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Liver transplantation represents the only definitive treatment for patients with end-stage liver disease. However, the shortage of liver donors provokes a dramatic gap between available grafts and patients on the waiting list. Whole liver bioengineering, an emerging field of tissue engineering, holds great potential to overcome this gap. This approach involves two main steps; the first is liver decellularization and the second is recellularization. Liver decellularization aims to remove cellular and nuclear materials from the organ, leaving behind extracellular matrices containing different structural proteins and growth factors while retaining both the vascular and biliary networks. Recellularization involves repopulating the decellularized liver with appropriate cells, theoretically from the recipient patient, to reconstruct the parenchyma, vascular tree, and biliary network. The aim of this review is to identify the major advances in decellularization and recellularization strategies and investigate obstacles for the clinical application of bioengineered liver, including immunogenicity of the designed liver extracellular matrices, the need for standardization of scaffold fabrication techniques, selection of suitable cell sources for parenchymal repopulation, vascular, and biliary tree reconstruction. In vivo transplantation models are also summarized for evaluating the functionality of bioengineered livers. Finally, the regulatory measures and future directions for confirming the safety and efficacy of bioengineered liver are also discussed. Addressing these challenges in whole liver bioengineering may offer new solutions to meet the demand for liver transplantation and improve patient outcomes.

Summary: Background: Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years. Prolonged follow-up of responders after treatment cessation shows sustained response and a low risk of relapse in the months following cessation. To date, the optimal duration of anti-PD-1 therapy for metastatic melanoma remains unestablished. The objective of this work was to evaluate the optimal duration of ICI administration. Methods: We emulated target trials using the cloning, weighting and censoring approach. Each emulation trial aimed to compare the effect of discontinuing versus continuing ICIs at a specific timepoint, among patients still under treatment and with disease control at that time. Patients were from MelBase between 2015 and 2021. Findings: 435 participants in the MelBase cohort were eligible and were included in the 6-month discontinuation emulated trial. The results showed significantly lower OS when treatment was discontinued, than when treatment was prolonged for at least three months. The 48-month survival difference was 37.8% (95% confidence interval [CI] 19.8–60.5), and the corresponding restricted mean survival time difference was 8.3 months (95% CI: 4.1–12.7). Neither the 12-month nor the 18-month discontinuation emulated trials showed evidence of benefit of either discontinuing or continuing ICIs at either of these timepoints. The 24-month discontinuation emulated trial results were more in favor of discontinuing than continuing treatment at that time point, with an absolute 48-month survival rate that was 10.5% higher (95% CI 4.4–18.1). Interpretation: These results suggest that a one-year course of immunotherapy is both necessary and sufficient for patients with advanced melanoma. Prolonged treatment beyond 2 years does not appear to be beneficial in terms of survival and could even be detrimental. Funding: This work was supported by a grant from Bristol Myers Squibb, Merck Sharp Dhome, Pierre Fabre, Novartis, Sun Pharm, Regeneron, Sanofi, Nektar, Therapeutics and Oncyte.

Objective To evaluate the feasibility of lung ultrasonography (LUS) performed by novice users’ general practitioners (GPs) in diagnosing lower respiratory tract infections (LRTIs) in primary health care settings.Design A prospective interventional multicenter study (December 2019–March 2020).Settings and subjects Patients aged >3 months, suspected of having LRTI consulting in three different general practices (GPs) (rural, semirural and urban) in France.Main outcome measures Feasibility of LUS by GPs was assessed by (1) the proportion of patients where LUS was not performed, (2) technical breakdowns, (3) interpretability of images by GPs, (4) examination duration and (5) patient perception and acceptability.Results A total of 151 patients were recruited, and GPs performed LUS for 111 (73.5%) patients (LUS group). In 99.1% (n = 110) of cases, GPs indicated that they were able to interpret images. The median [IQR] exam duration was 4 [3–5] minutes. LRTI was diagnosed in 70.3% and 60% of patients in the LUS and no-LUS groups, respectively (p = .43). After LUS, GPs changed their diagnosis from ‘other’ to ‘LRTI’ in six cases (+5.4%, p

