Sorbonne Université

Accurate soil organic carbon models are key to understand the mechanisms governing carbon sequestration in soil and to help develop targeted management strategies to carbon budget. The accuracy and reliability of soil organic carbon (SOC) models remains strongly limited by incorrect initialization of the conceptual kinetic pools and lack of stringent model evaluation using time-series datasets. Notably, due to legacy effects of management and land use change, the traditional spin-up approach for initial allocation of SOC among kinetic pools can bring substantial uncertainties in predicting the evolution of SOC stocks. The AMG model can fulfill these conditions as it is a parsimonious yet accurate SOC model using widely-available input data. In this study, we first evaluated the performance of AMGv2 before and after optimizing the potential mineralization rate (k 0) of SOC stock following a leave-one-site-out cross-validation based on 24 long-term field experiments (LTEs) in the Southwest of China. Then, we used Rock-Eval® thermal analysis results as input variables in the PARTY SOC machine learning model to estimate the initial stable SOC fraction (C S /C 0) for the 14 LTEs where soil samples were available. The results showed that initializing the C S /C 0 ratio using PARTY SOC combined with the optimized k 0 further improved the accuracy of model simulations (R 2 = 0.87, RMSE = 0.25, d = 0.90). Combining average measured C S /C 0 and k 0 optimization across all 24 LTEs also improved the model predictive capability by 25% compared to using default parameterization, thus suggesting promising avenue for upscaling model applications at the regional level where only a few measurement data on SOC stability can be available. In conclusion, the new version of the AMG model developed in the Tuojiang River Basin context exhibits excellent performance. This result paves the way for further calibration and validation of the AMG model in a wider set of contexts, with the potential to significantly improve confidence in SOC predictions in croplands over regional scales.

Increased severity or recurrence risk of some specific infectious diarrhea, such a salmonellosis or Clostridium difficile colitis, have been reported after an appendectomy in human patients. While several other mammals also possess an appendix, the suspected protective function against diarrhea conferred by this structure is known only in humans. From a retrospective collection of veterinary records of 1251 primates attributed to 45 species, including 13 species with an appendix and 32 without, we identified 2855 episodes of diarrhea, 13% of which were classified as severe diarrhea requiring a therapeutic medication or associated with a fatal issue. We identified a lower risk of severe diarrhea among primate species with an appendix, especially in the early part of life when the risk of diarrhea is maximal. Moreover, we observed a delayed onset of diarrhea and of severe diarrhea in species possessing an appendix. Interestingly, none of the primates with an appendix were diagnosed, treated or died of an acute appendicitis during the 20 years of veterinarian follow-up. These results clarify the function of the appendix among primates, as protection against diarrhea. This supports its presumed function in humans and is congruent with the existence of a selective advantage conferred by this structure.

Objective Mesial Temporal Lobe Epilepsy‐associated Hippocampal Sclerosis (MTLE‐HS) is a syndrome associated with various aetiologies. We previously identified CD34‐positive extravascular stellate cells (CD34+ cells) possibly related to BRAF V600E oncogenic variant in a subset of MTLE‐HS. We aimed to identify the BRAF V600E oncogenic variants and characterise the CD34+ cells. Methods We analysed BRAF V600E oncogenic variant by digital droplet Polymerase Chain Reaction in 53 MTLE‐HS samples (25 with CD34+ cells) and 9 non‐expansive neocortical lesions resected during epilepsy surgery (5 with CD34+ cells). Ex vivo multi‐electrode array recording, immunolabelling, methylation microarray and single nuclei RNAseq were performed on BRAF wildtype MTLE‐HS and BRAF V600E mutant non‐expansive lesion of hippocampus and/or neocortex. Results We identified a BRAF V600E oncogenic variant in 5 MTLE‐HS samples with CD34+ cells (19%) and in 5 neocortical samples with CD34+ cells (100%). Single nuclei RNAseq of resected samples revealed two unique clusters of abnormal cells (including CD34+ cells) associated with senescence and oligodendrocyte development in both hippocampal and neocortical BRAF V600E mutant samples. The co‐expression of the oncogene‐induced senescence marker p16 INK4A and the outer subventricular zone radial glia progenitor marker HOPX in CD34+ cells was confirmed by multiplex immunostaining. Pseudotime analysis showed that abnormal cells share a common lineage from progenitors to myelinating oligodendrocytes. Epilepsy surgery led to seizure freedom in 8 of the 10 patients with BRAF mutant lesions. Interpretation BRAF V600E underlies a subset of MTLE‐HS and epileptogenic non‐expansive neocortical focal lesions. Detection of the oncogenic variant may help diagnosis and opens perspectives for targeted therapies.

