@phdthesis{Weh2024,
  author    = {Weh, Manuel},
  title     = {Chiral Perylene Bisimide Cyclophanes},
  doi       = {10.25972/OPUS-31529},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-315296},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {This work illustrates how the targeted tailoring of supramolecular cavities can not only accomplish high binding due to optimized stereoelectronic shape matches between host and guest but also how molecular engineering of the binding site by a refined substitution periphery of the cavity makes enantiospecific guest recognition and host mediated chirality transfer feasible. Moreover, an enzyme mimic, following the Pauling-Jencks model of enzyme catalysis was realized by the smart design of a PBI host composed of moderately twisted chromophores, which drives the substrate inversion according to the concepts of transition state stabilization and ground state destabilization. The results of this thesis contribute to a better understanding of structure-specific interactions in host-guest complexes as well as the corresponding thermodynamic and kinetic properties and represent an appealing blueprint for the design of new artificial complex structures of high stereoelectronic shape complementarity in order to achieve the goal of sophisticated supramolecular receptors and enzyme mimicry.},
  language  = {en}
}
@phdthesis{Glaser2024,
  author    = {Glaser, Julia},
  title     = {Nachhaltiges Lernen an der Hochschule: Untersuchungen zu Randbedingungen und Transfereffekten von digitalen {\"U}bungstests auf das Behalten von Lehrinhalten},
  doi       = {10.25972/OPUS-35866},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358665},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Learning accompanies us throughout our lives, from early childhood education through school, training and university to learning at work. However, much of what we learn is quickly forgotten. The use of practice tests is a learning strategy that contributes to the acquisition of sustainable knowledge, i.e. knowledge that is permanently available and can be retrieved when it is needed. This dissertation first presents findings from previous research on testing in real educational contexts and discusses theoretically why certain learner or situational characteristics might influence the effectiveness of the testing effect. Furthermore, a cycle of three experiments is presented, which were used to investigate whether the positive effect of practice tests on retention (testing effect) depends on personal or situational characteristics and also promotes the retention of lecture content that was not directly tested (transfer) in the context of regular psychology lectures in teacher training courses. In an additional chapter, feedback from students on the implementation of the study in the classroom context is examined in more detail. Finally, the results of the three studies are discussed and placed in relation to the theories presented. The central conclusion from the studies presented is that the testing effect appears to be a very effective learning strategy that can be used effectively in university teaching and leads to better learning outcomes regardless of learner characteristics. However, the practice tests should cover the entire range of relevant content, as transfer effects to non-tested content are not to be expected.},
  subject      = {Transfer},
  language  = {en}
}
@phdthesis{HuttererneeHerzog2024,
  author    = {Hutterer, n{\´e}e Herzog, Katharina},
  title     = {Treatment-like use of discrimination training to reduce generalization of conditioned fear},
  doi       = {10.25972/OPUS-31728},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317286},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Anxiety patients overgeneralize fear, also because of an inability to perceptually discriminate threat and safety signals. Therefore, some studies have developed discrimination training that successfully reduced the occurrence of fear generalization. The present work is the first to take a treatment-like approach by using discrimination training after generalization has occurred. Therefore, two studies were conducted with healthy participants using the same fear conditioning and generalization paradigm, with two faces as conditioned stimuli (CSs), and four facial morphs between CSs as generalization stimuli (GSs). Only one face (CS+) was followed by a loud scream (unconditioned stimulus, US). In Study 1, participants underwent either fear-relevant (discriminating faces) or fear-irrelevant discrimination training (discriminating width of lines) or a non-discriminative control training between the two generalization tests, each with or without feedback (n = 20 each). Generalization of US expectancy was reduced more effectively by fear-relevant compared to fear-irrelevant discrimination training. However, neither discrimination training was more effective than non-discriminative control training. Moreover, feedback reduced generalization of US expectancy only in discrimination training. Study 2 was designed to replicate the effects of the discrimination-training conditions in a large sample (N = 244) and examine their benefits in individuals at risk for anxiety disorders. Again, feedback reduced fear generalization particularly well for US expectancy. Fear relevance was not confirmed to be particularly fear-reducing in healthy participants, but may enhance training effects in individuals at risk of anxiety disorder. In summary, this work provides evidence that existing fear generalization can be reduced by discrimination training, likely involving several (higher-level) processes besides perceptual discrimination (e.g., motivational mechanisms in feedback conditions). Its use may be promising as part of individualized therapy for patients with difficulty discriminating similar stimuli.},