Alors que l’inclusion scolaire est un droit pour tous les élèves quels qu’ils soient depuis 2005, elle peine encore parfois à se mettre en place au sein du système scolaire et particulièrement dans le secondaire. Si les élèves à besoins éducatifs particuliers sont présents dans les classes, les apprentissages ne leur sont pas toujours accessibles et les échecs sont nombreux. Cette étude menée auprès de 131 élèves de 3e dans un collège rural s’est intéressée à caractériser des profils de classe (plutôt que des profils d’élèves) à partir de questionnaires permettant aux enseignants de ces classes d’optimiser l’hétérogénéité et de l’appréhender comme une richesse pour leur mise en œuvre pédagogique. Les résultats montrent que les élèves étudiés ne présentent pas nécessairement le profil le plus pertinent pour développer les compétences linguistiques en français mais les analyses nous permettent de faire ressortir d’autres points d’entrée pouvant être des leviers au développement de ces compétences. La formation nous apparait comme une clé essentielle.

Secondary plasma cell leukemia (sPCL) is a rare form of aggressive plasma cell malignancy arising mostly at end-stage refractory multiple myeloma and consequently presenting limited therapeutic options. We analyzed 13 sPCL for their sensitivity to BH3 mimetics targeting either BCL2 (venetoclax) or BCLXL (A1155463) and showed that 3 sPCL were efficiently killed by venetoclax and 3 sPCL by A1155463. Accordingly, BH3 profiling of 2 sPCL sensitive to BCLXL inhibition confirmed their high BCLXL primed profile. While targeting BCLXL using BH3 mimetics induces platelets on-target drug toxicity, the recent development of DT2216, a clinical-stage BCLXL proteolysis targeting chimera PROTAC compound, provides an alternative strategy to target BCLXL. Indeed, DT2216 specifically degrades BCLXL via VHL E3 ligase, without inducing thrombocytopenia. We demonstrated in human myeloma cell lines and sPCL that sensitivity to DT2216 strongly correlated with the sensitivity to A1155463. Interestingly, we showed that low doses of DT2216 (nM range) were sufficient to specifically degrade BCLXL after 48 hours of treatment, consistent with VHL expression, in all cell lines but irrespectively to DT2216 sensitivity. In myeloma cells, DT2216 induced apoptotic cell death and triggered BAX and BAK activation. In conclusion, our study demonstrated that patients with sPCL addicted to BCLXL, a small but a very challenging group, could potentially receive therapeutic benefit from DT2216. Clinical trials of DT2216 in this subset of sPCL patients are warranted.

Evaporation reduction is one of the advantages provided by floating photovoltaic (FPV) power plants. However, few studies have yet been carried out to understand how to optimise the layout of FPV power plants in order to provide better water management. Indeed, the interaction between atmospheric conditions, water bodies, and the FPV plant creates a dynamic system that is challenging to study and accurately model. This paper investigates the impact on evaporation of various characteristics of FPV plants, such as float technology, plant positioning and orientation, distribution, and coverage ratio. This study was performed using Computational Fluid Dynamics (CFD) of the surrounding atmosphere, with the impact of the FPV plant modelled using specific boundary conditions to reduce computational costs. The numerical results show that the coverage ratio is the most important factor in reducing evaporation. Full coverage could reduce evaporation by 52.8% for a plant with a large footprint on the water and by 43.4% for a plant with a smaller footprint. Other parameters have only a moderate impact, allowing the fine-tuning of evaporation reduction. The optimal configuration would involve covering the entire water body with a single large water footprint island positioned downwind of the prevailing transversal winds. This setup significantly reduces evaporation, thereby enhancing water conservation and making an FPV power plant a valuable tool in sustainable water management.

Introduction Understanding suicide in more isolated territories is a challenge because of the entanglement of cultural identity with historical, geographical and sociocultural specificities. This knowledge is a necessary precondition for the implementation of targeted prevention strategies in regions such as the French overseas territories (FOT), where data concerning suicidal risk factors is still incomplete. We aim to untangle sociocultural and clinical suicide risk factors by integrating a novel anthropological and psycholinguistic approach into the psychological autopsy method. This article describes the protocol of the clinical study ‘Contribution of Psychological Autopsy to the Understanding of Suicidal Behaviours in Overseas France’ (AUTOPSOM study), designed to identify common or new specific suicide risk factors in four FOT.Methods and analysis A multicentre epidemiological study will be carried out in four FOTs (French Polynesia, Martinique, La Reunion and French Guiana) and at a comparison site in mainland France (La Somme). The methodology will be based on a mixed-methods (quantitative and qualitative) approach using a psychological autopsy to collect clinical data and life events in the deceased’s life. We implemented an exploratory multimethod strategy that combines a succession of epidemiological, anthropological, psycholinguistic and psychological methods with a semiautomated analysis of the discourse of relatives bereaved by suicide.Ethics and dissemination The study protocol (first version) was approved by the French Ethics Committee (CPP OUEST II, approval #22.04267.000122) and the Ethics Committee of French Polynesia (JOPF of 5 April 2022; CEPF opinion n°91 of 29 March 2022). The overall results and the perspectives established at the end of the study will be communicated to the bereaved relatives according to their will and serve for local suicide prevention purposes.Trial registration number NCT05773898.

