Pascal Pineau

Guinea has the highest incidence of hepatocellular carcinoma (HCC) in Sub-Saharan Africa (> 21 cases/100,000 habitants/year). This high incidence is largely attributed to the combination of a high prevalence of chronic hepatitis B virus (HBV) infection and significant exposure to aflatoxin B1 (AFB1), a known carcinogen. However, the clinical presentation of HCC in Guinea has not been well-documented to date. We conducted a retrospective analysis of 216 HCC cases from patients who received care between 2015 and 2023 at the Donka University Hospital in Conakry, the main tertiary care institution of the country. Demographical, clinical, and biological data were extracted from medical records and analyzed using both descriptive and inferential statistics. The median age of patients was relatively young, at 43.0 years (IQR = 34.5-55.0) with a male-to-female ratio of 3.1 (162/54). Half of the male patients were younger than 41 years. Chronic HBV infection was the predominant risk factor accounting for 75.0% of cases. Almost all patients have been exposed to HBV at some moment of their lives (total anti-HBc seropositivity: 92.2%). Chronic HBV infection was rarely replicative with only 7.8% of patients tested positive for HBeAg. Hepatitis C virus Infection was observed in a small subset of cases (7.9%). Toxic risk factors such as alcohol (12.5%) or tobacco (19.4%) were also rather infrequent. HBV-infected patients were significantly younger than non-HBV patients (median age: 40.0 vs. 50.5 years, p = 0.0109). Susu ethnicity, a Mande-speaking group primarily residing in Guinea's coastal plain was associated with an earlier onset of HCC than other ethnic groups (median age: 37.0 vs. 46.0 years, p = 0.0007). HBV infection is the major risk factor of HCC in Guinea with an earlier onset of the disease by nearly a decade compared to other risk factors. A notable ethnic variation was observed with Susu patients displaying a predisposition to early HCC. Further molecular research is needed to precisely assess the potential role of AFB1 in liver carcinogenesis of Guinean populations.

Despite decades of concern over the carcinogenic potential of agricultural pesticides, toxicological studies relying on single endpoints have yet to establish a definitive link between environmental pesticide exposure and cancer in real-world contexts. Here we use an integrative spatial Bayesian framework that merges high-resolution environmental pesticide risk modelling with comprehensive cancer registry data to map pesticide-linked cancer clusters in Peru with unprecedented precision. Our process-based model, encompassing 31 key pesticide active ingredients, together with an innovative stratification of cancer cases by developmental lineage, reveals a robust spatial association between environmental pesticide exposure risk and cancer incidence. In pesticide-associated cancer hotspots, exposomic profiling of liver tissue—a primary target of chemical carcinogens—uncovers a distinct transcriptomic signature of pesticide exposure, implicating a non-genotoxic mode of action that disrupts core regulatory circuitries sustaining cell identity. Collectively, these findings strongly support a mechanistic link between pesticide exposure and cancer, challenging assumptions of human non-carcinogenicity derived from reductionist experimental models. This study redefines the exposome as a lineage-conditioned, mechanistically tractable framework and shows how complex pesticide mixtures can contribute to carcinogenic trajectories, with profound and far-reaching implications for global health policy and socio-ecological equity.

Background: HDV, a defective virus dependent on hepatitis B for assembly, can lead to severe liver diseases and an increased risk of progressing to complications such as hepatocellular carcinoma. Given the high prevalence of HDV in Gabon, especially in central Africa, understanding the epidemiology and associated risks is crucial. Aim: This study aimed to assess the serological and molecular features of HDV among HBsAg‐positive patients in the urban and rural areas of Gabon. Method: The study was conducted from April 2019 to December 2022 in the Franceville area and from January to June 2023 in the Libreville area. We enrolled 145 newly diagnosed HBsAg‐positive individuals in Franceville (101) and Libreville (44). Plasma samples were collected for serological and molecular analyses, including tests for HDV antibodies and RNA detection. Result: The results showed an overall HDV prevalence of 26.2%, with higher rates in Libreville (18/44; 40.9%) compared to Franceville (20/101; 19.8%). Molecular analysis identified the circulation of genotypes I, VII, and VIII, with a predominance of replicative forms. The prevalence of replicative HDV RNA activity was 29.4%, indicating a need for accessible treatment options. Demographic analysis revealed a predominantly male population with an average age of 40. Conclusion: These findings provide valuable insights into the epidemiology of HDV in Gabon and emphasise the importance of targeted interventions and further research to address public health challenges associated with HDV infection in the region.

