University of Angers

Background The global increase in caesarean sections (CS), currently at 21.1% of all deliveries, has led to a rise in uterine scar defects, or ‘niches’, at the hysterotomy site. These niches, detectable in 13%–84% of cases via transvaginal ultrasound (TVS) and 42%–84% through sonohysterography (SHG), may contribute to gynaecological complications, including abnormal uterine bleeding, chronic pain and secondary infertility. Niche-associated risks for in vitro fertilisation (IVF) outcomes remain underexplored, and this study aims to evaluate their impact on clinical pregnancy rates. Methods and analysis This multicentre, prospective, non-interventional study will involve 250 women with a history of CS and secondary infertility undergoing IVF in 14 reproductive units of French Hospital. Participants will be assessed using SHG and TVS to determine niche presence (measurements of the length, depth and width of the niche, and residual myometrial thickness (RMT)). A niche is diagnosed by an indentation of at least 2 mm at the site of the caesarean scar, with a large niche defined as RMT <3 mm. The primary outcome is clinical pregnancy rate, with secondary outcomes including live birth rates, biochemical pregnancies and obstetric complications. Multivariate logistic regression will control for confounders. The duration of the inclusion period is estimated to be 42 months. Ethics and dissemination The study protocol was approved by the relevant French medical review board, ‘Comité de Protection des Personnes Sud Méditerranée IV’, on 10 November 2020 and recorded prospectively (before the inscription of the first participant) under the number ID-RCB: 2020-A02068-31. The study will be conducted according to the guidelines of the Declaration of Helsinki. Informed consent will be obtained from all participants. The findings will be published in peer-reviewed journals and presented at relevant meetings. Trial registration number ClinicalTrials.gov, ID: NCT04869007 . Registered on 16 August 2020.

Excessive brain tissue pulsations (BTP), measured by ultrasound, have been associated with depression and are hypothesized to contribute to brain damage in this population at risk for cerebrovascular lesions. However, previous research has been limited by small sample sizes. To address this issue, our study pooled data from three separate investigations, resulting in the largest cohort of depressed participants with BTP measurements to date. We analysed 123 participants (74 individuals with depression and 49 healthy controls) using ultrasound tissue pulsatility imaging (TPI) to assess resting BTP. Results showed that both MeanBTP and MaxBTP were significantly associated with depression, as determined by multiple linear regression models that included age, sex and blood pressure as covariates. Additionally, we found that age, sex and diastolic blood pressure were significant predictors of BTP. Specifically, BTP decreased with age, was higher in men, and was more strongly predicted by diastolic blood pressure than by systolic blood pressure. In this large cohort, we replicated the association between depression and increased BTP, supporting the notion that elevated BTP may be a potential mechanism underlying brain damage over time. Our findings suggest that TPI could serve as a valuable surrogate marker for brain health in clinical practice.

Monoanionic and neutral nickel(II) and platinum(II) bis(dithiolene) complexes based on the 5,6-diethyl-5,6-dihydro-1,4-dithiin-2,3-dithiolate (de-dddt) chiral ligand have been prepared in racemic and enantiopure forms. The neutral closed-shell species have been generated...

We demonstrate a fully automated polarization-insensitive fiber optical parametric amplifier (PI-FOPA) self-adjusting its parameters to compensate for drifts in real-time. The automation algorithm adjusts the PI-FOPA parameters to set and maintain the target polarization independent gain for a selected channel. We employ this PI-FOPA in a long-reach access network scenario to simultaneously amplify WDM downstream in the C band and WDM upstream in the L band, whereas the downstream and the upstream are equivalent to 10x 100 Gbit/s polarization-division multiplexed QPSK signals and 10x bursty 10 Gbit/s on-off keying signals respectively. The PI-FOPA provides net gain >17dB across all channels and the total output signal power up to 24.6 dBm. This demonstration denotes the first ever simultaneous amplification of WDM signals by a PI-FOPA in C&L bands and on both sides of the PI-FOPA pump.

Background The prognosis for patients with relapse of localized rhabdomyosarcoma (RMS) remains poor, with limited evidence for optimal second‐line therapy. This study describes the management and outcomes of relapsed RMS patients in France. Methods We retrospectively reviewed all nonmetastatic RMS patients enrolled in France in the RMS 2005 study who relapsed between 2006 and 2019 after achieving complete local control, defined as complete remission or stable residue ≥ 6 months after treatment completion. Data were extracted from the RMS 2005 database and medical records. Results Ninety‐five patients relapsed at a median age of 6.0 years (range: 1.0–27.0). The median time from diagnosis to relapse was 17.5 months (range: 7.4–82.0). Most patients had embryonal RMS (65.3%) and local/locoregional relapses (71.6%). The first relapse treatment included chemotherapy (all except two patients), radiotherapy (52.6%), and surgery (48.4%). Second‐line chemotherapy yielded a 58.5% objective response rate after 3 ± 1 cycles. Fifty‐five patients achieved second complete remission. With a median follow‐up of 7.2 years from the first relapse (range: 0.3–11.3), 5‐year progression‐free survival was 26% (95% CI: 18–36), and 5‐year overall survival was 35% (95% CI: 25–45). Importantly, no patient survived relapse without receiving locoregional treatment (surgery and/or radiotherapy). Conclusion This study confirmed the inconsistencies in therapy and the poor prognosis for relapsed RMS but highlighted the potential for long‐term survival in patients who received surgery and/or radiotherapy, emphasizing the crucial role of achieving local control in improving outcomes at relapse.

