@article{BuhlBeissertGaffaletal.2020, author = {Buhl, Timo and Beissert, Stefan and Gaffal, Evelyn and Goebeler, Matthias and Hertl, Michael and Mauch, Cornelia and Reich, Kristian and Schmidt, Enno and Sch{\"o}n, Michael P. and Sticherling, Michael and Sunderk{\"o}tter, Cord and Traidl-Hoffmann, Claudia and Werfel, Thomas and Wilsman-Theis, Dagmar and Worm, Margitta}, title = {COVID-19 and implications for dermatological and allergological diseases}, series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, volume = {18}, journal = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, number = {8}, doi = {10.1111/ddg.14195}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217860}, pages = {815 -- 824}, year = {2020}, abstract = {COVID-19, caused by the coronavirus SARS-CoV-2, has become pandemic. A further level of complexity opens up as soon as we look at diseases whose pathogenesis and therapy involve different immunological signaling pathways, which are potentially affected by COVID-19. Medical treatments must often be reassessed and questioned in connection with this infection. This article summarizes the current knowledge of COVID-19 in the light of major dermatological and allergological diseases. It identifies medical areas lacking sufficient data and draws conclusions for the management of our patients during the pandemic. We focus on common chronic inflammatory skin diseases with complex immunological pathogenesis: psoriasis, eczema including atopic dermatitis, type I allergies, autoimmune blistering and inflammatory connective tissue diseases, vasculitis, and skin cancers. Since several other inflammatory skin diseases display related or comparable immunological reactions, clustering of the various inflammatory dermatoses into different disease patterns may help with therapeutic decisions. Thus, following these patterns of skin inflammation, our review may supply treatment recommendations and thoughtful considerations for disease management even beyond the most frequent diseases discussed here.}, language = {en} } @article{LeverkusGustafssonLindenmayeretal.2020, author = {Leverkus, Alexandro B and Gustafsson, Lena and Lindenmayer, David B and Castro, Jorge and Rey Benayas, Jos{\´e} Mar{\´i}a and Ranius, Thomas and Thorn, Simon}, title = {Salvage logging effects on regulating ecosystem services and fuel loads}, series = {Frontiers in Ecology and the Environment}, volume = {18}, journal = {Frontiers in Ecology and the Environment}, number = {7}, doi = {10.1002/fee.2219}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216111}, pages = {391 -- 400}, year = {2020}, abstract = {Salvage logging, or logging after natural disturbances such as wildfires, insect outbreaks, and windstorms, is carried out to recover some of a forest's natural and/or economic capital. However, trade-offs between management objectives and a lack of consensus on the ecological consequences of salvage logging impair science-based decision making on the management of forests after natural disturbances. We conducted a global meta-analysis of the impacts of salvage logging on regulating ecosystem services and on fuel loads, as a frequent post-disturbance objective is preventing subsequent wildfires that could be fueled by the accumulation of dead trunks and branches. Salvage logging affected ecosystem services in a moderately negative way, regardless of disturbance type and severity, time elapsed since salvage logging, intensity of salvage logging, and the group of regulating ecosystem services being considered. However, prolonging the time between natural disturbance and salvage logging mitigated negative effects on regulating ecosystem services. Salvage logging had no overall effect on surface fuels; rather, different fuel types responded differently depending on the time elapsed since salvage logging. Delaying salvage logging by ~2-4 years may reduce negative ecological impacts without affecting surface fuel loads.}, language = {en} } @article{GoelSiegertKraussetal.2020, author = {Goel, Mahima and Siegert, Marie and Krauss, Gert and Mohanraj, John and Hochgesang, Adrian and Heinrich, David C. and Fried, Martina and Pflaum, Jens and Thelakkat, Mukundan}, title = {HOMO-HOMO Electron Transfer: An Elegant Strategy for p-Type Doping of Polymer Semiconductors toward Thermoelectric Applications}, series = {Advanced Materials}, volume = {32}, journal = {Advanced Materials}, number = {43}, doi = {10.1002/adma.202003596}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217850}, year = {2020}, abstract = {Unlike the conventional p-doping of organic semiconductors (OSCs) using acceptors, here, an efficient doping concept for diketopyrrolopyrrole-based polymer PDPP[T]\(_{2}\)-EDOT (OSC-1) is presented using an oxidized p-type semiconductor, Spiro-OMeTAD(TFSI)\(_{2}\) (OSC-2), exploiting electron transfer from HOMO\(_{OSC-1}\) to HOMO\(_{OSC-2}\). A shift of work function toward the HOMO\(_{OSC-1}\) upon doping is confirmed by ultraviolet photoelectron spectroscopy (UPS). Detailed X-ray photoelectron spectroscopy (XPS) and UV-vis-NIR absorption studies confirm HOMO\(_{OSC-1}\) to HOMO\(_{OSC-2}\) electron transfer. The reduction products of Spiro-OMeTAD(TFSI)\(_{2}\) to Spiro-OMeTAD(TFSI) and Spiro-OMeTAD is also confirmed and their relative amounts in doped samples is determined. Mott-Schottky analysis shows two orders of magnitude increase in free charge carrier density and one order of magnitude increase in the charge carrier mobility. The conductivity increases considerably by four orders of magnitude to a maximum of 10 S m\(^{-1}\) for a very low doping ratio of 8 mol\%. The doped polymer films exhibit high thermal and ambient stability resulting in a maximum power factor of 0.07 µW m\(^{-1}\) K\(^{-2}\) at a Seebeck coefficient of 140 µV K\(^{-1}\) for a very low doping ratio of 4 mol\%. Also, the concept of HOMO\(_{OSC-1}\) to HOMO\(_{OSC-2}\) electron transfer is a highly efficient, stable and generic way to p-dope other conjugated polymers.}, language = {en} } @article{ChenWaxmanWangetal.2020, author = {Chen, Si and Waxman, Susannah and Wang, Chao and Atta, Sarah and Loewen, Ralitsa and Loewen, Nils A.