Abstract While pet ownership is normative in many occidental countries, whether humans’ proximal contacts with pets have implications for attitudes and behaviors toward other (non pet) animals, nature, and fellow humans, has received limited empirical attention. In a large representative sample, we investigate whether pet ownership and positive contact with pets are associated with more positive attitudes and heightened concerns for non-pet animals, nature, and human outgroups. A cross-sectional questionnaire survey was conducted among Canadian adults (619 pet owners, 450 non-pet owners). Pet owners reported more positive attitudes toward non-pet animals (e.g., wild, farm animals), higher identification with animals, more positive attitudes toward human outgroups, higher biospheric environmental concerns, higher human–environment interdependence beliefs, and lower usual meat consumption. Positive contact with pets was also associated with most of these outcomes. Solidarity with animals, a dimension of identification with animals, emerged as a particularly clear predictor of these outcomes and mediated the associations between positive contact with pets and positive attitudes toward non-pet animals, biospheric, egoistic, and altruistic environmental concerns, human–environment interdependence beliefs, and diet. Our results provide support for the capacity of pets to shape human consideration for a broad range of social issues, beyond the specific context of human-pet relations.

BackgroundMajor depressive disorder is one of the leading causes of disability worldwide. Although most international guidelines recommend psychological and psychosocial interventions as first-line treatment for mild to moderate depression, access remains limited in France due to the limited availability of trained clinicians, high costs for patients in the context of nonreimbursement, and the fear of stigmatization. Therefore, online blended psychological treatment such as Deprexis could improve access to care for people with depression. It has several advantages, such as easy accessibility and scalability, and it is supported by evidence. ObjectiveThis study aims to evaluate the real-life acceptability of Deprexis for people with depression in France outside of a reimbursement pathway. MethodsDeprexis Acceptability Study Measure in Real Life (DARE) was designed as a multicenter cross-sectional study in which Deprexis was offered to any patient meeting the inclusion criteria during the fixed inclusion period (June 2022-March 2023). Inclusion criteria were (1) depression, (2) age between 18 and 65 years, (3) sufficient French language skills, and (4) access to the internet with a device to connect to the Deprexis platform. Exclusion criteria were previous or current diagnoses of bipolar disorder, psychotic symptoms, and suicidal thoughts during the current episode. The primary objective was to measure the prospective acceptability of Deprexis, a new digital therapy. Secondary objectives were to examine differences in acceptability according to patient and clinician characteristics and to identify reasons for refusal. All investigators received video-based training on Deprexis before enrollment to ensure that they all had the same level of information and understanding of the program. ResultsA total of 245 patients were eligible (n=159, 64.9% were women and n=138, 56.3% were single). The mean age was 40.7 (SD 14.1) years. A total of 78% (n=191) of the patients had moderate to severe depression (according to the Patient Health Questionnaire-9 [PHQ-9]). More than half of the population had another psychiatric comorbidity (excluding bipolar disorder, psychotic disorders, and suicidal ideation). A total of 33.9% (n=83) of patients accepted the idea of using Deprexis; the main reason for refusal was financial at 83.3% (n=135). Multivariate logistic regression identified factors that might favor the acceptability of Deprexis. Among these, being a couple, being treated with an antidepressant, or having a low severity level favored the acceptance of Deprexis. ConclusionsDARE is the first French study aiming at evaluating the prospective acceptability of digital therapy in the treatment of depression. The main reason for the refusal of Deprexis was financial. DARE will allow better identification of factors influencing acceptability in a natural setting. This study highlights the importance of investigating factors that may be associated with the acceptability of digital interventions, such as marital status, medication use, and severity of depression.

