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Regorafenib plus modified gemcitabine-oxaliplatin in patients with advanced biliary tract cancer. The randomized phase Ib/II BREGO study
No full textInternational audienceBackground: New therapeutic options are needed for biliary tract cancer (BTC). Regorafenib, a multikinase inhibitor, shows promise in refractory digestive cancers and may be beneficial with conventional chemotherapy for BTC.Patients and Methods: The BREGO study evaluated regorafenib with modified gemcitabine-oxaliplatin (mGEMOX) in advanced or metastatic BTC. Phase I determined the recommended dose (RP2D) of regorafenib (80, 120 or 160 mg, days 1-14) combined with mGEMOX (gemcitabine 900 mg.m−2 IV, 30 min, followed by oxaliplatin 80mg.m−2 IV, 120 min, days 1 and 8). Phase II randomized (1:2) patients to mGEMOX alone (arm A) or mGEMOX + regorafenib (arm B, RP2D, days 1-14), assessing efficacy and safety, with the primary outcome being progression-free survival (PFS). Metabolic tumor features and response were also assessed.Results: In phase Ib, 22 patients were enrolled; in phase II, 66 patients (arm A, n = 24; arm B, n = 42). Four dose-limiting toxicities were observed, but no maximum tolerated dose was reached. The RP2D was 160 mg.d−1. Median PFS (7.2 vs7.8 months; P = .825) and overall survival (15.1 vs 13.5 months; P = .356) were similar between arms. However, posttreatment 18F-FDG tumor uptake (SULpeak) significantly correlated with PFS (P = .001) and OS (P = .016). Baseline plasma stanniocalcin 1 levels < 265 pg.mL−1 were associated with longer PFS (P = .030) and OS (P = .060) in both arms.Conclusions: Combining regorafenib and mGEMOX is feasible as first-line treatment for BTC but did not increase PFS as expected in the phase II cohort. Identifying new biomarkers can help target patients with advanced BTCs who may benefit from regorafenib-associated therapy
Des échanges épistolaires entre “Paralysés” aux échanges épistolaires et numériques avec des valides : le système des Cordées en France, 1932-2022
No full textInternational audienceThis article explains the history of the Cordées. This form of correspondence between people with disabilities was initiated and organized by the French association APF France Handicap as early as 1932 and continues to this day. The material that was analyzed includes letters and interviews with participants, as well as articles from Faire Face magazine and the Edelweiss newsletter. A four-stage presentation of the origins and evolution of the Epistolary Rope Teams is presented: 1) the passed-around notebooks, 2) the Cordées structuration, with an increase and then decrease in participants, 3) the Cordées’ social composition transformation, with the inclusion of able-bodied people and family caregivers, and 4) today’s Cordées, with the switch to digital technology, thematic diversification, and a significant decrease in participants.Cet article vise à expliquer l'histoire des Cordées -type d'échanges épistolaires entre personnes en grande dépendance pour les actes de la vie quotidienne impulsées et structurées au sein de l'APF France Handicap à partir de 1933 et ayant encore cours aujourd'hui. Le matériau analysé est composé de lettres et d'interviews de cordistes, d'articles issus de la revue Faire Face et de la newsletter l'Edelweiss. Ces données ont permis de remonter aux origines des Cordées et de proposer une présentation en quatre étapes de leur évolution : le recours aux cahiers circulants, la structuration des cordées en parallèle d'une croissance puis d'une décroissance du nombre de cordistes, la transformation de la composition sociale des cordées avec l'ouverture aux personnes valides et proches aidants, et, enfin les cordées d'aujourd'hui avec le passage au numérique, une diversification thématique et une décroissance importante du nombre de cordistes
Integrated Study of Martian Dust: Detection of Local Dust Storms, Estimation of Vertical Distribution, and Surface Pressure Analysis Using OMEGA Observations
