@phdthesis{Kumar2024,
  author    = {Kumar, Manish},
  title     = {Structural and compositional effects on tree-water relation},
  doi       = {10.25972/OPUS-32624},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326245},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Forests are essential sources of tangible and intangible benefits, but global climate change associated with recurrent extreme drought episodes severely affects forest productivity due to extensive tree die-back. On that, it appeals to an urgency for large-scale reforestation efforts to mitigate the impact of climate change worldwide; however, there is a lack of understanding of drought-effect on sapling growth and survival mechanisms. It is also challenging to anticipate how long trees can survive and when they succumb to drought. Hence, to ensure success of reforestation programs and sustainable forest productivity, it is essential to identify drought-resistant saplings. For that, profound knowledge of hydraulic characteristics is needed. To achieve this, the study was split into two phases which seek to address (1) how the hydraulic and anatomical traits influence the sapling's growth rate under drought stress. (2) how plant water potential regulation and physiological traits are linked to species' water use strategies and their drought tolerance. The dissertation is assembled of two study campaigns carried out on saplings at the Chair of Botany II, University of W{\"u}rzburg, Germany. The first study involved three ecologically important temperate broadleaved tree species — saplings of 18-month (Acer pseudoplatanus, Betula pendula, and Sorbus aucuparia) — grown from seeds in contrasting conditions (inside a greenhouse and outside), with the latter being subjected to severe natural heat waves. In the second study, two additional temperate species (Fagus sylvatica and Tilia cordata) were added. The drying-out event was conducted using a randomised blocked design by monitoring plant water status in a climate-controlled chamber and a greenhouse. In campaign I, I present the result based on analysed data of 82 plants of temperate deciduous species and address the juvenile growth rate trade-off with xylem safety-efficiency. Our results indicate biomass production varies considerably due to the contrasted growing environment. High hydraulic efficiency is necessary for increased biomass production, while safety-efficiency traits are decoupled and species-specific. Furthermore, productivity was linked considerably to xylem safety without revealing a well-defined pattern among species. Moreover, plasticity in traits differed between stressed and non-stressed plants. For example, safety-related characteristics were more static than efficiency-related traits, which had higher intra-specific variation. Moreover, we recorded anatomical and leaf traits adjustments in response to a stress condition, but consistency among species is lacking. In campaign II, I combined different ways to estimate the degree of isohydry based on water potential regulation and connected the iso-anisohydric spectrum (i.e., hydroscape area, HSA) to hydraulic traits to elucidate actual plant performance during drought. We analysed plant water potential regulation (Ψpd and Ψmd) and stomatal conductance of 28-29 month saplings of five species. I used a linear mixed modelling approach that allowed to control individual variations to describe the water potential regulation and tested different conceptual definitions of isohydricity. The combined methods allowed us to estimate species' relative degree of isohydry. Further, we examined the traits coordination, including hydraulic safety margin, HSM; embolism resistance, P88; turgor loss, Ψtlp; stomata closure, Ps90; capacitance, C; cuticular conductance, gmin, to determine time to hydraulic failure (Thf). Thf is the cumulative effect of time to stomata closure (Tsc) and time after stomatal closure to catastrophic hydraulic failure (Tcrit). Our results show the species' HSA matches their stomatal stringency, which confirms the relationship between stomatal response and leaf water potential decline. Species that close stomata at lower water potential notably had a larger HSA. Isohydric behaviour was mostly associated with leaf hydraulic traits and poorly to xylem safety traits. Species' degree of isohydry was also unrelated to the species' time to death during drying-out experiments. This supports the notion that isohydry behaviours are linked to water use rather than drought survival strategies. Further, consistent with our assumptions, more isohydric species had larger internal water storage and lost their leaf turgor at less negative water potentials. Counter to our expectations, neither embolism resistance nor the associated hydraulic safety margins were related to metrics of isohydry. Instead, our results indicate traits associated with plant drought response to cluster along two largely independent axes of variation (i.e., stomatal stringency and xylem safety). Furthermore, on the temporal progression of plant drought responses, stomatal closure is critical in coordinating various traits to determine species' hydraulic strategies. Desiccation avoidance strategy was linked to Tsc and coordinated traits response of Ps90, Ψtlp, and HSA, whereas desiccation tolerance was related to Tcrit and traits such as lower P88 value, high HSM, and lower gmin. Notably, the shoot capacitance (C) is crucial in Thf and exhibits dichotomous behaviour linked to both Tsc and Tcrit. In conclusion, knowledge of growth rate trade-offs with xylem safety-efficiency combined with traits linked to species' hydraulic strategies along the isohydry could substantially enhance our ability to identify drought-resistant saplings to ensure the success of reforestation programs and predicting sensitivity to drought for achieving sustainable forest ecosystems.},
  subject      = {Wachstumsrate},
  language  = {en}
}
@phdthesis{Jorgacevic2024,
  author    = {Jorgacevic, Ivana},
  title     = {Elucidating the interconnection of GvHD and Western diet-induced atherosclerosis},
  doi       = {10.25972/OPUS-32579},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325792},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Allogeneic hematopoietic cell transplantation (Allo-HCT) is the main and only treatment for many malignant and non-malignant haematological disorders. Even though the treatment has improved through the years and patient life expectancy has increased, graft versus host disease (GvHD) is still considered the main obstacle and one of the main reasons for increased mortality. Furthermore, improved patient's survival and life expectancy brought into question the late post-HCT complications. The leading cause of late death after allo-HCT is the relapse of primary disease as well as chronic GvHD (cGvHD). However, a clear relationship was also described with pulmonary complications, endocrine dysfunction and infertility, and cataracts in post-HCT patients. In the last years big concern regarding a cumulative cardiovascular incidence in long-term survivors has been raised. Severe cardiovascular disease (CVD) is caused by atherosclerosis which is considered a chronic inflammatory disease of blood vessels. As such, it takes a long time from endothelial damage, as the onset event, and followed plaque formation to a manifestation of severe consequences, such as stroke, coronary heart disease, or peripheral arterial disease. Endothelial damage is well documented in patients post-HCT. In the context of allo-HCT, the endothelial damage is induced by the conditioning regimen with or without total body irradiation (TBI). Furthermore, endothelial cells (ECs) have been documented as a target of GvHD and increased concentration of circulating endothelial cells (CEC) coinciding with an increase in the number of circulating alloreactive T cells. According to 2021 ESC Guidelines on CVD prevention, the main atherosclerotic CVD (ASCVD) risk factors are blood apolipoprotein B (ApoB)-containing lipoproteins (of which low-density lipoprotein (LDL) is the most abundant), high blood pressure, cigarette smoking and diabetes mellitus (DM). GvHD is considered a high-risk factor for the onset of dyslipidaemia, hypertension, and DM. Overall, the risk of premature cardiovascular death is 2.7 fold increased in comparison to the general population, while the cumulative incidence of cardiovascular complications was shown to