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SMYD3 (SET and MYND domain-containing protein 3) is a protein lysine methyltransferase that was initially described as an H3K4 methyltransferase involved in transcriptional regulation. SMYD3 has been reported to methylate and regulate several nonhistone proteins relevant to cancer, including mitogen-activated protein kinase kinase kinase 2 (MAP3K2), vascular endothelial growth factor receptor 1 (VEGFR1), and the human epidermal growth factor receptor 2 (HER2). In addition, overexpression of SMYD3 has been linked to poor prognosis in certain cancers, suggesting SMYD3 as a potential oncogene and attractive cancer drug target. Here we report the discovery of a novel SMYD3 inhibitor. We performed a thermal shift assay (TSA)-based high-throughput screening (HTS) with 410,000 compounds and identified a novel benzodiazepine-based SMYD3 inhibitor series. Crystal structures revealed that this series binds to the substrate binding site and occupies the hydrophobic lysine binding pocket via an unprecedented hydrogen bonding pattern. Biochemical assays showed substrate competitive behavior. Following optimization and extensive biophysical validation with surface plasmon resonance (SPR) analysis and isothermal titration calorimetry (ITC), we identified BAY-6035, which shows nanomolar potency and selectivity against kinases and other PKMTs. Furthermore, BAY-6035 specifically inhibits methylation of MAP3K2 by SMYD3 in a cellular mechanistic assay with an IC50

The crystal structure of the human selenocysteine-containing protein glutathione peroxidase 4 (GPX4) was determined at 1.0 Å resolution. A mass-spectrometry-based approach was developed to monitor the formation of adducts of the active-site selenocysteine Sec46 with covalent inhibitors. The crystal structure of Sec46-containing GPX4 in complex with the covalent inhibitor ML162 [(S)-enantiomer] was determined at 1.54 Å resolution., Wild-type human glutathione peroxidase 4 (GPX4) was co-expressed with SBP2 (selenocysteine insertion sequence-binding protein 2) in human HEK cells to achieve efficient production of this selenocysteine-containing enzyme on a preparative scale for structural biology. The protein was purified and crystallized, and the crystal structure of the wild-type form of GPX4 was determined at 1.0 Å resolution. The overall fold and the active site are conserved compared with previously determined crystal structures of mutated forms of GPX4. A mass-spectrometry-based approach was developed to monitor the reaction of the active-site selenocysteine Sec46 with covalent inhibitors. This, together with the introduction of a surface mutant (Cys66Ser), enabled the crystal structure determination of GPX4 in complex with the covalent inhibitor ML162 [(S)-enantiomer]. The mass-spectrometry-based approach described here opens the path to further co-complex crystal structures of this potential cancer drug target in complex with covalent inhibitors.

Due to its frequent mutations in multiple lethal cancers, KRAS is one of the most-studied anticancer targets nowadays. Since the discovery of the druggable allosteric binding site containing a G12C mutation, KRASG12C has been the focus of attention in oncology research. We report here a computationally driven approach aimed at identifying novel and selective KRASG12C covalent inhibitors. The workflow involved initial enumeration of virtual molecules tailored for the KRAS allosteric binding site. Tools such as pharmacophore modeling, docking, and free-energy perturbations were deployed to prioritize the compounds with the best profiles. The synthesized naphthyridinone scaffold showed the ability to react with G12C and inhibit KRASG12C . Analogues were prepared to establish structure-activity relationships, while molecular dynamics simulations and crystallization of the inhibitor-KRASG12C complex highlighted an unprecedented binding mode.

We explore motion parameters, more specifically gait parameters, as an objective indicator to assess simulator sickness in Virtual Reality (VR). We discuss the potential relationships between simulator sickness, immersion, and presence. We used two different camera pose (position and orientation) estimation methods for the evaluation of motion tasks in a large-scale VR environment: a simple model and an optimized model that allows for a more accurate and natural mapping of human senses. Participants performed multiple motion tasks (walking, balancing, running) in three conditions: a physical reality baseline condition, a VR condition with the simple model, and a VR condition with the optimized model. We compared these conditions with regard to the resulting sickness and gait, as well as the perceived presence in the VR conditions. The subjective measures confirmed that the optimized pose estimation model reduces simulator sickness and increases the perceived presence. The results further show that both models affect the gait parameters and simulator sickness, which is why we further investigated a classification approach that deals with non-linear correlation dependencies between gait parameters and simulator sickness. We argue that our approach could be used to assess and predict simulator sickness based on human gait parameters and we provide implications for future research.

