Technologie Médicale (France)

Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: This retrospective study included 80 eyes from 61 consecutive patients with AMD who underwent multimodal imaging with color fundus images (CFIs), fundus autofluorescence (FAF), RAR imaging (Mirante, NIDEK), and en face optical coherence tomography (OCT) with B-scans (Cirrus HD-OCT 5000, Zeiss). Two independent retina specialists graded the AMD stage and the presence of pigment migration across modalities. Sensitivity and positive predictive value (PPV) of RAR were calculated using en face OCT as the reference standard. Results: RAR demonstrated high diagnostic performance, with a sensitivity of 94.7% and a PPV of 93.4% relative to en face OCT. RAR frequently identified pigment migration that was not visible on CFI or FAF, particularly in early AMD and in eyes with media opacity. Distinct morphologic patterns—including hyperreflective foci, thickened retinal pigment epithelium, refractile drusen, and cuticular drusen—were consistently identifiable on RAR. In four eyes with geographic atrophy, RAR detected perifoveal pigment redistribution at least six months before foveal involvement was confirmed by OCT and FAF. Conclusions: RAR imaging is a rapid, sensitive, and clinically practical technique for detecting pigment migration in AMD. By complementing en face OCT and enhancing visualization in cases where standard imaging is limited, RAR may strengthen early disease surveillance, support prognostic assessment, and improve multimodal diagnostic workflows in routine practice.

Drug toxicity and side effects are the cause of clinical trials failure, resulting in wasted investment and time. Liver injury is one of the leading causes of drug rejection in the clinical phase. Machine learning models have been developed to predict induced liver damage with significant results. We carried out a systematic review to identify and describe the AI strategies reported in the scientific literature for drug induced liver injury prediction. Using combinations of keywords, we retrieved articles from Google Scholar and PubMed database and analyzed them according to defined criteria. PRISMA guidelines were used in the articles selection process. The main algorithms reported were Random Forest, Support Vector Machine, Decision Tree, Neural network, K-Nearest Neighbors, XGBoosting and Logistic Regression. Random Forest seemed to perform better than others in same study. The US FDA DILI rank database was the main source of drugs and the AI models integrated diverse features as physicochemical properties, molecular fingerprints and genes expression. The diversity of training data ensures that the training data can provide more discriminating information for the model. Voting combinations-based ensemble is one of innovative strategy used for improving accuracy. Artificial intelligence remains a tool of choice for risk assessment and a definite ally in drug research and development.

The catalytically inactive caspase-8-homologous protein, c-FLIP, is a potent antiapoptotic protein highly expressed in various types of cancers. c-FLIP competes with caspase-8 for binding to the adaptor protein FADD (Fas-Associated Death Domain) following death receptors' (DRs) activation via the ligands of the TNF-R family. As a consequence, the extrinsic apoptotic signaling pathway involving DRs is inhibited. The inhibition of c-FLIP activity in tumor cells might enhance DR-mediated apoptosis and overcome immune and anticancer drug resistance. Based on an in silico approach, the aim of this work was to identify new small inhibitory molecules able to bind selectively to c-FLIP and block its anti-apoptotic activity. Using a homology 3D model of c-FLIP, an in silico screening of 1880 compounds from the NCI database (National Cancer Institute) was performed. Nine molecules were selected for in vitro assays, based on their binding affinity to c-FLIP and their high selectivity compared to caspase-8. These molecules selectively bind to the Death Effector Domain 2 (DED2) of c-FLIP. We have tested in vitro the inhibitory effect of these nine molecules using the human lung cancer cell line H1703, overexpressing c-FLIP. Our results showed that six of these newly identified compounds efficiently prevent FADD/c-FLIP interactions in a molecular pull-down assay, as well as in a DISC immunoprecipitation assay. The overexpression of c-FLIP in H1703 prevents TRAIL-mediated apoptosis; however, a combination of TRAIL with these selected molecules significantly restored TRAIL-induced cell death by rescuing caspase cleavage and activation. Altogether, our findings indicate that new inhibitory chemical molecules efficiently prevent c-FLIP recruitment into the DISC complex, thus restoring the caspase-8-dependent apoptotic cascade. These results pave the way to design new c-FLIP inhibitory molecules that may serve as anticancer agents in tumors overexpressing c-FLIP.

