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Fetal and maternal outcome in the pregnancies of patients with systemic sclerosis and very early diagnosis of systemic sclerosis in France: a prospective study
No full textInternational audienceBACKGROUND: Prospective data on pregnancies in systemic sclerosis are scarce. We aimed to examine the frequency of adverse pregnancy outcomes and maternal disease progression in systemic sclerosis, as well as the factors that predict these events. METHODS: In this analysis, we studied pregnant women with systemic sclerosis (American College of Rheumatology-European League Against Rheumatism 2013 classification) or with Very Early Diagnosis of Systemic Sclerosis (VEDOSS criteria) included in the GR2 French prospective study. Frequency of composite adverse pregnancy outcomes (preterm birth at 34 weeks or less, placental insufficiency complications, small for gestational age, or fetal or neonatal death) and maternal disease course were the primary objectives. The secondary objectives were to assess other complications related to pregnancy (including delivery outcomes and postpartum complications) and compare these results with outcomes for age-matched controls from the French perinatal survey (ENP) 2016 (ie, general population), and to identify predictive factors associated with composite adverse pregnancy outcomes and maternal disease course using univariate analysis. FINDINGS: Between May 1, 2014, and Dec 27, 2020, we included 58 pregnancies (in 52 women), with 53 (91·4%) resulting in livebirths. Of the 53 ongoing pregnancies beyond 22 weeks of gestation, 14 (26·4%) had a composite adverse pregnancy outcome, including two (3·8%) preterm deliveries at 34 weeks of gestation or less, 12 (22·6%) placental insufficiency complications (pre-eclampsia or fetal growth restriction), and six (11·3%) small for gestational age. Among the 53 pregnancies, six (11·3%) severe postpartum haemorrhage events occurred. When compared with the 2016 ENP survey results, pre-eclampsia (seven [13·2%] of 53 vs 16 [3·0%] of 530, p=0·0010, preterm birth before 37 weeks of gestation (seven [13·2%] of 53 vs 31 [5·8%] of 530, p=0·047), birthweight of less than 2500 g (11 [21·1%] of 52 vs 23 [4·3%] of 530, p<0·0001), and severe postpartum haemorrhage (six [11·3%] of 53 vs seven [1·4%] of 516, p=0·0001) were more frequent than in the general population. No factors were significantly associated with the composite adverse pregnancy outcome in univariate analysis. Systemic sclerosis or VEDOSS worsened in 23 (39·7%) of 58 pregnancies, mainly during the postpartum period. In the univariate analysis, diffuse cutaneous systemic sclerosis (odds ratio 3·7 [95% CI 1·1-12·4]) and previous cutaneous vascular involvement (3·7 [1·2-11·5]) were associated with maternal disease progression, whereas the presence of anticentromere antibodies was inversely associated with stable disease (0·2 [0·1-0·8]). INTERPRETATION: Despite 53 (91·4%) of 58 livebirths, systemic sclerosis pregnancies were associated with higher rates of adverse pregnancy outcomes and severe postpartum haemorrhage. Disease worsened in 23 (39·7%) of 58 pregnancies, particularly during the postpartum period, especially in women with diffuse cutaneous systemic sclerosis, previous cutaneous vascular involvement, and antibodies other than anticentromere. FUNDING: Lupus France, Association des Sclérodermiques de France, Association Gougerot Sjögren, Association Francophone Contre la Polychondrite Chronique Atrophiante, AFM-Telethon, Société Nationale Française de Médecine Interne, Société Française de Rhumatologie, Cochin Hospital, French Health Ministry, Fondation for Research in Rheumatology, Association Prix Véronique Roualet, Union Chimique Belge
A new potential mosquito-borne virus: detection of Human-derived Jingmenvirus in several-species of mosquitoes from Yaoundé, Cameroon
No full textPosted 09 Sep, 2025 on Research SquareInternational audienceBackgroundTick-borne Jingmenviruses are becoming an increasing arbovirus concern due to the rising number of reported infections in humans and animals, as well as their wide geographic distribution. The involvement of other hematophagous arthropods as vectors of Jingmenviruses is still unknown.MethodsMosquitoes were sampled in two different biotopes in Cameroon (Yaoundé and Garoua) during the rainy and the dry seasons in 2022 and 2023. Metatranscriptomics Next Generation Sequencing was conducted using Illumina technology. Viral sequences detection revealed the presence of several contigs with high sequence identity to a human-derived Jingmenvirus (HdJV) previously discovered in plasma from an individual from Yaoundé, Cameroon. A draft viral genome was constituted for each Jingmenvirus-positive samples. Maximum likelihood