[Image: see text] 6-(4-(Diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one, or DNMDP, potently and selectively inhibits phosphodiesterases 3A and 3B (PDE3A and PDE3B) and kills cancer cells by inducing PDE3A/B interactions with SFLN12. The structure–activity relationship (SAR) of DNMDP analogs was evaluated using a phenotypic viability assay, resulting in several compounds with suitable pharmacokinetic properties for in vivo analysis. One of these compounds, BRD9500, was active in an SK-MEL-3 xenograft model of cancer.

Objective: Clinical urine tests are a key component of prenatal care. As of now, urine test strips are evaluated through a time consuming, often error-prone and operator-dependent visual color comparison of test strips and reference cards by medical staff. Methods and procedures: This work presents an automated pipeline for urinalysis with urine test strips using smartphone camera images in home environments, combining several image processing and color combination techniques. Our approach is applicable to off-the-shelf test strips in home conditions with no additional hardware required. For development and evaluation of our pipeline we collected image data from two sources: i) A user study (26 participants, 150 images) and ii) a lab study (135 images). Results: We trained a region-based convolutional neural network that is able to detect the urine test strip location and orientation in images with a wide variety of light conditions, backgrounds and perspectives with an accuracy of 85.5%. The reference card can be robustly detected through a feature matching approach in 98.6% of the images. Color comparison by Hue channel (0.81 F1-Score), Matching factor (0.80 F1-Score) and Euclidean distance (0.70 F1-Score) were evaluated to determine the urinalysis results. Conclusion: We show that an automated smartphone-based colorimetric analysis of urine test strips in a home environment is feasible. It facilitates examinations and provides the possibility to shift care into an at-home environment. Clinical impact: The findings demonstrate that routine urine examinations can be transferred into the home environment using a smartphone. Simultaneously, human error is avoided, accuracy is increased and medical staff is relieved.

SUMMARYMutations affecting isocitrate dehydrogenase (IDH) enzymes are prevalent in glioma, leukemia, and other cancers. Although mutant IDH inhibitors are effective against leukemia, they appear less active in aggressive glioma, underscoring the need for alternative treatment strategies. Through a chemical synthetic lethality screen, we discovered that IDH1 mutant glioma cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including dihydroorotate dehydrogenase (DHODH). We developed a genetically engineered mouse model of mutant IDH1-driven astrocytoma and used it and multiple patient-derived models to show that the brain-penetrant DHODH inhibitor BAY 2402234 displays monotherapy efficacy against IDH mutant gliomas. Mechanistically, this vulnerability selectively applies to de novo pyrimidine, but not purine, synthesis because glioma cells engage disparate programs to produce these nucleotide species and because IDH oncogenes increase DNA damage upon nucleotide pool imbalance. Our work outlines a tumor-selective, biomarker-guided therapeutic strategy that is poised for clinical translation.

BACKGROUND Fitness trackers and smart watches are frequently used to collect data in longitudinal medical studies. They allow continuous recording in real-life settings, potentially revealing previously uncaptured variabilities of biophysiological parameters and diseases. Adequate device accuracy is a prerequisite for meaningful research. OBJECTIVE This study aims to assess the heart rate recording accuracy in two previously unvalidated devices: Fitbit Charge 4 and Samsung Galaxy Watch Active2. METHODS Participants performed a study protocol comprising 5 resting and sedentary, 2 low-intensity, and 3 high-intensity exercise phases, lasting an average of 19 minutes 27 seconds. Participants wore two wearables simultaneously during all activities: Fitbit Charge 4 and Samsung Galaxy Watch Active2. Reference heart rate data were recorded using a medically certified Holter electrocardiogram. The data of the reference and evaluated devices were synchronized and compared at 1-second intervals. The mean, mean absolute error, mean absolute percentage error, Lin concordance correlation coefficient, Pearson correlation coefficient, and Bland-Altman plots were analyzed. RESULTS A total of 23 healthy adults (mean age 24.2, SD 4.6 years) participated in our study. Overall, and across all activities, the Fitbit Charge 4 slightly underestimated the heart rate, whereas the Samsung Galaxy Watch Active2 overestimated it (−1.66 beats per minute [bpm]/3.84 bpm). The Fitbit Charge 4 achieved a lower mean absolute error during resting and sedentary activities (seated rest: 7.8 vs 9.4; typing: 8.1 vs 11.6; laying down [left]: 7.2 vs 9.4; laying down [back]: 6.0 vs 8.6; and walking slowly: 6.8 vs 7.7 bpm), whereas the Samsung Galaxy Watch Active2 performed better during and after low- and high-intensity activities (standing up: 12.3 vs 9.0; walking fast: 6.1 vs 5.8; stairs: 8.8 vs 6.9; squats: 15.7 vs 6.1; resting: 9.6 vs 5.6 bpm). CONCLUSIONS Device accuracy varied with activity. Overall, both devices achieved a mean absolute percentage error of just