In the quest for lead‐free chiral metal‐halide materials, 2D double perovskites appear as very promising candidates especially for spintronic applications. However, compared to highly crystalline Pb²⁺ compounds, the more challenging synthetic procedure for compounds based on Ag⁺ and Bi³⁺/Sb³⁺ so far limited the number of these chiral materials to very few reported examples, as highlighted by the absence of crystal structure based on the extensively used (S/R)‐1‐phenylethylammonium (S/R‐MBA) cations in chiral metal halides. This study presents the successful preparation and characterization of a complete series of 2D bromide‐based and iodide‐based double perovskites based on the cations (S/R)‐1‐(4‐bromophenyl)ethylammonium (S/R‐4BrMBA), which allows to describe their structures, thin film processing, and resulting chiroptical properties. The strong modulation of the structure and circular dichroism (CD) properties at the nanoscale is unprecedented, since the thin films of (S/R‐4BrMBA)4AgBiBr8 strongly evolve from a single‐phase compound with small intrinsic CDiso to a polymorphic material showing a strong increase in the CD signal due to macroscopic effects.

Background: The literature is scant on the associations between employment-related variables and suicidal ideation. Aims: The objectives were to explore these associations in the national French working population. Methods: The study relied on two independent national French surveys and their samples of 22,420 workers (employees and self-employed workers) and 25,628 employees, respectively. Employment variables included occupation, economic activity of the company, public/private sector, company size, permanent/temporary work, full/part time, seniority, and employee/self-employed worker. Suicidal ideation was assessed using one item. The associations between employment variables and suicidal ideation were studied using bi- and multivariable weighted analyses (Rao-Scott Chi-2 test and logistic regression). Gender differences were explored and covariates were taken into account. Results: The associations between employment variables and suicidal ideation were mostly not statistically significant. Some differences in suicidal ideation between occupations and economic activities were difficult to interpret due to overlaps in the confidence intervals. The prevalence of suicidal ideation increased with seniority among employees. Limitations: The study design was cross-sectional. Conclusion: The studied employment variables may have little effect on suicidal ideation. As suicidal ideation is a risk factor for suicide, more research is needed to explore the work-related risk factors for suicide and suicidal ideation.

Purpose Hematopoietic cell transplantation (HCT) is a common treatment for people diagnosed with hematological cancers. However, it can cause side effects that may affect work participation. This scoping review aims to provide an overview of the factors that influence the work participation of hematological cancer survivors who have undergone HCT. Methods We conducted a scoping review following the Joanna Briggs Institute guidelines and developed our search strategy in collaboration with a scientific librarian and searched nine databases (CINAHL, MEDLINE, EMBASE, Cochrane, PubMed, PsycINFO, Web of Science, Scopus, ProQuest Dissertations, & Theses Global) for primary studies in French or English until February 2024. Two reviewers extracted the data and analyzed it thematically. We synthesized and presented the findings using a narrative description approach. Results We identified 940 publications, of which 36 met the eligibility criteria. Our findings underscore the significance of considering individuals over 50, those undergoing allogeneic HCT, women, and those with lower incomes. We noted disparities in evaluating or describing work participation. Conclusion It is crucial for researchers and healthcare professionals in hematological care to be aware of the intersecting factors that influence work participation. There are still significant gaps in how workplace dynamics, legislation, and healthcare systems affect the return to work process.

Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses. Here we apply a multilayer-omics approach to reveal dynamic peripheral immune landscapes during the AIT-initiation phase in venom allergy patients (VAP) versus pollen-allergic and healthy controls. Already at baseline, VAP exhibit altered abundances of several cell types, including classical monocytes (cMono), CD4⁺ hybrid type 1-type 17 cells (Th1-Th17 or Th1/17) and CD8⁺ counterparts (Tc1-Tc17 or Tc1/17). At 8-24 h following AIT launch in VAP, we identify a uniform AIT-elicited pulse of late-transitional/IL-10-producing B cells, IL-6 signaling within Th2 cells and non-inflammatory serum-IL-6 levels. Sequential induction of activation and survival protein markers also immediately occur. A disequilibrium between serum IL-6 and cMono in VAP baseline is restored at day seven following AIT launch. Our longitudinal analysis discovers molecular switches during initiation-phase insect-venom AIT that secure long-term outcomes. Trial number: NCT02931955.

Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by ectopic calcification of tissues rich in elastic fibres (OMIM 264800). To date, PXE is considered a metabolic disease linked to an imbalance between pro‐ and anti‐calcifying factors. The occurrence of sporadic erythematous flareups of PXE skin lesions is a complaint that we heard about on several occasions at the French PXE reference centre. However, this rare clinical aspect had never been extensively studied. We have had the opportunity to investigate a 13‐year‐old patient experiencing an erythematous flareup of his PXE lesions. We conducted this work to identify what type of inflammation was implicated in his lesions. An incisional skin biopsy on a recent erythematous inguinal PXE lesion was performed and sent for histological and transcriptomic analyses. The findings were compared to a non‐erythematous PXE‐affected skin biopsy obtained from another young PXE patient. Histological examination revealed perivascular T‐cell infiltrates with Th1 polarity and elevated expression of cytotoxicity markers in RNAseq and RT‐qPCR analyses. There was no increase in Th17 or Th2 markers. Our findings support the previous evidence of a possible inflammatory component in the development of PXE. Whether Th1‐dependent inflammation contributes to the pathology as an active process or is an aggravating factor requires further investigations.

Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy affecting the elderly, for which therapeutic options are limited. DNA hypomethylating agents (HMAs) provide transient responses, failing to eradicate the malignant clone. Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization, evidenced by alterations in histone marks H3K9me2 and H3K9me3. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In solid cancers, the antitumor efficacy of HMAs involves the derepression of TEs, mimicking a state of viral infection. In this study, we demonstrate a significant disorganization of heterochromatin in CMML HSCs and progenitors (HSPCs) characterized by an increase in the repressive mark H3K9me2, mainly at the level of TEs, and a repression of immune and age-associated transcripts. Combining HMAs with G9A/GLP H3K9me2 methyltransferase inhibitors reactivates these pathways, selectively targeting mutated cells while preserving wild-type HSCs, thus offering new therapeutic avenues for this severe myeloid malignancy.

Our aim was to describe the pharmacokinetics of paracetamol and its metabolites in extreme preterm neonates in the context of patent ductus arteriosus treatment. Factors associated with inter-individual variability and metabolic pathways were studied. The association between drug exposure and clinical outcomes were investigated. Preterm neonates of 23–26 weeks’ gestational age received paracetamol within 12 h after birth. Plasma concentrations of paracetamol and its metabolites were measured throughout 5 days of treatment. Clinical success was defined as ductus closure on two consecutive days or at day 7. Aspartate aminotransferase and alanine aminotransferase levels were used as surrogates for liver damage. Data from 30 preterm neonates were available for pharmacokinetic analysis. Paracetamol pharmacokinetics were described using a two-compartment model with significant positive effects of weight on clearance and of birth length on peripheral compartment volume. Paracetamol was mainly metabolised into sulphate (89%) then glucuronide (6%), and the oxidative metabolic pathway was reduced (4%). The glucuronidation pathway increased with gestational age, whereas the sulfation pathway decreased. No difference was observed in drug exposure between successful and unsuccessful patients. No increase in aspartate aminotransferase and alanine aminotransferase levels were observed during treatment, and no association was found with either paracetamol or oxidative metabolite exposures. The relative proportions of the metabolic pathways were characterised with gestational age. In the range of observed drug exposures, no association was found with clinical response or liver biomarkers. These findings may suggest that paracetamol concentrations were within the range that already guarantee a maximum effect on ductus closure.

Background and purpose X‐linked Charcot‐Marie‐Tooth disease type 1 (CMTX1) ranks as the second most prevalent hereditary neuropathy and, currently, has no definitive cure. Emerging preclinical trials offer hope for potential clinical studies in the near future. While it is widely accepted that experimental groups in these trials should be balanced for age and gender, there is a current shortfall in data regarding phenotype–genotype correlations. Our aim was to provide a more detailed understanding of these correlations to facilitate the formation of well‐matched patient groups in upcoming clinical trials. Methods We conducted a retrospective evaluation of CMTX1 patients from 13 designated reference centers in France. Data on genetics, clinical features, and nerve conduction were systematically gathered. Results We analyzed the genotype–phenotype correlations in 275 CMTX1 patients belonging to 162 families and carrying 87 distinct variants. Patients with variants affecting the transmembrane domains demonstrated significantly greater severity, as evidenced by a Charcot‐Marie‐Tooth Examination Score of 10.5, compared to 7.1 for those with intracellular domain variants and 8.7 for extracellular domain variants (p < 0.000). These patients also experienced an earlier age of onset, showed slower ulnar nerve conduction velocities and had more substantial loss of motor amplitude. Conclusions This study confirms the presence of a correlation between the mutated protein domain and the clinical phenotype. Patients with a variant in the transmembrane domains demonstrated a more severe clinical and electrophysiological profile. Consequently, the genotype could play a prognostic role in addition to its diagnostic role, and it will be essential to consider this in future clinical trials.