No full textInternational audienceUnderstanding the Martian dust cycle is essential for clarifying the atmospheric circulation and meteorological phenomena. Unlike Earth, Mars has a thin atmosphere primarily composed of CO2, where atmospheric dust plays a dominant role in regulating the energy balance and driving atmospheric motion. Among various dust-related phenomena, Local Dust Storms (LDS), defined as storms that span less than 1.6 × 106 km2 or last fewer than three Martian days (Cantor et al., 2001), are particularly important for studying localized dust lifting and its potential connection to regional or global dust events (Martin and Zurek, 1993; Cantor et al., 2001; Hinson and Wang, 2010; Wang and Richardson, 2015). However, due to their limited spatial extent and short lifetimes, LDS have remained challenging to detect and characterize comprehensively.In this study, we developed a method for identifying LDS using data from the OMEGA (Observatoire pour la Minéralogie, l'Eau, les Glaces et l'Activité) imaging spectrometer onboard Mars Express (Bibring et al., 2004). Specifically, we used the strong CO₂ absorption band at 2.77 µm to retrieve dust optical depth. This band is sensitive to altitudes around 20–30 km and offers the critical advantage of being largely insensitive to surface reflectance properties. Applying this retrieval method to data from Martian Years (MY) 27 through 29, we detected 146 LDS events. Our statistical analysis revealed clear seasonal and diurnal patterns. LDS occurrences were most frequent during southern summer (Ls = 270°–360°), consistent with past findings that identify this season as conducive to dust activity (e.g., Smith, 2004; Montabone et al., 2015). However, we also observed an anomalously high frequency of LDS during northern summer in MY27 (Ls = 130°–150°), a period not typically associated with elevated dust activity. Furthermore, a noticeable increase in LDS activity was detected just before the onset of the Global Dust Storm (GDS) in MY28. Diurnally, LDS were most often observed near noon, implying that storm initiation may begin in the morning hours. Their spatial distribution varied significantly with season. During Ls = 0°–180°, LDS tended to be confined to specific regions such as Chryse Planitia and southern Acidalia. In contrast, during Ls = 180°–360°, LDS appeared more widely across mid-latitudes, with a notable absence in the northern high-latitude region (above 40°N). These results offer new insight into the role of LDS in the broader Martian dust cycle, particularly their potential influence on triggering regional or global events
Kre6-dependent β-1,6-glucan biosynthesis only occurs in the conidium of Aspergillus fumigatus
No full textInternational audienceABSTRACT The structural role of β-1,6-glucan has remained under-investigated in filamentous fungi compared to other fungal cell wall polymers, and previous studies have shown that the cell wall of the mycelium of A. fumigatus did not contain β-1,6-glucans. In contrast, the current solid-state NMR investigations showed that the conidial cell wall contained a low amount of β-1,6-glucan. ssNMR comparisons of the A. fumigatus and C. albicans β-1,6-glucans showed they are structurally similar. The deletion of the KRE6 gene which is the only KRE gene in the A. fumigatus genome resulted in a mutant depleted of β-1,6-glucan which has a growth phenotype similar to the parental strain. Even though it is not an essential polymer in A. fumigatus , β-1,6-glucan plays a role in cell wall organization since the kre6 Δ mutant showed a higher sensitivity to Congo-red and Calcofluor white which are known to be general cell wall inhibitors. It is also another example of the significant structural differences seen between conidium and mycelium of filamentous fungi. IMPORTANCE This study shows for the first time that β-1,6-glucans are found in Aspergillus fumigatus . Interestingly, this polysaccharide was specifically identified in conidia
Vers un outil web aidant les acteurs de l'aménagement du territoire (de la planification au design) à mieux intégrer les sols dans leurs processus et leurs pratiques.