Maternity records (”Mutterpass”) are a central tool in Germany’s antenatal care. Its digitalisation offers advantages such as improved readability, data standardisation, analysability, digital assistance and the avoidance of media breaks. Despite the examined necessity and technical possibility, no system has been implemented yet. In this work, we address this gap by assessing physicians’ and midwives’ perception, motivation, acceptance and requirements of a digital maternity record and its user interface in particular. Nine medical professionals participated in semi-structured interviews. Based on the results, an interface prototype was subsequently developed. The prototype laid a particular focus on two different gravidogram implementations. Thirteen medical professionals participated in the interactive user interface study, which aimed to assess general acceptance, completion time, error rate and implemented assistance functions compared to the analogue counterpart. Results show that the implementation of the digital maternity logbook is of value and that its advantages are both accepted and demanded by medical professionals. Eight key requirements were identified. A tabular gravidogram prototype, inspired by the analogue maternity record, was favoured over a more novel list prototype. Users presented a clear learning curve of the digital system. Nevertheless, the digital average completion time is 30% higher than its analogue counterpart. The digital prototype lead to a lower average number of errors per entry (0.45±0.3 vs. 0.58±0.4). With respect to digital maternity records, this work underlines user acceptance, summarizes key user requirements and presents a first step on the path to a digital maternity record interface for medical professionals. On a broader scale, it delivers insights based on several metrics with respect to digitalisation in an area that is still highly dominated by long established paper-based tools.

Mutations affecting isocitrate dehydrogenase (IDH) enzymes are prevalent in glioma, leukemia, and other cancers. Although mutant IDH inhibitors are effective against leukemia, they seem to be less active in aggressive glioma, underscoring the need for alternative treatment strategies. Through a chemical synthetic lethality screen, we discovered that IDH1-mutant glioma cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including dihydroorotate dehydrogenase (DHODH). We developed a genetically engineered mouse model of mutant IDH1-driven astrocytoma and used it and multiple patient-derived models to show that the brain-penetrant DHODH inhibitor BAY 2402234 displays monotherapy efficacy against IDH-mutant gliomas. Mechanistically, this reflects an obligate dependence of glioma cells on the de novo pyrimidine synthesis pathway and mutant IDH's ability to sensitize to DNA damage upon nucleotide pool imbalance. Our work outlines a tumor-selective, biomarker-guided therapeutic strategy that is poised for clinical translation.

