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Andrade, C.

Publications and source records attributed to Andrade, C..

5 recordsLinked to original sources

Integrated Skin Sensitization Assessment Using Consensus Modelling and Tiered New Approach Methodology: A SaferSkin Case Study

The transition toward animal-free safety assessment of chemicals has accelerated the development of New Approach Methodologies (NAMs) for predicting skin sensitization. However, individual in silico models and experimental NAM assays frequently produce inconsistent or contradictory results, limiting their reliability when used in isolation. To address this challenge, we present a tiered integrated assessment framework implemented through the open source SaferSkin application, which enables systematic comparison and integration of multiple predictive models and experimental data within a transparent weight-of-evidence workflow. In this case study, a diverse set of 21 reference compounds was evaluated using a battery of in silico approaches, including the OECD QSAR Toolbox, VEGA, CASE Ultra and additional machine-learning models implemented within SaferSkin. The platform enables side-by-side comparison of predictions and integration of experimental data through Bayesian network models, allowing probabilistic updating of predictions as new evidence becomes available. Our results demonstrate that reliance on any single predictive model is insufficient for robust hazard identification due to frequent disagreement between models. In contrast, consensus interpretation across multiple modelling approaches combined with targeted experimental evidence substantially improves predictive confidence. The integrated weight-of-evidence framework showed strong concordance with reference classifications and was further supported by independent validation using the Pred-Skin Bayesian model. Importantly, the tiered workflow enables resolution of ambiguous cases. For example, lower-tier predictions for ethyl (2E,4Z)-deca-dienoate were inconsistent across models, whereas targeted third-tier testing using the SENS-IS assay identified the compound as a strong sensitiser (GHS Category 1A). Overall, this study demonstrates how integrated modelling, Bayesian evidence updating and targeted NAM testing can reduce uncertainty in skin sensitization assessment. The SaferSkin framework provides a transparent and reproducible approach for implementing Next Generation Risk Assessment (NGRA) strategies and supports the development of animal-free regulatory toxicology and Safe-and-Sustainable-by-Design chemical innovation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/711911v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@196a52eorg.highwire.dtl.DTLVardef@13690a6org.highwire.dtl.DTLVardef@1528703org.highwire.dtl.DTLVardef@11e05d2_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

pharmacology and toxicology↗

Blood, sweat, and beers: investigating mosquito biting preferences amidst noise and intoxication in a cross-sectional cohort study at a large music festival

IntroductionWe live in a world split between mosquito magnets and those lucky enough to remain (nearly) untouched. The reasons why some people attract more mosquito bites than others remain largely mysterious. In the Mosquito Magnet Trial, we investigated differences in mosquito attraction amongst festivalgoers with varying levels of hygiene and intoxication. MethodsOur study was conducted in a slightly steamy pop-up laboratory inside four connected shipping containers at Lowlands Festival in The Netherlands (August 18-20, 2023). Participants completed an anonymous questionnaire on hygiene, diet, and festival-related behaviour (including alcohol uptake and shared sleeping arrangements). Mosquito attraction was measured using a custom designed setup: a transparent cage with perforations where female Anopheles mosquitoes were offered a choice between a sugar-feeder and the participants arm. Mosquitoes could only smell, not bite, the participants arm. Attraction was quantified through video imaging, measuring arm landings relative to total landings. Mosquito attraction was correlated with questionnaire responses and skin microbiota profiles collected from forearm skin swabs. ResultsAmongst the 465 included participants, mosquitoes showed a clear fondness for those who drank beer over those who abstained from the liquid gold (Fold Change 1.35, 95% CI 1.12-1.63, PFDR<0.001). Attraction was also contagious: participants that successfully lured a fellow human into their tent the previous night also proved more enticing to mosquitoes (FC 1.34, 95% CI 1.14-1.58, PFDR=0.002). Meanwhile, skipping the morning showering routine and using sunscreen reduced mosquito attraction (FC 0.52, 95% 0.38-0.70, PFDR<0.001). Streptococci were more abundant on the skin of highly attractive individuals (Puncorrected=0.017), and the overall abundance of malodour associated bacteria was high - possibly reflecting the containers smell. ConclusionThe Mosquito Magnet Trial, to our knowledge the largest study of its kind, was conducted in a loosely controlled setting with a selection bias towards science loving festivalgoers. That said, using our custom designed experimental set-up, we found that mosquitoes are drawn to those who avoid sunscreen, drink beer, and share their bed. They simply have a taste for the hedonists among us.