be up to 47\% at ten years after reduced intensity conditioning (RIC), post-HCT. However, up to date, there are no available studies elucidating the interconnection between GvHD and atherosclerosis. The goal of this study was, therefore, to investigate the involvement of GvHD in the progression of atherosclerosis as well as to elucidate whether cytotoxic, CD8+ T cells that were shown to play a significant role in endothelial damage during the course of skin GvHD on one hand, and inducers of formation of unstable plaque on the other, are involved in this interconnection. For that purpose we established a novel minor histocompatibility anti gens (miHAg) allo-HCT Western diet (WD)-induced atherosclerosis mouse model. We were able to show that GvHD has a significant impact on atherosclerosis development in B6.Ldlr-/- recipient mice even in the absence of overt clinical disease activity. It seems that the impact is at least partly induced by CD8+ T cells, that showed significantly increased infiltration of aortic lesions in mice facing subclinical GvHD. As studies have shown in regular atherosclerotic mouse models as well as in humans, these CD8+ T cells exhibited not only increased expression of genes involved in activation, survival and differentiation to cytotoxic phenotype, but also some genes pointing out their exhaustion, that were absent in CD4+ T cell cluster. When anti-CD8β antibody was applied once per week along with WD feeding for eight weeks, the plaque formation was significantly reduced in aorta and aortic root pointing out the importance of these cells in an alloreactivity induced lesion formation. Furthermore, anti-CD8β treatment led to significantly decreased necrotic core formation followed by overall increase in plaque stability. Strikingly, bone marrow plus T cells (BMT) recipients fed WD showed significantly increased serum cholesterol levels in comparison to bone marrow (BM) (a group lacking alloreactive T cells that induce GvHD). This effect was reversed when anti-CD8β treatment was applied, suggesting, at least partly, an impact of alloreactive CD8+ T cells on cholesterol levels. Expression of genes responsible for lipid metabolism pointed out the tendency of the liver to regulate the increased cholesterol levels, however, the mechanism behind this phenotype still remains to be revealed. On the other hand, the impact of obesity, induced by chronic high-fat diet (HFD) feeding, has been shown to be an independent risk factor for gastrointestinal GvHD. Similarly, in major histocompatibility complex (MHC) disparate allo-HCT mouse model, we have noticed that even short-term WD intake leads to a significant decrease in survival of mice post-HCT. When the concentration of transplanted alloreactive T cells was reduced, the survival was improved, pointing out the involvement of these cells in the pathogenesis. Additionally, bioluminescence imaging (BLI) during initiation and effector phase of acute GvHD (aGvHD) revealed increased infiltration of alloreactive T cells in mice fed WD. Studies in an obesity model, we could confirm the involvement of specifically CD4+ T cells in WD induced impact, as the relative number of these cells was significantly increased in small intestine on day six post-HCT in mice fed WD. This increased intestinal infiltration was preceded by increase in the number of alloreactive T cells expressing intestine homing receptor (α4β7 integrin) in peripheral lymph nodes (LNs). Even though the number of T cells was not changed in the spleen of WD fed mice, the subset of CD4+ and CD8+ T cells that were highly secreting TNFα was increased as well as the expression of genes regulating pro-inflammatory cytokines such as IL-6 and interferon (IFN)γ pointing out significant WD-induced inflammation. Moreover, slight tendency towards increased intestinal permeability and load of translocated luminal bacteria, that we observed, could induce severe endotoxemia and dysregulated systemic immune response that could lead to detrimental induction of cell death. Justifying our speculations, we noted increased levels of transaminases and an increase in lactate dehydrogenase (LDH) levels (pointing out significant tissue damages). However, the exact mechanism behind this detrimental WD impact still remains to be elucidated.},
  subject      = {Periphere Stammzellentransplantation},
  language  = {en}
}
@phdthesis{Waltmann2024,
  author    = {Waltmann, Maria},
  title     = {Neurocognitive mechanisms of loss of control in Binge Eating Disorder},
  doi       = {10.25972/OPUS-36430},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-364300},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Binge Eating Disorder (BED) is a common, early-onset mental health condition characterised by uncontrollable episodes of overeating followed by negative emotions such as guilt and shame. An improved understanding of the neurocognitive mechanisms underlying BED is central to the development of more targeted and effective treatments. This thesis comprises a systematic review and three empirical studies contributing to this endeavour. BED can be thought of as a disorder of cognitive-behavioural control. Indeed, self-report evidence points towards enhanced impulsivity and compulsivity in BED. However, retrospective self-reports do not capture the mechanisms underlying impulsive and compulsive lapses of control in the moment. The systematic review therefore focussed on the experimental literature on impulsivity and compulsivity in BED. The evidence was very mixed, although there was some indication of altered goal-directed control and behavioural flexibility in BED. We highlight poor reliability of experimental paradigms and the failure to properly account for weight status as potential reasons for inconsistencies between studies. Moreover, we propose that impulsivity and/or compulsivity may be selectively enhanced in negative mood states in BED and may therefore not be consistently detected in lab-based studies. In the empirical studies, we explored the role of behavioural flexibility in BED using experimental and neuroimaging methods in concert with computational modelling. In the first empirical study, we assessed the reliability of a common measure of behavioural flexibility, the Probabilistic Reversal Learning Task (PRLT). We demonstrate that the behavioural and computational metrics of the PRLT have sufficient reliability to justify past and future applications if calculated using hierarchical modelling. This substantially improves reliability by reducing error variance. The results support the use of the PRLT in the second and third empirical studies on development and BED. Because a majority of patients develop BED as adolescents or young adults, we speculated that it may emerge as a consequence of disrupted or deficient maturation of behavioural flexibility. Little is known about typical development in this domain. We therefore investigated normative development of reversal learning from adolescence to adulthood in the second empirical study. Typically- developing adolescents exhibited less adaptive and more erratic and explorative behaviour than adults. This behaviour was accounted for by reduced sensitivity to positive feedback in a reinforcement learning model, and partially mediated by reduced activation reflecting uncertainty in the medial prefrontal cortex, a region known to mature substantially during adolescence. In the third empirical study, we investigated reversal learning in BED, paying special attention to potential biases associated with learning from wins vs learning from losses. We speculated that negative urgency could make it more difficult for BED patients to learn and make decisions under pressure to avoid losses. To dissociate between effects of excess weight and BED, we collected data from obese individuals with and without BED as well as normal-weight controls. As hypothesised, there were subtle neurocognitive differences between obese participants with and without BED with regard to learning to obtain rewards and to avoid losses. Obese individuals showed relatively impaired learning to obtain rewards, while BED patients showed relatively impaired learning to avoid losses. This was reflected in differential learning signals in the brain and associated with BED symptom severity. In sum, this thesis shows that the evidence on impulsivity and compulsivity in BED is inconsistent and offers potential explanations for this inconsistency. It highlights the need for reliability in interindividual difference research and indicates ways to improve it. Further, it charts the typical development of reversal learning from adolescence to adulthood and underscores the relevance of exploration in the context of learning and decision-making in adolescence. Finally, it demonstrates qualitative differences between BED and obesity, hinting at a pivotal role of aversive states in loss of control in BED.},