Velcrin compounds are a class of small molecules that induce complex formation between PDE3A and SLFN12, killing cancer cells that express elevated levels of these two proteins by a mechanism independent of PDE3A enzymatic inhibition. Instead, PDE3A binding stimulates the RNase activity of SLFN12, resulting in cleavage of the specific SLFN12 substrate, tRNA-Leu-TAA. Cleavage of tRNA-Leu-TAA in turn causes ribosomal pausing, inhibition of protein synthesis, and cancer cell death. Unlike traditional targeted therapies that leverage dependencies created in cancer cells by genomic alterations, velcrins instead kill cancer cells by a gain-of-function mechanism dependent on the RNase activity of SLFN12. In a collaboration between the Broad Institute and Bayer Pharmaceuticals, we developed the first velcrin, BAY 2666605, to enter Phase I clinical trials. BAY 2666605 is active in cell line and patient-derived xenografts of several tumor types, specifically where elevated levels of the two biomarkers, PDE3A and SLFN12, are expressed. Biomarker-positive tumors are especially enriched among melanomas, and we have consistently observed tumor regression in biomarker-positive melanoma tumor models in vivo. BAY 2666605 furthermore shows drug-like properties, excellent brain penetration, increased stimulation of SLFN12 RNase activity, and reduced inhibition of PDE3A enzymatic activity compared with most other velcrins and approved PDE3A inhibitors. BAY 2666605 has recently entered a First-in-Human study (NCT04809805) in patients with advanced solid tumors that co-express PDE3A and SLFN12, including melanoma, ovarian cancer, and sarcoma. Citation Format: Stefan Gradl, Sooncheol Lee, Martin Lange, Xiaoyun Wu, Silvia Goldoni, Timothy Lewis, Charlotte Kopitz, Colin Garvie, Philip Lienau, Stephanie Hoyt, Henrik Seidel, Stephan Kaulfuss, Manuel Ellermann, Luc de Waal, Adrian Tersteegen, Sven Golfier, Detlev Suelzle, Christa Hegele-Hartung, James Carr, Frederick Brookfield, Michael Bruening, Melanie Berthold, Thibaud Jourdan, Monica Schenone, Galen Gao, Joseph McGaunn, Antje Wengner, Elisa Aquilanti, Franziska Siegel, Marine Garrido, Annette Walter, Isabelle Genvresse, Andrew Cherniack, Stuart Schreiber, Knut Eis, Ashley Eheim, Matthew Meyerson, Heidi Greulich. BAY 2666605: The first PDE3A-SLFN12 complex inducer for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr ND04.

BAY 2666605, co-developed by the Broad Institute and Bayer Pharmaceuticals, is a selective and potent molecular glue, part of a family of small molecules recently baptized as ‘velcrins’, that induces complex formation between phosphodiesterase 3A (PDE3A) and SLFN12. BAY 2666605 has recently entered a First-in-Human study (NCT04809805) in patients with advanced solid tumors and here we describe its pre-clinical pharmacology profile. DNMDP, the precursor to BAY 2666605, was discovered in a phenotypic screen of genomically annotated cancer cell lines and sensitivity to treatment correlated to high expression of PDE3A (1). Upon treatment, SLFN12 is recruited into a stable complex with PDE3A where its RNase activity is enhanced and required for response (2). BAY 2666605 is a potent complex inducer (EC50 = 7 nM) and cytotoxic in vitro with nanomolar potency (IC50 = 1nM, in the most sensitive cell lines). Cancer cells with high expression of PDE3A and co-expression of SLFN12 are killed by a mechanism independent of PDE3A enzymatic inhibition. PDE3A-SLFN12 binding is required for cytotoxicity. Biomarker-positive lines are enriched in the melanoma lineage and show dose-dependent sensitivity to BAY 2666605 both in vitro and in vivo. Notably, we have consistently observed tumor regression in biomarker-positive melanoma models, including in PDX models (10mg/kg po BID). Based on target expression data from TCGA and tumor arrays, various other tumor types also co-express PDE3A and SLFN12, such as sarcomas and ovarian cancer. To this end, we show that BAY 2666605 inhibits tumor growth of PDX models of sarcoma and ovarian cancer in vivo. BAY 2666605 has excellent brain penetration, making glioblastoma a promising indication. Biomarker-positive GBM models are sensitive to BAY 2666605 both in vitro and in vivo. In a subset of orthotopic GBM models BAY 2666605 treatment has significant impact on survival. In BAY 2666605 treated models we have observed MCL1 downregulation and this biomarker will be evaluated in clinical settings. Our pre-clinical data indicate that BAY 2666605 is a potent anti-tumor agent with first-in-class potential and broad indication space. 1. de Waal et al. Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics, Nat. Chem. Biol. 12, 102-108 (2016) 2. Garvie et al. Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase, Nat. Commun. 12, 4375 (2021) Citation Format: Silvia Goldoni, Martin Lange, Charlotte Kopitz, Stefan Kaulfuss, Sven Golfier, Adrian Tersteegen, Stefanie Bunse, Melanie Berthold, Thibaud Jordan, Philip Lienau, Franziska Siegel, Annette Walter, Henrik Seidel, Elisa Aquilanti, Andrew Baker, Xiaoyun Wu, Sooncheol Lee, Stefan Gradl, Emmanuelle di Tomaso, Matthew Meyerson, Knut Eis, Ashley Eheim, Heidi Greulich. Preclinical profiling of BAY 2666605: The first PDE3A-SLFN12 complex inducer for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2663.