  subject      = {Furcht},
  language  = {en}
}
@phdthesis{Kuehnemundt2024,
  author    = {K{\"u}hnemundt, Johanna},
  title     = {Defined microphysiologic 3D tumour models with aspects from the tumour microenvironment for the evaluation of cellular immunotherapies},
  doi       = {10.25972/OPUS-27667},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276674},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cells is highly effective in haematological malignancies. This success, however, has not been achieved in solid tumours so far. In contrast to hematologic malignancies, solid tumours include a hostile tumour microenvironment (TME), that poses additional challenges for curative effects and consistent therapeutic outcome. These challenges manifest in physical and immunological barriers that dampen efficacy of the CAR T cells. Preclinical testing of novel cellular immunotherapies is performed mainly in 2D cell culture and animal experiments. While 2D cell culture is an easy technique for efficacy analysis, animal studies reveal information about toxicity in vivo. However, 2D cell culture cannot fully reflect the complexity observed in vivo, because cells are cultured without anchorage to a matrix and only short-term periods are feasible. Animal studies provide a more complex tissue environment, but xenografts often lack human stroma and tumour inoculation occurs mostly ectopically. This emphasises the need for standardisable and scalable tumour models with incorporated TME-aspects, which enable preclinical testing with enhanced predictive value for the clinical outcome of immunotherapies. Therefore, microphysiologic 3D tumour models based on the biological SISmuc (Small Intestinal mucosa and Submucosa) matrix with preserved basement membrane were engaged and improved in this work to serve as a modular and versatile tumour model for efficacy testing of CAR T cells. In order to reflect a variety of cancer entities, TME-aspects, long-term stability and to enhance the read-out options they were further adapted to achieve scalable and standardisable defined microphysiologic 3D tumour models. In this work, novel culture modalities (semi-static, sandwich-culture) were characterised and established that led to an increased and organised tissue generation and long-term stability. Application of the SISmuc matrix was extended to sarcoma and melanoma models and serial bioluminescence intensity (BLI)-based in vivo imaging analysis was established in the microphysiologic 3D tumour models, which represents a time-efficient read-out method for quality evaluation of the models and treatment efficacy analysis, that is independent of the cell phenotype. Isolation of cancer-associated-fibroblasts (CAFs) from lung (tumour) tissue was demonstrated and CAF-implementation further led to stromal-enriched microphysiologic 3D tumour models with in vivo-comparable tissue-like architecture. Presence of CAFs was confirmed by CAF-associated markers (FAP, α-SMA, MMP-2/-9) and cytokines correlated with CAF phenotype, angiogenesis, invasion and immunomodulation. Additionally, an endothelial cell barrier was implemented for static and dynamic culture in a novel bioreactor set-up, which is of particular interest for the analysis of immune cell diapedesis. Studies in microphysiologic 3D Ewing's sarcoma models indicated that sarcoma cells could be sensitised for GD2-targeting CAR T cells. After enhancing the scale of assessment of the microphysiologic 3D tumour models and improving them for CAR T cell testing, the tumour models were used to analyse their sensitivity towards differently designed receptor tyrosine kinase-like orphan receptor 1 (ROR1) CAR T cells and to study the effects of the incorporated TME-aspects on the CAR T cell treatment respectively. ROR1 has been described as a suitable target for several malignancies including triple negative breast cancer (TNBC), as well as lung cancer. Therefore, microphysiologic 3D TNBC and lung cancer models were established. Analysis of ROR1 CAR T cells that differed in costimulation, spacer length and targeting domain, revealed, that the microphysiologic 3D tumour models are highly sensitive and can distinguish optimal from sub-optimal CAR design. Here, higher affinity of the targeting domain induced stronger anti-tumour efficacy and anti-tumour function depended on spacer length, respectively. Long-term