  subject      = {Binge-eating Disorder},
  language  = {en}
}
@phdthesis{Steinmueller2024,
  author    = {Steinm{\"u}ller, Sophie Anna Maria},
  title     = {Benzimidazole-Based Photoswitches and Photoswitchable Cannabinoid 2 Receptor Ligands},
  doi       = {10.25972/OPUS-34894},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-348943},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The field of photopharmacology has attracted considerable attention due to applying the spatial and temporal precision of light to pharmacological systems. Photoswitchable biologically active compounds have proven useful in the field of G protein-coupled receptors (GPCRs), which are of tremendous therapeutic relevance. Generally, the pharmacology of GPCRs is complex, perhaps even more complex than originally thought. Suitable tools are required to dissect the different signalling pathways and mechanisms and to unravel how they are connected in a holistic image. This is reflected in the enormous scientific interest in CB2R, as the neuroprotective and immunomodulatory effects attributed to CB2R agonists have not yet translated into effective therapeutics. This work focused on the development of a novel photoswitchable scaffold based on the privileged structure of benzimidazole and its application in photoswitchable CB2R ligands as photopharmacological tools for studying the CB2R. The visible-light photoswitchable ligand 10d enables the investigation of CB2R activation with regard to βarr2 bias, exhibiting a unique pharmacological profile as a "cis-on" affinity switch at receptor level and as a "trans-on" efficacy-switch in βarr2-mediated receptor internalization. The novel photoswitchable scaffold developed in this work further serves as a guide for the development of novel photoswitchable GPCR ligands based on the privileged structure of benzimidazole. To obtain a different tool compound for studying CB2R activation and signalling mechanisms, a previously reported putatively dualsteric CB2R ligand was rendered photoswitchable, by linking the orthosteric agonist to a CB2R-selective PAM via photoswitchable azobenzene. Compound 27-para exhibits a desirable "cis-on" behaviour across all investigated assays with >10-fold higher potency compared to its trans-isomer and can be used as an efficacy-switch employing specific concentrations.},
  subject      = {Cannabinoide},
  language  = {en}
}
@phdthesis{Kreisz2024,
  author    = {Kreisz, Philipp},
  title     = {Group S1 bZIP transcription factors regulate sink tissue development by controlling carbon and nitrogen resource allocation in \(Arabidopsis\) \(thaliana\)},
  doi       = {10.25972/OPUS-32192},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321925},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The evolutionary success of higher plants is largely attributed to their tremendous developmental plasticity, which allows them to cope with adverse conditions. However, because these adaptations require investments of resources, they must be tightly regulated to avoid unfavourable trade-offs. Most of the resources required are macronutrients based on carbon and nitrogen. Limitations in the availability of these nutrients have major effects on gene expression, metabolism, and overall plant morphology. These changes are largely mediated by the highly conserved master kinase SNF1-RELATED PROTEIN KINASE1 (SnRK1), which represses growth and induces catabolic processes. Downstream of SnRK1, a hub of heterodimerising group C and S1 BASIC LEUCINE ZIPPER (bZIP) transcription factors has been identified. These bZIPs act as regulators of nutrient homeostasis and are highly expressed in strong sink tissues, such as flowers or the meristems that initiate lateral growth of both shoots and roots. However, their potential involvement in controlling developmental responses through their impact on resource allocation and usage has been largely neglected so far. Therefore, the objective of this work was to elucidate the impact of particularly S1 bZIPs on gene expression, metabolism, and plant development. Due to the high homology and suspected partial redundancy of S1 bZIPs, higher order loss-of-function mutants were generated using CRISPR-Cas9. The triple mutant bzip2/11/44 showed a variety of robust morphological changes but maintained an overall growth comparable to wildtype plants. In detail however, seedlings exhibited a strong reduction in primary root length. In addition, floral transition was delayed, and siliques and seeds were smaller, indicating a reduced supply of resources to the shoot and root apices. However, lateral root density and axillary shoot branching were increased, suggesting an increased ratio of lateral to apical growth in the mutant. The full group S1 knockout bzip1/2/11/44/53 showed similar phenotypes, albeit far more pronounced and accompanied by growth retardation. Metabolomic approaches revealed that these architectural changes were accompanied by reduced sugar levels in distal sink tissues such as flowers and roots. Sugar levels were also diminished in leaf apoplasts, indicating that long distance transport of sugars by apoplastic phloem loading was impaired in the mutants. In contrast, an increased sugar supply to the proximal axillary buds and elevated starch levels in the leaves were measured. In addition, free amino acid levels were increased in bzip2/11/44 and bzip1/2/11/44/53, especially for the important transport forms asparagine and glutamine. The increased C and N availability in the proximal tissues could be the cause of the increased axillary branching in the mutants. To identify bZIP target genes that might cause the observed shifts in metabolic status, RNAseq experiments were performed. Strikingly, clade III SUGARS WILL EVENTUALLY BE EXPORTED (SWEET) 8 genes were abundant among the differentially expressed genes. As SWEETs are crucial for sugar export to the apoplast and long-distance transport through the phloem, their reduced expression is likely to be the cause of the observed changes in sugar allocation. Similarly, the reduced expression of GLUTAMINE AMIDOTRANSFERASE 1_2.1 (GAT1_2.1), which exhibits glutaminase activity, could be an explanation for the abundance of glutamine in the mutants. Additional experiments (ATAC-seq, DAP� seq, PTA, q-RT-PCR) supported the direct induction of SWEETs and GAT1_2.1 by S1 bZIPs. To confirm the involvement of these target genes in the observed S1 bZIP mutant phenotypes, loss-of-function mutants were obtained, which showed moderately increased axillary branching. At the same time, the induced overexpression of bZIP11 in axillary meristems had the opposite effect. Collectively, a model is proposed for the function of S1 bZIPs in regulating sink tissue development. For efficient long-distance sugar transport, bZIPs may be required to induce the expression of clade III SWEETs. Thus, reduced SWEET expression in the S1 bZIP mutants would lead to a decrease in apoplastic sugar loading and a reduced supply to distal sinks such as shoot or root apices. The reduction in long� distance transport could lead to sugar accumulation in the leaves, which would then increasingly be transported via symplastic routes towards proximal sinks such as axillary branches and lateral roots or sequestered as starch. The reduced GAT1_2.1 levels lead to an abundance of glutamine, a major nitrogen transport form. The combined effect on C and N allocation results in increased nutrient availability in proximal tissues, promoting the formation of lateral plant organs. Alongside emerging evidence highlighting the power of bZIPs to steer nutrient allocation in other species, a novel but evolutionary conserved role for S1 bZIPs as regulators of developmental plasticity is proposed, while the generation of valuable data sets and novel genetic resources will help to gain a deeper understanding of the molecular mechanisms involved},
  subject      = {Molekularbiologie},
  language  = {en}
}
@phdthesis{Papay2024,