Velcrin compounds are small molecules which act as molecular glues to form a PDE3A-SLFN12 complex. This complex formation induces apoptosis in cancer cells expressing elevated levels of PDE3A and SLFN12 (de Waal et al., Nat Chem Biol 2016; Wu et al., J Bio Chem 2020). Unlike traditional targeted therapies that leverage dependencies created by genomic alterations in cancer cells, velcrins instead kill cancer cells by a gain-of-function mechanism dependent on stimulation of SLFN12 RNase activity by complex formation with PDE3A (Garvie et al., Nat Commun 2021). Based on in-vivo tool compounds which were discovered by hit-to-lead optimization from a phenotypic screen (Lewis et al., ACS Med Chem Lett 2019), the team set out to optimize the properties of the tool compounds. While already showing excellent potency and in-vivo efficacy in various tumor models, the compounds were only approximately tenfold selective against PDE3A when compared to their cell killing activity. PDE3A/B activity most notably influences cardiohemodynamics and inhibition of PDE3A/B was to be reduced to generate a larger safety window. Co-crystallization of analogs with PDE3A showed the binding mode of the velcrin class and changes in the solvent exposed region of the PDE3A binders led to steep activity changes in complex formation and cell killing. Careful optimization of the ratio of cell killing to PDE3A activity while optimizing DMPK and safety pharmacology led to the discovery of BAY 2666605. BAY 2666605 has recently entered a First-in-Human study (NCT04809805) in patients with advanced solid tumors that co-express PDE3A and SLFN12, including melanoma, ovarian cancer, and sarcoma. We will discuss the discovery and structure activity relationships of BAY 2666605. Citation Format: Stefan Gradl. Discovery and structure activity relationships of BAY 2666605: PDE3A-SLFN12 complex inducer for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2134.

Gait supervision plays an important role in the diagnosis, analysis and rehabilitation of motor impairments and neurodegenerative disorders. For example, in Parkinson's disease, gait assessment is used for progression observation and medication guidance. Previous work has presented the potential of virtual reality (VR) supported gait applications. While virtual environments and user representation strategies are used for gait applications, the influence of appearance and context cues on gait performance is not extensively researched. In this paper, we analyzed the influence of avatar appearance, environment awareness, and camera perspective on gait parameters relevant for clinical application. Four different avatar appearances, varying in abstraction, two environmental settings, as well as an egocentric and exocentric camera perspective were compared in three walking tasks on a treadmill. Our results show that variability, as an indicator for gait stability, is significantly impacted by VR exposure in comparison to a real world (in vivo) baseline. Further, our results revealed that walking tasks influence gait behavior significantly different in VR compared to in vivo. Overall, these findings suggest that particular care has to be taken when assessing gait characteristics acquired from subjects immersed in VR and that equivalence of results with in vivo may not be blindly assumed.

This study compared how two virtual display conditions of human body expressions influenced explicit and implicit dimensions of emotion perception and response behavior in women and men. Two avatars displayed emotional interactions (angry, sad, affectionate, happy) in a “pictorial” condition depicting the emotional interactive partners on a screen within a virtual environment and a “visual” condition allowing participants to share space with the avatars, thereby enhancing co-presence and agency. Subsequently to stimulus presentation, explicit valence perception and response tendency (i.e. the explicit tendency to avoid or approach the situation) were assessed on rating scales. Implicit responses, i.e. postural and autonomic responses towards the observed interactions were measured by means of postural displacement and changes in skin conductance. Results showed that self-reported presence differed between pictorial and visual conditions, however, it was not correlated with skin conductance responses. Valence perception was only marginally influenced by the virtual condition and not at all by explicit response behavior. There were gender-mediated effects on postural response tendencies as well as gender differences in explicit response behavior but not in valence perception. Exploratory analyses revealed a link between valence perception and preferred behavioral response in women but not in men. We conclude that the display condition seems to influence automatic motivational tendencies but not higher level cognitive evaluations. Moreover, intragroup differences in explicit and implicit response behavior highlight the importance of individual factors beyond gender. Supplementary Information The online version contains supplementary material available at 10.1007/s00221-020-06020-5.

