University of Paris-Saclay

In pediatric pelvic or perineal rhabdomyosarcoma, organ preservation rates are high following neoadjuvant chemotherapy. We assessed the impact of combining external beam radiation therapy (EBRT) and brachytherapy (BT) on local control and functional outcomes. We retrospectively analyzed records of all children who received both EBRT and a BT boost in our department from 2005 to 2023. Data collected included tumor relapse, local control, survival and late toxicity rates. Treatment was administered as part of a multimodal conservative radio-surgical approach. Eighteen patients were identified, with a median age of 4years (range, 2.9 - 8.6years). According to the Intergroup Rhabdomyosarcoma Study (IRS) risk groups, 10 patients were classified as IRS-III and 8 as IRS-IV. Seven patients had metastases at diagnosis. The median number of chemotherapy cycles prior to local treatment was 8 (range, 5-10). Nine patients (50%) underwent prior conservative surgery, followed by radiation therapy consisting of both BT and EBRT. This combination was indicated for at least one the following reasons: nodal invasion (n=11, 61%), risk of peritoneal dissemination (n=3, 17%) and/or local extension (n=7, 39%). The median prescribed dose was 20Gy (range 12-30Gy) for BT and 50.4Gy (range, 18.8-55Gy) for EBRT. Two patients were treated with HDR BT, while the remaining received LDR (n=4) or PDR (n=12).The median follow-up period was 4.6years (range, 2.9-6.6years). At the last follow-up, failure free-survival was 67%, local control was 78% and overall survival was 83%. Four patients experienced grade II late urinary toxicities, including dysuria or incontinence in two patients. One patient required secondary cystectomy, and another received botulinum toxin injections in the bladder neck. Organ preservation with favorable functional outcome can be achieved in pelvic and perineal rhabdomyosarcoma by combining BT and EBRT, with or without prior surgery. This approach requires close collaboration to develop customized radiation therapy plans. Extended follow-up is necessary to assess long-term functional outcomes.

ABSTRACT Soil organic carbon (SOC) plays a central role in climate mitigation, ecosystem functioning, and soil health. Its prominence in recent European and international policy frameworks, such as the European Climate Law, the Soil Monitoring and Resilience Directive and the Carbon Removal Certification Framework, has created new demands for actionable, policy-relevant science. This paper reviews how advances in the understanding of organo-mineral associations can inform soil carbon policies, with a particular focus on the estimation of C sequestration potential in soils and the design of meaningful soil health indicators. It examines different approaches to estimate SOC storage potentials, including carbon saturation concepts and data-driven pedoclimatic benchmarking, and discusses the strengths and limitations of proposed indicators such as the SOC/clay ratio. The importance of terminology consistency, methodology harmonization, and stratification of results per pedoclimatic context is highlighted throughout. We argue for tiered and context-sensitive approaches to support robust, fair, and operational frameworks for soil monitoring and carbon accounting. By aligning scientific tools with the diversity of European landscapes and policy objectives, we can ensure that the rich and evolving understanding of organo-mineral interactions continues to shape credible, effective, and fair soil and carbon policies.

End-of-life legislation and the authorization of euthanasia or assisted suicide are highly debated topics in France. The challenges raised by the right to access continuous deep sedation and requests for assisted dying outside the current legal framework present many ethical challenges in clinical settings. Between 2017 and 2023, our Clinical ethics center was solicited 30 times regarding assisted dying requests and conducted full-fledged clinical ethics consultations in 14 of these situations. This experience offers a valuable opportunity for enhancing our understanding of these clinical situations and of the ethical considerations involved in several ways. First, it allows us to identify the tensions that requests for assisted dying may cause at the patient's bedside. Secondly, our experience allows us to confirm the relevance of clinical ethics consultations for all stakeholders involved in these situations. Finally, taking a closer look at the arguments exchanged by all concerned parties during the consultation process provides novel insights about the ethical debate about continuous deep sedation and assisted dying, in both the French context and internationally, by highlighting the issues of ambivalence, timing, and personal as well as professional responsibility.