  author    = {Papay, Marion},
  title     = {Notwendigkeit der pr{\"a}operativen Reposition von distalen, nach dorsal dislozierten Radiusfrakturen bei bestehender Operationsindikation im Hinblick auf das Schmerzniveau sowie postoperative Ergebnisse},
  doi       = {10.25972/OPUS-36388},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363882},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die distale Radiusfraktur geh{\"o}rt zu den h{\"a}ufigsten Frakturen in Deutschland mit einem Inzidenzanstieg im Alter unter Betonung des weiblichen Geschlechts. Dabei zeigt sich ein zunehmender Trend in Richtung operative Versorgung, allen voran die Versorgung mittels winkelstabiler Plattensysteme. Instabile, distale Radiusfrakturen werden dabei vor geplanter operativer Versorgung im Rahmen der Initialbehandlung {\"u}blicherweise geschlossen reponiert und im Gipsverband retiniert. Ziel der vorliegenden monozentrischen, prospektiv randomisierten Studie mit zwei Studiengruppen war es herauszufinden, ob sich das Unterlassen der Reposition vor geplanter Operation nachteilig auf das Schmerzniveau in der pr{\"a}operativen Phase auswirkt und ob sich durch die Dislokation Nachteile in Bezug auf den Nervus medianus im Sinne eines Traktionsschadens sowie bez{\"u}glich des klinisch-radiologischen Ausheilungsergebnisses zeigen. Die Studie zeigte, dass das Schmerzempfinden w{\"a}hrend der pr{\"a}operativen Gipsbehandlung unabh{\"a}ngig von einer vorherigen Reposition war. F{\"u}r den prim{\"a}ren Endpunkt an Tag 1 nach der Akutbehandlung konnte statistisch signifikante Nichtunterlegenheit der Gruppe ohne Reposition gegen{\"u}ber der Gruppe mit Reposition nachgewiesen werden. Gleiches galt f{\"u}r Tag 2, sowohl f{\"u}r die absoluten Schmerzniveaus als auch f{\"u}r die Schmerzlinderung. Das Unterlassen der Reposition hatte zudem keine nachteiligen Effekte auf den Nervus medianus. Gleiches zeigte sich f{\"u}r das klinische und radiologische Ausheilungsergebnis. F{\"u}r die funktionellen DASH- und Krimmer-Scores konnte ein Jahr postoperativ ebenfalls statistisch signifikante Nichtunterlegenheit der Gruppe ohne Reposition nachgewiesen werden. Diese Erkenntnisse best{\"a}tigen die in der Literatur vorhandenen Ergebnisse verschiedener Studien dahingehend, dass das Unterlassen der Reposition keine nachteiligen Effekte auf das postoperative Outcome hat. Einige Studien verdeutlichen zudem, dass es nach Reposition, insbesondere bei Vorliegen gewisser Risiko- und Instabilit{\"a}tsfaktoren, ohnehin zur sekund{\"a}ren Dislokation kommt, sodass die generelle Notwendigkeit der Reposition vor Gipsanlage sowohl vor einer operativen als auch vor einer konservativen Weiterbehandlung angezweifelt werden muss.},
  subject      = {distale Radiusfraktur},
  language  = {de}
}
@article{OPUS4-31269,
  title     = {Measurement of prompt photon production in √ s(NN) = 8.16 TeV \(p\) Pb collisions with ATLAS},
  series = {Physics letters B},
  volume    = {796},
  journal   = {Physics letters B},
  organization    = {The ATLAS Collaboration},
  doi       = {10.1016/j.physletb.2019.07.031},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312697},
  pages     = {230-252},
  year      = {2019},
  abstract  = {The inclusive production rates of isolated, prompt photons in p Pb collisions at root s(NN) = 8.16 TeV are studied with the ATLAS detector at the Large Hadron Collider using a dataset with an integrated luminosity of 165 nb(-1) recorded in 2016. The cross-section and nuclear modification factor R-p pb are measured as a function of photon transverse energy from 20 GeV to 550 GeV and in three nucleon-nucleon centre-of-mass pseudorapidity regions, (-2.83, -2.02), (-1.84, 0.91), and (1.09, 1.90). The cross-section and R-p pb values are compared with the results of a next-to-leading-order perturbative QCD calculation, with and without nuclear parton distribution function modifications, and with expectations based on a model of the energy loss of partons prior to the hard scattering. The data disfavour a large amount of energy loss and provide new constraints on the parton densities in nuclei. (C) 2019 The Author. Published by Elsevier B.V.},
  language  = {en}
}
@phdthesis{vonderHeide2024,
  author    = {von der Heide, Julia Magdalena},
  title     = {Ist eine Berechnung der Geometrie der Halswirbelk{\"o}rper anhand ihrer Morphologie im Kindesalter und somit eine Individualisierung der CVM-Methode m{\"o}glich?},
  doi       = {10.25972/OPUS-36075},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360753},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Ziel der vorliegenden Studie war es zu untersuchen, ob anhand geometrischer Merkmale der HWK im Kindesalter eine sichere individuelle Vorhersage der Morphologie der HWK zum Ende der Entwicklung m{\"o}glich ist. Hierdurch k{\"o}nnte eine Individualisierung der CVM-Methode und somit eine Einsch{\"a}tzung des bereits verstrichenen Wachstums erfolgen. Zu diesem Zweck wurden insgesamt 1377 FRS-Aufnahmen von 267 Patienten - 110 weibliche und 157 m{\"a}nnliche - aus dem Archiv der Poliklinik f{\"u}r Kieferorthop{\"a}die des Universit{\"a}tsklinikums W{\"u}rzburg digitalisiert und untersucht. Die HWK wurden im Programm OnyxCeph (Herst.: Image Instruments GmbH) quantifiziert und die berechneten Werte mit der Software SPSS statistisch ausgewertet. Mittels linearer Regressionen wurde versucht, anhand der Morphologie der Wirbelk{\"o}rper vor dem puberalen Wachstumsschub auf die Geometrie der HWK im Erwachsenenalter zu schließen. Zur Illustrierung wurden Streudiagramm und die dazugeh{\"o}rigen Abfolgen von R{\"o}ntgenbildern dargestellt. Eine Sch{\"a}tzung der Geometrie der HWK im Erwachsenenalter w{\"u}rde bei den separat betrachteten Parametern und bei einer gemeinsamen Betrachtung der Parameter kaum zu korrekten Einsch{\"a}tzungen f{\"u}hren. Die Streudiagramme mit den Bilderabfolgen st{\"u}tzen diese These ebenfalls und illustrieren die m{\"o}gliche Fehleinsch{\"a}tzung der Geometrie. Die Ergebnisse der Studie zeigen erneut, dass die Geometrie der HWK im Erwachsenenalter sehr variabel ist, wie komplex die Entwicklung der HWK ist und dass anhand ihrer Geometrie im Kindesalter keine sichere Einsch{\"a}tzung der skelettalen Reife m{\"o}glich ist. Eine Individualisierung der CVM-Methode ist anhand der in dieser Studie untersuchten Parameter nicht m{\"o}glich. Somit l{\"a}sst sich schlussfolgern, dass die CVM-Methode nicht als alleinige Methode zur pr{\"a}zisen skelettalen Alterseinsch{\"a}tzung verl{\"a}sslich genutzt werden kann, sondern f{\"u}r eine sichere Beurteilung weitere Reifeindikatoren hinzugezogen werden sollten. Allerdings sollten hierzu zus{\"a}tzliche radiologische Untersuchungen, wie beispielsweise die Handr{\"o}ntgenaufnahme, nur dann durchgef{\"u}hrt werden, wenn diese dem ALARA-Prinzip entsprechen.},
  subject      = {Skelett},
  language  = {de}
}
@phdthesis{Roger2024,
  author    = {Roger, Chantal},
  title     = {Photophysics and Spin Chemistry of Triptycene Bridge Donor-Acceptor-Triads},
  doi       = {10.25972/OPUS-36303},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363031},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The goal of this thesis was to investigate the influence of rotational restriction between individual parts and of the varying electron density in the bridging unit of D B A systems on the exchange interaction 2J, and thus the electronic coupling between a donor state and an acceptor state. A better understanding of how to influence the underlaying spin dynamics in such donor acceptor systems can open up the door to new technologies, such as modern molecular electronics or optoelectronic devices. Therefore, three series of molecules consisting of a TAA electron donor, a TTC or ATC bridging unit and a PDI electron acceptor were studied. To investigate the influence of rotational restriction on 2J and the electronic coupling, a series of four rotationally hindered triads (chapter 6) was synthesised. The dihedral angle between the TAA and the TTC as well as between the TTC and the PDI was restricted by ortho methyl groups at the phenylene linkers of the connecting ends to the TTC bridge, producing a twist around the linking single bond which minimises the π overlap. The triads exhibit varying numbers of ortho methyl groups and therefore different degrees of rotational restriction. In order to shine light on the influence of varying electron density on 2J and the electronic coupling, a series of four substituted