phylogenetic reconstructions were used to position mosquito-associated viruses within the diversity of Jingmenviruses. Statistical analyses were conducted to estimate the prevalence of infected mosquitoes and the effect of different variables (region, season, year, mosquito species) on Jingmenvirus detection.ResultsHdJV was identified during the dry and the rainy seasons in 4 species of mosquitoes: Aedes albopictus, Culex quinquefasciatus and Culex wansoni from Yaoundé, and Anopheles gambiae s.l. from Garoua. The overall prevalence of HdJV-infected mosquitoes was estimated to 0.90% [0.41–1.69]; and the unique variable significantly associated with HdJV detection was the sampling area: Yaoundé showed the highest prevalence (2.29% [0.95–4.68]) compared to Garoua (0.18% [0.01–0.79]). Mosquito-associated Jingmenviruses shared a high nucleotide identity (between 98.64–100% according to the segment) and clustered in the same clade in the phylogenetic analysis, that they belong to the same viral species circulating in different mosquito species. The viral genome shared between 96.4% and 98.9% nucleotide identity with a HdJV detected in the plasma of a patient suffering from febrile illness originating from the same area, suggesting the possible involvement of mosquitoes as vectors of arboviral Jingmenviruses in human infections.ConclusionsThis finding provides new insights into the ecology and transmission dynamics of Jingmenviruses, highlighting mosquitoes as potential vectors, alongside ticks, in the zoonotic transmission of this virus group
Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome
No full textInternational audienceBackground Patients with antiphospholipid syndrome (APS) display a wide range of clinical manifestations with similar immunological profile with the presence of lupus anticoagulant in around 70% of them. Although antiphospholipid antibodies (aPL) profile influences the risk of thrombosis in APS, APS risk stratification remains to be improved.Objectives Our study aimed to evaluate thrombin generation test (TGT) interest to improve disease severity stratification in APS patients.Patients/methods In this monocentric, transversal study, we included unselected primary thrombotic APS patients, fulfilling APS classification criteria and treated by vitamin K antagonist (VKA). 28 non-APS patients under VKA followed in our hospital were included as controls. TGT was performed on plasma samples with the calibrated automated thrombogram in our core laboratory.Results Between January 2020 and March 2023, 114 thrombotic APS patients (without systemic lupus erythematosus) were included (female 71 (62.3%), mean age 50±14 years old, median duration since the last APS event of 51 months (IQR 23–129 months)). APS patients had prolonged lag time (LT) and time to peak (TTP) compared with anticoagulated controls. History of relapse, catastrophic APS (CAPS), all aPL positivities and elevated Bb fragments were strongly associated with a prolonged LT and TTP.Conclusions Our findings suggest that APS patients under VKA had significantly prolonged TGT times compared with anticoagulated controls, with the greatest prolongations in patients with history of relapse or CAPS. Thus, TGT might be a useful tool to improve APS disease severity stratification without temporary cessation of VKA
Fabrication of a bioreactor combining soft lithography and vat photopolymerisation to study tissues and multicellular organisms under dynamic culture conditions
No full textInternational audienceDespite its capability to create much more realistic microenvironments for in vitro culturing of animal or human biological models, the spread of microfluidic tools in the world of biology and medicine has still not reached the predicted scale. Major obstacles to their widespread acceptance by end-users are manufacturing cost and operational complexity. 3D printing is a technology that is now widely democratised, thanks to its ease of use and very attractive cost/performance ratio. In particular, photopolymerisation through a liquid crystal screen is experiencing a very significant growth. Here, we describe the methodology we developed to evaluate this microfabrication technique and selected a photoprintable resin to manufacture a fluidic microsystem dedicated to tissue or micro-organism culture. The first originality of our approach lies in the architecture of the microsystem, which is made up of an elementary culture chamber in two parts, making it very easy to open after the culture period to carry out ex situ biochemical analyses. The second one is the nature of the materials used to make up the culture chamber, which consists of polydimethylsiloxane and a photoprinted resin. This hybrid assembly, combining an elastomer and a rigid plastic material, ensures a better seal and better dimensional control once the assembly is complete. We demonstrate the ability of our protocol to flexibly fabricate different culture chambers with dimensions down to 100 microns and we show for one of them three applications: a 2D layer of cell lines, a parasitic worm and a 3D microtissue from a pancreatic cancer patient