}, title = {Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {258}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, issn = {0721-832X}, doi = {10.1007/s00417-020-04691-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231893}, pages = {1211-1216}, year = {2020}, abstract = {Purpose To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). Wehypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT)that removes the TM. Methods Sixty-four porcine anterior segment cultures were randomly assigned to groups with (n= 32) and without circumferential AIT (n= 32). Cultures were exposed to 0.1, 1, and 10μM netarsudil (N= 8 eyes per concentration). For each concentration,IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters wereassessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series). Results Netarsudil at 1μM reduced IOP both in eyes with TM (-0.60 ± 0.24 mmHg,p= 0.01) and in eyes without TM (-1.79 ±0.42 mmHg,p< 0.01). At this concentration, vessels of the distal outflow tract dilated by 72\%. However, at 0.1μMnetarsudilelevated IOP in eyes with TM (1.59 ± 0.36 mmHg,p< 0.001) as well as in eyes without TM (0.23 ± 0.32 mmHg,p<0.001). Vessels of the distal outflow tract constricted by 31\%. Similarly, netarsudil at a concentration of 10μM elevated IOP both in eyeswith TM (1.91 ± 0.193,p< 0.001) and in eyes without TM (3.65 ± 0.86 mmHg,p< 0.001). At this concentration, outflow tractvessels constricted by 27\%. Conclusion In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameterchanges of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal}, language = {en} } @article{LiesnerKirschPfisteretal.2020, author = {Liesner, Marvin and Kirsch, Wladimir and Pfister, Roland and Kunde, Wilfried}, title = {Spatial action-effect binding depends on type of action-effect transformation}, series = {Attention, Perception, \& Psychophysics}, volume = {82}, journal = {Attention, Perception, \& Psychophysics}, issn = {1943-3921}, doi = {10.3758/s13414-020-02013-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232781}, pages = {2531-2543}, year = {2020}, abstract = {Spatial action-effect binding denotes the mutual attraction between the perceived position of an effector (e.g., one's own hand) and a distal object that is controlled by this effector. Such spatial binding can be construed as an implicit measure of object ownership, thus the belonging of a controlled object to the own body. The current study investigated how different transformations of hand movements (body-internal action component) into movements of a visual object (body-external action component) affect spatial action-effect binding, and thus implicit object ownership. In brief, participants had to bring a cursor on the computer screen into a predefined target position by moving their occluded hand on a tablet and had to estimate their final hand position. In Experiment 1, we found a significantly lower drift of the proprioceptive position of the hand towards the visual object when hand movements were transformed into laterally inverted cursor movements, rather than cursor movements in the same direction. Experiment 2 showed that this reduction reflected an elimination of spatial action-effect binding in the inverted condition. The results are discussed with respect to the prerequisites for an experience of ownership over artificial, noncorporeal objects. Our results show that predictability of an object movement alone is not a sufficient condition for ownership because, depending on the type of transformation, integration of the effector and a distal object can be fully abolished even under conditions of full controllability.}, language = {en} } @article{SchicklerReichertGeigeretal.2020, author = {Schickler, Marc and Reichert, Manfred and Geiger, Philip and Winkler, Jens and Funk, Thomas and Weilbach, Micha and Pryss, R{\"u}diger}, title = {Flexible development of location-based mobile augmented reality applications with AREA}, series = {Journal of Ambient Intelligence and Humanized Computing}, volume = {11}, journal = {Journal of Ambient Intelligence and Humanized Computing}, issn = {1868-5137}, doi = {10.1007/s12652-020-02094-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232773}, pages = {5809-5824}, year = {2020}, abstract = {Mobile applications have garnered a lot of attention in the last years. The computational capabilities of mobile devices are the mainstay to develop completely new application types. The provision of augmented reality experiences on mobile devices paves one alley in this field. For example, in the automotive domain, augmented reality applications are used to experience, inter alia, the interior of a car by moving a mobile device around. The device's camera then detects interior parts and shows additional information to the customer within the camera view. Another application type that is increasingly utilized is related to the combination of serious games with mobile augmented reality functions. Although the latter combination is promising for many scenarios, technically, it is a complex endeavor. In the AREA (Augmented Reality Engine Application) project, a kernel was implemented that enables location-based mobile augmented reality applications. Importantly, this kernel provides a flexible architecture that fosters the development of individual location-based mobile augmented reality applications. The work at hand shows the flexibility of AREA based on a developed serious game. Furthermore, the algorithm framework and major features of it are presented. As the conclusion of this paper, it is shown that mobile augmented reality applications require high development efforts. Therefore, flexible frameworks like AREA are crucial to develop respective applications in a reasonable time.}, language = {en} } @article{YangHeydarianKozjakPavlovicetal.2020, author = {Yang, Tao and Heydarian, Motaharehsadat and Kozjak-Pavlovic, Vera and Urban, Manuela and Harbottle, Richard P. and Rudel, Thomas}, title = {Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {10}, journal = {Frontiers in Cellular and Infection Microbiology}, number = {422}, issn = {2235-2988}, doi = {10.3389/fcimb.2020.00422}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211372}, year = {2020}, abstract = {Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRNA library screen and next-generation sequencing to identify factors involved in epithelial cell infection. Folliculin (FLCN), a 64 kDa protein with a tumor repressor function was identified as a novel host factor important for N. gonorrhoeae survival after uptake. We further determined that FLCN did not affect N. gonorrhoeae adherence and invasion but was essential for its survival in the cells by modulating autophagy. In addition, FLCN was also required to maintain cell to cell contacts in the epithelial layer. In an infection model with polarized cells, FLCN inhibited the polarized localization of E-cadherin and the transcytosis of gonococci across polarized epithelial cells. In conclusion, we demonstrate here the connection between FLCN and bacterial infection and in particular the role of FLCN in the intracellular survival and transcytosis of gonococci across polarized epithelial cell layers.