Université Toulouse III - Paul Sabatier

We present two types of FBT for which diagnostic orientation was initially erroneous because of the challenging antenatal diagnosis of FBT. Autopsy enabled to rectify the initial antenatal diagnosis and establish the FBT phenotypic profile. image

Given a complex manifold X and a smooth positive function $\eta$ η thereon, we perturb the standard differential operator $d=\partial + \bar{\partial }$ d = ∂ + ∂ ¯ acting on differential forms to a first-order differential operator $D_\eta$ D η whose principal part is $\eta \partial + \bar{\partial }$ η ∂ + ∂ ¯ . The role of the zero-th order part is to force the integrability property $D_\eta ^2=0$ D η 2 = 0 that leads to a cohomology isomorphic to the de Rham cohomology of X , while the components of types $(0,\,1)$ ( 0 , 1 ) and $(1,\,0)$ ( 1 , 0 ) of $D_\eta$ D η induce cohomologies isomorphic to the Dolbeault and conjugate-Dolbeault cohomologies. We compute Bochner-Kodaira-Nakano-type formulae for the Laplacians induced by these operators and a given Hermitian metric on X . The computations throw up curvature-like operators of order one that can be made (semi-)positive under appropriate assumptions on the function $\eta$ η . As applications, we obtain vanishing results for certain harmonic spaces on complete, non-compact, manifolds and for the Dolbeault cohomology of compact complex manifolds that carry certain types of functions $\eta$ η . This study continues and generalises the one of the operators $d_h=h\partial + \bar{\partial }$ d h = h ∂ + ∂ ¯ that we introduced and investigated recently for a positive constant h that was then let to converge to 0 and, more generally, for constants $h\in \mathbb {C}$ h ∈ C . The operators $d_h$ d h had, in turn, been adapted to complex structures from the well-known adiabatic limit construction for Riemannian foliations. Allowing now for possibly non-constant functions $\eta$ η creates positivity in the curvature-like operator that stands one in good stead for various kinds of applications.

Congenital absence of the vas deferens (CAVD) is a syndrome with a heterogeneous presentation: bilateral (CBAVD) or unilateral (CUAVD), complete or partial and associated or not with other anomalies of the male urogenital system. A turning point came in 1968 when CBAVD was associated with cystic fibrosis and its CFTR gene mutations. Genetic studies then revealed that a minority of CBAVD but a majority of CUAVD are CFTR ‐independent. In the literature, reference is classically made to two sources from the 18th and 19th century: Hunter and Reverdin. This scarcity prompted us to look for additional observations of CAVD. By a meticulous bibliographical search, we identified a corpus of 10 European observations (8 CUAVD and 2 CBAVD) some of them richly illustrated. They were collected between 1755 and 1876 throughout adult men autopsies. We also provided their primary and unambiguous sources. Analysis of the reported data revealed some interesting facts: both CBAVD cases were unlikely linked to cystic fibrosis and half of CUAVD cases were associated with an ipsilateral kidney absence, suggesting a CFTR ‐independent pathophysiology. Moreover, the anatomical details of the anomalies raise interesting embryological questions we have tried to address in the light of current data. This work made it possible to identify new historical sources dealing with male genital tract pathologies. It sheds light on the origins of andrology and opens up interesting prospects for research and education in the field.

Microplastics provide a persistent substrate that can facilitate microbial transport across ecosystems. Since most marine plastic debris originates from land and reaches the ocean through rivers, the potential dispersal of freshwater bacteria into the sea represents a significant concern. To address this question, we explored the plastisphere on microplastic debris (MPs) and on pristine microplastics (pMPs) as well as the bacteria living in surrounding waters, along the river-sea continuum in nine major European rivers sampled during the 7 months of the Tara Microplastics mission. In both marine and riverine waters, we found a clear niche partitioning among MPs and pMPs plastispheres when compared to the bacteria living in the surrounding waters. Across this large dataset, we found that bacterial community structure varied along the river salinity gradient, with plastisphere communities exhibiting almost complete segregation between freshwater and marine ecosystems. We also described for the first time a virulent human pathogenic bacterium (Shewanella putrefaciens), capable of infecting human intestinal epithelial cells, detected exclusively on MPs in riverine environments. Our findings indicate that salinity is the main driver of plastisphere communities along the river-to-sea continuum, helping to mitigate the risk of pathogens transfer between freshwater and marine systems. Graphical Abstract

