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Considering the evolving and unpredictable job market, adaptability is an important skill for young adults. Such adaptability implies that schools need to teach key social competences, like communication, collaboration, or problem-solving. In this area, a gender gap has consistently been found, showing that boys display social competences less than girls. A large-scale nationwide multilab longitudinal experiment--the ProFAN project--was conducted in France among more than 10,000 vocational high-school students. Its primary goal was to develop and test an intervention promoting a range of psychological and psychosocial variables in vocational high schools, including social competences. This 2-year long, three-wave field experiment compared the effects of a cooperative learning method--the jigsaw classroom, that entails positive goal and resource interdependence--to two control conditions: one that involves cooperation with resource independence, and the other that remains business-as-usual. This article focuses on the differential development of perceived social competences of adolescent boys and girls over time, comparing the three pedagogical methods. Results of longitudinal multilevel modeling replicate the gender gap in perceived social competences and show that this gap widens with time. However, and most importantly, the analyses revealed that such widening of the gender gap was greater in the two control conditions than in the jigsaw condition, in which the evolution of boys' and girls' perceptions of social competences remained similar over time. Contributions to the understanding of the development and teaching of social competences in education settings are discussed.

Abstract Background Idiopathic intracranial hypertension (IIH) is a cause of chronic headaches that are probably driven by raised intracranial pressure (ICP). Cerebral venous sinus pressure is thought to play a role in the underlying pathology, but its relation with intracranial pressure requires further investigation. We aimed to evaluate the concordance between lumbar puncture opening pressure (LPOP) as indicator of the ICP and cerebral venous sinus pressure in patients investigated for IIH. Methods In this case-series replication study, all patients with IIH suspicion and who underwent cerebral venous sinus pressure measurement followed immediately by LP opening pressure (LPOP) measurement were retrospectively included. Pearson’s correlation and measurement agreement (Bland-Altman plots) between venous pressure and LPOP were analyzed. Results 52 consecutive patients (46 women; median age, 31 years [IQR = 25–42]) were included. The mean pressure in the superior sagittal sinus (SSS) and in the torcular were 20.9mmHg (SD ± 7.3) and 20.8 mmHg (SD ± 6.8), respectively. The mean LPOP was 22mmHg (SD ± 6.4). Pressure measured in the transverse venous sinus, the torcular, and the SSS correlated with LPOP (p

As part of our ongoing antileishmanial structure–activity relationship study, a structural simplification of the 3‐nitroimidazo[1,2‐a]pyridine ring to a 5-nitroimidazole moiety was conducted. A series of novel 2,4-disubsituted 5-nitroimidazole derivatives, including the 5-nitroimidazole analog of Hit A and the 4-phenylsulfonylmethyl analog of fexinidazole, were obtained by using the vicarious nucleophilic substitution of hydrogen (VNS) reaction, to substitute position 4, and by using the tetrakis(dimethylamino)ethylene methodology to modulate position 2. The molecular structures of eight novel 5-nitroimidazoles were characterized by 1H NMR, 13C NMR, LC/MS, and HRMS. The in vitro antileishmanial activity of these compounds was evaluated against the promastigote form of Leishmania infantum and their influence on cell viability was assessed on the human hepatocyte HepG2 cell line. The 4-phenylsulfonylmethyl analog of fexinidazole showed the best selectivity index of the series, displaying good activity against both the promastigote form of L. infantum (EC50 = 0.8 µM, SI > 78.1) and the promastigote form of Leishmania donovani (EC50 = 4.6 µM, SI > 13.6), and exhibiting low cytotoxicity on the HepG2 cell line (CC50 > 62.5 µM).