}, language = {en} } @article{HorasvanHerckMaieretal.2020, author = {Horas, Konstantin and van Herck, Ulrike and Maier, Gerrit S. and Maus, Uwe and Harrasser, Norbert and Jakob, Franz and Weissenberger, Manuel and Arnholdt, J{\"o}rg and Holzapfel, Boris M. and Rudert, Maximilian}, title = {Does vitamin D deficiency predict tumour malignancy in patients with bone tumours? Data from a multi-center cohort analysis}, series = {Journal of Bone Oncology}, volume = {25}, journal = {Journal of Bone Oncology}, doi = {10.1016/j.jbo.2020.100329}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230314}, year = {2020}, abstract = {Vitamin D deficiency is a global health concern that is estimated to afflict over one billion people globally. The major role of vitamin D is that of a regulator of calcium and phosphate metabolism, thus, being essential for proper bone mineralisation. Concomitantly, vitamin D is known to exert numerous extra-skeletal actions. For example, it has become evident that vitamin D has direct anti-proliferative, pro-differentiation and pro-apoptotic actions on cancer cells. Hence, vitamin D deficiency has been associated with increased cancer risk and worse prognosis in several malignancies. We have recently demonstrated that vitamin D deficiency promotes secondary cancer growth in bone. These findings were partly attributable to an increase in bone remodelling but also through direct effects of vitamin D on cancer cells. To date, very little is known about vitamin D status of patients with bone tumours in general. Thus, the objective of this study was to assess vitamin D status of patients with diverse bone tumours. Moreover, the aim was to elucidate whether or not there is an association between pre-diagnostic vitamin D status and tumour malignancy in patients with bone tumours. In a multi-center analysis, 25(OH)D, PTH and calcium levels of 225 patients that presented with various bone tumours between 2017 and 2018 were assessed. Collectively, 76\% of all patients had insufficient vitamin D levels with a total mean 25(OH)D level of 21.43 ng/ml (53.58 nmol/L). In particular, 52\% (117/225) of patients were identified as vitamin D deficient and further 24\% of patients (55/225) were vitamin D insufficient. Notably, patients diagnosed with malignant bone tumours had significantly lower 25(OH)D levels than patients diagnosed with benign bone tumours [19.3 vs. 22.75 ng/ml (48.25 vs. 56.86 nmol/L); p = 0.04). In conclusion, we found a widespread and distressing rate of vitamin D deficiency and insufficiency in patients with bone tumours. However, especially for patients with bone tumours sufficient vitamin D levels seem to be of great importance. Thus, we believe that 25(OH)D status should routinely be monitored in these patients. Collectively, there should be an increased awareness for physicians to assess and if necessary correct vitamin D status of patients with bone tumours in general or of those at great risk of developing bone tumours.}, language = {en} } @article{AuerHuegelschaefferFischeretal.2020, author = {Auer, Daniela and H{\"u}gelsch{\"a}ffer, Sophie D. and Fischer, Annette B. and Rudel, Thomas}, title = {The chlamydial deubiquitinase Cdu1 supports recruitment of Golgi vesicles to the inclusion}, series = {Cellular Microbiology}, volume = {22}, journal = {Cellular Microbiology}, number = {5}, doi = {10.1111/cmi.13136}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208675}, pages = {e13136}, year = {2020}, abstract = {Chlamydia trachomatis is the main cause of sexually transmitted diseases worldwide. As obligate intracellular bacteria Chlamydia replicate in a membrane bound vacuole called inclusion and acquire nutrients for growth and replication from their host cells. However, like all intracellular bacteria, Chlamydia have to prevent eradication by the host's cell autonomous system. The chlamydial deubiquitinase Cdu1 is secreted into the inclusion membrane, facing the host cell cytosol where it deubiquitinates cellular proteins. Here we show that inactivation of Cdu1 causes a growth defect of C. trachomatis in primary cells. Moreover, ubiquitin and several autophagy receptors are recruited to the inclusion membrane of Cdu1-deficient Chlamydia . Interestingly, the growth defect of cdu1 mutants is not rescued when autophagy is prevented. We find reduced recruitment of Golgi vesicles to the inclusion of Cdu1 mutants indicating that vesicular trafficking is altered in bacteria without active deubiquitinase (DUB). Our work elucidates an important role of Cdu1 in the functional preservation of the chlamydial inclusion surface.}, language = {en} } @article{MaternKochPetersmannetal.2020, author = {Matern, Johannes and Koch, Raphael and Petersmann, Astrid and Kocher, Thomas and Eickholz, Peter and Lorenz, Katrin and Kim, Ti-Sun and Meyle, J{\"o}rg and Kaner, Doğan and Schlagenhauf, Ulrich and Gravemeier, Martina and Harks, Inga and Ehmke, Benjamin}, title = {Effect of periodontal therapy on adipokine biomarkers in overweight}, series = {Journal of Clinical Periodontology}, volume = {47}, journal = {Journal of Clinical Periodontology}, number = {7}, doi = {10.1111/jcpe.13288}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215546}, pages = {842 -- 850}, year = {2020}, abstract = {Aim The aim of this study was to evaluate the effect of non-surgical periodontal therapy on circulating levels of the systemic inflammation-associated biomarkers orosomucoid (ORM), high-sensitivity C-reactive protein (hsCRP), chemerin, and retinol-binding protein 4 (RBP4) in overweight or normal-weight patients with periodontitis at 27.5 months after therapy. Materials and methods This exploratory subanalysis includes patients from the ABPARO-trial (ClinicalTrials.gov NCT00707369). The per-protocol collective provided untreated periodontitis patients with high (≥28 kg/m\(^{2}\)) or moderate (21-24 kg/m\(^{2}\)) BMI. Out of the per-protocol collective, 80 patients were randomly selected and stratified for BMI group, sex, and treatment group (antibiotics/placebo), resulting in 40 overweight and normal-weight patients. Patients received non-surgical periodontal therapy and maintenance at 3-month intervals. Plasma samples from baseline and 27.5 months following initial treatment were used to measure the concentrations of ORM, hsCRP, chemerin, and RBP4. Results At the 27.5-month examination, ORM and hsCRP decreased noticeably in the overweight group (ORM: p = .001, hsCRP: p = .004) and normal-weight patients (ORM: p = .007, hsCRP: p < .001). Chemerin decreased in the overweight group (p = .048), and RBP4 concentrations remained stable. Conclusion Non-surgical periodontal therapy reduced systemically elevated inflammation-associated biomarkers in periodontitis patients. These improvements were more pronounced in overweight patients than in normal-weight patients.