Putative EGF ligand and receptor of<i>Echinococcus multilocularis</i>that are critical for parasite development
No full textThe neglected zoonosis alveolar echinococcosis (AE) is caused by infiltrative growth of the metacestode larval stage of the cestode Echinococcus multilocularis within host organs. We previously demonstrated that metacestode growth depends on the mitotic activity of a population of parasite stem cells, called germinative cells, but it is not yet clear which molecular mechanisms govern Echinococcus stem cell dynamics such as cell-cycle progression, selfrenewal and differentiation. Based on previous reports showing that epidermal growth factor (EGF) signalling contributes to Echinococcus stem cell regulation, we herein characterized three EGF receptors of the parasite and demonstrated by RNAi and inhibitor assays that one of these, EmER1, is crucial for the development of metacestode vesicles from parasite stem cells. We also showed that EmER1 serves as a target for afatinib, an EGF receptor inhibitor with profound anti-parasitic activities in vitro and in vivo. By bioinformatic analyses and membrane-bound yeast two-hybrid assays, we identified a parasite-derived, neuregulin-like cognate ligand for EmER1, EmNRG, the expression of which is strongly upregulated in metacestode vesicles during clonal expansion of germinative cells. Furthermore, we demonstrate that RNAi knockdown of the EmNRG encoding gene drastically affects the ability of germinative cells to produce metacestode vesicles. We propose that EmNRG and EmER1 form a cognate ligand-receptor system utilized by E. multilocularis to regulate asymmetric versus symmetric division decisions of stem cells. These data are relevant for further studies into Echinococcus stem cell dynamics and for the development of EGF signalling-based antiinfectives against echinococcosis.</div
Le sexe influence-t-il les dommages musculaires induits par l’exercice : une question de méthodologie ?
No full textInternational audienceINTRODUCTIONLes dommages musculaires induits par l’exercice (DMIE) peuvent affecter négativement la performance sportive et augmenter le risque de blessure musculaire. L’évaluation des DMIE peut participer à l’établissement de protocoles favorisant la récupération et/ou maximisant les adaptations induites par l’entraînement. Des réponses contradictoires liées au sexe à la suite de DMIE ont été observées. Pour une diminution similaire (%) de la force après un exercice excentrique chez des hommes et des femmes ayant un même niveau de force maximale rapporté à la masse maigre, les dommages musculaires, évalués par la concentration sanguine de créatine kinase (CK), étaient plus élevés chez les hommes. Les auteurs évoquent la possibilité que les œstrogènes puissent conférer un effet protecteur aux femmes en améliorant la stabilité de la cellule musculaire. Cependant, d’autres études ont démontré que le niveau d’œstrogènes chez la femme n’était pas associé avec les DMIE. Des différences méthodologiques dans l’analyse des variations de CK pourraient expliquer les divergences de résultats observés dans la littérature. L’utilisation de valeurs absolues ou normalisées ainsi que les méthodes de normalisation peuvent varier selon les études et affecter l’interprétation et expliquer la mise en évidence ou non d’un effet lié au sexe. L’objectif de cette étude est d’appliquer une approche méthodologique pour étudier l’effet du sexe sur les DMIE avec une identification préalable des facteurs susceptibles de les influencer suite à un exercice excentrique.METHODE237 participants (149 hommes et 88 femmes) ont été inclus dans cette étude. Les données anthropométriques ont été relevées et la force maximale sur une presse à cuisses a été déterminée sur la jambe dominante par la réalisation d’un profil force-vitesse. Les participants ont effectué 8 séries de 10 répétitions excentriques sur la jambe dominante à 85% de la force maximale. Les cinétiques de récupération de la force maximale isométrique et de la concentration en CK ont été déterminées à partir de mesures effectuées avant et après l’effort, puis à 24 h, 48 h et 72 h après l’effort.RESULTATSL’effet du sexe sur les concentrations de CK est significatif lorsque les comparaisons sont : i) effectuées en valeurs absolues (p < 0,001), ii) en delta de CK (niveau de CK mesuré moins la valeur de repos, p < 0,001), iii) en delta de CK normalisé à la masse musculaire engagée (p < 