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Inhalation is a major route of chemical exposure for both consumers and workers. Physiologically-based kinetic (PBK) modeling is a promising tool to understand the absorption, distribution, metabolism, and excretion (ADME) of inhaled chemicals and to predict systemic concentrations of chemicals in humans. New Approach Methodologies (NAMs) can help generate essential input parameters for PBK models. However, validated NAM-based test methods to assess uptake of inhaled chemicals are currently lacking. Reliable information on respiratory uptake is required to determine relevant exposure concentrations for evaluation of systemic effects using NAMs. This manuscript describes a project that aims to apply robust and reliable in vitro models to study cellular uptake, intracellular accumulation, absorption and systemic exposure of chemicals following inhalation. To evaluate the robustness and predictivity of different NAM-based barrier models, to examine appropriate in vitro to in vivo scaling strategies, and to assess sensitivity and uncertainty in the resulting PBK models, the project will focus on relatively data-rich chemicals, specifically per- and polyfluoroalkyl substances (PFAS). While some have been widely explored and others remain data-poor, the entire chemical family is of interest due to its health hazards. Therefore, the work combines experimental and modeling approaches by generating in vitro data on the respiratory uptake and benchmark this to existing human in vivo data, developing biokinetic models to better understand chemical fate within the test systems, and refining inhalation PBK models to improve estimates of systemic uptake. Read-Across (RAx) will be employed as data gap filling technique to infer on the apparent permeability of non-tested PFAS. Together, the in vitro and in silico results will inform and parameterize PBK models, ultimately enabling more reliable predictions of systemic availability. The project will deliver a workflow to combine in vitro and in silico methods to assess the uptake of inhaled substances, that could be modified and applied to other inhaled substances. Standardized in vitro models for respiratory uptake will improve the evaluation of inhalation as a route of exposure contributing to systemic effects, which is a key requirement for quantitative in vitro to in vivo extrapolation (qIVIVE) and supports the implementation of next-generation risk assessment (NGRA).
Power imbalance is a core characteristic in many definitions of workplace bullying. Yet, research on preventive and conditional factors related to power imbalance remains limited. This study investigates whether social support from the supervisor and colleagues moderates the relationship between exposure to bullying behaviors and the perceived power imbalance with the perpetrator(s), as seen from the target’s perspective. Grounded in conservation of resources theory, we hypothesized that both types of social support would mitigate this relationship. Drawing on data from 374 Norwegian child welfare social workers, findings from a bootstrapped general linear model with tests for interaction effects contradicted this expectation. Instead, colleague- and supervisor-support were found to exacerbate the positive association between bullying behaviors and perceived power imbalance. More specifically, results indicated that in the context of low exposure, targets experienced less power imbalance when they have access to social support. In cases of high exposure, bullying behaviors were associated with high power imbalance, irrespective of levels of support. Such a reversed buffering effect may be explained by considering the nature of the support provided: while emotional support may heighten the target’s awareness of the bullying without alleviating the mistreatment itself, instrumental support may be most effective to help reduce the power imbalance. Thus, the type of support received may be critical in influencing the perceived power dynamics in bullying situations.
Accurate forecasting of agricultural commodity prices is crucial for maintaining market stability, effective risk management, and informed decision-making, particularly in developing economies with high price volatility and heterogeneous market structures. Traditional statistical models and recurrent deep learning approaches often struggle to capture nonlinear dynamics, abrupt fluctuations, and long-range temporal dependencies in agricultural price series. To overcome these limitations, this study proposes a CNN-Transformer hybrid architecture that combines the local feature extraction of Convolutional Neural Networks (CNNs) with the global dependency modelling of Transformer self-attention mechanisms, specifically designed to address limitations of existing hybrid models such as sequential bottlenecks, vanishing gradients, and limited scalability. The framework is evaluated on weekly potato prices from four structurally diverse Indian markets-Azadpur, Ludhiana, Dehradun, and Farrukhabad, covering varying data lengths and volatility regimes. Systematic hyperparameter tuning and extensive experiments demonstrate that the CNN-Transformer consistently outperforms established benchmarks, including CNN, LSTM, Bi-LSTM, GRU, CNN-LSTM, and standalone Transformer models, across RMSE, MAE, and MAPE metrics.
Background:Microplastic pollution has emerged as a global environmental crisis with potential adverse consequences on human health. Mixtures of microplastics with fungal particles including mycelial fragments or spores are highly probable exposure scenarios occurring in various occupational settings or in moldy built indoor environments. However, immunotoxic outcomes associated with such exposure remain poorly characterized. Most studies have focused on single-exposure components. Here, we investigated, for the first time, the immunotoxic effects of microplastics mixed with spores or mycelial fragments from Aspergillus fumigatus on human neutrophil-like cells. Materials and methods:Differentiated HL60 neutrophil-like cells were exposed to 0-100 μg/mL HDPE microplastics mixed with 106 heat-inactivated mycelial fragments or spores for 24 h. Results and discussion:HDPE combined with fungal fragments induced significant release of IL-6 and IL-8 while the mixtures with fungal spores induced only IL-6 release from the neutrophil-like cells. Most importantly, we observed a trend of decreasing IL-6 levels with increasing doses of HDPE microplastics in mixture with fungal particles, indicating possible dysregulation of the pro-inflammatory response. The tested doses of HDPE microplastics in mixture with fungal particles showed no significant acute effects on the cell viability. Using HEK293-TLR reporter cells, we found no significant activation of TLR2 and TLR4 by HDPE microplastics, fungal particles, or their combination, suggesting that the release of IL-6 and IL-8 is induced through other innate immune-signaling pathways. Taken together, fungal particles as microbial contaminants, seem to be the main drivers of the immune responses triggered by exposure to mixed HDPE microplastics and fungal particles. Among these, fungal mycelial fragments appear to be the most potent compared to fungal spores that are typically monitored for risk assessments.
The present study examined the reciprocal associations between personality traits and workplace bullying, and mechanisms underlying these associations. Data were drawn from a large longitudinal probability sample of the Swedish workforce (N = 2,024). Workplace bullying was measured using both self-labelling and behavioural experience methods, and personality was assessed through the Big Five traits. Two mechanisms were proposed and tested: an interpersonal conflict mechanism and an emotional distress mechanism. The results showed reciprocal associations between bullying and neuroticism, indicating that personality may both influence exposure to bullying and be shaped by it. Both mechanisms fully mediated the association from neuroticism to subsequent bullying, suggesting that emotional reactivity and conflict involvement explain why individuals high in neuroticism are at greater risk of becoming targets. Emotional distress also fully mediated the effects from exposure to bullying to subsequent increases in neuroticism and decreases in conscientiousness. These findings imply that prolonged exposure to bullying may erode emotional stability and self-regulatory capacity over time. Overall, the study highlights that in cases of exposure to bullying, personality should not be viewed as a fixed risk factor but as a dynamic system interacting with the social environment, where bullying can gradually alter dispositional functioning through emotional and interpersonal processes.