Background As the population ages, the number of elderly patients with an indication for pituitary surgery is rising. Information on the outcome of patients aged over 75 is limited. This study reports a large series assessing the feasibility of surgical resection in this specific age range, focusing on surgical complications and postoperative results. Methods A retrospective cohort study of patients with pituitary adenomas and Rathke’s cleft cysts was conducted. All patients were aged 75 years or over and treated by a single expert neurosurgical team. A control population included 2379 younger adult patients operated by the same surgeons during the same period. Results Between 2008 and 2022, 155 patients underwent surgery. Indication was based on vision impairment in most patients (79%). Median follow-up was 13 months (range: 3–96). The first surgery was performed with an endoscopic transsellar approach, an extended endonasal transtuberculum approach and a microscopic transcranial approach in 96%, 3%, and 1% of patients, respectively. Single surgery was sufficient to obtain volume control in 97% of patients. From Kaplan-Meier estimates, 2-year and 5-year disease control with a single surgery were 97.3% and 86.2%, respectively. Resection higher than 80% was achieved in 77% of patients. No vision worsening occurred. In acromegaly and Cushing’s disease, endocrine remission was obtained in 90% of non-invasive adenomas. Surgical complications were noted in 5% of patients, with 30-day mortality, hematoma, cerebrospinal fluid leak, meningitis, and epistaxis occurring in 0.6%, 0.6%, 1.9%, 0.6%, and 1.3% respectively. New endocrine anterior deficits occurred in only 5%, while no persistent diabetes insipidus was noted. Compared with younger patients, the complication rate was not statistically different. Conclusions Surgery beyond the age of 75, mainly relying on an endoscopic endonasal transsellar approach, is effective and safe, provided that patients are managed in tertiary centers.

Association with hypomethylating agents is a promising strategy to improve the efficacy of immune checkpoint inhibitors-based therapy. The NIBIT-M4 was a phase Ib, dose-escalation trial in patients with advanced melanoma of the hypomethylating agent guadecitabine combined with the anti-CTLA-4 antibody ipilimumab that followed a traditional 3 + 3 design (NCT02608437). Patients received guadecitabine 30, 45 or 60 mg/m²/day subcutaneously on days 1 to 5 every 3 weeks starting on week 0 for a total of four cycles, and ipilimumab 3 mg/kg intravenously starting on day 1 of week 1 every 3 weeks for a total of four cycles. Primary outcomes of safety, tolerability, and maximum tolerated dose of treatment were previously reported. Here we report the 5-year clinical outcome for the secondary endpoints of overall survival, progression free survival, and duration of response, and an exploratory integrated multi-omics analysis on pre- and on-treatment tumor biopsies. With a minimum follow-up of 45 months, the 5-year overall survival rate was 28.9% and the median duration of response was 20.6 months. Re-expression of immuno-modulatory endogenous retroviruses and of other repetitive elements, and a mechanistic signature of guadecitabine are associated with response. Integration of a genetic immunoediting index with an adaptive immunity signature stratifies patients/lesions into four distinct subsets and discriminates 5-year overall survival and progression free survival. These results suggest that coupling genetic immunoediting with activation of adaptive immunity is a relevant requisite for achieving long term clinical benefit by epigenetic immunomodulation in advanced melanoma patients.

Introduction While numerous randomized controlled trials (RCTs) have been conducted in the field of trauma, a substantial portion of them are yielding negative results. One potential contributing factor to this trend could be the lack of agreement regarding the chosen definitions across different trials. The primary objective was to identify the terminology and definitions utilized for the characterization of multiple trauma patients within randomized controlled trials (RCTs). Methods A systematic review of the literature was performed in MEDLINE, EMBASE and clinicaltrials.gov between January 1, 2002, and July 31, 2022. RCTs or RTCs protocols were eligible if they included multiple trauma patients. The terms employed to characterize patient populations were identified, and the corresponding definitions for these terms were extracted. The subsequent impact on the population recruited was then documented to expose clinical heterogeneity. Results Fifty RCTs were included, and 12 different terms identified. Among these terms, the most frequently used were “ multiple trauma” ( n = 21, 42%), "severe trauma" ( n = 8, 16%), "major trauma" ( n = 4, 8%), and trauma with hemorrhagic shock" ( n = 4, 8%). Only 62% of RCTs ( n = 31) provided a definition for the terms used, resulting a total of 21 different definitions. These definitions primarily relied on the injury severity score (ISS) ( n = 15, 30%), displaying an important underlying heterogeneity. The choice of the terms had an impact on the study population, affecting both the ISS and in-hospital mortality. Eleven protocols were included, featuring five different terms, with "severe trauma" being the most frequent, occurring six times (55%). Conclusion This systematic review uncovers an important heterogeneity both in the terms and in the definitions employed to recruit trauma patients within RCTs. These findings underscore the imperative of promoting the use of a unique and consistent definition.