animal behavior and cognition↗

Unveiling the antiviral capabilities of targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2

The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the enzymes in charge of pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated quinone-based compounds, discovering potent HsDHODH inhibition (low nanomolar IC50) and promising in vitro anti-SARS-CoV-2 activity (low micromolar EC50). These compounds exhibited low toxicity, indicating potential for further development. Additionally, we employed computational tools like molecular docking and QSAR models to analyze protein-ligand interactions. These findings represent a significant step forward in the search for effective antiviral treatments and have great potential to impact the development of new broad-spectrum antiviral drugs.

biochemistry↗

Regeneration of Starfish Radial Nerve Cord restores animal mobility and unveils a new coelomocyte population

The potential to regenerate a damaged body part is expressed to a different extent in animals. Echinoderms, in particular starfish, are known for their outstanding potential to regenerate cell, tissue, organ, and body parts. For instance, humans have restricted abilities to restore organ systems being dependent on limited sources of stem cells. In particular, the potential to regenerate the central nervous system is extremely limited, explaining the lack of natural mechanisms that could overcome the development of neurodegenerative diseases and the presence of traumatisms. Therefore, understanding the molecular and cellular mechanisms of regeneration in starfish could lead to the development of new therapeutic approaches in humans. In this study, we tackle the problem of starfish central nervous system regeneration by examining anatomical and behavioral traits, including external anatomic anomalies, the dynamics of coelomocytes populations and neuronal tissue architecture. We noticed that several anatomic anomalies were evident and detected that the injured arm could not be used anymore to lead the starfish movement. Those seem to be related to defense mechanisms and protection of the wound. In particular, histology showed that tissue patterns during regeneration resemble those described in holothurians and in starfish arm tip regeneration. Flow cytometry coupled with imaging flow cytometry unveiled a new coelomocyte population during the late phase of the regeneration process. Morphotypes of previously characterized coelomocytes populations were described based on IFC data. Further studies of this new coelomocyte population might provide insights on their involvement in radial nerve cord regeneration.

zoology↗

A combined characterization of coelomic fluid cell types in the spiny starfish Marthasterias glacialis: inputs from flow cytometry and imaging

Coelomocytes is a generic name for a collection of cellular morphotypes, present in many coelomate animals, that has been reported as highly variable across echinoderm classes. The roles attributed to the major types of the free circulating cells present in the coelomic fluid of echinoderms include immune response, phagocytic digestion and clotting. The main aim of the present study is the thorough characterization of coelomocytes present in the coelomic fluid of Marthasterias glacialis (class Asteroidea) through the combined use of flow cytometry (FC) and fluorescence plus transmission electron microscopy. Two coelomocyte populations (here named P1 and P2) were identified by flow cytometry and subsequently studied in terms of abundance, morphology, ultrastructure, cell viability and cell cycle profiles. Ultrastructurally, P2 diploid cells showed two main morphotypes, similar to phagocytes and vertebrate thrombocytes, whereas the small P1 haploid cellular population was characterized by a low mitotic activity, relatively undifferentiated cytotype and a high nucleus/cytoplasm ratio. These last cells resemble stem-cell types present in other animals. P1 and P2 cells differ also in cell viability and cell cycle profiles. Additionally, two other morphotypes were only detected by fluorescence microscopy and a third one when using a combined microscopy/FC approach.

cell biology↗