triptycene triads (chapter 7) was synthesised. The electron density in the TTC bridging unit was varied by electron donating and electron withdrawing groups in 12,13 position of the TTC bridging unit and thus varying its HOMO/LUMO energy. The last series of two anthracene bridge triads (chapter 8) connected both approaches by restricting the rotation with ortho methyl groups and simultaneously by varying the bridge energies. In order to obtain the electronic properties, steady state absorption and emission spectra of all triads were investigated (chapter 4). Here, all triads show spectral features associated with the separate absorption bands of TAA and the PDI moiety. The reduced QYs, compared to the unsubstituted PDI acceptor, indicate a non radiative quenching mechanism in all triads. The CV data (chapter 5) were used to calculate the energies of possible CSSs and those results were used to assign the CR dynamics into the different Marcus regions. fs TA measurements reveal that all triads form a CSS upon excitation of the PDI moiety. The lifetimes of the involved states and the rate constants were determined by global exponential fits and global target analysis. The CR dynamics upon depopulation of the CSSs were investigated using external magnetic field dependent ns TA spectroscopy. The ns TA maps show that all triads recombine via CRT pathway populating the local 3PDI state in toluene and provided the respective lifetimes. The approximate QYs of triplet formation were determined using actinometry. The magnetic field dependent ns TA data reveal the exchange interaction 2J between singlet and triplet CSS for each triad. Those magnetic field dependent ns TA data in toluene were furthermore treated using a quantum mechanical simulation (done by U.E. Steiner) to extract the rate constants kT and kS for CRT and CRS, respectively. However, the error margins of kS were rather wide. Finally, the electronic couplings between the donor and the acceptor states were obtained by combining the aforementioned experimental results of the rate constants and applying the Bixon Jortner theoretical description of diabatic ET and Andersons perturbative theory of the exchange coupling. Therefore, the experimentally determined values of 2J and the calculated values of kCS and kT were used. The rate constant kS was calculated based on the electronic coupling V1CSS 1S0. The rotationally hindered triads (chapter 6) show a strong influence of the degree of rotational restriction on the lifetimes and rate constants of the CS processes. The rate constants of CS are increasing with increasing rotational freedom. The magnetic field dependent decay data show that the exchange interactions increase with increasing rotational freedom. Based on the CR dynamics, the calculated electronic couplings of the ET processes reflect the same trend along the series. Here, only singlet couplings turned out to be strongly influenced while the triplet couplings are not. Therefore, this series shows that the ET dynamics of donor acceptor systems can strongly be influenced by restricting the rotational freedom. In the substituted triptycene triads (chapter 7), decreasing electron density in the bridging unit causes a decrease of the CS rate constants. The magnetic field dependent decay data show that with decreasing electron density in the bridge the exchange interaction decreases. The CR dynamics-based rate constants and the electronic couplings follow the same trend as the exchange interaction. This series shows that varying the HOMO/LUMO levels of the connecting bridge between donor and acceptor strongly influences the ET processes. In the anthracene bridge triads (chapter 8), the CS process is slow in both triads. The CR was fast in the anthracene triad and is slowed down in the methoxy substituted anthracene bridge triad. The increase of the exchange interaction with increasing electron density in the bridge was more pronounced than in the substituted triptycene triads. Thus, the variation of electron density in the bridge strongly influences the ET processes even though the rotation is restricted. In this thesis, it was shown that the influence of the rotational hindrance as well as the electron density in a connecting bridge have strong influence on all ET processes and the electronic coupling in donor acceptor systems. These approaches can therefore be used to modify magnetic properties of new materials.},
  subject      = {Rotation},
  language  = {en}
}
@phdthesis{Krings2024,
  author    = {Krings, Moritz},
  title     = {Universit{\"a}re Psychiatrie um 1900 : Die Anfangsjahre der psychiatrischen Klinik in W{\"u}rzburg},
  doi       = {10.25972/OPUS-36140},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361407},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Ende des 19. Jahrhunderts standen sich in Deutschland zwei verschiedene Arten psychiatrischer Institutionen gegen{\"u}ber, die Anstaltspsychiatrien auf der einen, die universit{\"a}ren psychiatrischen Kliniken auf der anderen Seite. Die psychiatriehistorische Forschung widmete sich {\"u}berwiegend psychiatrischen Anstalten w{\"a}hrend Kliniken hier unterrepr{\"a}sentiert sind. Die vorliegende Arbeit m{\"o}chte zur historischen Kenntnis universit{\"a}rer psychiatrischer Einrichtungen beitragen. Hierzu werden die Charakteristika einer psychiatrischen Klinik um 1900 anhand des Beispiels der psychiatrischen Klinik der Universit{\"a}t W{\"u}rzburg betrachtet. Der Fokus liegt hierbei neben Lage und Aufbau der Klinik sowie deren Personal auf den drei Bereichen Patient*innen, Forschung und Lehre.},
  subject      = {Julius-Maximilians-Universit{\"a}t W{\"u}rzburg},
  language  = {de}
}
@phdthesis{Kappes2024,
  author    = {Kappes, Alexander},
  title     = {High-Redshift Blazars Observed by the International LOFAR Telescope},
  doi       = {10.25972/OPUS-36144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361444},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {This work presents the first ILT observations of high redshift blazars and their study in terms of jet evolution, morphology, and interaction with the surrounding medium. Each of these represents a highly topical area of astronomywith a large number of open questions. To better understand Active Galactic Nuclei (AGN) and their fundamental inner workings, new techniques are needed to exploit the full potential of the next generation of radio interferometers. Some of these tools are presented here and applied to one of the latest generation of software radio telescopes. A major focus of the studies presented is on the unification model, where the observed blazars are discussed for their properties to be rotated counterparts of Fanaroff-Riley Class II (FR-II) radio galaxies, when classified as Flat Spectrum Radio Quasars (FSRQs). In addition, multiwavelength information has been included in the analysis. Both studies are feasibility studies that will serve as a basis for future similar studies. The characteristics discussed and their interpretation do not allow conclusions to be drawn for their respective populations. However, by applying them to a larger number of targets, population studies will be possible. The first chapters introduce the necessary topics, AGN, principles of radio observations and ILT, in the necessary depth to provide the reader with a solid knowledge base. They are particularly important for understanding the current limits and influences of uncertainties in the observation, calibration and imaging process. But they also shed light on realistic future improvements. A particular focus is on the development and evolution of the LOw-Frequency ARray (LOFAR)-Very Long Baseline Interferometry (VLBI) pipeline. With the tools at hand, the first study addresses the high redshift blazar S5 0836+710 \$(z=2.218)\$, which has been observed at various wavelengths and resolutions. It has a disrupted one-sided jet with an associated extended region further out. Despite the excellent wavelength coverage, only the additional ILT observations provided a complete picture of the source. With the data, the extended region could be classified as a hotspot moving at slightly relativistic speeds.. With the ILT data it was also possible to extract the flux of the core region of the AGN, and in projection to reveal the mixed counter-hotspot behind it. This also allowed constraints on jet parameters and environmental properties to be modelled, which were previously