As the global imperative for decarbonization gains momentum, the need for action in chemistry laboratories becomes increasingly apparent. This study examines the 2019 carbon footprint of three French chemistry laboratories encompassing energy, purchases, travels, and commutes. The average per capita carbon footprint stands at 5.6 teqCO2/year, positioning chemistry laboratories slightly above the median calculated across all disciplines. Key contributors are purchases (31–42%) and heating (23–33%), driven by fume hoods, heavy equipment and consumables. Attainable mitigations strategies suggest a 40-50% reduction by 2030. Pivotal efforts involve transitioning heating sources to renewables, extending equipment lifespan, collaborative resource management, as well as a limitation in the use of planes and thermic cars. Such changes imply actions at the level of the government, the university and the individual. We suggest fostering a sustainable research environment in chemistry laboratories by rationalizing experimental practices and dedicating time to consider the socio-environmental implications of research.

Understanding how climate change influences ocean-driven melting of the Antarctic ice shelves is one of the greatest challenges for projecting future sea level rise. The East Antarctic ice shelf cavities host cold water masses that limit melting, and only a few short-term observational studies exist on what drives warm water intrusions into these cavities. We analyse nine years of continuous oceanographic records from below Fimbulisen and relate them to oceanic and atmospheric forcing. On monthly time scales, warm inflow events are associated with weakened coastal easterlies reducing downwelling in front of the ice shelf. Since 2016, however, we observe sustained warming, with inflowing Warm Deep Water temperatures reaching above 0 °C. This is concurrent with an increase in satellite-derived basal melt rates of 0.62 m yr⁻¹, which nearly doubles the basal mass loss at this relatively cold ice shelf cavity. We find that this transition is linked to a reduction in coastal sea ice cover through an increase in atmosphere–ocean momentum transfer and to a strengthening of remote subpolar westerlies. These results imply that East Antarctic ice shelves may become more exposed to warmer waters with a projected increase of circum-Antarctic westerlies, increasing this region’s relevance for sea level rise projections.

In this biography of Martin Heidegger (1889–1976), now available in English, the connections between the German philosopher's life and work are synthesized. Critically, but without polemics, the book creates a portrait of Heidegger in his time, using all available sources—lectures, letters, and the notorious “black notebooks.” The book chronicles Heidegger's “changing destinies”: after the First World War, an uncompromising Catholicism gave way to a vigorous striving for a philosophical revolution—fertile ground for National Socialism. The book reflects a life of light and shadow. Heidegger was a great philosopher and teacher who cultivated friendships and love affairs with Jews but also was an anti-Semitic nationalist who lamented the “Judaization” of German intellectual life.

KIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mechanisms underlying its cellular roles remain elusive. Interestingly, unusual coupling between the nucleotide- and microtubule-binding sites of this kinesin-6 has been reported, but little is known about how its divergent sequence leads to atypical motility properties. We present here the first high-resolution structure of its motor domain that delineates the highly unusual structural features of this motor, including a long L6 insertion that integrates into the core of the motor domain and that drastically affects allostery and ATPase activity. Together with the high-resolution cryo-electron microscopy microtubule-bound KIF20A structure that reveals the microtubule-binding interface, we dissect the peculiarities of the KIF20A sequence that influence its mechanochemistry, leading to low motility compared to other kinesins. Structural and functional insights from the KIF20A pre-power stroke conformation highlight the role of extended insertions in shaping the motor's mechanochemical cycle. Essential for force production and processivity is the length of the neck linker in kinesins. We highlight here the role of the sequence preceding the neck linker in controlling its backward docking and show that a neck linker four times longer than that in kinesin-1 is required for the activity of this motor.