Ce papier présente les premiers résultats d’une recherche exploratoire qui vise le recadrage de la définition de projet sous l’angle de la création de valeur. Les projets majeurs se caractérisent par la variété et le nombre de parties prenantes avec des attentes multiples et souvent contradictoires. Les outils et méthodes de programmation architecturale ne sont pas adaptées pour répondre à cette complexité. Cependant, peu de recherche s’est penchée sur cette question. Cette recherche utilise une adaptation de la méthodologie de science de la conception inspirée de la théorie de l’activité dans le but de démontrer la nécessité de recadrer des pratiques actuelles de définition de projet. Les résultats confirment le besoin de revoir les pratiques actuelles de programmation architecturale par l’entremise de nouveaux outils axés sur la participation. Le papier se veut aussi un essai sur le potentiel de l’adoption de la théorie de l’activité en science de la conception afin de guider le recadrage des activités associées au projet.

Background and objectivesHepatitis E virus (HEV) can be considered an emerging zoonotic pathogen and is an important cause of acute viral hepatitis in high-income countries. Corsica has been identified as a hyperendemic region for HEV. We aimed to characterize the prevalence of IgG among children and estimate the annual force of infection of HEV.MethodsFrom April 2020 to June 2021, we collected 856 “residual sera” in 13 medical biology laboratories. Sera were tested using the Wantaï HEV IgG assay. Data were weighted according to the distribution by sex and age of the real Corsican population. Serocatalytic models were applied to assess the annual force of infection of HEV.ResultsThe weighted seroprevalence was 30.33% [27.15–34.0]. The seroprevalence was only associated with increasing age (7.25–40.52%; p < 0.001). The annual probability of infection was 5.4% for adults and children above 10-year-old and 2.2% for children under 10 yo.ConclusionOur study demonstrates that in the hyperendemic island of Corsica, (i) exposure of the population to HEV is homogeneous at the spatial level with no difference between genders; (ii) HEV exposure occurs from birth, resulting in 7.4% seropositivity at the age of 4 years; and (iii) super exposure is observed after the age of 9 years. Accordingly, specific studies should be conducted to determine the breadth of the situation identified in our study. The role of the environment and its contamination by domestic or wild swine excreta should be investigated using a One Health approach.

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from Acacia auriculiformis stem bark. Column chromatography and NMR spectroscopy were used to purify and characterize betulin from an ethyl acetate soluble fraction of acacia bark. Betulin, a known inducer of apoptosis, was screened against a panel of 16 disease-related protein kinases. Betulin was shown to inhibit Abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase, casein kinase 1ε (CK1ε), glycogen synthase kinase 3α/β (GSK-3 α/β), Janus kinase 3 (JAK3), NIMA Related Kinase 6 (NEK6), and vascular endothelial growth factor receptor 2 kinase (VEGFR2) with activities in the micromolar range for each. The effect of betulin on the cell viability of doxorubicin-resistant K562R chronic myelogenous leukemia cells was then verified to investigate its putative use as an anti-cancer compound. Betulin was shown to modulate the mitogen-activated protein (MAP) kinase pathway, with activity similar to that of imatinib mesylate, a known ABL1 kinase inhibitor. The interaction of betulin and ABL1 was studied by molecular docking, revealing an interaction of the inhibitor with the ABL1 ATP binding pocket. Together, these data demonstrate that betulin is a multi-target inhibitor of protein kinases, an activity that can contribute to the anticancer properties of the natural compound and to potential treatments for leukemia.