Summary A key limitation in cancer transcriptomics is the lack of accompanying genomic profiling such as whole-genome sequencing (WGS) or copy number alteration (CNA) data. Here we address this by showing that RNA-seq alone can be used to infer chromosomal aberrations and identify biologically meaningful patterns in lung cancer. Through a large-scale meta-analysis of publicly available RNA-seq datasets from non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and matched controls, we reconstructed large scale CNA profiles and identified deletions in 3p, 9p, and 17p as the most frequent genomic events. Validation against paired WGS data confirmed a high degree of accuracy for RNA-seq-based inference. Our analyses revealed that while deletion-associated transcriptional heterogeneity exists, approximately 25% of differentially expressed genes were shared across all three deletion classes, indicating a conserved oncogenic program in lung cancer. Enrichment analysis linked these shared genes to pathways governing cell division, DNA replication, and extracellular matrix organization, while deletion-specific effects reflected disruption of tumor suppressor pathways, notably p53 signaling in 17p-deleted tumors, leading to deregulation of NOS2 and PLOD2. Integrating gene-level expression data, we identified both shared and deletion-specific biomarkers: TPX2 was consistently overexpressed across all deletion groups, while PTPRZ1 and CLDN9 were uniquely associated with del3p and del9p, respectively. Experimental validation in lung cancer cell lines confirmed these predictions, particularly the upregulation of CLDN9 in del9p carriers. By demonstrating that RNA-seq data can capture large-scale chromosomal events and reveal their transcriptional consequences, this study establishes an efficient framework for genomic inference and biomarker discovery, introducing CLDN9 as a novel, deletion-specific marker with potential prognostic and therapeutic value for 9p-deleted lung cancers.

This review summarizes current knowledge on the mineralocorticoid receptor (MR), a nuclear receptor encoded by the NR3C2 gene, and its ligand aldosterone. In epithelial tissues, such as the kidney, colon, salivary glands, and skin, particularly within the sweat glands, the MR plays a key role in regulating sodium reabsorption. In non-epithelial tissues, such as the brain, adipose tissue, and heart, glucocorticoids are the main physiological MR ligands due to the absence of the 11β-hydroxysteroid dehydrogenase type 2. MR expression begins during development with tissue-specific patterns. In the kidney, MR levels peak mid-gestation, decrease at birth, and then increase postnatally. Loss of MR function, as observed in pseudohypoaldosteronism type 1 causes salt-wasting syndrome. Similar patterns are seen in the heart and brain, especially the hippocampus, where it influences stress regulation. On the contrary, MR expression is maintained at birth in the lung for neonatal fluid clearance via epithelial sodium channels. It is also present in tissues such as skin, retina, and gastrointestinal tract, indicating broad physiological roles. MR expression during fetal development correlates with adaptations to extra-uterine life, such as changes in amniotic fluid osmolality and aldosterone levels. MR gene expression and activity are tightly regulated through multiple mechanisms. These include transcriptional control via two promoters, post-transcriptional regulation involving RNA-binding proteins and microRNAs, and post-translational modifications, such as phosphorylation, sumoylation, and ubiquitination. These regulatory levels ensure appropriate MR function across different tissues and developmental stages and may have implications for conditions such as hypertension and heart failure.

Laser surface hardening process is an advanced technology used to enhance metal surface properties through phase transformation. In recent decades, it has gained significant attention for its efficiency and precision. The glassmaking industry has shown interest in this technology as an alternative to laser cladding process, which causes environmental risks and machining challenges. This study aims to enhance AISI 431 stainless steel mold hardness without molten powder deposition. Surface hardening of AISI 431 stainless steel was carried out using continuous wave diode (940-1020 nm) and fiber (1070 nm) 4 kW laser sources. The influence of process parameters such as laser power (500-3040 W), scanning speed (4.5-8.5 mm/s) and number of laser head passes (1-4) were investigated on the hardened zone’s geometry, microhardness, and microstructure. Microstructural analysis was conducted using optical microscopy and scanning electron microscopy (SEM). The current findings revealed a significant increase in microhardness due to martensite formation, which decreased with depth as martensite content reduced. Results showed that beyond a certain limit, the hardness reaches a maximum value that, regardless of the parameters, can no longer increase. This mainly depends on several factors, such as material properties, processing parameters, and cooling conditions. Achieving a target hardness is possible by adjusting the number of passes, while the desired depth will primarily depend on the power and scanning speed.