Patients with familial adenomatous polyposis (FAP) harbor mutations in the APC gene and will develop adenoma and early colorectal cancer. There is no validated treatment, and animal models are not sufficient to study FAP. Our aim was to investigate the early events associated with FAP using the intestinal organoid model in a single‐center study using biopsies from nonadenomatous and adenomatous colonic mucosa of FAP patients and from healthy controls (HCs). We analyzed intestinal stem cell (ISC) activity and regulation through organoid development and expression of mRNA and proteins, as well as within colonic crypts. We used several compounds to regulate the signaling pathways controlling ISCs, such as WNT, EGFR, PI3K‐AKT, TGF‐β, yes‐associated protein (YAP), and protease‐activated receptors. In addition to their high proliferative capacity, nonadenomatous and adenomatous organoids were characterized by cysts and cysts with buds, respectively, suggesting abnormal maturation. Adenomatous organoids were enriched in the stem cell marker LGR5 and dependent on EGF and TGF‐β for their growth. Downstream of EGFR, AKT, β‐catenin, and YAP were found to be activated in the adenomatous organoids. While the p110β isoform of PI3K was predominant in adenomatous organoids and essential for their growth, p110α was associated with the immature state of nonadenomatous organoids. We conclude that organoids offer a relevant model for studying FAP, and this work highlights abnormal behaviors of immature cells in both nonadenomatous and adenomatous mucosa of FAP patients, which could be targeted therapeutically. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

We report an original reactivity of base‐stabilized C‐phosphonio‐silyne with N2O allowing the synthesis of a base‐stabilized diazosilenyl cation. This silicon analogue of diazoalkenes exhibits a remarkable stability thanks to ligand coordination. In addition, a particular stabilizing effect of the silicon atom of diazoalkene moiety was predicted by DFT calculations.

We report an original reactivity of base‐stabilized C‐phosphonio‐silyne with N2O allowing the synthesis of a base‐stabilized diazosilenyl cation. This silicon analogue of diazoalkenes exhibits a remarkable stability thanks to ligand coordination. In addition, a particular stabilizing effect of the silicon atom of diazoalkene moiety was predicted by DFT calculations.

Remorins are multifunctional proteins, regulating immunity, development and symbiosis in plants. When associating to the membrane, remorins sequester specific lipids into functional membrane nanodomains. The multigenic protein family contains six groups, classified upon their protein-domain composition. Membrane targeting of remorins occurs independently from the secretory pathway. Instead, they are directed into different nanodomains depending on their phylogenetic group. All family members contain a C-terminal membrane anchor and a homo-oligomerization domain, flanked by an intrinsically disordered region of variable length at the N-terminal end. We here combined molecular imaging, NMR spectroscopy, protein structure calculations and advanced molecular dynamics simulation to unveil a stable pre-structuration of coiled-coil dimers as nanodomain-targeting units, containing a tunable fuzzy coat and a bar code-like positive surface charge before membrane association. Our data suggest that remorins fold in the cytosol with the N-terminal disordered region as a structural ensemble around a dimeric anti-parallel coiled-coil core containing a symmetric interface motif reminiscent of a hydrophobic Leucine zipper. The domain geometry, the charge distribution in the coiled-coil remorins and the differences in structures and dynamics between C-terminal lipid anchors of the remorin groups provide a selective platform for phospholipid binding when encountering the membrane surface.

Background Several major sensitization profiles have been described in children with asthma, but it remains unclear how these profiles relate to asthma phenotypes. The aim of this study was to determine allergenic sensitization profiles in a megacity cohort (SAMP). Methods This was a cross‐sectional analysis performed from 2011 to 2015 including preschool and school‐age children with severe and moderate asthma from the SAMP cohort. We performed ALEX multiplex array and carried out cluster analysis. Results Data from 367 children were analyzed: 224 of preschool age and 143 of school age, respectively 84 (38%) and 114 (80%) presented at least one allergic sensitization. At preschool age, three clusters were identified: Cluster 1, Few sensitizations to inhaled allergen molecular families and non‐type 2 (T2) inflammation (n = 61); Cluster 2, Predominant sensitization to HDM molecular families (n = 16); Cluster 3, Severe asthma with multiple sensitizations to inhaled and food allergen molecular families (n = 7). At school age, five clusters were identified: Cluster 1, Few sensitizations to inhaled allergen molecular families and non‐T2 inflammation (n = 43); Cluster 2, Predominant sensitization to HDM molecular families (n = 31); Cluster 3, Predominant sensitization to PR‐10 protein family (n = 25); Cluster 4, Severe asthma with predominant sensitization to tropomyosin family (n = 11); Cluster 5, Severe asthma with multiple sensitizations to inhaled and food allergen molecular families (n = 4). Conclusion These results underline the heterogeneity of sensitization profiles in severe allergic childhood asthma. The most severe asthma phenotypes were associated with multiple sensitizations to both inhaled and food allergen molecular families as expected, and to the tropomyosin molecular family, a novel finding.

