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Analysis of predictors of rabies-positive biting animals in Cambodia using spatio-temporal Bayesian regression modelling
No full textInternational audienceCambodia is endemic for rabies, a fatal zoonotic viral disease transmitted through dog bites. The Institut Pasteur du Cambodge through its Rabies Prevention Center is the main institution in charge of rabies prevention and surveillance in the country. Its main tool for prevention is post-exposure prophylaxis (PEP) for bite victims. Allocation of specific PEP regimen is done based on the assessment of the severity of the wound and the information collected by IPC doctors from patients regarding the attack’s characteristics and the attacking animal’s health status. Furthermore, a small proportion of patients bring animals for testing, 60% of which were tested positive for rabies. Using the data collected from patient interviews from 2000 to 2016, we used a Bayesian spatio-temporal regression model to identify predictors for two outcomes: i) a patient bringing an animal for testing and ii) an animal testing positive for rabies. The ultimate aim of the analysis was to provide information that could help with allocation of PEP resources. Notably non-owned animals, a large number of bite victims, and unprovoked attacks were all predictive of a positive test. A suspected rabies status assigned by doctor based on animal symptom description was also highly predictive of a rabies test, with 94.6% of tested animals that were assigned as sick being positive for rabies. Furthermore, we identified three Provinces of Cambodia with higher odds of positive tests: Kampong Cham, Kandal and Kampong Thom. This information could help allocate limited PEP resources, though this study showed IPC already a strong protocol to identify patients exposed to a rabies suspect dog
Deep learning models reading clinical data and liver omics strongly distinguish NASH from steatosis and suggest new genes involved in liver disease severity
No full textBackground & Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is a frequent co-morbidity of obesity and diabetes, with prevalence increasing worldwide. Recognising liver disease stages and elucidating the molecular underpinning of their progression are thus medically important. Methods Using data gathered from 300 patients with obesity of the ABOS cohort, we selected non-redundant clinical variables, gene expressions and CpGs methylation levels most associated with severity using unsupervised approaches to train a multi-module, multi-layer perceptron predicting patients liver status. Results The combination of five models trained on the three modalities reached an AUC of 0.945 on a validation set, with accuracies above 81% for simple steatosis and 88% for NASH, outperforming other machine learning models so far. The latent space of our clinical data module retrieved patient clusters identified previously, but not the gene expression and DNA methylation ones. While all three modules are needed to reach the best prediction accuracy in all classes, the gene expression module impacted the decision the most. Independently trained models put more weights on the same genes, underlying their importance. Impactful genes were linked to immune responses and extracellular matrix. Many of those genes were previously unassociated with MASLD onset or progression. Conclusions A multi-omics deep-learning model can recognise steatohepatitis from simple liver steatosis with an AUC of 0.945 and identify new genes potentially involved in NAFLD progression. Gene expressions profiles predicting disease severity are largely different from those specific of clinical variable clusters. Impact and implications: This study suggests that clinical variables are not sufficient to recognise the severity of steatotic liver disease with high accuracy, but model efficiency increases when used together with liver epigenetics and transcriptomics
The potential of attractive insecticide-treated nets (ITNs) in reducing malaria transmission: a modeling study
No full textInternational audienceRecent studies suggest that insecticide-treated nets (ITNs) may actively attract malaria vectors, increasing their likelihood of coming into contact with the insecticide while potentially reducing personal protection. The impact of such attractive ITN on malaria transmission at the community level remains unclear. In this study, we developed a model to compare the effectiveness of attractive, inert and deterrent ITNs under varying levels of human usage and different degrees of physiological or behavioral resistance to insecticides in malaria vectors. We developed a model to simulate the host-seeking, feeding and mortality (HSFM) of mosquito vectors facing ITNs. This model allows mosquitoes to choose between two rooms based on the presence and remote influence (attractive, inert or deterrent) of ITNs. The HSFM model was then integrated into a malaria transmission model to compare the Plasmodium transmission potential of mosquitoes exposed to these different type of ITNs under various scenarios of ITN coverage, physiological resistance, quantitative behavioral resistance, and qualitative behavioral resistance. The model predicts that attractive ITNs consistently reduce malaria transmission potential of vectors more effectively than inert or deterrent ITNs, even in the presence of resistant vector phenotypes. For instance, at intermediate use rate (50%), strongly attractive ITNs are expected to reduce transmission by up to 67% compared to deterrent ITNs. In resistant vector populations, attractive ITNs remained more effective overall, though the reduction in transmission were less pronounced. Our findings suggest that both inert and attractive ITNs could enhance malaria control efforts, outperforming current deterrent ITNs, even in resistant vector populations. Shifting from deterrent to inert or attractive ITNs could significantly improve vector control strategies, warranting further research and product development to fully explore and optimize this approach
Structural characterization and biosynthesis of quinovosan, a deoxyhexose homopolymer involved in crust architecture of Bacillus subtilis spores