Exploring the potential of sodium‐based materials is of utmost importance, especially for next‐generation solid‐state batteries. Herein, Na3PS4 thiophosphate solid electrolyte is focused on. While its tetragonal α phase is initially studied for Na solid‐state batteries, the impact of heat treatment and the phase transitions of amorphous and semicrystalline polymorphs obtained by mechanochemical synthesis remains poorly understood. The structural evolution is evaluated as function of the temperature of amorphous and semicrystalline Na3PS4 polymorphs obtained by mechanochemical processes. Both samples are heat‐treated during an in situ synchrotron X‐ray diffraction measurement, and multiple phase transitions are detected, some of them being irreversible. A novel and abundant orthorhombic intermediary phase is observed when the heat treatment is performed on the amorphous sample. The ionic conductivity of both amorphous and semicrystalline samples undergoes significant enhancement after heat treatment, reaching 0.09 and 0.16 × 10−3 S cm−1, respectively. This research sheds light on the thermal dynamics of Na3PS4 polymorphs, providing valuable insights into their crystallization processes, especially in the amorphous‐to‐cubic transition. The discovered intermediate phases underscore the potential for further advancements in sodium‐based solid‐state battery technologies.

Introduction The high incidence of morbidity and mortality associated with the post-cardiac arrest (CA) period highlights the need for novel therapeutic interventions to improve the outcome of out-of-hospital cardiac arrest (OHCA) patients admitted to the intensive care unit (ICU). The aim of this study is to assess the ability of high-dose intravenous vitamin C (Vit-C) to improve post-CA shock.Methods and analysis This is a single-blind, open-label, multicentre, randomised controlled trial, involving 234 OHCA patients with post-CA shock planned to be enrolled in 10 French ICUs. Patients will be randomised to receive standard-of-care (SOC) or SOC with early high-dose intravenous Vit-C administration (200 mg/kg per day, within 6 hours after return of spontaneous circulation, for 3 days). The primary endpoint is the cumulative incidence of vasopressor withdrawal at 72 hours after enrolment, with death considered as a competing event. The main secondary endpoints are neurological outcome, mortality due to refractory shock, vasopressor-free days and organ failure monitored by the sequential organ failure assessment score.Ethics and dissemination The study protocol was approved by a French Ethics Committee (EC) on 21 February 2023 (Comité de Protection des Personnes Ile de France 1, Paris, France). Due to the short enrolment period to avoid any delay in treatment, the EC approved the study inclusion before informed consent was obtained. As soon as possible, patient and their relative will be asked for their deferred informed consent. The data from the study will be disseminated through conference presentations and peer-reviewed publications.Trial registration number NCT05817851.

Background Regular screening reduces mortality from colorectal cancer (CRC). The Canton of Vaud, Switzerland, has a regional screening programme offering faecal immunochemical tests (FITs) or colonoscopy. Participation in the screening programme has been low, particularly among complex patients. Patient navigation has strong evidence for increasing the CRC screening rate.Design and objective This feasibility study tested patient navigation performed by medical assistants for complex patients at an academic primary care practice.Baseline measurements A review of 328 patients’ medical charts revealed that 51% were up-to-date with screening (16% within the programme), 24% were ineligible, 5% had a documented refusal and 20% were not up-to-date, of whom 58 (18%) were complex patients.Intervention (February 2023 to May 2023) We tried to help complex patients participate in the screening programme using either in-person or telephone patient navigation. Each intervention was piloted by a physician-researcher and then performed by a medical assistant. Based on the reach, effectiveness, adoption, implementation, maintenance framework, we collected: Intervention participation and refusal, screening acceptance and completion and both patients and medical assistant acceptability (ie, qualitative interviews).Results Only 4/58 (7%) patients participated in the in-person patient navigation test phase due to scheduling problems. All four patients accepted a prescription and 2/4 (50%) completed their test. We piloted a telephone intervention to bypass scheduling issues but all patients refused a telephone discussion with the medical assistant. At two months after the last intervention, the proportion of patients up-to-date increased from 51% to 56%.Conclusion Our overall approach was resource-intensive and had little impact on the overall participation rate. It was likely not sustainable. New approaches and reimbursement for a specific patient navigator role are needed to increase CRC screening of complex patients.

The Group for the Promotion of Pharmaceutical Chemistry in Academia (GP2A) held its 31st annual conference in August 2023 at the Faculty of Pharmacy of Aix-Marseille University, Marseille, France. There were 8 keynote presentations, 10 early career researcher oral presentations and 23 poster presentations. Among them, four awards were delivered, two for best oral communications and two for the best poster presentations.