}, language = {en} } @article{HutmacherKuhbandner2020, author = {Hutmacher, Fabian and Kuhbandner, Christof}, title = {Does the Attentional Boost Effect Depend on the Intentionality of Encoding? Investigating the Mechanisms Underlying Memory for Visual Objects Presented at Behaviorally Relevant Moments in Time}, series = {Frontiers in Psychology}, volume = {11}, journal = {Frontiers in Psychology}, doi = {10.3389/fpsyg.2020.584187}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215902}, year = {2020}, abstract = {Pictures in a rapid serial visual presentation (RSVP) stream are better remembered when they are simultaneously presented with targets of an unrelated detection task than when they are presented with distractors. However, it is unclear whether this so-called "attentional boost effect" depends on the intentionality of encoding. While there are studies suggesting that the attentional boost effect even occurs when encoding is incidental, there are several methodological issues with these studies, which may have undermined the incidental encoding instructions. The present study (N = 141) investigated the role of the intentionality of encoding with an improved experimental design. Specifically, to prevent a spill-over of intentional resources to the pictures in the RSVP stream, the speed of the stream was increased (to four pictures per second) and each picture was presented only once during the course of the experiment. An attentional boost effect was only found when encoding was intentional but not when encoding was incidental. Interestingly, memory performance for incidentally encoded pictures was nevertheless substantially above chance, independently of whether images were presented with search-relevant targets or distractors. These results suggest that the attentional boost effect is a memory advantage that occurs only under intentional encoding conditions, and that perceptual long-term memory representations are formed as a natural product of perception, independently of the presence of behaviorally relevant events.}, language = {en} } @article{GlutschAmaralGarbeetal.2020, author = {Glutsch, Valerie and Amaral, Teresa and Garbe, Claus and Thoms, Kai-Martin and Mohr, Peter and Hauschild, Axel and Schilling, Bastian}, title = {Indirect Comparison of Combined BRAF and MEK Inhibition in Melanoma Patients with Elevated Baseline Lactate Dehydrogenase}, series = {Acta Dermato-Venereologica}, volume = {100}, journal = {Acta Dermato-Venereologica}, doi = {10.2340/00015555-3526}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230190}, year = {2020}, abstract = {The approval of BRAF and MEK inhibitors has signifi-cantly improved treatment outcomes for patients with BRAF-mutated metastatic melanoma. The 3 first-line targeted therapy trials have provided similar results, and thus the identification of predictive biomarkers may generate a more precise basis for clinical deci-sion-making. Elevated baseline lactate dehydrogenase (LDH) has already been determined as a strong prog-nostic factor. Therefore, this indirect analysis compa-red subgroups with elevated baseline LDH across the pivotal targeted therapy trials co-BRIM, COMBI-v and COLUMBUS part 1. The Bucher method was used to compare progression-free survival, objective response rate and overall survival indirectly. The results show a non-significant risk reduction for progression in the subgroup with elevated baseline LDH receiving vemu-rafenib plus cobimetinib compared with dabrafenib plus trametinib and encorafenib plus binimetinib. Al-though an indirect comparison, these data might pro-vide some guidance for treatment recommendations in melanoma patients with elevated LDH.}, language = {en} } @article{WhisnantJuergesHennigetal.2020, author = {Whisnant, Adam W. and J{\"u}rges, Christopher S. and Hennig, Thomas and Wyler, Emanuel and Prusty, Bhupesh and Rutkowski, Andrzej J. and L'hernault, Anne and Djakovic, Lara and G{\"o}bel, Margarete and D{\"o}ring, Kristina and Menegatti, Jennifer and Antrobus, Robin and Matheson, Nicholas J. and K{\"u}nzig, Florian W. H. and Mastrobuoni, Guido and Bielow, Chris and Kempa, Stefan and Liang, Chunguang and Dandekar, Thomas and Zimmer, Ralf and Landthaler, Markus and Gr{\"a}sser, Friedrich and Lehner, Paul J. and Friedel, Caroline C. and Erhard, Florian and D{\"o}lken, Lars}, title = {Integrative functional genomics decodes herpes simplex virus 1}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-15992-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229884}, year = {2020}, abstract = {The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution. Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.}, language = {en} } @article{JobsVontheinKoenigetal.2020, author = {Jobs, Alexander and Vonthein, Reinhard and K{\"o}nig, Inke R. and Sch{\"a}fer, Jane and Nauck, Matthias and Haag, Svenja and Fichera, Carlo Federico and Stiermaier, Thomas and Ledwoch, Jakob and Schneider, Alisa and Valentova, Miroslava and von Haehling, Stephan and St{\"o}rk, Stefan and Westermann, Dirk and Lenz, Tobias and Arnold, Natalie and Edelmann, Frank and Seppelt, Philipp and Felix, Stephan and Lutz, Matthias and Hedwig, Felix and Borggrefe, Martin and Scherer, Clemens and Desch, Steffen and Thiele, Holger}, title = {Inferior vena cava ultrasound in acute decompensated heart failure: design rationale of the CAVA-ADHF-DZHK10 trial}, series = {ESC Heart Failure}, volume = {7}, journal = {ESC Heart Failure}, number = {3}, doi = {10.1002/ehf2.12598}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212692}, pages = {973 -- 983}, year = {2020}, abstract = {Aims Treating patients with acute decompensated heart failure (ADHF) presenting with volume overload is a common task. However, optimal guidance of decongesting therapy and treatment targets are not well defined. The inferior vena cava (IVC) diameter and its collapsibility can be used to estimate right atrial pressure, which is a measure of right-sided