treatment for 14 days with ROR1 CAR T cells was demonstrated in dynamic microphysiologic 3D lung tumour models, which did not result in complete tumour cell removal, whereas direct injection of CAR T cells into TNBC and lung tumour models represented an alternative route of application in addition to administration via the medium flow, as it induced strong anti-tumour response. Influence of the incorporated TME-aspects on ROR1 CAR T cell therapy represented by CAF-incorporation and/or TGF-β supplementation was analysed. Presence of TGF-β revealed that the specific TGF-β receptor inhibitor SD-208 improves ROR1 CAR T cell function, because it effectively abrogated immunosuppressive effects of TGF-β in TNBC models. Implementation of CAFs should provide a physical and immunological barrier towards ROR1 CAR T cells, which, however, was not confirmed, as ROR1 CAR T cell function was retained in the presence of CAFs in stromal-enriched microphysiologic 3D lung tumour models. The absence of an effect of CAF enrichment on CAR T cell efficacy suggests a missing component for the development of an immunosuppressive TME, even though immunomodulatory cytokines were detected in co-culture models. Finally, improved gene-edited ROR1 CAR T cells lacking exhaustion-associated genes (PD-1, TGF-β-receptor or both) were challenged by the combination of CAF-enrichment and TGF-β in microphysiologic 3D TNBC models. Results indicated that the absence of PD-1 and TGF-β receptor leads to improved CAR T cells, that induce strong tumour cell lysis, and are protected against the hostile TME. Collectively, the microphysiologic 3D tumour models presented in this work reflect aspects of the hostile TME of solid tumours, engage BLI-based analysis and provide long-term tissue homeostasis. Therefore, they present a defined, scalable, reproducible, standardisable and exportable model for translational research with enhanced predictive value for efficacy testing and candidate selection of cellular immunotherapy, as exemplified by ROR1 CAR T cells.},
  subject      = {Immuntherapie},
  language  = {en}
}
@phdthesis{Eck2024,
  author    = {Eck, Philipp},
  title     = {Symmetry Breaking and Spin-Orbit Interaction on the Triangular Lattice},
  doi       = {10.25972/OPUS-35918},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359186},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Since the prediction of the quantum spin Hall effect in graphene by Kane and Mele, \(Z_2\) topology in hexagonal monolayers is indissociably linked to high-symmetric honeycomb lattices. This thesis breaks with this paradigm by focusing on topological phases in the fundamental two-dimensional hexagonal crystal, the triangular lattice. In contrast to Kane-Mele-type systems, electrons on the triangular lattice profit from a sizable, since local, spin-orbit coupling (SOC) and feature a non-trivial ground state only in the presence of inversion symmetry breaking. This tends to displace the valence charge form the atomic position. Therefore, all non-trivial phases are real-space obstructed. Inspired by the contemporary conception of topological classification of electronic systems, a comprehensive lattice and band symmetry analysis of insulating phases of a \(p\)-shell on the triangular lattice is presented. This reveals not only the mechanism at the origin of band topology, the competition of SOC and symmetry breaking, but sheds also light on the electric polarization arising from a displacement of the valence charge centers from the nuclei, i. e., real-space obstruction. In particular, the competition of SOC versus horizontal and vertical reflection symmetry breaking gives rise to four topologically distinct insulating phases: two kinds of quantum spin Hall insulators (QSHI), an atomic insulator and a real-space obstructed higher-order topological insulator. The theoretical analysis is complemented with state-of-the-art first principles calculations and experiments on trigonal monolayer adsorbate systems. This comprises the recently discovered triangular QSHI indenene, formed by In atoms, and focuses on its topological classification and real-space obstruction. The analysis reveals Kane-Mele-type valence bands which profit from the atomic SOC of the triangular lattice. The realization of a HOTI is proposed by reducing SOC by considering lighter adsorbates. Further the orbital Rashba effect is analyzed in AgTe, a consequence of mirror symmetry breaking, the formation of local angular momentum polarization and SOC. As an outlook beyond topology, the Fermi surface and electronic susceptibility of Group V adsorbates on silicon carbide are investigated. In summary, this thesis elucidates the interplay of symmetry breaking and SOC on the triangular lattice, which can promote non-trivial insulating phase.},
  subject      = {Topologie},
  language  = {en}
}
@book{SmithPasqualiniMachtEllgring2024,
  author    = {Smith Pasqualini, Marcia and Macht, Michael and Ellgring, Heiner},
  title     = {Cognitive Behavioral Therapy for People with Parkinson's Disease and Caregivers : A Guide for Mental Health Professionals},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-226-3},
