr/616519/)International audienceThis paper addresses the general problem of re-identification in natural conditions with multiple camera traps, poor video quality and small datasets. We focus on generalizable re-identification of dogs in cross-camera setups, adapting from short-term to long-term scenarios. Long-term re-identification across multiple cameras presents challenges due to variations in background, camera angles, and lighting conditions. While realistic, few animal re-identification methods are tested under such settings, mainly due to the lack of datasets and high complexity of annotation. Short-term datasets are often used to train re-identification networks, since they can be simply generated through web scraping algorithms. We introduce two publicly available datasets: the YT-BB-Dog, a short-term dataset with 2723 dogs from YouTube videos, and the Sibetan, a long-term dataset featuring 59 dogs recorded over 5 days and 12 cameras placed in Sibetan, Bali, Indonesia. Our goal is to use the YT-BB-Dog to train a feature extractor robust to covariate shifts, enabling better generalization in unknown domains. Our experiments revealed that state-of-the-art (SOTA) methods trained on the YT-BB-Dog are heavily influenced by background variations and perform poorly on complex scenarios like Sibetan. To address this, we propose Background Invariant Feature extractOR (BIFOR), a three-step method that leverages a novel mini-batch sampling technique with triplet loss and online hard mining. BIFOR achieves SOTA performance on Sibetan, improving rank-1 accuracy of the baseline by more than 9%. We also present a complete pipeline combining detection, tracking, and re-identification based on BIFOR
Spatial self-organization of cancer stem cell niches revealed by live single-cell imaging
No full textInternational audienceBackground: Phenotypic plasticity is a major factor in tumor heterogeneity and treatment resistance. In particular, cancer stem cells (CSCs) represent a small subpopulation within tumors that possesses self-renewal and tumor-forming capabilities. Understanding reprogramming, maintenance, and lineage properties of CSCs requires dedicated tools to disentangle the respective influences of phenotypic inheritance and cell-cell interactions.Methods: Here, we set up ultra-wide field microscopy to image breast cancer cell lines expressing a stemness fluorescent reporter over several days. The fluorescent reporter distinguishes three phenotypes: CSCs, cancer differentiated cells (CDCs), and intermediate/transiting cancer cells (iCCs).Results: Spatial statistics indicate significant zonation in which CSCs cluster together and are spatially separated from CDCs, forming patterns resembling niches. Surprisingly, single-cell time series reveal spontaneous reprogramming events from CDC to CSC even in unperturbed populations. We identify that such transitions are prone to arise during the cell cycle. Moreover, lineage analysis shows that the phenotype is partially inherited from ancestor cells. However, such heredity is not sufficient to explain the spatial properties of the cell population, which also depend on cell-cell interactions. Indeed, we find that phenotypic transitions of cancer cells are influenced by the phenotypic state of neighboring cells. Reprogramming into CSCs is respectively promoted and inhibited by the presence of CSCs and CDCs in the neighborhood.Conclusions: Altogether, our results disentangle how phenotypic inheritance and intercellular interactions orchestrate the spatio-temporal self-organization of cancer cell heterogeneity, maintaining a subpopulation of CSCs within niches
Mapping unconventional Leishmania in human and animal leishmaniasis: A scoping review protocol on pathogen diversity, geographic distribution and knowledge gaps
No full textSource Agritrop Cirad (https://agritrop.cirad.fr/616272/)International audienceIntroduction: Leishmaniases are a vector-borne parasitic diseases with diverse clinical manifestations involving multiple Leishmania species and animal hosts. While most leishmaniasis cases are caused by a few well characterized Leishmania species, reports describe infections by unconventional or emerging Leishmania taxa, atypical clinical presentations from classical species, and occurrences of atypical Leishmania in animal hosts. These underrecognized infections present diagnostic and therapeutic challenges and are rarely reflected in surveillance systems or clinical guidelines. A systematic mapping of this evolving landscape is needed to guide future diagnostics, policy, and research priorities. Methods and analysis: Following the Joanna Briggs Institute (JBI) methodology and PRISMA-ScR guidelines, we will search PubMed, Embase, Cochrane Library (CENTRAL), PROSPERO, Web of Science, and Global Index Medicus, as well as relevant grey literature. Eligible studies will include human cases with clinical presentations that diverge from those typically associated with well-characterized Leishmania species, reports involving unconventional or emerging Leishmania species, and animal cases of veterinary relevance caused by non-classical species, regardless of study design. Dual independent screening of records and data extraction using a standardized charting form will be conducted. Discrepancies between reviewers will be resolved by consensus. Data will be summarized descriptively through tables, figures, and thematic synthesis. Research gaps will be identified to inform future studies and public health strategies. Dissemination: This review will use data from published sources and findings will be disseminated through publication in a peer-reviewed journal, presentations at scientific conferences, and sharing with relevant stakeholders. The results are intended to inform clinicians, researchers, and policymakers about the evolving landscape of leishmaniasis and to highlight priorities for future research and surveillance
Evolving paradigms in pulmonary hypertension: Highlights of the 6th French Pulmonary Hypertension Network Meeting
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Drivers of rabies post-exposure prophylaxis noncompletion in Cambodia
No full textSource Agritrop Cirad (https://agritrop.cirad.fr/616209/) * Autres projets (id;sigle;titre): FEF2025-31;;(FRA) VIRAGE//International audienceBackground: Achieving the “Zero by 30” goal—zero human deaths due to dog-mediated rabies by 2030—depends heavily on the timely and complete administration of post-exposure prophylaxis vaccination (PEPV) to exposed individuals. This study aims to assess trends and evaluate rabies PEPV noncompletion following the introduction of the abridged 1-week protocol, and identify its drivers in Cambodia, which bears a high rabies burden. Methodology: A retrospective analysis of patients attending the three Institut Pasteur du Cambodge (IPC) rabies prevention centers (RPCs) between 2019 and 2022 was conducted to assess exposure categories and PEPV completion. Multivariate regression was used to identify factors associated with noncompletion. Results: Among the 239,874 patients with a category II or III exposure requiring PEPV who attended the three IPC RPCs from 2019 to 2022, 6.4% did not complete the full three-session PEPV regimen or the two-session regimen for the previously immunized patients. Greater travel time to the RPC was strongly associated with lower attendance and completion rates. In addition, noncompletion was more common among males and working-age youth (15–29). Attendance and completion dropped sharply during Covid-19 mobility restriction periods and, conversely, rose markedly following a social media event publicizing a rabies-related death in 2019. Other factors significantly associated with PEPV noncompletion included year of PEPV administration, RPC location, species of the biting animal, health and living status, mode of attack and type of attack, and time between exposure and the first PEPV dose received. Conclusions: Although overall PEPV noncompletion rates were low at IPC's RPCs, this study revealed significant temporal and spatial variations. Travel time to RPC emerged as a major barrier to both RPC attendance and PEPV completion, underscoring the need to decentralize PEPV delivery to reduce access inequities. High-risk groups, particularly males and youth (15–29), would benefit from targeted communication strategies and flexible service hours. These findings can inform rabies prevention strategies in Cambodia by guiding the development of more equitable and effective PEPV delivery systems—critical to achieve the “Zero by 30” goal