haemodynamic congestion. The CAVA-ADHF-DZHK10 trial is designed to test the hypothesis that ultrasound assessment of the IVC in addition to clinical assessment improves decongestion as compared with clinical assessment alone. Methods and results CAVA-ADHF-DZHK10 is a randomized, controlled, patient-blinded, multicentre, parallel-group trial randomly assigning 388 patients with ADHF to either decongesting therapy guided by ultrasound assessment of the IVC in addition to clinical assessment or clinical assessment alone. IVC ultrasound will be performed daily between baseline and hospital discharge in all patients. However, ultrasound results will only be reported to treating physicians in the intervention group. Treatment target is relief of congestion-related signs and symptoms in both groups with the additional goal to reduce the IVC diameter ≤21 mm and increase IVC collapsibility >50\% in the intervention group. The primary endpoint is change in N-terminal pro-brain natriuretic peptide from baseline to hospital discharge. Secondary endpoints evaluate feasibility, efficacy of decongestion on other scales, and the impact of the intervention on clinical endpoints. Conclusions CAVA-ADHF-DZHK10 will investigate whether IVC ultrasound supplementing clinical assessment improves decongestion in patients admitted for ADHF.}, language = {en} } @article{JanzenBakirciWielandetal.2020, author = {Janzen, Dieter and Bakirci, Ezgi and Wieland, Annalena and Martin, Corinna and Dalton, Paul D. and Villmann, Carmen}, title = {Cortical Neurons form a Functional Neuronal Network in a 3D Printed Reinforced Matrix}, series = {Advanced Healthcare Materials}, volume = {9}, journal = {Advanced Healthcare Materials}, number = {9}, doi = {10.1002/adhm.201901630}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215400}, year = {2020}, abstract = {Impairments in neuronal circuits underly multiple neurodevelopmental and neurodegenerative disorders. 3D cell culture models enhance the complexity of in vitro systems and provide a microenvironment closer to the native situation than with 2D cultures. Such novel model systems will allow the assessment of neuronal network formation and their dysfunction under disease conditions. Here, mouse cortical neurons are cultured from embryonic day E17 within in a fiber-reinforced matrix. A soft Matrigel with a shear modulus of 31 ± 5.6 Pa is reinforced with scaffolds created by melt electrowriting, improving its mechanical properties and facilitating the handling. Cortical neurons display enhance cell viability and the neuronal network maturation in 3D, estimated by staining of dendrites and synapses over 21 days in vitro, is faster in 3D compared to 2D cultures. Using functional readouts with electrophysiological recordings, different firing patterns of action potentials are observed, which are absent in the presence of the sodium channel blocker, tetrodotoxin. Voltage-gated sodium currents display a current-voltage relationship with a maximum peak current at -25 mV. With its high customizability in terms of scaffold reinforcement and soft matrix formulation, this approach represents a new tool to study neuronal networks in 3D under normal and, potentially, disease conditions.}, language = {en} } @article{KollmannPretzschKunzetal.2020, author = {Kollmann, Cath{\´e}rine T. and Pretzsch, Elise B. and Kunz, Andreas and Isbert, Christoph and Krajinovic, Katica and Reibetanz, Joachim and Kim, Mia}, title = {Anorectal angle at rest predicting successful sacral nerve stimulation in idiopathic fecal incontinence—a cohort analysis}, series = {International Journal of Colorectal Disease}, volume = {35}, journal = {International Journal of Colorectal Disease}, issn = {0179-1958}, doi = {10.1007/s00384-020-03720-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232379}, pages = {2293-2299}, year = {2020}, abstract = {Purpose Sacral nerve stimulation is an effective treatment for patients suffering from fecal incontinence. However, less is knownabout predictors of success before stimulation. The purpose of this study was to identify predictors of successful sacral nervestimulation in patients with idiopathic fecal incontinence. Methods Consecutive female patients, receiving peripheral nerve evaluation and sacral nerve stimulation between September2008 and October 2014, suffering from idiopathic fecal incontinence were included in this study. Preoperative patient'scharac-teristics, anal manometry, and defecography results were collected prospectively and investigated by retrospective analysis. Mainoutcome measures were independent predictors of treatment success after sacral nerve stimulation. Results From, all in all, 54 patients suffering from idiopathic fecal incontinence receiving peripheral nerve evaluation, favorableoutcome was achieved in 23 of 30 patients after sacral nerve stimulation (per protocol 76.7\%; intention to treat 42.6\%). From allanalyzed characteristics, wide anorectal angle at rest in preoperative defecography was the only independent predictor offavorable outcome in multivariate analysis (favorable 134.1 ± 13.9° versus unfavorable 118.6 ± 17.1°). Conclusions Anorectal angle at rest in preoperative defecography might present a predictor of outcome after sacral nervestimulation in patients with idiopathic fecal incontinence.}, language = {en} } @article{OhlebuschBorstFrankenbachetal.2020, author = {Ohlebusch, Barbara and Borst, Angela and Frankenbach, Tina and Klopocki, Eva and Jakob, Franz and Liedtke, Daniel and Graser, Stephanie}, title = {Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-70152-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230024}, year = {2020}, abstract = {Hypophosphatasia (HPP) is a rare genetic disease with diverse symptoms and a heterogeneous severity of onset with underlying mutations in the ALPL gene encoding the ectoenzyme Tissue-nonspecific alkaline phosphatase (TNAP). Considering the establishment of zebrafish (Danio rerio) as a new model organism for HPP, the aim of the study was the spatial and temporal analysis of alpl expression in embryos and adult brains. Additionally, we determined functional consequences of Tnap inhibition on neural and skeletal development in zebrafish. We show that expression of alpl is present during embryonic stages and in adult neuronal tissues. Analyses of enzyme function reveal zones of pronounced Tnap-activity within the telencephalon and the mesencephalon. Treatment of zebrafish embryos with chemical Tnap inhibitors followed by axonal and cartilage/mineralized tissue staining imply functional consequences of Tnap deficiency on neuronal and skeletal development. Based on the results from neuronal and skeletal tissue analyses, which demonstrate an evolutionary conserved role of this enzyme, we consider zebrafish as a promising species for modeling HPP in order to discover new potential therapy strategies in the long-term.