Introduction: Interactions between host and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are incompletely understood. Studies have highlighted the roles of L-dopa decarboxylase (DDC), interferon-inducible truncated isoform of angiotensin-converting enzyme 2 (dACE2), and immunomodulatory hypoxia-regulated gene erythropoietin (EPO) in viral infections. This study investigated the expression levels of DDC, dACE2, and EPO in 136 coronavirus disease 2019 (COVID-19) patients and 88 controls. Methodology: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to quantify mRNA levels of DDC, dACE2, and EPO; and the SARS-CoV-2 viral load in nasopharyngeal swabs. Results: Significantly elevated levels of dACE2 (p = 0.003), DDC (p = 0.004), and EPO (p = 0.006) were observed in patients compared to controls. No correlation with the viral load (DDC: r = 0.12, p = 0.136; EPO: r = 0.02, p = 0.802; dACE2: r = 0.05, p = 0.491), and no associations with age or gender (all p > 0.05) were noted. There were positive correlations between DDC and dACE2 mRNA levels in infected (r = 0.31, p = 0.0002) and uninfected individuals (r = 0.25, p = 0.015); and between DDC and EPO in infected (r = 0.22, p = 0.008) and uninfected individuals (r = 0.27, p = 0.010). There was a positive correlation between dACE2 and EPO mRNA levels in both groups (infected: r = 0.22, p = 0.007; uninfected: r = 0.38, p = 0.0002). Conclusions: DDC, dACE2, and EPO may contribute to COVID-19 pathogenesis through mechanisms independent of viral load, age, or gender.

In the original publication [...].

Pierre Tiollais, médecin et biologiste français, est décédé le 5 août 2024 à l’âge de 89 ans. Il a marqué l’histoire de la médecine par sa contribution au clonage et au séquençage du génome du virus del’hépatite B (VHB), ainsi que par le développement d’un des premiers vaccins recombinants contre ce virus. Professeur à l’Institut Pasteur et à l’Université Paris VII (maintenant Université Paris Cité), il a joué un rôle clé dans l’utilisation de la biologie moléculaire et du génie génétique, notamment dans la lutte contre le VHB et le virus de l’immunodéficience humaine (VIH). Son travail a contribué à sauver des millions de vies humaines grâce à des campagnes de vaccination. Pierre Tiollais était aussi reconnu pour son mentorat bienveillant et son engagement au service de la communauté scientifique.

Medulloblastoma (MB) is the most common malignant brain tumor in children, typically arising during infancy and childhood. Despite multimodal therapies achieving a response rate of 70% in children older than 3 years, treatment remains challenging. Ferroptosis, a form of regulated cell death, can be induced in medulloblastoma cells in vitro using erastin or RSL3. Using two independent medulloblastoma RNA-sequencing cohorts (MB-PBTA and MTAB-10767), we investigated the expression of ferroptosis-related molecules through multiple approaches, including Weighted Gene Co-Expression Network Analysis (WGCNA), molecular subtype stratification, protein–protein interaction (PPI) networks, and univariable and multivariable overall survival analyses. A prognostic expression score was computed based on a cross-validated ferroptosis signature. In training and validation cohorts, the regulation of the ferroptosis transcriptional program distinguished the four molecular subtypes of medulloblastoma. WGCNA identified nine gene modules in the MB tumor transcriptome; five correlated with molecular subtypes, implicating pathways related to oxidative stress, hypoxia, and trans-synaptic signaling. One module, associated with disease recurrence, included epigenetic regulators and nucleosome organizers. Univariable survival analyses identified a 45-gene ferroptosis prognostic signature associated with nutrient sensing, cysteine and methionine metabolism, and trans-sulfuration within a one-carbon metabolism. The top ten unfavorable ferroptosis genes included CCT3, SNX5, SQOR, G3BP1, CARS1, SLC39A14, FAM98A, FXR1, TFAP2C, and ATF4. Patients with a high ferroptosis score showed a worse prognosis, particularly in the G3 and SHH subtypes. The PPI network highlighted IL6 and CBS as unfavorable hub genes. In a multivariable overall survival model, which included gender, age, and the molecular subtype classification, the ferroptosis expression score was validated as an independent adverse prognostic marker (hazard ratio: 5.8; p-value = 1.04 × 10⁻⁹). This study demonstrates that the regulation of the ferroptosis transcriptional program is linked to medulloblastoma molecular subtypes and patient prognosis. A cross-validated ferroptosis signature was identified in two independent RNA-sequencing cohorts, and the ferroptosis score was confirmed as an independent and adverse prognostic factor in medulloblastoma.