Computational Science Hub (CSH)

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Browsing Computational Science Hub (CSH) by Classification "610"

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    Modelling and simulation for preclinical cardiac safety assessment of drugs with human iPSC-derived cardiomyocytes
    (2020) Kügler, Philipp
    As a potentially life threatening side effect, pharmaceutical compounds may trigger cardiac arrhythmias by impeding the heart’s electrical and mechanical function. For this reason, any new compound needs to be tested since 2005 for its proarrhythmic risk both during the preclinical and the clinical phase of the drug development process. While intensive monitoring of cardiac activity during clinical tests with human volunteers constitutes a major cost factor, preclinical in vitro tests with non cardiac cells and in vivo tests with animals are currently under serious debate because of their poor extrapolation to drug cardiotoxicity in humans. For about five years now, regulatory agencies, industry and academia are working on an overhaul of the cardiac drug safety paradigm that is built a) on human heart muscle cells, that can be abundantly bioengineered from donor stem cells without ethical concerns (human induced pluripotent stem cell derived cardiomyocytes, hiPSC-CMs), and b) on computational models of human cardiac electrophysiology both at the cellular and the organ level. The combined use of such human in vitro and human in silico models during the preclinical phase is expected to improve proarrhythmia test specificity (i.e. to lower the false-positive rate), to better inform about the need of thorough heart monitoring in the clinic, and to reduce or even replace animal experiments. This review article starts by concisely informing about the electrical activity of the human heart, about its possible impairment due to drug side effects, and about hiPSC-CM assays for cardiac drug safety testing. It then summarizes the mathematical description of human cardiac electrophysiology in terms of mechanistic ODE and PDE models, and illustrates how their numerical analysis may provide insight into the genesis of drug induced arrhythmias. Finally, this paper surveys proarrhythmic risk estimation methods, that involve the simulation of human heart muscle cells, and addresses opportunities and challenges for future interdisciplinary research.
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    Visual tracking of a moving target in 360-degree virtual reality: analysis of the effects on attention and mood
    (2025) Sellner, T.; Ehmann, P.; Spielmann, J.; Gogolla, F.; Rösgen, A.; Mayer, J.; Schoenfeld, M. A.; Flor, H.
    The training of attentional capacities is an important part of many rehabilitative efforts, for example, in the treatment of stroke. The Helix-Arena is an innovative virtual reality (VR) training device, which enables multimodal training in a 360-degree virtual environment. A pursuit training was developed for the Helix-Arena. In this study, we evaluate the effectiveness of the pursuit training in the Helix-Arena compared to a control group [CG, training on a personal computer (PC)] in 34 healthy participants. The experimental group (EG, N = 19) participated in four training sessions in the Helix-Arena over a period of 2 weeks. The control group (N = 15) completed similar training sessions in a non-VR environment on a PC. During each training session, changes in attention (Test of Attentional Performance battery, TAP) and general mood (Positive and Negative Affect Schedule, PANAS) were assessed pre- and post-training. A significantly higher pre-to-post improvement was observed in the EG for the TAP subtest attention shift in the subcategory invalid instructor ( p = 0.04) than that in the CG. In addition, we found a higher positive affect after the training in the EG but not in the CG (p < 0.01). These results suggest advantages of the VR environment for attentional and affective processes. The VR training can thus improve not only cognitive abilities but also training motivation. In a next step, the training can be used with patients in a rehabilitation context, but it is also suitable for educational and gaming contexts.