Introduction Adolescents face unique challenges in accessing appropriate information and services regarding sexuality and reproductive health (SRH). This poor access can lead to sexual behaviours that could put them at risk of unintended pregnancies and sexually transmitted infections. Adolescents living with HIV (ALHIV) have specific SRH needs that remain unmet. We explored the SRH knowledge, practices and needs of ALHIV in Abidjan, Côte d’Ivoire. Methods Between April and September 2023, a qualitative study using semi-structured individual interviews was conducted with nine male and nine female ALHIV without previous pregnancies, and eight ALHIV who became pregnant. All consented and were ALHIV acquired perinatally, aged 15–19 years, informed of their HIV status, and followed in three paediatric HIV care centres in Abidjan. participating in the paediatric IeDEA West African Cohort and enrolled in the ANRS12390 OPTIMISE-AO project aimed at improving HIV disclosure process and adherence to antiretroviral treatment. A focus group discussion was conducted with five peer-educators, aged 23–31 years, participating in the OPTIMISE-AO project to gather their perspectives on adolescent SRH. Interviews were conducted in French, and a thematic analysis was performed. Results All participants expressed difficulty in talking about SRH with their parents or health professionals and turned to their friends for advice. All feared transmitting HIV. One-third of female participants reported having experienced non-consensual sex and sexual violence. Participants reported low levels of condom use, despite having good knowledge of its purpose. Reasons for not using condoms included difficulties in negotiating for girls, as well as having an undetectable viral load, which was seen by adolescents as a condition for waiving condom use. As hormonal contraceptives were subject to many negative beliefs justifying their non-use, alternative methods, such as emergency contraceptive pills or traditional plants, were used to prevent pregnancy. Conclusion ALHIV reported unmet SRH needs, particularly in terms of accessing reliable information and appropriate support. Integrating SRH care into paediatric HIV care, organising SRH discussion groups led by peer-educators, and improving access to a range of contraceptives may address these needs to enhance SRH outcomes for ALHIV.

Environmental challenges are rarely confined to national, disciplinary, or linguistic domains. Convergent solutions require international collaboration and equitable access to new technologies and practices. The ability of international, multidisciplinary and multilingual research teams to work effectively can be challenging. A major impediment to innovation in diverse teams often stems from different understandings of the terminology used. These can vary greatly according to the cultural and disciplinary backgrounds of the team members. In this paper we take an empirical approach to examine sources of terminological confusion and their effect in a technically innovative, multidisciplinary, multinational, and multilingual research project, adhering to Open Science principles. We use guided reflection of participant experience in two contrasting teams—one applying Deep Learning (Artificial Intelligence) techniques, the other developing guidance for Open Science practices—to identify and classify the terminological obstacles encountered and reflect on their impact. Several types of terminological incongruities were identified, including fuzziness in language, disciplinary differences and multiple terms for a single meaning. A novel or technical term did not always exist in all domains, or if known, was not fully understood or adopted. Practical matters of international data collection and comparison included an unanticipated need to incorporate different types of data labels from country to country, authority to authority. Sometimes these incongruities could be solved quickly, sometimes they stopped the workflow. Active collaboration and mutual trust across the team enhanced workflows, as incompatibilities were resolved more speedily than otherwise. Based on the research experience described in this paper, we make six recommendations accompanied by suggestions for their implementation to improve the success of similar multinational, multilingual and multidisciplinary projects. These recommendations are conceptual drawing on a singular experience and remain to be sources for discussion and testing by others embarking on their research journey.

With the emergence of the digital transition, the need to control the processing of digital information has significantly increased. In the EU in particular, Law Enforcement Agencies (LEAs) are caused to exchange information. In recent years, many regulations have emerged to control data processing and exchange. Texts other than the GDPR, such as the “Law Enforcement Directive (LED)”, appeared to regulate specifically their data processing. And although many new formalisms have emerged to represent legal norms and rules, few are provided with a reasoning mechanism. The explainability of the results of systems using these formalisms also remains a major issue when dealing with critical decision situations. This paper aims to propose a framework to operate formal rules from regulations and guide a user in its decision process in a situation of data processing by LEAs by focusing on both the operability of the rules through reasoning and the explainability of the results from the reasoning.