No full textInternational audienceSoil is an essential part of the Earth continental surface, but it is submitted to a multitude of threats. The associated degradation is at risk for human being and ecosystems. That is why the integration of soil in spatial planning and design is essential. Spatial planners and designers however usually lack knowledge on soils. In addition, soils are not directly considered in current sectorial regulations. The European soil monitoring law should help increase awareness on soils and promote the use of the various tools and methods already developed to qualify soils. To fill the lack of tools to help planners and designers find out the right soil tools/methods to answer their needs along their process, the EU funded SPADES project is developing a webtool called Navigator. The objective of this abstract is to present the users’ need analysis to the soil community to get its feedback as a target group of the soil-planner Navigator. The users’ needs analysis is based on meetings with stakeholders from the pilots involved in the SPADES project, on a taskforce of stakeholders from the SPADES pilots and other volunteers. National and international events are also opportunities to interact directly with professionals and experts
Quand les « profs de gym » étaient naturistes. La nature au secours de l’éducation en temps de crise (1936-1948)
No full textInternational audienceLa période 1936-1948 est riche tant en crises qu’en ruptures. Pour autant, elle n’est pas exempte de continuités. Le recours à la nature dans les programmes scolaires d’éducation physique en est une des illustrations. Partant de ce premier constat, il s’agit d’interroger la place mais surtout le rôle conféré à la nature au sein de l’école, en particulier, en éducation physique. Plus précisément, quelle attention réserve-t-on aux discours et aux pratiques de ceux qui prônent alors un retour salvateur à la nature, autrement dit les naturistes ? Parmi l’éventail des propositions naturistes existantes, quels choix font les acteurs de l’école ? Pour ce faire, un large corpus de sources (textes officiels, revues, ouvrages d’époque) a été mobilisé. Concernant les résultats, on montrera que les thèses et les pratiques naturistes s’imposent au sein de l’éducation physique scolaire lors de cette période de crise. Celles-ci n’échappent pas cependant à un processus de sélection et de transposition scolaires. Elles sont mises ainsi au service d’usages éducatifs fort différents sous-tendant des projets politiques et culturels antagonistes. Quoi qu’il soit, c’est le naturisme d’Hébert et du Dr Carton qui tire le mieux son épingle du jeu
AI assisted detection of foraminifera in µCT-scanned sediment cores
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Decision-making Tool for Early Liver Retransplantation: The Early Liver Retransplantation Score
No full textInternational audienceBackground: Retransplantation (ReLT) is the only therapeutic option to treat early liver graft failure and to achieve the best graft/recipient combination that is essential to optimize patient and graft survival. This national study aimed to establish a donor and a recipient early liver retransplantation score (ELRS) to predict the risk of graft loss after early ReLT.Methods: Using the French national transplantation database, we analyzed all adult recipients who underwent a first or a second ReLT between 2007 and 2022 within the first 90 d post-liver transplantation (N = 477). Patients were randomly divided into derivation (DC) and validation cohorts (VC). A global transplant risk score was first derived from the DC using variables from donors and recipients using a Cox model and then tested in the VC. Two separate recipient and donor-risk scores have been built from this global score and were used to assess donor-recipient matching.Results: The factors at ReLT associated with 1-y graft loss were: for the donor: age >70 y, arterial hypertension, BMI >25 kg/m2; for the recipient: absence of hepatic artery thrombosis, mechanical ventilation, glomerular filtration rate <60 mL/min, ReLT after day 8 post-LT, and the presence of at least 1 complication at ReLT. Correlation between observed and predicted graft loss rate was close for the VC (r = 0.8). Four risk levels ranging from 48% to 79% 1-y graft survival were identified from the matching of donor and recipient scores.Conclusions: ELRS provides a decision-making tool to guide clinicians through the selection of candidates for early ReLT and to optimize donor-recipient matching to reduce the risk of graft loss
A new human in vitro model of cytotypic and testosterone-producing organoids derived from testicular tissue of transgender women
No full textInternational audienceStudy question: Can testicular tissue from trans women (trans tissue) be used to create human testicular organoids?Summary answer: Testosterone-producing and cytotypic human testicular organoids with bicompartmental architecture can be successfully generated from trans tissue.What is known already: Testicular organoids are a promising tool for studying testicular function and the effects of toxicants. Immature testicular cells are currently the most efficient at forming organoids that closely recapitulate seminiferous tubule-like architecture and functions. However, the scarcity of immature human testicular tissue limits its use in high-throughput applications. Conversely, trans tissue is abundantly available and characterized by an immature phenotype.Study design size duration: Trans tissue-derived organoids (trans organoids) were histologically and androgenically compared to