The broadly utilized biocide triclosan (TCS) is continuously discharged in water compartments worldwide, where it is detected at concentrations of ng-µg/L. Given its lipophilicity and bioaccumulation, TCS is considered potentially harmful to human and environmental health and also as a potential endocrine disruptor (ED) in different species. In aquatic organisms, TCS can induce a variety of effects: however, little information is available on its possible impact on invertebrate development. Early larval stages of the marine bivalve Mytilus galloprovincialis have been shown to be sensitive to environmental concentrations of a number of emerging contaminants, including EDs. In this work, the effects of TCS were first evaluated in the 48 h larval assay in a wide concentration range (0.001–1,000 μg/L). TCS significantly affected normal development of D-veligers (LOEC = 0.1 μg/L; EC 50 = 236.1 μg/L). At selected concentrations, the mechanism of action of TCS was investigated. TCS modulated transcription of different genes involved in shell mineralization, endocrine signaling, ceramide metabolism, and biotransformation, depending on larval stage (24 and 48 h post-fertilization-hpf) and concentration (1 and 10 μg/L). At 48 hpf and 10 μg/L TCS, calcein staining revealed alterations in CaCO 3 deposition, and polarized light microscopy showed the absence of shell birefringence due to the mineralized phase. Observations by scanning electron microscopy highlighted a variety of defects in shell formation from concentrations as low as 0.1 μg/L. The results indicate that TCS, at environmental exposure levels, can act as a developmental disruptor in early mussel larvae mainly by interfering with the processes of biomineralization.

Given a topological space X, a thickening kernel is a monoidal presheaf on (R≥0,+)\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$({{\mathbb {R}}}_{\ge 0},+)$$\end{document} with values in the monoidal category of derived kernels on X. A bi-thickening kernel is defined on (R,+)\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$({{\mathbb {R}}},+)$$\end{document}. To such a thickening kernel, one naturally associates an interleaving distance on the derived category of sheaves on X. We prove that a thickening kernel exists and is unique as soon as it is defined on an interval containing 0, allowing us to construct (bi-)thickenings in two different situations. First, when X is a “good” metric space, starting with small usual thickenings of the diagonal. The associated interleaving distance satisfies the stability property and Lipschitz kernels give rise to Lipschitz maps. Second, by using (Guillermou et al. in Duke Math J 161:201–245, 2012), when X is a manifold and one is given a non-positive Hamiltonian isotopy on the cotangent bundle. In case X is a complete Riemannian manifold having a strictly positive convexity radius, we prove that it is a good metric space and that the two bi-thickening kernels of the diagonal, one associated with the distance, the other with the geodesic flow, coincide.

Purpose Flexible ureteroscopy (fURS) is steadily gaining popularity in the management of renal calculi, including those located in the lower pole (LP). Due to difficulty in accessing to the LP of kidney in minority of cases with fURS and reports of lower stone-free rate (SFR), it is still considered as a challenge in selected cases. The purpose of the review was to analyze the various aspects of fURS for LP stones. Methods An extensive review of the recent literature was done including different factors such as anatomy, preoperative stenting, stone size, flexible scopes, types of lasers, laser fibers, suction, relocation, stone-free rates, and complications. Results The significance of various lower pole anatomical measurements remain a subject of debate and requires standardization. Recent improvements in fURS such as single-use digital scopes with better vision and flexibility, high power laser, thulium fiber laser, smaller laser fiber, and accessories have significantly contributed to make flexible ureteroscopy more effective and safer in the management of LP stone. The utilization of thulium fiber lasers in conjunction with various suction devices is being recognized and can significantly improve SFR. Conclusions With the significant advancement of various aspects of fURS, this treatment modality has shown remarkable efficacy and gaining widespread acceptance in management of LP kidney stones. These developments have made the fURS of LP stones less challenging.

The role of antiviral treatment in COVID‐19 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS‐2), using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020‐000936‐23), randomized to either standard of care (SoC) or SoC + remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS‐2 score lower than 3 (in patients with NEWS‐2<7 at hospitalization) or 5 (in patients with NEWS‐2 ≥7 at hospitalization), distinguishing between patients with low or high viral load at hospitalization. The model can fit well the different observed patients trajectories, showing that clinical evolution is associated with viral dynamics, albeit with large inter‐individual variability. Remdesivir antiviral activity was 22 and 78% in patients with low or high viral loads, respectively, which is not sufficient to generate a meaningful effect on NEWS‐2. However simulations predicted that antiviral activity greater than 99% could reduce by 2 days the time to clinical improvement in patients with high viral load, irrespective of NEWS2 score at hospitalization, while no meaningful effect was predicted in patients with low viral loads. Our results demonstrate that time to clinical improvement is associated with time to viral clearance and that highly effective antiviral drugs could hasten clinical improvement in hospitalized patients with high viral loads.