@article{KerwagenFuchsUllrichetal.2023,
  author    = {Kerwagen, Fabian and Fuchs, Konrad F. and Ullrich, Melanie and Schulze, Andres and Straka, Samantha and Krop, Philipp and Latoschik, Marc E. and Gilbert, Fabian and Kunz, Andreas and Fette, Georg and St{\"o}rk, Stefan and Ertl, Maximilian},
  title     = {Usability of a mHealth solution using speech recognition for point-of-care diagnostic management},
  series = {Journal of Medical Systems},
  volume    = {47},
  journal   = {Journal of Medical Systems},
  number    = {1},
  doi       = {10.1007/s10916-022-01896-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324002},
  year      = {2023},
  abstract  = {The administrative burden for physicians in the hospital can affect the quality of patient care. The Service Center Medical Informatics (SMI) of the University Hospital W{\"u}rzburg developed and implemented the smartphone-based mobile application (MA) ukw.mobile1 that uses speech recognition for the point-of-care ordering of radiological examinations. The aim of this study was to examine the usability of the MA workflow for the point-of-care ordering of radiological examinations. All physicians at the Department of Trauma and Plastic Surgery at the University Hospital W{\"u}rzburg, Germany, were asked to participate in a survey including the short version of the User Experience Questionnaire (UEQ-S) and the Unified Theory of Acceptance and Use of Technology (UTAUT). For the analysis of the different domains of user experience (overall attractiveness, pragmatic quality and hedonic quality), we used a two-sided dependent sample t-test. For the determinants of the acceptance model, we employed regression analysis. Twenty-one of 30 physicians (mean age 34 ± 8 years, 62\% male) completed the questionnaire. Compared to the conventional desktop application (DA) workflow, the new MA workflow showed superior overall attractiveness (mean difference 2.15 ± 1.33), pragmatic quality (mean difference 1.90 ± 1.16), and hedonic quality (mean difference 2.41 ± 1.62; all p < .001). The user acceptance measured by the UTAUT (mean 4.49 ± 0.41; min. 1, max. 5) was also high. Performance expectancy (beta = 0.57, p = .02) and effort expectancy (beta = 0.36, p = .04) were identified as predictors of acceptance, the full predictive model explained 65.4\% of its variance. Point-of-care mHealth solutions using innovative technology such as speech-recognition seem to address the users' needs and to offer higher usability in comparison to conventional technology. Implementation of user-centered mHealth innovations might therefore help to facilitate physicians' daily work.},
  language  = {en}
}
@article{HepbasliGredyUllrichetal.2021,
  author    = {Hepbasli, Denis and Gredy, Sina and Ullrich, Melanie and Reigl, Amelie and Abeßer, Marco and Raabe, Thomas and Schuh, Kai},
  title     = {Genotype- and Age-Dependent Differences in Ultrasound Vocalizations of SPRED2 Mutant Mice Revealed by Machine Deep Learning},
  series = {Brain Sciences},
  volume    = {11},
  journal   = {Brain Sciences},
  number    = {10},
  issn      = {2076-3425},
  doi       = {10.3390/brainsci11101365},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248525},
  year      = {2021},
  abstract  = {Vocalization is an important part of social communication, not only for humans but also for mice. Here, we show in a mouse model that functional deficiency of Sprouty-related EVH1 domain-containing 2 (SPRED2), a protein ubiquitously expressed in the brain, causes differences in social ultrasound vocalizations (USVs), using an uncomplicated and reliable experimental setting of a short meeting of two individuals. SPRED2 mutant mice show an OCD-like behaviour, accompanied by an increased release of stress hormones from the hypothalamic-pituitary-adrenal axis, both factors probably influencing USV usage. To determine genotype-related differences in USV usage, we analyzed call rate, subtype profile, and acoustic parameters (i.e., duration, bandwidth, and mean peak frequency) in young and old SPRED2-KO mice. We recorded USVs of interacting male and female mice, and analyzed the calls with the deep-learning DeepSqueak software, which was trained to recognize and categorize the emitted USVs. Our findings provide the first classification of SPRED2-KO vs. wild-type mouse USVs using neural networks and reveal significant differences in their development and use of calls. Our results show, first, that simple experimental settings in combination with deep learning are successful at identifying genotype-dependent USV usage and, second, that SPRED2 deficiency negatively affects the vocalization usage and social communication of mice.},
  language  = {en}
}
@phdthesis{Ullrich2014,
  author    = {Ullrich, Melanie},