No full textInternational audienceBacillus subtilis spores persist on food-processing equipment surfaces, contributing to the contamination of finished products and food loss. Their outermost layer, the crust, influences spore adhesion, notably through its glycans, whose structures remain unknown. Here, we report the identification and structural characterization of quinovosan, a novel homopolymeric polysaccharide composed of D-quinovose residues found in a non-covalently bound form within the crust. We showed that quinovosan consists of two-thirds α- and one-third β-D-quinovosyl residues. Of the nine quinovosyl residues forming the repeating unit of quinovosan, five were monosubstituted at O-3 and two of them were disubstituted at O-2 and O-3, and finally two were in non-reducing terminal positions. Our findings also indicate that quinovosan slightly contributes to spore adhesion and plays a key role in crust architecture. Its amphiphilic nature may promote interactions between hydrophilic molecules and hydrophobic proteins, thereby contributing to the supramolecular organization of the crust. Finally, we identified the yfnHGFED operon as responsible for quinovosan biosynthesis. Specifically, yfnH and yfnG are required for quinovose biosynthesis, while yfnF, yfnE, and yfnD likely participate in quinovosan assembly. Based on these findings, we propose a quinovosan biosynthetic pathway in B. subtilis
Transcatheter tricuspid valve replacement using the LuX-Valve Plus system: 1-year compassionate use outcomes
No full textInternational audienc
Pig models in translational surgery
No full textInternational audienceBackground: Because rodents are too small to perform surgical procedures on people, large mammals are frequently required for surgical studies. Because of its similar overall anatomy and physiology, the pig has a very high translational value and is thus frequently used as the first choice in surgical research. Summary: In cardiovascular treatments, it helped design stents, improve coronary bypass grafting, and perform heart valve xenotransplants. Future efforts will be concentrated on improving the models and, as a result, the trustworthiness of the preclinical findings. Pigs have been used in gastro-intestinal surgery for a variety of purposes, including the development of meshes for abdominal defect repair and the enhancement of surgical methods aimed at compensating functional impairments. A special application has been made in liver regeneration and transplantation procedures, which have promising future prospects, as well as in metabolic surgical research for metabolic illness interventional treatment. Pigs have mostly been used in endocrine surgery to develop pancreatic and islets transplantation for type 1 diabetes therapy, with little research on the other glands. Osteoarticular and neurosurgery are two fields where the pig is increasingly being used: for ethical reasons rather than non-human primate models in neurosurgery, and because this species’ rapid growth allows for the testing of the biomechanical properties of orthopedic devices in the context of skeletal growth. In general, the pig has a current and future role in testing novel surgical equipment or bioengineering solutions, establishing new minimally invasive techniques, and training in robotic surgery, regardless of discipline. Finally, pig-to-human organ xenotransplantation poses a significant translational surgical hurdle. If the research has reached a milestone with some alive patients receiving heart or kidney transplants from pigs with various genetic alterations, more evidence is needed to demonstrate the safety and long-term effectiveness of the procedure, as well as to expand it to other organs such as the liver. Key Messages: In conclusion, the pig model has resulted in significant breakthroughs in surgical research, with future prospects centered mostly on xenotransplantation. The use of the pig in biomedical research will have to deal with rising societal ethical standards
Diversity of the Ixodes ricinus Microbiome Across Belgian Ecoregions and Its Association with Pathogen and Symbiont Presence
No full textInternational audienc
CSF1R regulates monocyte subset differentiation and intracellular metabolism
No full textInternational audienceAbstract Monocytes are key circulating effectors of vascular homeostasis, innate immunity and inflammation. Following their generation in mouse bone marrow, classical (Ly6C high ) monocytes are mobilized into the blood circulation where they mature into non-classical (Ly6C low ) patrolling monocytes or are recruited into peripheral tissues where they differentiate into tissue resident or inflammatory macrophages. Monocytes and macrophages express CSF1R (CD115), the receptor for lineage-specific growth factors CSF1 and IL34. Here, we report that acute CSF1R blockade or genetic deletion negatively interferes with monocyte intracellular metabolism and reduces blood Ly6C low monocytes in part by blunting differentiation of Ly6C high monocytes. Based upon lineage-specific deletion of GFPT1 (Glutamine-Fructose-6-Phosphate Transaminase 1), the hexosamine biosynthetic pathway (HBP) is identified as a novel regulator of CSF1R expression and monocyte subset diversity. Our findings provide new insights into the link between CSF1R signaling, metabolic regulation, and monocyte survival and differentiation
Detection of pathogenic Leptospira spp. in peridomestic Rattus norvegicus in Hong Kong
No full textInternational audienceLeptospirosis is a zoonotic bacterial disease that has a global impact on human and animal health. Rats are known as natural reservoirs of pathogenic Leptospira species. In the Hong Kong Special Administrative Region (SAR), the infection status of peridomestic rat species is not known. In this study, 250 rats belonging to four species (Rattus norvegicus, R. tanezumi, R. andamanensis, and Niviventer huang) were sampled from different ecological habitats across Hong Kong SAR in 2019, 2020, and 2022. The DNA extracted from the kidney tissues of the rats were screened using a polymerase chain reaction (PCR) for the pathogen-specific leptospiral gene lipL32. The positive samples were then confirmed by PCR targeting the lfb-1 gene and were further sequenced for species group (SG) identification. The prevalence of pathogenic Leptospira in rats was 2.8 % (95 % confidence interval (CI) 1.23-5.93). Sequencing of the lipL32 and lfb-1 genes revealed two pathogenic species in seven R. norvegicus including Leptospira interrogans (belonging to lfb-1 SG 8 and a novel SG) and L. borgpetersenii (belonging to lfb-1 SG1). Of the seven positive brown rats, five were caught from streets and within food stores in densely populated districts of Sham Shui Po and Kowloon City and the other two were trapped inside a chicken farm located in Yuen Long District. The results of this study demonstrate molecular evidence of pathogenic Leptospira spp. in the most common peridomestic rat species in Hong Kong SAR and highlight their potential role as a source of leptospirosis for humans and animals. The transmission of leptospirosis between humans, animals, and the contaminated environment emphasizes the necessity of addressing this disease through the One Health approach. Regular surveillance of Leptospira spp. in peridomestic rats, combined with and rat population control and environmental hygiene measures are essential to reduce the risk of Leptospira transmission from rats to domestic animals and humans