  doi       = {10.25972/WUP-978-3-95826-227-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-345196},
  publisher      = {W{\"u}rzburg University Press},
  pages     = {xii, 344},
  year      = {2024},
  abstract  = {The need for mental health support within the Parkinson's disease (PD) community has never been greater, yet many practitioners lack the knowledge or experience to address the unique challenges associated with PD. This book serves as a practical guide for mental health professionals to assist individuals with PD and caregivers through the use of cognitive-behavioral therapy techniques, with the goal of enhancing their well-being and quality of life. The book includes a review of information about PD and mental health, and four structured group programs designed to address issues that are common in people with PD and caregivers: • Coping with stress and illness • Communicating about PD • Emotional expression in PD • Interventions for caregivers The programs presented in this book can be utilized as they are, personalized for individual use, or adapted for research protocols. Additionally, the information can serve as a valuable resource for people with PD and their family members, who can learn about PD and be introduced to evidence-based strategies that can be used conjointly with professionals to improve their experience of living with PD.},
  subject      = {Parkinson-Krankheit},
  language  = {en}
}
@techreport{BolzNaumannRichter2024,
  type      = {Working Paper},
  author    = {Bolz, Simon J. and Naumann, Fabrice and Richter, Philipp M.},
  title     = {Unilateral Environmental Policy and Offshoring},
  doi       = {10.25972/OPUS-35903},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359033},
  pages     = {66},
  year      = {2024},
  abstract  = {Expanding on a general equilibrium model of offshoring, we analyze the effects of a unilateral emissions tax increase on the environment, income, and inequality. Heterogeneous firms allocate labor across production tasks and emissions abatement, while only the most productive can benefit from lower labor and/or emissions costs abroad and offshore. We find a non-monotonic effect on global emissions, which decline if the initial difference in emissions taxes is small. For a sufficiently large difference, global emissions rise, implying emissions leakage of more than 100\%. The underlying driver is a global technique effect: While the emissions intensity of incumbent non-offshoring firms declines, the cleanest firms start offshoring. Moreover, offshoring firms become dirtier, induced by a reduction in the foreign effective emissions tax in general equilibrium. Implementing a BCA prevents emissions leakage, reduces income inequality in the reforming country, but raises inequality across countries.},
  subject      = {Umweltpolitik},
  language  = {en}
}
@article{ReppenhagenBeckerKugleretal.2023,
  author    = {Reppenhagen, Stephan and Becker, Roland and Kugler, Andreas and John, Dominik and Kopf, Sebastian and Anetzberger, Hermann},
  title     = {Hand dominance is not of significance in performing fundamental arthroscopic skills simulation training tasks},
  series = {Arthroscopy, Sports Medicine, and Rehabilitation},
  volume    = {5},
  journal   = {Arthroscopy, Sports Medicine, and Rehabilitation},
  number    = {5},
  issn      = {2666-061X},
  doi       = {10.1016/j.asmr.2023.100767},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350432},
  year      = {2023},
  abstract  = {Purpose To compare the performance of the dominant and nondominant hand during fundamental arthroscopic simulator training. Methods Surgical trainees who participated in a 2-day simulator training course between 2021 and 2023 were classified, according to their arthroscopic experience in beginners and competents. Only right-handed individuals with complete data sets were included in the study. Ambidexterity was trained using a box trainer (Fundamentals of Arthroscopic Surgery Training, Virtamed AG, Schlieren, Switzerland).Two tasks, periscoping for learning camera guidance and triangulation for additional instrument handling, were performed 4 times with the camera in the dominant hand and then in the nondominant hand. For each task, exercise time, camera path length, and instrument path length were recorded and analyzed. Results Out of 94 participants 74 right-handed individuals (22 females, 52 males) were classified to novices (n = 43, less than 10 independently performed arthroscopies) and competents (n = 31, more than 10 independently performed arthroscopies). Competents performed significantly better than novices. No significant difference was found after changing the guiding hand for the camera from the dominant to the nondominant hand regarding the camera path length and the instrument path length. Notably, tasks were performed even faster when using the camera in the nondominant hand. Conclusions Our data demonstrate that the learned manual skills during basic arthroscopic training are quickly transferred to the contralateral side. In consequence, additional fundamental skills training for camera guidance and instrument handling of the nondominant hand are not necessary. Clinical Relevance For skillful arthroscopy, camera guidance and instrument handing must be equally mastered with both hands. It is important to understand how hand dominance may affect learning during arthroscopic simulator training.},