0,001) et iv) en delta de CK normalisé à la force appliquée (p < 0,001). Cependant, l’effet du sexe s’efface (p = 0,63) lorsque l’on compare des hommes et des femmes avec un niveau de force similaire et que les valeurs de CK sont normalisées à la masse musculaire impliquée.DISCUSSIONL’approche méthodologique constitue un critère déterminant dans la comparaison des DMIE entre les hommes et les femmes. La présence ou l’absence de différence entre les sexes selon la méthodologie utilisée participe à expliquer les résultats contradictoires rapportés dans la littérature. Plus que le sexe, la force et la masse musculaire sollicitées lors de l’exercice semblent être les paramètres d’intérêt dont il faut tenir compte pour interpréter les résultats
Addressing data imbalance in urban informal settlement mapping from earth observation using ensemble learning: A case study in Rio de Janeiro
No full textInternational audienceInformal settlements pose major challenges for public health, infrastructure, and urban planning due to their high density and unregulated growth. Remote sensing has emerged as a key tool for mapping these areas, but strong class imbalance -where informal settlements represent a small fraction of urban land -remains a critical barrier. Existing methods often rely on simple undersampling, discarding valuable training data from formal residential zones. We propose BALISE, a novel ensemble learning approach that leverages the full extent of available data to improve informal settlement detection from remote sensing. Our framework combines Sentinel-2 multispectral imagery and the Copernicus Digital Elevation Model with auxiliary features derived from OpenStreetMap. We evaluate our method on a use case in Rio de Janeiro, using a spatial crossvalidation strategy that rigorously tests generalization across five different urban zones. BALISE improves both F1-score and Kappa coefficient by approximately 2 points over standard undersampling, offering a robust and transferable tool for remote sensing-based urban analysis in fragmented and socially complex environments.</div
La réflexivité des patients diabétiques : analyse comparative et contribution à l'éducation thérapeutique du patient
No full textInternational audienceL’éducation thérapeutique du patient (ETP) constitue depuis plusieurs décennies un enjeu majeur pour les systèmes de santé confrontés à la progression des maladies chroniques. Si les initiatives se sont multipliées, elles demeurent souvent centrées sur la transmission de savoirs médicaux, négligeant la richesse des expériences et des compétences développées par les patients eux-mêmes. C’est précisément sur ce point que ce manuscrit apporte une contribution originale et essentielle. L’auteur propose en effet d’explorer une dimension encore trop peu étudiée : la réflexivité des patients. En s’appuyant sur une recherche approfondie, combinant des approches qualitatives et quantitatives, il démontre que les personnes atteintes de diabète mobilisent des savoirs expérientiels et des pratiques réflexives qui méritent d’être reconnus et intégrés dans les dispositifs d’ETP. Loin d’être une posture abstraite, la réflexivité apparaît ici comme une compétence concrète, capable de transformer la relation de soins, de renforcer l’autonomie des patients et d’améliorer l’efficacité des programmes éducatifs. Ce travail s’inscrit dans une perspective innovante, celle d’un modèle d’ « ETP réflexive », qui place la co-construction, l’accompagnement coopératif et la valorisation des savoirs expérientiels au cœur du processus éducatif. Cette proposition, nourrie par des données empiriques solides et une réflexion théorique exigeante, ouvre de nouvelles pistes pour la formation des professionnels de santé, mais aussi pour l’élaboration des politiques publiques. La pertinence de ce travail dépasse largement le cadre du diabète et du contexte nigérien. Elle interpelle l’ensemble des acteurs de santé, en Afrique comme ailleurs, sur la nécessité d’inventer des approches éducatives plus humanistes, plus participatives et plus durables. Dans un monde où les systèmes de santé sont mis à rude épreuve, la reconnaissance de la réflexivité des patients n’est pas un luxe, mais une condition de leur résilience et de leur transformation. Je souhaite que ce manuscrit inspire non seulement les chercheurs et les praticiens, mais aussi les décideurs, afin que la réflexivité devienne une dimension pleinement intégrée des pratiques éducatives et des politiques de santé. C’est donc avec un grand intérêt et une réelle estime que je recommande la lecture de ce travail, qui conjugue rigueur scientifique, profondeur humaine et engagement pour l’avenir des soins
Refining Bariatric Surgery: A Nationwide 15-Year Study to Reduce Morbidity and Improve Recovery.