inconclusive. Technically, this study shows that the ILT can be used as an effective VLBI array for compact sources with small angular scales. However, the detection of faint components beyond redshifts of \$z=2\$ may require the capabilities of the Square Kilometre Array (SKA) to provide a significant number of detections to enable statistical conclusions. The second study uses a much improved calibration pipeline to analyse the high redshift blazar GB1508+5714 \$(z=4.30)\$. The ILT data revealed a previously unseen component in the eastern direction. A spectral index map was generated from the Karl G. Jansky Very Large Array (VLA) data, showing spectral index values of \$-1.2_{-0.2}^{+0.4}\$ for the western component, steeper than \$-1.1\$ for the eastern region, and \$0.023 \pm 0.007\$ for the core. Using the information provided by the ILT observation, as well as multi-wavelength information from other observations ranging from the long radio wavelengths to the \$\gamma\$ regime, four models were developed to interpret the observed flux with different emission origins. This also allowed to test a proposed interaction channel of the electrons provided by the jet, to cool off via inverse compton scattering with the Cosmic Microwave Background (CMB) photons, rather than by the usual synchrotron emission. This is referred to as cmb quenching in the literature, which could be shown in the study, to be necessary in any case. Finally, one of the four models was considered in which the hotspots in the detected components are unresolved and mixed by the lobe emission, with the X-ray emission coming from the lobes and partially mixed by the bright core region. The results of this preferred model are consistent with hotspots in a state of equipartition and lobes almost so. The study shows that high redshift blazars can be studied with the ILT, and expanding the sample of high redshift blazars resolved at multiple frequencies will allow a statistical study of the population. Finally, this work successfully demonstrates the powerful capabilities of the ILT to address questions that were previously inaccessible. The current state of the LOFAR-VLBI pipeline, when properly executed, allows work on the most challenging objects and will only improve in the future. In particular, this gives a glimpse of the possibilities that SKA will bring to astronomy.},
  subject      = {Blazar},
  language  = {en}
}
@phdthesis{GoettlergebLang2024,
  author    = {G{\"o}ttler [geb. Lang], Anna},
  title     = {Auswirkung der bariatrischen Operation auf die Aktivit{\"a}t des autonomen Nervensystems im kardialen und peripheren Kompartiment},
  doi       = {10.25972/OPUS-36932},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369328},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die vorliegende Arbeit thematisiert die Aktivit{\"a}t des autonomen Nervensystems im Vergleich vor versus nach bariatrischer Operation bei ProbandInnen mit morbider Adipositas. Wir untersuchten, ob die Operation und der damit einhergehende Gewichtsverlust drei Monate nach dem bariatrischen Eingriff zu einer Ver{\"a}nderung der Aktivit{\"a}t des autonomen Nervensystems im thorakalen und im motorischen/peripheren Kompartiment f{\"u}hrt. Als Parameter dienen f{\"u}r das thorakale Kompartiment die Herzfrequenzvariabilit{\"a}t und f{\"u}r das periphere/motorische Kompartiment vaskul{\"a}re (lnRHI und AI) und sudomotorische (Schweißvolumen, Antwortlatenz) Parameter. Unsere Ergebnisse im thorakalen Kompartiment zeigen einen Anstieg der Herzfrequenzvariabilit{\"a}t 3 Monate nach bariatrischer Operation. Wir schließen uns daher der Hypothese an, die mit morbider Adipositas assoziierte Erh{\"o}hung der sympathischen Aktivit{\"a}t im thorakalen Kompartiment k{\"o}nne durch bariatrische Operationen reversibel sein. Im peripheren/motorischen Kompartiment k{\"o}nnen wir keine eindeutige Ver{\"a}nderung der Aktivit{\"a}t des autonomen Nervensystems vor versus nach bariatrischer Operation beobachten. Andere Studien konnten hierzu deutlichere Ergebnisse erheben, die ebenfalls eine erh{\"o}hte sympathische Aktivit{\"a}t im motorischen Kompartiment zeigten, welche nach bariatrischer Operation reversibel war. Insgesamt k{\"o}nnen wir die These einer autonomen Imbalance bei Adipositas sowie einer Verringerung der sympathischen Aktivit{\"a}t im thorakalen Kompartiment nach bariatrischer Operation unterst{\"u}tzen. Die Ver{\"a}nderungen im autonomen Nervensystem leisten m{\"o}glicherweise einen Beitrag zur Verbesserung der kardiovaskul{\"a}ren Gesundheit und der metabolischen Situation nach der bariatrischen Operation.},
  subject      = {Vegetatives Nervensystem},
  language  = {de}
}
@phdthesis{Gaballa2024,
  author    = {Gaballa, Abdallah Hatem Hassan Hosny Ahmed},
  title     = {PAF1c drives MYC-mediated immune evasion in pancreatic ductal adenocarcinoma},
  doi       = {10.25972/OPUS-36045},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360459},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The expression of the MYC proto-oncogene is elevated in a large proportion of patients with pancreatic ductal adenocarcinoma (PDAC). Previous findings in PDAC have shown that this increased MYC expression mediates immune evasion and promotes S-phase progression. How these functions are mediated and whether a downstream factor of MYC mediates these functions has remained elusive. Recent studies identifying the MYC interactome revealed a complex network of interaction partners, highlighting the need to identify the oncogenic pathway of MYC in an unbiased manner. In this work, we have shown that MYC ensures genomic stability during S-phase and prevents transcription-replication conflicts. Depletion of MYC and inhibition of ATR kinase showed a synergistic effect to induce DNA damage. A targeted siRNA screen targeting downstream factors of MYC revealed that PAF1c is required for DNA repair and S-phase progression. Recruitment of PAF1c to RNAPII was shown to be MYC dependent. PAF1c was shown to be largely dispensable for cell proliferation and regulation of MYC target genes. Depletion of CTR9, a subunit of PAF1c, caused strong tumor regression in a pancreatic ductal adenocarcinoma model, with long-term survival in a subset of mice. This effect was not due to induction of DNA damage, but to restoration of tumor immune surveillance. Depletion of PAF1c resulted in the release of RNAPII with transcription elongation factors, including SPT6, from the bodies of long genes, promoting full-length transcription of short genes. This resulted in the downregulation of long DNA repair genes and the concomitant upregulation of short genes, including MHC class I genes. These data demonstrate that a balance between long and short gene transcription is essential for tumor progression and that interference with PAF1c levels shifts this balance toward a tumor-suppressive transcriptional program. It also directly links MYC-mediated S-phase progression to immune evasion. Unlike MYC, PAF1c has a stable, known folded structure; therefore, the development of a small molecule targeting PAF1c may disrupt the immune evasive function of MYC while sparing its physiological functions in cellular growth.},
  subject      = {Myc},
  language  = {en}
}
@phdthesis{Doehler2024,
  author    = {D{\"o}hler, Ida},
  title     = {Reduktion von Blutungskomplikationen bei Patientinnen und Patienten mit oraler Antikoagulation in der elektiven Allgemein- und Viszeralchirurgie durch individuelles Risiko-adjustiertes Bridging},