Introduction Prevention of relapse in schizophrenia is a major public health issue. A recent network meta-analysis investigating interventions for relapse prevention in schizophrenia found that the efficacity of family psychoeducation and systemic integrated interventions were superior to treatment as usual at 12 months (Bighelli I, Leucht S et al. Lancet Psychiatry 2021). Other studies also found that multi-family therapies (MFT) were superior to treatment as usual and family psychoeducation in preventing relapses at 2 and 4 years (McFarlane WR, Lukens EP et al. Archives of General Psychiatry.1995). Considering this, we developped in our community center an MFT program based on systemic approach and psychoeducation. Objectives Investigate the subjective experience of participants of an MFT group focusing on schizophrenia. Methods A qualitative study was designed to explore personal experience of participants using the Interpretative Phenomenological Analysis (IPA) method in order to analyse participant’s feedback during semi-directive interviews. By using IPA, participants are experts of their experience. Eight participants took part in this study: 4 patients and 4 parents. Results Within all participant’s feedback around 10 different themes emerged. We identified three major themes which we have described as: “Affiliation to the group”, “Framework of Discovery”, “Benefits of MFT”. According to “Affiliation to the group”, all participants report movements of adhesion or rejection towards the group. This theme has been subdivided into two sub-themes: “Temporality”, and “Identification/differentiation”. These sub-themes revealed inter-individuals’ differences. According to “Framework of discovery”, the MFT group has been identified as a secure place allowing self and other’s discovery place. This theme has been divided into two sub-themes: “discovering skills” and “improving oneself and relatives’ understanding”. Participants experience taking a step back and decentering oneself from usual personnal position. According to “Benefits of MFT”, participants report the feeling of belonging to a group, the impact on self-esteem, on mentalization skills, and on the reflexion on family members’ experience of the disease. Conclusions This study is, to our knowledge, the first qualitative study examining the subjective experience of members who participated in a psychoeducational and systemic MFT group focusing on schizophrenia. It provides insight into the families’ experience, both from the patient’s and from each family member’s perspective. Results highlight that participants seized the MFT group as a learning space at several levels: personal, intra-family and inter-family. These data could enlighten professionals working with families on the potential apprehensions of participants, their representations of the group and what process MFT could initiate. Disclosure of Interest None Declared

Introduction Guidelines for relapse prevention in schizophrenia recommend psychoeducation for patients and caregivers (Bighelli I, Leucht S et al. Lancet Psychiatry 2021). Considering that, in 2021, we implemented in our Psychiatric community center a multifamily therapy (MFT). The program is based on systemic approach and psychoeducation, focusing on schizophrenia. Objectives Describe participants of MFT groups focusing on schizophrenia. * Patients’ characteristics : age, gender, duration of psychiatric follow-up, history of hospitalization * Caregivers’ characterics: status, age. Methods We carried out a descriptive study of the different profile of MFT groups participants in our community center from 2021 to today. Results Since 2021, 4 MFT groups took place including 50 participants: 18 patients suffering from schizophrenia and 32 relatives. Image 1 illustrates the different participants of each group. Each group was different. Some patients came with both their parents, even if divorced, some came only with their mother. Some came with a sibling. Nevertheless, the numbers of fathers and siblings did not always allow us to work in sub-groups. Considering patients: 18 patients benefited from our program. 8 female and 10 male patients (55.6%) were admitted and distributed in each group as described in image 2. The mean age of patients was 31.9 years old [20.1 – 57.5]. Each group was made up of patients with psychiatric follow-up ranging from 1 year to more than 20 years, and having experienced between 1 to more than 5 psychiatric hospitalizations. It appears that Group 4 was noticeably younger than the other groups with a mean age of 22.4 years old [20.4 – 26.7] and a shorter history in psychiatry with less hospitalisations (image 3). Considering relatives: 15 mothers, 9 fathers, 5 siblings, 1 spouse, 1 aunt and 1 uncle benefited from psychoeducation to caregivers. The relatives were from 47 to 81 years old for the parents, and from 17 to 50,7 for the siblings. Unlike parents, siblings generally attended a limited number of sessions. Image: Image 2: Image 3: Conclusions This descriptive study reflects the work carried out with 18 patients and their relatives in an MFT group providing psychoeducation to patients suffering from schizophrenia and their caregivers. 50 persons benefited from psychoeducation in 2 years. We learned from these results to improve the constitution of our groups and the benefits of our psychoeducation program. We were careful to include families with siblings as we know they are affected by the mental illness in the family and are often left aside of all care/support proposals. We questioned ourselves on the advantages of homogeneous or heterogeneous groups, considering age, history of follow up. How could it impact affiliation to the group or differentiation movements ? How useful or harmful it is for sharing experiences between the families. A proper study would be necessary to answer these questions. Disclosure of Interest None Declared