Abstract In this work, we propose a model-based deep learning reconstruction algorithm for optical projection tomography (ToMoDL), to greatly reduce acquisition and reconstruction times. The proposed method iterates over a data consistency step and an image domain artefact removal step achieved by a convolutional neural network. A preprocessing stage is also included to avoid potential misalignments between the sample center of rotation and the detector. The algorithm is trained using a database of wild-type zebrafish (Danio rerio) at different stages of development to minimise the mean square error for a fixed number of iterations. Using a cross-validation scheme, we compare the results to other reconstruction methods, such as filtered backprojection, compressed sensing and a direct deep learning method where the pseudo-inverse solution is corrected by a U-Net. The proposed method performs equally well or better than the alternatives. For a highly reduced number of projections, only the U-Net method provides images comparable to those obtained with ToMoDL. However, ToMoDL has a much better performance if the amount of data available for training is limited, given that the number of network trainable parameters is smaller.

Abstract Progress in neuroscience research hinges on technical advances in visualizing living brain tissue with high fidelity and facility. Current neuroanatomical imaging approaches either require tissue fixation (electron microscopy), do not have cellular resolution (magnetic resonance imaging) or only give a fragmented view (fluorescence microscopy). Here, we show how regular light microscopy together with fluorescence labeling of the interstitial fluid in the extracellular space provide comprehensive optical access in real-time to the anatomical complexity and dynamics of living brain tissue at submicron scale. Using several common fluorescence microscopy modalities (confocal, light-sheet and 2-photon microscopy) in mouse organotypic and acute brain slices and the intact mouse brain in vivo, we demonstrate the value of this straightforward ‘shadow imaging’ approach by revealing neurons, microglia, tumor cells and blood capillaries together with their complete anatomical tissue contexts. In addition, we provide quantifications of perivascular spaces and the volume fraction of the extracellular space of brain tissue in vivo.

A series of 61 thiazolidine-2,4-diones bearing a styryl group at position 5 was synthesized in 2–5 steps and their structure was proved by elemental and spectral analyses. The compounds obtained were evaluated in vitro against the promastigote stage of the kinetoplastid parasite Leishmania infantum and the human HepG2 cell line, to determine selectivity indices and to compare their activities with those of antileishmanial reference drugs. The study of structure–activity relationships indicated the potential of some derivatives bearing a nitro group on the phenyl ring, especially when located at the meta position. Thus, among the tested series, compound 14c appeared as a hit compound with good antileishmanial activity (EC50 = 7 µM) and low cytotoxicity against both the hepatic HepG2 and macrophage THP-1 human cell lines (CC50 = 101 and 121 µM, respectively), leading to good selectivity indices (respectively, 14 and 17), in comparison with the reference antileishmanial drug compound miltefosine (EC50 = 3.3 µM, CC50 = 85 and 30 µM, SI = 26 and 9). Regarding its mechanism of action, among several possibilities, it was demonstrated that compound 14c is a prodrug bioactivated, predominantly by L. donovani nitroreductase 1, likely leading to the formation of cytotoxic metabolites that form covalent adducts in the parasite. Finally, compound 14c is lipophilic (measured CHI LogD7.7 = 2.85) but remains soluble in water (measured PBS solubility at pH7.4 = 16 µM), highlighting the antileishmanial potential of the nitrostyrylthiazolidine-2,4-dione scaffold.

Abstract Background Data about critically ill metastatic cancer patients functional outcome after unplanned admission to the ICU are scarce. The aim of this study was to assess factors associated with 90-day return home and 1-year survival in this population. Study design and methods A multicenter retrospective study included all consecutive metastatic cancer patients admitted to the ICU for unplanned reason between 2017 and 2020. Results Among 253 included metastatic cancer patients, mainly with lung cancer, 94 patients (37.2%) could return home on day 90. One-year survival rate was 28.5%. Performance status 0 or 1 (OR, 2.18; 95% CI 1.21–3.93; P = 0.010), no malnutrition (OR, 2.90; 95% CI 1.61–5.24; P

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000–3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire’s mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history.