}, language = {en} } @article{HabensteinAminiGruebeletal.2020, author = {Habenstein, Jens and Amini, Emad and Gr{\"u}bel, Kornelia and el Jundi, Basil and R{\"o}ssler, Wolfgang}, title = {The brain of Cataglyphis ants: Neuronal organization and visual projections}, series = {Journal of Comparative Neurology}, volume = {528}, journal = {Journal of Comparative Neurology}, number = {18}, doi = {10.1002/cne.24934}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218212}, pages = {3479 -- 3506}, year = {2020}, abstract = {Cataglyphis ants are known for their outstanding navigational abilities. They return to their inconspicuous nest after far-reaching foraging trips using path integration, and whenever available, learn and memorize visual features of panoramic sceneries. To achieve this, the ants combine directional visual information from celestial cues and panoramic scenes with distance information from an intrinsic odometer. The largely vision-based navigation in Cataglyphis requires sophisticated neuronal networks to process the broad repertoire of visual stimuli. Although Cataglyphis ants have been subjected to many neuroethological studies, little is known about the general neuronal organization of their central brain and the visual pathways beyond major circuits. Here, we provide a comprehensive, three-dimensional neuronal map of synapse-rich neuropils in the brain of Cataglyphis nodus including major connecting fiber systems. In addition, we examined neuronal tracts underlying the processing of visual information in more detail. This study revealed a total of 33 brain neuropils and 30 neuronal fiber tracts including six distinct tracts between the optic lobes and the cerebrum. We also discuss the importance of comparative studies on insect brain architecture for a profound understanding of neuronal networks and their function.}, language = {en} } @article{StolteHechtXieetal.2020, author = {Stolte, Matthias and Hecht, Reinhard and Xie, Zengqi and Liu, Linlin and Kaufmann, Christina and Kudzus, Astrid and Schmidt, David and W{\"u}rthner, Frank}, title = {Crystal Engineering of 1D Exciton Systems Composed of Single- and Double-Stranded Perylene Bisimide J-Aggregates}, series = {Advanced Optical Materials}, volume = {8}, journal = {Advanced Optical Materials}, number = {18}, doi = {10.1002/adom.202000926}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218221}, year = {2020}, abstract = {Single crystals of three at bay area tetraphenoxy-substituted perylene bisimide dyes are grown by vacuum sublimation. X-ray analysis reveals the self-assembly of these highly twisted perylene bisimides (PBIs) in the solid state via imide-imide hydrogen bonding into hydrogen-bonded PBI chains. The crystallographic insights disclose that the conformation and sterical congestion imparted by the phenoxy substituents can be controlled by ortho-substituents. Accordingly, whilst sterically less demanding methyl and isopropyl substituents afford double-stranded PBI chains of complementary P and M atropo-enantiomers, single hydrogen-bonded chains of homochiral PBIs are observed for the sterically more demanding ortho-phenyl substituents. Investigation of the absorption and fluorescence properties of microcrystals and thin films of these PBIs allow for an unambiguous interpretation of these exciton systems. Thus, the J-aggregates of the double-stranded crystals exhibit a much larger (negative) exciton coupling than the single-stranded one, which in contrast has the higher solid-state fluorescence quantum yield.}, language = {en} } @article{BoetzlSchueleKraussetal.2020, author = {Boetzl, Fabian A. and Schuele, Maren and Krauss, Jochen and Steffan-Dewenter, Ingolf}, title = {Pest control potential of adjacent agri-environment schemes varies with crop type and is shaped by landscape context and within-field position}, series = {Journal of Applied Ecology}, volume = {57}, journal = {Journal of Applied Ecology}, number = {8}, doi = {10.1111/1365-2664.13653}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218265}, pages = {1482 -- 1493}, year = {2020}, abstract = {Increasing natural pest control in agricultural fields is an important aim of ecological intensification. Combined effects of landscape context and local placement of agri-environmental schemes (AES) on natural pest control and within-field distance functions of natural pest control agents have rarely been addressed but might affect the distribution of biocontrol providers. Importantly, it is currently unknown whether ecosystem services provided by adjacent AES are consistent for different crop types during crop rotation. In this study, we assessed whether crop rotation from oilseed rape to cereals altered within-field distance functions of ground-dwelling predators from adjacent agri-environmental fields along a gradient in landscape context. Additionally, we recorded crop pests, predation rates, parasitoids as well as crop yields on a total of 30 study sites. Distance functions varied between trophic levels: Carabid richness decreased while densities of carabid beetles, staphylinid beetles as well as crop yields increased towards the field centres. Distance functions of parasitoids and pests were modulated by the amount of semi-natural habitat in the surrounding landscape, while the effects of adjacent AES were limited. Distance decay functions found for ground-dwelling predators in oilseed rape in the previous year were not always present in cereals. Increasing distance to the field edge also increased effects of crop rotation on carabid beetle assemblages, indicating a source habitat function of field edges. Synthesis and applications. Distance functions of natural pest control are not universal and the effects of agri-environmental schemes (AES) in different adjacent crops during crop rotation vary and depend on ecological contrasts. A network of semi-natural habitats and spatially optimized AES habitats can benefit pest control in agricultural landscapes, but constraints as a result of crop type need to be addressed by annually targeted, spatially shifting agri-environment schemes for different crops.