No full textInternational audienceObjective: To evaluate the evolution of postoperative mortality and morbidity associated with bariatric surgery over a 15-year period using a nationwide database.Background: Bariatric surgery is a cornerstone in obesity management, demonstrating significant benefits in weight loss and comorbidity resolution. However, despite its proven efficacy, it remains underutilized, with only a small fraction of eligible patients undergoing surgery. Advances in surgical techniques and perioperative care have improved safety, yet long-term trends in mortality and morbidity require further evaluation.Methods: This retrospective cohort study utilized data from the SNDS (Système National des Données de Santé), France’s national health care database, covering all bariatric procedures performed between 2009 and 2023. Patients aged 18 to 65 years with a primary diagnosis of obesity were included. Outcomes assessed included 90-day and 180-day mortality, severe complications (Clavien-Dindo IV), reoperations, hospital readmissions, and postoperative medication use.Results: Among 486,161 first-time bariatric procedures, sleeve gastrectomy and gastric bypass dominated. The overall 90-day mortality rate was 0.1%, varying significantly by procedure (P < 0.001), with adjustable gastric banding exhibiting the lowest rate. Mortality decreased by 40% over time, but sleeve gastrectomy and gastric bypass showed a plateau effect since 2018. Reoperations declined (4.9%–4.5%), and intensive care unit admissions for severe complications fell by 58%. Medication analysis revealed reduced analgesic (-29.4%), antidepressant (-15.7%), and anxiolytic (-12.7%) use, while laxative consumption increased (+86.4%).Conclusions: Bariatric surgery has become safer over time, with declining mortality and complication rates. However, the stagnation of improvements in recent years highlights the need for further optimization strategies. These findings support the continued integration of surgery within a multimodal obesity treatment paradigm
The Plagiochilins from <i>Plagiochila</i> Liverworts: Binding to α-Tubulin and Drug Design Perspectives
No full textInternational audiencefirst_pagesettingsOrder Article ReprintsOpen AccessFeature PaperArticleThe Plagiochilins from Plagiochila Liverworts: Binding to α-Tubulin and Drug Design Perspectivesby Gérard Vergoten1 and Christian Bailly2,3,* [ORCID]1Inserm, U1286—INFINITE—Lille Inflammation Research International Center, ICPAL, University Lille, 3 Rue du Professeur Laguesse, 59000 Lille, France2CNRS, Inserm, CHU Lille, UMR9020-U1277—CANTHER—Cancer Heterogeneity Plasticity and Resistance to Therapies, University of Lille, 59000 Lille, France3Oncowitan, Scientific Consulting Office, Wasquehal, 59290 Lille, France*Author to whom correspondence should be addressed.AppliedChem 2023, 3(2), 217-228; https://doi.org/10.3390/appliedchem3020014Submission received: 18 April 2023 / Revised: 28 April 2023 / Accepted: 8 May 2023 / Published: 9 May 2023Downloadkeyboard_arrow_downBrowse FiguresVersions NotesAbstractAmong bryophytes, the Plagiochila genus represents a large group of leafy liverworts with over 500 species. Plagiochilins A to X are sesquiterpenoids isolated from Plagiochila species. The lead compound plagiochilin A (Plg-A), endowed with anticancer and antiparasitic properties, has been characterized as a potent mitosis inhibitor, acting selectively at the late stage of cytokinesis termed abscission. The compound perturbs the dynamics of microtubules, blocking cell cycle progression and triggering the death of malignant cells. Based on the compound’s mechanism of action and by analogy with other natural products bearing a dihydro-pyrone moiety, we postulated that Plg-A could bind to the pironetin site of α-tubulin. A molecular docking analysis was performed to compare the bindings of all 24 plagiochilins to α-tubulin and to establish structure–binding relationships. The identification of Plg-E and Plg-G as the best binders in the series highlighted the importance of the C13-OH or C=O group for α-tubulin recognition. This observation led to the testing of the natural-product ester plagiochilin A-15-yl n-octanoate and the corresponding alcohol (Plg-OH), both identified as robust α-tubulin binders. The study provides a rationale to potentially explain the mechanism of action of Plg-A and to guide the design of new derivatives