Strabismus is a visual disorder characterized by eye misalignment. The effect of Panum’s Fusional Area (PFA) compensates for small misalignments. However, prominent misalignments affect binocular vision and when present in childhood it may lead to amblyopia, a developmental disorder of the visual system. With the advent of Virtual Reality (VR) technology, possibilities for novel binocular treatments to amblyopia arise in which the measurement of strabismus is crucial to correctly compensate for it. Thus, VR yields great potential due to the ability of displaying content to each eye independently. Major research in VR addresses this topic using eye-tracking while there is a paucity of research on image-based assessment methods. In this work, we propose a VR application for measuring strabismus in nine lines of sight. We conducted a study with 14 healthy participants to evaluate the system under two conditions: no strabismus and an artificial deviation induced by prism lenses. Further, we evaluated the effect of PFA on the system by measuring its extent in horizontal and vertical lines of sight. Results show significant difference between the expected deviation induced by prism lenses and the measured deviation. The existing difference within the measurements can be explained with the recorded extent of the PFA.

We recently described glutathione peroxidase 4 (GPX4) as a promising target for killing therapy-resistant cancer cells via ferroptosis. The onset of therapy resistance by multiple types of treatment results in a stable cell state marked by high levels of polyunsaturated lipids and an acquired dependency on GPX4. Unfortunately, all existing inhibitors of GPX4 act covalently via a reactive alkyl chloride moiety that confers poor selectivity and pharmacokinetic properties. Here, we report our discovery that masked nitrile-oxide electrophiles, which have not been explored previously as covalent cellular probes, undergo remarkable chemical transformations in cells and provide an effective strategy for selective targeting of GPX4. The new GPX4-inhibiting compounds we describe exhibit unexpected proteome-wide selectivity and, in some instances, vastly improved physiochemical and pharmacokinetic properties compared to existing chloroacetamide-based GPX4 inhibitors. These features make them superior tool compounds for biological interrogation of ferroptosis and constitute starting points for development of improved inhibitors of GPX4. Nitrile-oxide electrophiles were identified as covalent inhibitors of GPX4 that exhibit increased selectivity and reduced off-target effects relative to chloroacetamide-based inhibitors.

Assessment of personality traits is highly relevant in team sports in order to analyze the performance of an athlete under pressure when in competitive situations, for team-strategic decisions, to optimize command transmission, and ultimately to understand top-level performers. It further facilitates the development and application of personalized exercises, coaching to improve performance in competition, and can be considered a valuable criterion for talent scouting and development. The current state of the art method to assess personality traits in sports relies on validated questionnaires. However, these often provide non-sport-specific, subjective self-reported information and lack the ability to measure how these characteristics are reflected in context-based performance.We developed a virtual reality (VR) tool for the assessment of personality traits in team sports, in our case for soccer. An evaluation of this tool within a study with 24 subjects yielded a benchmark of its immersion through user experience and provided an objective description of athletes’ personalities based on performance indicators extracted from activity-tracking. Within the tool, we implemented two realistic virtual soccer environments to assess the motivational orientation of soccer players (i.e. action-and state-orientation) which we discerned from the gold standard questionnaire.Results show that user experience and presence of the implemented virtual environments scored significantly higher compared to benchmark measurements. Additionally, a significant difference between the two groups of action and state-oriented athletes could be observed. Measures of failure rate, pass accuracy, number of perceived opponents, and achieved bonus goals are parameters that differ significantly among the two athlete groups. These findings show that VR technology is applicable for the assessment of athletes’ motivational orientation and thus demonstrate the feasibility of virtual environments as functional game scenario-based assessment tools for athletes.

Migraine attacks can be accompanied by many different symptoms, some of them appearing within 24 hours before the onset of the headache. In previous work, reduced habituation to an electrical pain stimulus at the head was observed in the pre-ictal phase within 24 hours before the headache attack. Based on these results, this work presents an application to track influence factors on migraine attacks and an Arduino-based control unit which replaces the traditional approach of manual electrical stimulation. The usability of both components of the project was evaluated in separate user studies. Results of the usability study show a good acceptance of the systems with a mean SUS score of 92.4. Additionally, they indicate that the developed control unit may substitute the current manual electrical stimulation. Overall, the designed system allows standardized repeatable measurements and is a first step towards the home-use of a device for establishing a new method for migraine prediction.