}, language = {en} } @article{RabevanOorschotJentschke2020, author = {Rabe, A. and van Oorschot, B. and Jentschke, E.}, title = {Suizidalit{\"a}t bei Krebspatienten}, series = {Der Onkologe}, volume = {26}, journal = {Der Onkologe}, issn = {Suizidalit{\"a}t bei Krebspatienten}, doi = {10.1007/s00761-020-00712-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232401}, pages = {163-168}, year = {2020}, abstract = {Hintergrund Die Diagnose Krebs und ihre Behandlung kann eine große Belastung f{\"u}r die Betroffenen darstellen. Neben k{\"o}rperlichen Beschwerden kann auch die Psyche in Mitleidenschaft gezogen werden. Fehlt es an entsprechenden Bew{\"a}ltigungsstrategien, kann der selbstbestimmte Tod als einziger Ausweg erscheinen. Ziel und Fragestellung Die vorliegende {\"U}bersichtsarbeit zur Suizidalit{\"a}t bei Krebspatienten befasst sich mit einem Thema, das in der Forschung und Praxis in Deutschland nur wenig Aufmerksamkeit findet. Material und Methoden Eine themenbezogene Literaturrecherche stellt die Basis der Arbeit dar. Ergebnisse Todesw{\"u}nsche unter Krebspatienten sind nicht selten und k{\"o}nnen Suizidgedanken/-absichten beinhalten. Psychische Beschwerden, insbesondere Hoffnungslosigkeit und Depression, sind ernstzunehmende Risikofaktoren. Das Erkennen einer hohen psychischen Belastung/von Todesw{\"u}nschen ist ein wichtiger Aspekt f{\"u}r die Suizidpr{\"a}vention. F{\"u}r die Praxis empfiehlt sich zun{\"a}chst die Verwendung von Frageb{\"o}gen. Bei auff{\"a}lligen Werten muss die Suizidalit{\"a}t proaktiv in einem pers{\"o}nlichen Gespr{\"a}ch exploriert werden. Betroffene sind meist ambivalent bez{\"u}glich ihrer Entscheidung f{\"u}r oder gegen das Leben. Dies stellt eine große Chance f{\"u}r Interventionen dar. Schlussfolgerungen Suizidalit{\"a}t kann verhindert werden, wenn die hohe Belastung erkannt wird. Bereits das Gespr{\"a}ch zwischen Arzt und Patient {\"u}ber Todesw{\"u}nsche kann eine erste Entlastung darstellen.}, language = {de} } @article{FroehlichSchwaneckGernertetal.2020, author = {Froehlich, Matthias and Schwaneck, Eva C. and Gernert, Michael and Gadeholt, Ottar and Strunz, Patrick-Pascal and Morbach, Henner and Tony, Hans-Peter and Schmalzing, Marc}, title = {Autologous Stem Cell Transplantation in Common Variable Immunodeficiency: A Case of Successful Treatment of Severe Refractory Autoimmune Encephalitis}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, number = {1317}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.01317}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206972}, year = {2020}, abstract = {Common variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults. It is associated with hypogammaglobulinemia, recurring infections and autoimmune phenomena. Treatment includes immunoglobulin substitution and immunosuppressants. Autoimmune neurological manifestations of CVID are rare and occur predominantly as granulomatous disease. We report the case of a 35-year-old woman with CVID who developed autoimmune encephalitis as demonstrated by double cerebral biopsy. Infectious or malignant causes could be excluded. Despite intensive immunosuppressive therapy with common regimens no significant improvement could be achieved. Ultimately, an autologous hematopoietic stem cell transplantation (HSCT) was performed, resulting in lasting complete remission of the encephalitis. To our knowledge, this is the first report of refractory autoimmune phenomena in CVID treated by autologous HSCT.}, language = {en} } @article{MairBiskupKressetal.2020, author = {Mair, Dorothea and Biskup, Saskia and Kress, Wolfram and Abicht, Angela and Br{\"u}ck, Wolfgang and Zechel, Sabrina and Knop, Karl Christian and Koenig, Fatima Barbara and Tey, Shelisa and Nikolin, Stefan and Eggermann, Katja and Kurth, Ingo and Ferbert, Andreas and Weis, Joachim}, title = {Differential diagnosis of vacuolar myopathies in the NGS era}, series = {Brain Pathology}, volume = {30}, journal = {Brain Pathology}, number = {5}, doi = {10.1111/bpa.12864}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216048}, pages = {877 -- 896}, year = {2020}, abstract = {Altered autophagy accompanied by abnormal autophagic (rimmed) vacuoles detectable by light and electron microscopy is a common denominator of many familial and sporadic non-inflammatory muscle diseases. Even in the era of next generation sequencing (NGS), late-onset vacuolar myopathies remain a diagnostic challenge. We identified 32 adult vacuolar myopathy patients from 30 unrelated families, studied their clinical, histopathological and ultrastructural characteristics and performed genetic testing in index patients and relatives using Sanger sequencing and NGS including whole exome sequencing (WES). We established a molecular genetic diagnosis in 17 patients. Pathogenic mutations were found in genes typically linked to vacuolar myopathy (GNE, LDB3/ZASP, MYOT, DES and GAA), but also in genes not regularly associated with severely altered autophagy (FKRP, DYSF, CAV3, COL6A2, GYG1 and TRIM32) and in the digenic facioscapulohumeral muscular dystrophy 2. Characteristic histopathological features including distinct patterns of myofibrillar disarray and evidence of exocytosis proved to be helpful to distinguish causes of vacuolar myopathies. Biopsy validated the pathogenicity of the novel mutations p.(Phe55*) and p.(Arg216*) in GYG1 and of the p.(Leu156Pro) TRIM32 mutation combined with compound heterozygous deletion of exon 2 of TRIM32 and expanded the phenotype of Ala93Thr-caveolinopathy and of limb-girdle muscular dystrophy 2i caused by FKRP mutation. In 15 patients no causal variants were detected by Sanger sequencing and NGS panel analysis. In 12 of these cases, WES was performed, but did not yield any definite mutation or likely candidate gene. In one of these patients with a family history of muscle weakness, the vacuolar myopathy was eventually linked to chloroquine therapy. Our study illustrates the wide phenotypic and genotypic heterogeneity of vacuolar myopathies and validates the role of histopathology in assessing the pathogenicity of novel mutations detected by NGS. In a sizable portion of vacuolar myopathy cases, it remains to be shown whether the cause is hereditary or degenerative.}, language = {en} } @article{KandelsPietschBisonetal.2020, author = {Kandels, Daniela and Pietsch, Torsten and Bison, Brigitte and Warmuth-Metz, Monika and Thomale, Ulrich-Wilhelm and Kortmann, Rolf-Dieter and Timmermann, Beate and Hern{\´a}iz Driever, Pablo and Witt, Olaf and Schmidt, Ren{\´e} and Gnekow, Astrid K.