  doi       = {10.25972/OPUS-37063},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370639},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Zahlreiche Studien zeigten, dass perioperatives Bridging der oralen Antikoagulation zu einem erh{\"o}hten Blutungsrisiko f{\"u}hrt. Ursache hierf{\"u}r k{\"o}nnte eine zu aggressive Herangehensweise bez{\"u}glich der Dosierung des Bridgings sein. Daher war das Ziel dieser Arbeit herauszufinden, ob ein Risiko-adjustiertes Bridging-Schema in der elektiven Allgemein- und Viszeralchirurgie zu einem geringeren Auftreten von postoperativen Blutungsereignissen f{\"u}hrt und ob trotzdem ein ad{\"a}quater Schutz vor thromboembolischen Ereignissen gegeben ist. Hierf{\"u}r wurde retrospektiv und monozentrisch das Auftreten der genannten postoperativen Ereignisse in zwei Zeitr{\"a}umen untersucht. Das erste Studienintervall erstreckte sich von Januar 2011 bis Dezember 2014 und spiegelt die Ereignisraten vor der internen Leitlinien{\"a}nderung wider. Es wurden 263 Personen eingeschlossen. Das zweite Intervall begann im Januar 2017 und endete im Dezember 2019, in diesem wurden 271 Personen untersucht. Zwischen diesen beiden Zeitr{\"a}umen wurde eine {\"u}berarbeitete klinikinterne Bridging-Leitlinie etabliert, welche an das individuelle thromboembolische Risiko, Alter, Gewicht und die Nierenfunktion der Patientinnen und Patienten angepasst war. Postoperative Major- (8.4\% vs. 4.1\%, p=0.039) und Minor-Blutungen (13.7\% vs. 6.3\%, p=0.004) nahmen im zweiten Intervall signifikant ab, w{\"a}hrend das thromboembolische Risiko weiterhin niedrig blieb (0.8\% vs. 1.1\%, p=1). Außerdem zeigte sich, dass es zu keiner signifikanten Zunahme der Mortalit{\"a}t, der Reoperationen, der L{\"a}nge des postoperativen station{\"a}ren Aufenthalts oder der Erythrozytenkonzentrat-Transfusionen kam. Die Ergebnisse dieser Arbeit zeigen, dass die differenzierte Bridging-Leitlinie f{\"u}r die Allgemein- und Viszeralchirurgie mit einer signifikant erniedrigten Blutungsrate assoziiert ist und eine Anpassung des Bridgings an die patientenspezifischen Risikofaktoren wichtig ist.},
  subject      = {Heparin},
  language  = {de}
}
@phdthesis{Polzin2024,
  author    = {Polzin, Charlotte},
  title     = {Entwicklung eines Screeningverfahrens f{\"u}r Linezolid-resistente Enterokokken und Aufnahme der Pr{\"a}valenz},
  doi       = {10.25972/OPUS-37066},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370665},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Enterokokken geh{\"o}ren zu den bedeutendsten nosokomialen Keimen. Die Verbreitung von Multiresistenzen bei diesen Keimen stellt das deutsche Gesundheitssystem aufgrund von wenigen verbleibenden Therapieoptionen von Infektionen vor große Probleme. Die KRINKO des Robert-Koch-Instituts empfiehlt als m{\"o}gliche Pr{\"a}ventionsmaßnahme ein regelm{\"a}ßiges Screening auf Enterokokken mit Vancomycin- bzw. Linezolid-Resistenzen. Ziel dieser Arbeit war es, ein kulturelles Screeningverfahren f{\"u}r Linezolid-resistente Enterokokken (LRE) zu entwickeln und dieses anschließend im Routinescreening des Universit{\"a}tsklinikums W{\"u}rzburg zu etablieren. Es wurde ein Verfahren entwickelt, welches sich aus einem Anreicherungsschritt mit 3 mg/l Linezolid versetzter selektiver Enterococcosel-Bouillon und einer anschließenden Subkultivierung auf Linezolid-Enterococcosel-Agar mit 4 mg/l Linezolid zusammensetzt. In einer Simulation von klinischen Bedingungen zeigte sich eine gute Sensitivit{\"a}t und Spezifit{\"a}t. Das entwickelte Screeningverfahren wurde mit einem geringen Sensitivit{\"a}tsverlust und ohne zus{\"a}tzliche Belastung f{\"u}r die Patienten in das bestehende Routinescreening f{\"u}r Vancomycin-resistente Enterokokken des Universit{\"a}tsklinikums W{\"u}rzburg eingegliedert. Die nachgewiesen LRE zeigten unterschiedliche Resistenzmechanismen, wobei bei dem Großteil der Isolate Resistenzgene nachgewiesen werden konnten. Des Weiteren zeigte sich ein breit gestreuter genetischer Hintergrund. Viele der Isolate geh{\"o}rten genetischen Gruppen an, welche bisher kaum in hospitalisierten Patienten nachgewiesen wurden. Durch die labortechnische Weiterentwicklung von Screeningverfahren f{\"u}r LRE k{\"o}nnen diese m{\"o}glicherweise bald routinem{\"a}ßig in vielen Kliniken etabliert werden.},
  subject      = {Enterococcus},
  language  = {de}
}
@article{ElliotGermainHilzetal.2019,
  author    = {Elliot, Perry M. and Germain, Dominique P. and Hilz, Max J. and Spada, Marco and Wanner, Christoph and Falissard, Bruno},
  title     = {Why systematic literature reviews in Fabry disease should include all published evidence},
  series = {European Journal of Medical Genetics},
  volume    = {62},
  journal   = {European Journal of Medical Genetics},
  doi       = {10.1016/j.ejmg.2019.103702},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226654},
  year      = {2019},
  abstract  = {Fabry disease is an X-linked inherited, progressive disorder of lipid metabolism resulting from the deficient activity of the enzyme α-galactosidase. Enzyme replacement therapy (ERT) with recombinant agalsidase, with intravenous infusions of either agalsidase beta or agalsidase alfa, is available and clinical experience now exceeds 15 years. There are very few randomised, placebo-controlled clinical trials evaluating the outcomes of ERT. Data are often derived from observational, registry-based studies and case reports. Pooled analysis of data from different sources may be limited by the heterogeneity of the patient populations, outcomes and treatment. Therefore, comprehensive systematic literature reviews of unpooled data are needed to determine the effects of ERT on disease outcomes. A systematic literature search was conducted in the Embase and PubMed (MEDLINE) databases to retrieve original articles that evaluated outcomes of ERT in patients with Fabry disease; the outcome data were analysed unpooled. The literature analysis included the full range of published literature including observational studies and case series/case reports. Considerable heterogeneity was found among the studies, with differences in sample size, statistical methods, ERT regimens and patient demographic and clinical characteristics. We have demonstrated the value of performing an unpooled systematic literature review of all published evidence of ERT outcomes in Fabry disease, highlighting that in a rare genetic disorder like Fabry disease, which is phenotypically diverse, different patient populations can require different disease management and therapeutic goals depending on age, genotype, and disease severity/level of organ involvement. In addition, these findings are valuable to guide the design and reporting of new clinical studies.},
  language  = {en}
}
@article{SondermannUtikalEnketal.2019,
  author    = {Sondermann, Wiebke and Utikal, Jochen Sven and Enk, Alexander H. and Schadendorf, Dirk and Klode, Joachim and Hauschild, Axel and Weichenthal, Michael and French, Lars E. and Berking, Carola and Schilling, Bastian and Haferkamp, Sebastian and Fr{\"o}hling, Stefan and von Kalle, Christof and Brinker, Titus J.},
  title     = {Prediction of melanoma evolution in melanocytic nevi via artificial intelligence: A call for prospective data},
  series = {European Journal of Cancer},
  volume    = {119},
  journal   = {European Journal of Cancer},
  doi       = {10.1016/j.ejca.2019.07.009},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239263},
  pages     = {30-34},
  year      = {2019},
  abstract  = {Recent research revealed the superiority of artificial intelligence over dermatologists to diagnose melanoma from images. However, 30-50\% of all melanomas and more than half of those in young patients evolve from initially benign lesions. Despite its high relevance for melanoma screening, neither clinicians nor computers are yet able to reliably predict a nevus' oncologic transformation. The cause of this lies in the static nature of lesion presentation in the current standard of care, both for clinicians and algorithms. The status quo makes it difficult to train algorithms (and clinicians) to precisely assess the likelihood of a benign skin lesion to transform into melanoma. In addition, it inhibits the precision of current algorithms since 'evolution' image features may not be part of their decision. The current literature reveals certain types of melanocytic nevi (i.e. 'spitzoid' or 'dysplastic' nevi) and criteria (i.e. visible vasculature) that, in general, appear to have a higher chance to transform into melanoma. However, owing to the cumulative nature of oncogenic mutations in melanoma, a more fine-grained early morphologic footprint is likely to be detectable by an algorithm. In this perspective article, the concept of melanoma prediction is further explored by the discussion of the evolution of melanoma, the concept for training of such a nevi classifier and the implications of early melanoma prediction for clinical practice. In conclusion, the authors believe that artificial intelligence trained on prospective image data could be transformative for skin cancer diagnostics by (a) predicting melanoma before it occurs (i.e. pre-in situ) and (b) further enhancing the accuracy of current melanoma classifiers. Necessary prospective images for this research are obtained via free mole-monitoring mobile apps.},
  language  = {en}
}
@phdthesis{Danner2024,
  author    = {Danner, Elisabeth},
