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Biology subjects

Hecht, H.

Publications and source records attributed to Hecht, H..

4 recordsLinked to original sources

AOPTK: Open-Source Software for AI-Assisted Toxicological Literature Analysis

Motivation: Toxicologists today face a challenge: although vast amounts of data describing how chemicals affect human health are available across scientific publications and regulatory reports, much of this information remains underutilized because extracting and interpreting evidence across thousands of studies is impractical to perform manually. Recent advances in artificial intelligence (AI), particularly in large language models (LLMs), provide new opportunities to automate toxicological literature analysis. Results: Herein, we present the Adverse Outcome Pathway Toolkit (AOPTK), an open-source Python package for AI-enhanced analysis of toxicological and biomedical literature. AOPTK supports (i) automated literature retrieval from databases such as PubMed Central and Europe PMC, (ii) direct processing of full-text articles in PDF format, and (iii) LLM-assisted analysis tools to identify chemicals and extract their relationships to biological effects under user-defined conditions. We demonstrate its utilities through a case-study identifying potential non-genotoxic carcinogens based on their ability to inhibit gap junction intercellular communication (GJIC). The LLM-enhanced analysis achieves 81% agreement with an expert-curated inhibitor list and 95% accuracy in predicting inhibition versus no inhibition when analysing the same subset of 86 publications. Automated retrieval and analysis of 1 124 publications from PubMed Central further demonstrated the feasibility of applying AOPTK to large-scale literature analyses. Availability: The package is developed open source on GitHub, disseminated through PyPI and Bioconda and releases are archived on Zenodo. Individual tools are available in the Galaxy platform for accessible data analysis with user-friendly, findable, accessible, interoperable, and reusable (FAIR) and end-to-end workflows provided via WorkflowHub. The tools are available on usegalaxy.eu and usegalaxy.cz and are developed open source on GitHub.

bioinformatics↗

Predicting Gravitational Self-Motion: Falling Down versus Falling Up

Humans have been shown to use an internalized representation or prior of Earth gravity to predict object motion. Often, this is shown using the fact that humans tend to neglect an objects acceleration when predicting its motion. This bias tends to be ameliorated when the acceleration acting on the object is Earth gravity. It is currently unclear whether this prior can also be used when assessing ones self-motion. We immersed two cohorts of 20 seated participants in a virtual environment of a street scene. They experienced simulated self-motion consistent with either flying straight upwards towards the ceiling (ANTI-GRAVITY) or falling downwards towards the ground (GRAVITY). After 0.8 s to 1.4 s of motion, the screen turned blank, and participants pressed a button to indicate when they thought they reached the surface they were moving towards. In Experiment 1, they were instructed to use their eye level as the reference (i.e., when they imagined the floor or ceiling to be aligned with their eyes). In Experiment 2, they used their feet or the top of theirs heads to judge when they had reached the ceiling or floor, respectively. In Experiment 1, no differences between the GRAVITY and ANTI-GRAVITY conditions were found in terms of accuracy or precision, contrary to our hypotheses. In Experiment 2 participants pressed the button significantly later in the ANTI-GRAVITY condition than in the GRAVITY condition, in line with the predictions of the use of a gravity prior, while precision remained unaffected. Speculatively, the instructions in Experiment 1 may have made the experience less ecologically valid and immersive, thus preventing participants from activating the strong gravity prior. Experiment 2 (head/feet as reference), on the other hand, provides convincing evidence for an involvement of this prior in the prediction of self-motion. In sum, the study provides evidence that humans can rely on an internalized representation of Earth gravity when predicting self-motion, at least under ecologically valid task conditions. The absence of effects in Experiment 1 and their presence in Experiment 2 suggest that activation of this gravity prior depends on the framing of the task.

animal behavior and cognition↗

Towards Bayesian-based quantitative adverse outcome pathways using in vitro data from open literature and continuous variables: a case example for liver fibrosis.

As toxicology shifts towards non-animal testing, quantitative models are essential to predict adverse health effects from molecular or cellular perturbations. Quantitative Adverse Outcome Pathways (qAOPs) represent such models, building on mechanistic knowledge and quantifying the Key Event Relationships (KERs) described in AOPs. Despite the recognized need, the number of qAOPs remains limited. Bayesian-based approaches are often chosen for developing qAOP for their flexibility, but most use discretized variables, limiting their predictive power. In addition, these models are mainly built from newly generated data, underexploiting the large amount of information available. This study successfully leverages data from public literature and presents an innovative framework based on continuous variables to develop a Bayesian-based quantitative model for a central KER towards liver fibrosis. The model predicts the probability of the expression fold change for two key markers of hepatic stellate cell activation (aSMA and COL1A1), given the effects on tissue injury, using in vitro data from 9 chemicals. We propose a newly developed workflow to assist in knowledge identification, organization, and extraction from scientific literature and chemical databases. Based on in vitro data and in vivo information from the Open TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System) database, we estimate a biologically relevant range in COL1A1 fold change that indicates an activated state of stellate cells and high liver fibrosis odds ratios. Our study provides a case example of integrating published data and continuous variables to build a Bayesian-based model, which constitutes an essential step for predicting liver fibrosis from in vitro data.

pharmacology and toxicology↗

Psychopathy and distance estimation

Research on psychopathy has so far been largely limited to the investigation of high-level processes, such as emotion perception and regulation. In the present work, we investigate whether psychopathy has an effect on the estimation of fundamental physical parameters, which are computed in the brain during early stages of sensory processing. We employed a simple task in which participants had to estimate their interpersonal distance from a moving avatar and stop it at a given distance. The face expression of the avatars were positive, negative, or neutral. Participants carried out the task online on their home computers. We measured the psychopathy level via a self-report questionnaire. Regardless of the degree of psychopathy, the facial expression of the avatars showed no effect on distance estimation. Our results show that individuals with a high degree of psychopathy underestimate distance of approaching avatars significantly less (let the avatar approach them significantly closer) than did participants with a lesser degree of psychopathy. Moreover, participants who scored high in Self-Centered Impulsivity underestimate the distance to approaching avatars significantly less (let the avatar approach closer) than participants with a low score. Distance estimation is considered an automatic process performed at early stages of visual processing. Therefore, our results imply that psychopathy affects basic early sensory processes, such as feature extraction, in the visual cortex.

neuroscience↗