PurposeNumerous scoring systems have been developed in order to determine the prognosis of spinal metastases. Predicting as accurately as possible the life expectancy of patients with spinal metastatic disease is very important, as it's the decisive factor in selecting the optimal treatment for the patient. The Revised Tokuhashi score (RTS) and the New England Spinal Metastasis score (NESMS) are popular scoring systems used to determine the optimal treatment modality. However, they sometimes provide conflicting results. We propose a novel prognostic scoring system, which combines the RTS and NESMS scores in order to predict with greater accuracy the prognosis.MethodsWe retrospectively reviewed the data of 64 patients with spinal metastasis enrolled between 2012 and 2021 in the Department of Orthopedic Surgery-Spine, Hôpital Maisonneuve-Rosemont, Montréal, Que. The new score per patient was calculated as a combination of the RTS of each patient and the patient's corresponding NESMS. The new score was then compared to the actual patient survival period and divided into 3 categories: Low, Moderate and Good prognosis. We then compared the accuracy of our new score to RTS.ResultsIn the Low Prognosis group, the reliability of predicting the prognosis was 51.9% in 27 patients. In the Moderate Prognosis group, the reliability of predicting the prognosis was 95.8% in 24 patients. In the Good Prognosis group, the reliability of predicting the prognosis was 100% in 13 patients. Our new score was found more accurate than RTS as the R2 parameter corresponding to the new score was significantly increased compared to the same parameter corresponding to the RTS score indicating a higher percentage of survival predictability for the new score as compared to the RTS score.ConclusionThis study demonstrates that a new prognostic scoring system, which would combine the RTS and the NESMS, is promising in providing an improved accuracy for predicting the actual patient survival, especially for the moderate and good prognosis patients. An appropriate prospective investigation with a larger sample size should be conducted in order to further investigate the validity of this novel scoring system and its overall predictive value.

IntroductionAcute liver failure (ALF) is defined as acute loss of liver function leading to hepatic encephalopathy associated with a high risk of patient death. Brain injury markers in serum and tissue can help detect and monitor ALF-associated brain injury. This study compares different brain injury parameters in plasma and tissue along with the progression of ALF.MethodALF was induced by performing an 85% liver resection. Following the resection, animals were recovered and monitored for up to 48 h or until reaching the predefined endpoint of receiving standard medical therapy (SMT). Blood and serum samples were taken at Tbaseline, T24, and upon reaching the endpoint (Tend). Control animals were euthanized by exsanguination following plasma sampling. Postmortem brain tissue samples were collected from the frontal cortex (FCTx) and cerebellum (Cb) of all animals. Glial fibrillary acidic protein (GFAP) and tau protein and mRNA levels were quantified using ELISA and qRT-PCR in all plasma and brain samples. Plasma neurofilament light (NFL) was also measured using ELISA.ResultsAll ALF animals (n = 4) were euthanized upon showing signs of brain herniation. Evaluation of brain injury biomarkers revealed that GFAP was elevated in ALF animals at T24h and Tend, while Tau and NFL concentrations were unchanged. Moreover, plasma glial fibrillary acidic protein (GFAP) levels were negatively correlated with total protein and positively correlated with both aspartate transaminase (AST) and alkaline phosphatase (AP). Additionally, lower GFAP and tau RNA expressions were observed in the FCTx of the ALF group but not in the CB tissue.ConclusionThe current large animal study has identified a strong correlation between GFAP concentration in the blood and markers of ALF. Additionally, the protein and gene expression analyses in the FCTx revealed that this area appears to be susceptible, while the CB is protected from the detrimental impacts of ALF-associated brain swelling. These results warrant further studies to investigate the mechanisms behind this process.