  title     = {Systolische Ejektionszeit - Referenzwerte und Einfluss kardiovaskul{\"a}rer Risikofaktoren in einer populationsbasierten Kohortenstudie},
  doi       = {10.25972/OPUS-37048},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370480},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die systolische Ejektionszeit (SET) und die pr{\"a}-Ejektionszeit (pET) sind Zeitintervalle, die sich zuverl{\"a}ssig mittels transthorakaler Echokardiographie erheben lassen und wichtige Aspekte in der kardialen Leistungsdiagnostik abbilden. Gleichwohl gibt es bislang f{\"u}r diese systolischen Zeitintervalle keine Normwerte. Die vorliegende Arbeit analysierte echokardiographische Daten von 4965 ProbandInnen der STAAB-Studie, einer umf{\"a}nglich ph{\"a}notypisierten populationsbasierten Kohortenstudie mit dem Ziel der Erstellung von Normwerten f{\"u}r die systolischen Zeitintervalle sowie der Identifizierung und Quantifizierung ihrer Determinanten mittels multivariable Regressionsanalysen. Aufgrund der starken Abh{\"a}ngigkeit der SET von der Herzfrequenz wurde die herzfrequenzkorrigierte SETc eingef{\"u}hrt, die in Anlehnung an die QTc-Zeit nach Fridericia berechnet wurde ("SET" /∛("RR-Intervall" )). Die Normwerte wurden anhand der gesunden Untergruppe (definiert durch Abwesenheit von kardiovaskul{\"a}ren Risikofaktoren oder Erkrankungen; N=966) aus STAAB generiert. Dem starken Einfluss von Geschlecht und Alter wurde dabei Rechnung getragen, indem f{\"u}r SET, SETc und pET alters- und geschlechtsspezifische Referenzwerte berechnet wurden. SETc war stark korreliert mit linksventrikul{\"a}rer Ejektionsfraktion sowie enddiastolischem Volumen und Schlagvolumen. Zudem zeigte sich ein deutlicher Zusammenhang von SETc mit spezifischen Markern der Nachlast (Ea und Ees). Aus der großen Liste der klinischen Marker, die in STAAB erhoben wurden, ergab sich eine gr{\"o}ßere Anzahl von Einflussfaktoren. Bedeutsame Determinanten der systolischen Zeitintervalle waren insbesondere das metabolische Syndrom (sowie dessen Komponenten), das Rauchverhalten und die Einnahme von β Blockern. Die Ergebnisse zeigen, dass die systolischen Zeitintervalle, insbesondere SETc, reliable Informationen {\"u}ber das kardiale Kontraktionsverhalten liefern k{\"o}nnen. Derzeit werden neue Substanzklassen untersucht, die unter anderem {\"u}ber die Modifizierung von SET wirken sollen. Hier zu nennen sind insbesondere Myosin-Aktivatoren bei Herzinsuffizienz mit reduzierter Pumpfunktion wie zum Beispiel Omecamtiv Mecarbil oder Myosin-Inhibitoren bei Hypertropher Obstruktiver Kardiomyopathie. Die hierzu laufenden Studien betrachten auch die Effekte dieser Medikamente auf die systolischen Zeitintervalle als bedeutsame Surrogate der klinischen Effekte und letztlich der Prognose. Die nun vorliegenden Normwerte dieser Zeitintervalle erlauben es, die pathologisch ver{\"a}nderten Werte bei diesen spezifischen Krankheitsbildern und klinischen Studien besser einzuordnen und zu verstehen.},
  subject      = {Referenzwert},
  language  = {de}
}
@phdthesis{Engelbrecht2024,
  author    = {Engelbrecht, Elisabeth},
  title     = {Retrospektive Auswertung des Therapieerfolges einer PTCD-Anlage bei Insuffizienz der Pankreatojejunostomie nach Pankreaskopfresektionen},
  doi       = {10.25972/OPUS-37039},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370395},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Trotz stetiger Weiterentwicklung und Verbesserungen in chirurgischen Anastomosetechniken treten postoperative Pankreasfisteln (POPF) in 20 - 25 \% der Patienten und Patientinnen als Komplikation nach partieller Pankreatikoduodenektomie (PPD) auf. Kommt es zu einer kombinierten Leckage aus Gallen- und Pankreassekret, wurde in dieser Arbeit die Definition einer komplizierten POPF (CPPF) eingef{\"u}hrt, welche eine seltene, aber schwerwiegende und gef{\"a}hrliche postoperative Komplikation darstellt. Neben einer Relaparotomie kann eine Restpankreatektomie als ultima ratio zur Beherrschung dieser schweren Komplikation notwendig werden, welche mit einer Mortalit{\"a}t von 50 \% verbunden ist. Die Internationale Studiengruppe der Pankreaschirurgie (ISGPS) entwickelte ein Klassifikationssystem f{\"u}r POPF, welches auf Abweichungen der {\"u}blichen postoperativen Behandlungsstrategie beruht. Jedoch wurden keine spezifischen Behandlungsalgorithmen bzw. Therapiekonzepte, insbesondere im Falle einer CPPF, vorgeschlagen. In dieser Arbeit soll die therapeutische Effektivit{\"a}t einer perkutanen transhepatischen Cholangiodrainage (PTCD) bei Patienten und Patientinnen mit einer CPPF evaluiert werden. Dazu wurde eine retrospektive Analyse an Patienten und Patientinnen durchgef{\"u}hrt, welche eine CPPF nach PPD entwickelten. Die Patienten und Patientinnen wurden hinsichtlich der gew{\"a}hlten Behandlungsstrategie, des Outcomes, postoperativer Komplikationen nach Clavien-Dindo-Klassifikation, des CCI (Comprehensive Complication Index), der 30- und 90-Tage-Mortalit{\"a}t sowie Restpankreatektomie, postoperativer Arrosionsblutungen und der Hospitalisierungsdauer nach Behandlung einer CPPF analysiert. Zwischen 2007 und 2018 entwickelten 56 (19,1 \%) von insgesamt 293 Patienten und Patientinnen eine relevante POPF (ISGPS Grad B/C) nach einer Pankreaskopfresektion. Darunter wurden 17 Patienten und Patientinnen mit einer komplizierten POPF (CPPF) identifiziert. 11 Patienten und Patientinnen erhielten als Behandlung eine PTCD und sechs Patienten und Patientinnen erhielten eine chirurgisch eingebrachte transhepatische Cholangiodrainage (CTCD) im Rahmen eines Revisionseingriffes. Es wurde keine Restpankreatektomie oder Reoperation nach einer initialen PTCD Therapie notwendig. In 4 von 17 F{\"a}llen kam es zu postoperativen Blutungen nach Einbringen einer transhepatischen Cholangiodrainage, der mediane CCI lag bei 44 ± 17,3, die mediane Hospitalisierungsdauer betrug 36 ± 19,2 Tage, die 30-Tage-Mortalit{\"a}t war 0 \% und die 90-Tage-Mortalit{\"a}t 17,7 \%. Es wurde kein Sterbefall in Verbindung mit einer PTCD beobachtet. Mit Hilfe dieser Studie kann gezeigt werden, dass eine PTCD eine praktikable, sichere und effektive Behandlungsoption f{\"u}r Patienten und Patientinnen mit einer CPPF bietet. Die Separierung von Galle und Pankreassaft stellt eine neuartige Behandlungsoption in ausgew{\"a}hlten Patienten und Patientinnen mit ausreichend drainierter CPPF nach PPD dar.},
  subject      = {Bauchspeicheldr{\"u}senkrebs},
  language  = {de}
}
@article{ChenLuChenetal.2017,
  author    = {Chen, Wei-Hua and Lu, Guanting and Chen, Xiao and Zhao, Xing-Ming and Bork, Peer},
  title     = {OGEE v2: an update of the online gene essentiality database with special focus on differentially essential genes in human cancer cell lines},
  series = {Nucleic Acids Research},
  volume    = {45},
  journal   = {Nucleic Acids Research},
  number    = {D1},
  doi       = {10.1093/nar/gkw1013},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181334},
  pages     = {D940-D944},
  year      = {2017},
  abstract  = {OGEE is an Online GEne Essentiality database. To enhance our understanding of the essentiality of genes, in OGEE we collected experimentally tested essential and non-essential genes, as well as associated gene properties known to contribute to gene essentiality. We focus on large-scale experiments, and complement our data with text-mining results. We organized tested genes into data sets according to their sources, and tagged those with variable essentiality statuses across data sets as conditionally essential genes, intending to highlight the complex interplay between gene functions and environments/experimental perturbations. Developments since the last public release include increased number of species and gene essentiality data sets, inclusion of non-coding essential sequences and genes with intermediate essentiality statuses. In addition, we included 16 essentiality data sets from cancer cell lines, corresponding to 9 human cancers; with OGEE, users can easily explore the shared and differentially essential genes within and between cancer types. These genes, especially those derived from cell lines that are similar to tumor samples, could reveal the oncogenic drivers, paralogous gene expression pattern and chromosomal structure of the corresponding cancer types, and can be further screened to identify targets for cancer therapy and/or new drug development. OGEE is freely available at http://ogee.medgenius.info.},
  language  = {en}
}