  title     = {Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-107355},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {SPRED proteins are inhibitors of the Ras/ERK/MAPK signaling pathway, an evolutionary highly conserved and very widespread signaling cascade regulating cell proliferation, differentiation, and growth. To elucidate physiological consequences of SPRED2 deficiency, SPRED2 KO mice were generated by a gene trap approach. An initial phenotypical characterization of KO mice aged up to five months identified SPRED2 as a regulator of chondrocyte differentiation and bone growth. Here, the loss of SPRED2 leads to an augmented FGFR-dependent ERK activity, which in turn causes hypochondroplasia-like dwarfism. However, long term observations of older KO mice revealed a generally bad state of health and manifold further symptoms, including excessive grooming associated with severe self-inflicted wounds, an abnormally high water uptake, clear morphological signs of kidney deterioration, and a reduced survival due to sudden death. Based on these observations, the aim of this study was to discover an elicitor of this complex and versatile phenotype. The observed kidney degeneration in our SPRED2 KO mice was ascribed to hydronephrosis characterized by severe kidney atrophy and apoptosis of renal tubular cells. Kidney damage prompted us to analyze drinking behavior and routine serum parameters. Despite polydipsia, which was characterized by a nearly doubled daily water uptake, the significantly elevated Na+ and Cl- levels and the resulting serum hyperosmolality could not be compensated in SPRED2 KOs. Since salt and water balance is primarily under hormonal control of aldosterone and AVP, we analyzed both hormone levels. While serum AVP was similar in WTs and KOs, even after experimental water deprivation and an extreme loss of body fluid, serum aldosterone was doubled in SPRED2 KO mice. Systematic investigation of contributing upstream hormone axes demonstrated that hyperaldosteronism developed independently of an overactivated Renin-Angiotensin system as indicated by halved serum Ang II levels in KO mice. However, aldosterone synthase expression in the adrenal gland was substantially augmented. Serum corticosterone, which is like aldosterone released from the adrenal cortex, was more than doubled in SPRED2 KOs, too. Similar to corticosterone, the production of aldosterone is at least in part under control of pituitary ACTH, which is further regulated by upstream hypothalamic CRH release. In fact, stress hormone secretion from this complete hypothalamic-pituitary-adrenal axis was upregulated because serum ACTH, the mid acting pituitary hormone, and hypothalamic CRH, the upstream hormonal inductor of HPA axis activity, were also elevated by 30\% in SPRED2 KO mice. This was accompanied by an upregulated ERK activity in paraventricular nucleus-containing hypothalamic brain regions and by augmented hypothalamic CRH mRNA levels in our SPRED2 KO mice. In vitro studies using the hypothalamic cell line mHypoE-44 further demonstrated that both SPRED1 and SPRED2 were able to downregulate CRH promoter activity, CRH secretion, and Ets factor-dependent CRH transcription. This was in line with the presence of various Ets factor binding sites in the CRH promoter region, especially for Ets1. Thus, this study shows for the first time that SPRED2-dependent inhibition of Ras/ERK/MAPK signaling by suppression of ERK activity leads to a downregulation of Ets1 factor-dependent transcription, which further results in inhibition of CRH promoter activity, CRH transcription, and CRH release from the hypothalamus. The consecutive hyperactivity of the complete HPA axis in our SPRED2 KO mice reflects an elevated endogenous stress response becoming manifest by excessive grooming behavior and self-inflicted skin lesions on the one hand; on the other hand, in combination with elevated aldosterone synthase expression, this upregulated HPA hormone release explains hyperaldosteronism and the associated salt and water imbalances. Both hyperaldosteronism and polydipsia very likely contribute further to the observed kidney damage. Taken together, this study initially demonstrates that SPRED2 is essential for the appropriate regulation of HPA axis activity and of body homeostasis. To further enlighten and compare consequences of SPRED2 deficiency in mice and particularly in humans, two follow-up studies investigating SPRED2 function especially in heart and brain, and a genetic screen to identify human SPRED2 loss-of-function mutations are already in progress.},
  subject      = {Renin-Angiotensin-System},
  language  = {en}
}
@article{BenzMerkelOffneretal.2013,
  author    = {Benz, Peter M. and Merkel, Carla J. and Offner, Kristin and Abeßer, Marco and Ullrich, Melanie and Fischer, Tobias and Bayer, Barbara and Wagner, Helga and Gambaryan, Stepan and Ursitti, Jeanine A. and Adham, Ibrahim M. and Linke, Wolfgang A. and Feller, Stephan M. and Fleming, Ingrid and Renn{\´e}, Thomas and Frantz, Stefan and Unger, Andreas and Schuh, Kai},
  title     = {Mena/VASP and alphaII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy},
  series = {Cell Communication and Signaling},
  volume    = {11},
  journal   = {Cell Communication and Signaling},
  number    = {56},
  doi       = {10.1186/1478-811X-11-56},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128760},
  year      = {2013},
  abstract  = {Background: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. Results: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Conclusions: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.},
  language  = {en}
}