reference organoids derived from immature (prepubertal and pubertal) and adult cisgender testicular tissues. Additionally, long-term testosterone production and gonadotrophic stimulation were assessed in trans organoids. To evaluate their cytotypic and transcriptomic resemblance to reference testicular tissue stages, trans organoids were compared at the gene expression level to prepubertal, pubertal, and adult cisgender tissues, along with their tissue of origin.Participants/materials setting methods: Testicular tissue samples from transgender women, as well as from prepubertal, pubertal, and adult cisgender donors, were used to generate testicular organoids and to compare organoid formation efficiency and testosterone production according to tissue origin. These samples also served as references for transcriptomic comparisons with organoids derived from transgender women's testicular tissue at Day 14 of culture. Testicular organoids were generated and cultured using 3D Petri Dish® platforms. Histochemistry and immunofluorescence staining were employed to characterize cellular composition and spatial organization. Testosterone production in culture media was assessed using electrochemiluminescence immunoassays. RNA was extracted and sequenced from organoids derived from transgender women, as well as from tissue samples of all donor groups. Deconvolution and differential gene expression analyses were performed to compare the organoids with testicular tissues across all groups.Main results and the role of chance: Trans organoids form compartmentalized, cytotypic de novo tissues similar to those from pubertal testicular tissue. Additionally, trans organoids exhibit significant testosterone production, sustain this function over extended culture periods, and respond to gonadotrophic stimulation. Deconvolved bulk RNAseq data indicate that cell population proportions within these organoids are close to those in prepubertal and pubertal testicular tissues. Gene expression clusters trans organoids alongside prepubertal and trans tissues. Functional analysis reveals that trans organoids share with prepubertal, pubertal, and trans tissues varied cellular processes. Factors such as the duration of hormone therapy, the expression of anti-Müllerian hormone-an immaturity marker-within the tubules, and the proportion of peritubular myoid cells in the donor tissue were found to predict the success of trans organoid formation.Large scale data: The bulk RNA-seq raw and preprocessed data are stored under restricted access in the Vrije Universiteit Brussel (VUB) Institutional Data Repository (VUB/IVTD/1/000001) due to participant privacy concerns. Access to the data will be considered by contacting Prof. Yoni Baert ([email protected]).Limitations reasons for caution: Hormonal data from trans women donors were not acquired in a convenient manner for this study. Deconvolution data allow only cell proportions to be compared, not absolute numbers.Wider implications of the findings: This study highlights the potential of trans organoids as a novel and ethically sustainable human-based model for male reproductive health research, reproductive toxicology, and endocrine disruption studies. While trans tissue is a valuable replacement for immature tissue, further research should focus on optimizing organoid architecture, evaluating their utility in reprotoxicity testing, and promoting germ cell differentiation.Study funding/competing interests: This study was conducted with financial support from the VUB Research Council (OZR4004) to S.M.S., the Scientific Research Foundation-Flanders (G026223N) and the Scientific Fund Willy Gepts to Y.B., the Strategic Research Program 89 from the VUB to E.G., and the Mireille Aerens Chair to T.V. The authors declare no conflict of interest
What Drives Generation Z’s Appetite for Crypto Investment? The Role of Financial Literacy, Gender, and Channels of Influence
No full textInternational audienceThis article investigates the factors influencing crypto knowledge and the growing interest in cryptoasset investment among French belonging to Generation Z . The empirical study of 1,050 young people reveals that general financial knowledge and gender have a significant effect on both crypto knowledge and ownership (men represent 85.2% of holders). Financial information channels exert a major influence in shaping investment behaviour. More precisely, financial websites and friends encourage real investment. Conversely, school, financial advisors and traditional media have a negative impact on actual crypto investment. When the wealth constraint is taken away, young potential investors have higher chances to be swayed by influencers and financial websites. These results highly question the role of social media in general, and finfluencers in particular, as a widely spread channel of financial information. While family, like friends, have a positive impact on the level of crypto knowledge, surprisingly, parents' socio-professional category has no influence. Nevertheless, those young raised in farming families are less likely to be or become crypto investors. This same negative effect on potential investment in cryptoassets is also found among young people with a strong interest in environmental issues. These findings, together with the high impact of the overconfidence bias, especially among men, and the importance of financial literacy in general and crypto literacy in particular, highlight the need for financial education in schools (starting at a young age) to mitigate risks and promote more informed and equitable investment participation across genders