  language  = {en}
}
@article{JaenschEvdokimovEgenolfetal.2024,
  author    = {J{\"a}nsch, Sarah and Evdokimov, Dimitar and Egenolf, Nadine and Meyer zu Altenschildesche, Caren and Kreß, Luisa and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Distinguishing fibromyalgia syndrome from small fiber neuropathy: a clinical guide},
  series = {Pain Reports},
  volume    = {9},
  journal   = {Pain Reports},
  number    = {1},
  doi       = {10.1097/PR9.0000000000001136},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350306},
  year      = {2024},
  abstract  = {Introduction: Fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) are distinct pain conditions that share commonalities and may be challenging as for differential diagnosis. Objective: To comprehensively investigate clinical characteristics of women with FMS and SFN to determine clinically applicable parameters for differentiation. Methods: We retrospectively analyzed medical records of 158 women with FMS and 53 with SFN focusing on pain-specific medical and family history, accompanying symptoms, additional diseases, and treatment. We investigated data obtained using standardized pain, depression, and anxiety questionnaires. We further analyzed test results and findings obtained in standardized small fiber tests. Results: FMS patients were on average ten years younger at symptom onset, described higher pain intensities requiring frequent change of pharmaceutics, and reported generalized pain compared to SFN. Pain in FMS was accompanied by irritable bowel or sleep disturbances, and in SFN by paresthesias, numbness, and impaired glucose metabolism (P < 0.01 each). Family history was informative for chronic pain and affective disorders in FMS (P < 0.001) and for neurological disorders in SFN patients (P < 0.001). Small fiber pathology in terms of skin denervation and/or thermal sensory threshold elevation was present in 110/158 (69.7 \%) FMS patients and 39/53 (73.6 \%) SFN patients. FMS patients mainly showed proximally reduced skin innervation and higher corneal nerve branch densities (p<0.001) whereas SFN patients were characterized by reduced cold detection and prolonged electrical A-delta conduction latencies (P < 0.05). Conclusions: Our data show that FMS and SFN differ substantially. Detailed pain, drug and family history, investigating blood glucose metabolism, and applying differential small fiber tests may help to improve diagnostic differentiation and targeted therapy.},
  language  = {en}
}
@article{BreyerGruenerKleinetal.2024,
  author    = {Breyer, Maximilian and Gr{\"u}ner, Julia and Klein, Alexandra and Finke, Laura and Klug, Katharina and Sauer, Markus and {\"U}{\c{c}}eyler, Nurcan},
  title     = {\(In\) \(vitro\) characterization of cells derived from a patient with the GLA variant c.376A>G (p.S126G) highlights a non-pathogenic role in Fabry disease},
  series = {Molecular Genetics and Metabolism Reports},
  volume    = {38},
  journal   = {Molecular Genetics and Metabolism Reports},
  issn      = {22144269},
  doi       = {10.1016/j.ymgmr.2023.101029},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350295},
  year      = {2024},
  abstract  = {Highlights • The GLA variant S126G is not associated with Fabry symptoms in the presented case • S126G has no effect on α-GAL A activity or Gb3 levels in this patient • S126G sensory neurons show no electrophysiological abnormalities Abstract Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency is caused by variants in the gene GLA. Variants of unknown significance (VUS) are frequently found in GLA and challenge clinical management. Here, we investigated a 49-year old man with cryptogenic lacunar cerebral stroke and the chance finding of the VUS S126G, who was sent to our center for diagnosis and initiation of a costly and life-long FD-specific treatment. We combined clinical examination with in vitro investigations of dermal fibroblasts (HDF), induced pluripotent stem cells (iPSC), and iPSC-derived sensory neurons. We analyzed α-GAL A activity in iPSC, Gb3 accumulation in all three cell types, and action potential firing in sensory neurons. Neurological examination and small nerve fiber assessment was normal except for reduced distal skin innervation. S126G iPSC showed normal α-GAL A activity compared to controls and no Gb3 deposits were found in all three cell types. Baseline electrophysiological characteristics of S126G neurons showed no difference compared to healthy controls as investigated by patch-clamp recordings. We pioneer multi-level cellular characterization of the VUS S126G using three cell types derived from a patient and provide further evidence for the benign nature of S126G in GLA, which is of great importance in the management of such cases in clinical practice.},
  language  = {en}
}