In this study we investigated the relation between caecal microbiota composition and movement patterns in laying hens. We used hens from Pure line matings of Hendrix Genetics to continuously monitor the movement of individuals in a connected three-tier aviary throughout the laying period, from 18 to 60 weeks of age. The aviary contained three vertical tiers: a top-level, mid-level, and lower-level. In addition, the aviary had a floor littered and an attached wintergarden which was accessible from approximately 21 WOA onwards. Differences in the hens’ use of space were observed including: differences in the number of visits and time spent in the wintergarden and litter areas. Microbiota characterization, using 16S rRNA gene sequencing from 237 samples, revealed an association (P < 0.05) between microbiome composition and the number of visits to the litter. We observed differences (adjusted P-value < 0.05) between hens that frequently visited the litter (>30 times/day) and those that visited the litter less often (<10 times/day) in five bacterial families and seven genera. Notably, hens classified as visiting the litter less often, showed an increased abundance of Coriobacteriales, Peptococcales, Oribacterium and Lachnoclostridium taxa. Overall, this study offers new insights on the potential role of the microbiota in hen movement patterns.

Impaired intestinal barrier function is a major feature of Crohn's disease, leading to exacerbated inflammation in response to the microbiota. In this context, the translocation of intestinal bacteriophages (phages) and their effects on the host haven't been fully investigated. We use phage fluorescence imaging coupled with ex vivo, in vitro, and in vivo models that mimic physiological and inflammatory conditions and find that phages can translocate across the intestinal barrier without disrupting its integrity. While changes in the epithelial barrier integrity selectively impact phage translocation rates, alterations in the permeability of the vascular endothelium do not affect phage crossing. Virome analysis confirms that viral sequences shared between the blood and fecal samples of patients with Crohn's disease are more abundant than in healthy subjects, suggesting that a barrier defect facilitates intestinal phage translocation.

Trait-based approaches are key to understanding eco-evolutionary processes but rarely account for animal behaviour despite its central role in ecosystem dynamics. We propose integrating behaviour into trait-based ecology through movement traits-standardised and comparable measures of animal movement derived from biologging data, such as daily displacements or range sizes. Accounting for animal behaviour will advance trait-based research on species interactions, community structure and ecosystem functioning. Importantly, movement traits allow for quantification of behavioural reaction norms, offering insights into species' acclimation and adaptive capacity to environmental change. We outline a vision for a 'living' global movement trait database that enhances trait data curation by (1) continuously growing alongside shared biologging data, (2) calculating traits directly from individual-level data using standardised, consistent methodology and (3) providing information on multi-level (species, individual, within-individual) trait variation. We present a proof-of-concept 'MoveTraits' database with 52 mammal and 97 bird species, demonstrating calculation workflows for 5 traits across multiple timescales. Movement traits have significant potential to improve trait-based global change predictions and contribute to global biodiversity assessments as Essential Biodiversity Variables. By making animal movement data more accessible and interpretable, this database could bridge the gap between movement ecology and biodiversity policy, facilitating evidence-based conservation.

BackgroundMost individuals self-excluding from gambling have lost control over their gambling behavior. Commercial solicitations are prohibited during the self-exclusion period, but resume immediately afterwards. The self-exclusion system appears insufficient, particularly for short self-exclusions and among the heaviest gamblers. We assessed the impact of extending suspension of commercial solicitations on gambling intensity.MethodsIn this parallel randomized study, we included 2548 French online gamblers who self-excluded for up to 3 months from May–November 2022. They were assigned 1:1 to optimized self-exclusion with extended commercial solicitations ban for 9 months or standard procedure. The primary outcome was the change in total loss over the past 4 weeks at Month 9. We also assessed total deposit, total stakes, compulsivity, number and duration of gaming sessions and subsequent self-exclusions at 6, 9, 12 and 18 months.ResultsParticipants were randomized to the optimized group (n = 1265) or standard group (n = 1283). The results didn’t show a significant difference in the reduction in total losses. The optimized group showed significantly reduced 4-week total deposits versus standard group at 6 months (455.68 euros vs. 319.65 euros, p = 0.017), 9 months (451.92 euros vs. 343.21 euros, p = 0.040), and 12 months (484.27 euros vs. 370.02 euros, p = 0.025). Significance was lost at 18 months (492.61 euros vs. 404.73 euros, p = 0.087).ConclusionsAn extended 9-month ban on direct commercial solicitations after self-exclusion significantly reduces gambling deposits during, and 3 months after, the ban. This supports the effectiveness of improving self-exclusion procedure. Future research should explore longer bans and indirect commercial solicitations.Trial registration: NCT05413564.