Prader–Willi syndrome (PWS) is a rare genetic neurodevelopmental condition characterized by cognitive disabilities, behavioral problems, hypothalamic dysfunction with obesity, and sleep disorders. A few studies have reported autonomic nervous system dysfunction. Our aim was to investigate dysautonomia by combining sleep studies and standard autonomic testing in regularly followed children with PWS. In this retrospective study, heart rate variability was analyzed during each sleep stage (polysomnography) using time and frequency domains in PWS children (N = 37) compared with age-matched controls (N = 20). Cardiovascular autonomic testing (Ewing tests) and sweating assessment (electrochemical skin conductance) were also performed in patients over 6 years (N = 23). Autonomic testing: Heart rate changes with active standing and with deep breathing were impaired in 47% and 22% of the children, respectively. Asymptomatic orthostatic hypotension (OH) was found in 26%. Baroreflex sensitivity in supine position was in normal range (14.1 ± 6.7 ms/mmHg). Electrochemical skin conductance was normal. Sleep study: 46% of the children with PWS had obstructive sleep apnea and 24% had central sleep apnea. None of these events were observed in the control group. Mean R-R and time domain heart rate variability parameters were significantly lower compared with controls in N2 and Rapid Eye Movement (REM) sleep stages. Narcoleptic-like phenotype was found in 47% associated with lower low-frequency (LF) power (sympathetic index) in REM sleep. Our study confirms a decreased vagal modulation during both wakefulness and sleep in children with PWS. OH in some patients suggests a sympathetic dysfunction. These changes may contribute to the increased cardiovascular risk in PWS.

Background For children with HIV on antiretroviral therapy (ART), transitioning to dolutegravir-containing regimens is recommended. The aim of this study was to assess whether introducing viral load testing to inform new nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) for children with HIV and viraemia alongside dolutegravir-based ART is beneficial and of good economic value. Methods We used the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model to project clinical and cost implications of three strategies among a simulated cohort of South African children aged 8 years with HIV receiving abacavir–lamivudine–efavirenz: (1) continue current ART (no dolutegravir; abacavir–lamivudine–efavirenz); (2) transition all children with HIV to dolutegravir, keeping current NRTIs (dolutegravir; abacavir–lamivudine–dolutegravir); or (3) transition to dolutegravir based on viral load testing (viral load plus dolutegravir), keeping current NRTIs if virologically suppressed (abacavir–lamivudine–dolutegravir, 70% of cohort) or switching abacavir to zidovudine (zidovudine) if viraemic (zidovudine–lamivudine–dolutegravir, 30%). We assumed 50% of children who had viraemia after abacavir–lamivudine exposure had NRTI resistance; with resistance, we assumed zidovudine–lamivudine–dolutegravir was more effective than abacavir–lamivudine–dolutegravir. We designated a strategy as preferred if it was most effective and least costly or had an incremental cost-effectiveness ratio less than half the South African 2020 gross domestic product per capita. Findings Under base-case assumptions, the viral load plus dolutegravir strategy would be the most effective (projected undiscounted life expectancy of 39·72 life-years) and least costly strategy (US$24 600 per person); the no dolutegravir strategy was the least effective (34·49 life-years) and most expensive ($26 480 per person). In sensitivity analyses, the 24-week virological suppression probability and subsequent monthly virological failure risks (ie, late failure) were most influential on cost-effectiveness. Only with a high late-failure risk for zidovudine–lamivudine–dolutegravir (ie, ≥0·3% per month in the base case or >0·5% per month if abacavir also confers low virological suppression probability in the presence of NRTI resistance [65%]) would the dolutegravir strategy become preferred above the viral load plus dolutegravir strategy. Interpretation For programmes transitioning to dolutegravir-based regimens, our model predicted that doing so would be more effective and less costly than continuing current ART regimens, regardless of NRTI choice. Whether viral load testing for children with HIV is necessary to inform NRTI choice depends substantially on the comparative outcomes of abacavir and zidovudine after switching to dolutegravir-containing ART. Funding The Eunice Kennedy Shriver Institute for Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the Massachusetts General Hospital Executive Committee on Research, the Massachusetts General Hospital, and the Medical Research Council.