}, title = {Loss of efficacy of subsequent nonsurgical therapy after primary treatment failure in pediatric low-grade glioma patients—Report from the German SIOP-LGG 2004 cohort}, series = {International Journal of Cancer}, volume = {147}, journal = {International Journal of Cancer}, number = {12}, doi = {10.1002/ijc.33170}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216130}, pages = {3471 -- 3489}, year = {2020}, abstract = {First-line treatment of pediatric low-grade glioma using surgery, radio- or chemotherapy fails in a relevant proportion of patients. We analyzed efficacy of subsequent surgical and nonsurgical therapies of the German cohort of the SIOP-LGG 2004 study (2004-2012, 1558 registered patients; median age at diagnosis 7.6 years, median observation time 9.2 years, overall survival 98\%/96\% at 5/10 years, 15\% neurofibromatosis type 1 [NF1]). During follow-up, 1078/1558 patients remained observed without (n = 217), with 1 (n = 707), 2 (n = 124) or 3 to 6 (n = 30) tumor volume reductions; 480/1558 had 1 (n = 332), 2 (n = 80), 3 or more (n = 68) nonsurgical treatment-lines, accompanied by up to 4 tumor-reductive surgeries in 215/480; 265/480 patients never underwent any neurosurgical tumor volume reduction (163/265 optic pathway glioma). Patients with progressing tumors after first-line adjuvant treatment were at increased risk of suffering further progressions. Risk factors were young age (<1 year) at start of treatment, tumor dissemination or progression within 18 months after start of chemotherapy. Progression-free survival rates declined with subsequent treatment-lines, yet remaining higher for patients with NF1. In non-NF1-associated tumors, vinblastine monotherapy vs platinum-based chemotherapy was noticeably less effective when used as second-line treatment. Yet, for the entire cohort, results did not favor a certain sequence of specific treatment options. Rather, all can be aligned as a portfolio of choices which need careful balancing of risks and benefits. Future molecular data may predict long-term tumor biology.}, language = {en} } @article{HuangWangDewhurstetal.2020, author = {Huang, Zhenguo and Wang, Suning and Dewhurst, Rian D. and Ignat'ev, Nikolai V. and Finze, Maik and Braunschweig, Holger}, title = {Boron: Its Role in Energy-Related Processes and Applications}, series = {Angewandte Chemie International Edition}, volume = {59}, journal = {Angewandte Chemie International Edition}, number = {23}, doi = {10.1002/anie.201911108}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218514}, pages = {8800 -- 8816}, year = {2020}, abstract = {Boron's unique position in the Periodic Table, that is, at the apex of the line separating metals and nonmetals, makes it highly versatile in chemical reactions and applications. Contemporary demand for renewable and clean energy as well as energy-efficient products has seen boron playing key roles in energy-related research, such as 1) activating and synthesizing energy-rich small molecules, 2) storing chemical and electrical energy, and 3) converting electrical energy into light. These applications are fundamentally associated with boron's unique characteristics, such as its electron-deficiency and the availability of an unoccupied p orbital, which allow the formation of a myriad of compounds with a wide range of chemical and physical properties. For example, boron's ability to achieve a full octet of electrons with four covalent bonds and a negative charge has led to the synthesis of a wide variety of borate anions of high chemical and electrochemical stability—in particular, weakly coordinating anions. This Review summarizes recent advances in the study of boron compounds for energy-related processes and applications.}, language = {en} } @article{Lichtenberg2020, author = {Lichtenberg, Crispin}, title = {Main-Group Metal Complexes in Selective Bond Formations Through Radical Pathways}, series = {Chemistry - A European Journal}, volume = {26}, journal = {Chemistry - A European Journal}, number = {44}, doi = {10.1002/chem.202000194}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214758}, pages = {9674 -- 9687}, year = {2020}, abstract = {Recent years have witnessed remarkable advances in radical reactions involving main-group metal complexes. This includes the isolation and detailed characterization of main-group metal radical compounds, but also the generation of highly reactive persistent or transient radical species. A rich arsenal of methods has been established that allows control over and exploitation of their unusual reactivity patterns. Thus, main-group metal compounds have entered the field of selective bond formations in controlled radical reactions. Transformations that used to be the domain of late transition-metal compounds have been realized, and unusual selectivities, high activities, as well as remarkable functional-group tolerances have been reported. Recent findings demonstrate the potential of main-group metal compounds to become standard tools of synthetic chemistry, catalysis, and materials science, when operating through radical pathways.}, language = {en} } @article{GrabenhenrichTrendelenburgBellachetal.2020, author = {Grabenhenrich, Linus and Trendelenburg, Val{\´e}rie and Bellach, Johanna and Y{\"u}rek, Song{\"u}l and Reich, Andreas and Fiandor, Ana and Rivero, Daniela and Sigurdardottir, Sigurveig and Clausen, Michael and Papadopoulos, Nikolaos G. and Xepapadaki, Paraskevi and Sprikkelman, Aline B. and Dontje, Bianca and Roberts, Graham and Grimshaw, Kate and Kowalski, Marek L. and Kurowski, Marcin and Dubakiene, Ruta and Rudzeviciene, Odilija and Fern{\´a}ndez-Rivas, Montserrat and Couch, Philip and Versteeg, Serge A. and van Ree, Ronald and Mills, Clare and Keil, Thomas and Beyer, Kirsten}, title = {Frequency of food allergy in school-aged children in eight European countries—The EuroPrevall-iFAAM birth cohort}, series = {Allergy}, volume = {75}, journal = {Allergy}, number = {9}, doi = {10.1111/all.14290}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214746}, pages = {2294 -- 2308}, year = {2020}, abstract = {Background The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent-reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. Methods A follow-up assessment at age 6-10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double-blind, placebo-controlled oral food challenges (DBPCFC). Results A total of 6105 children participated in this school-age follow-up (57.8\% of 10 563 recruited at birth). For 982 of 6069 children (16.2\%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face-to-face interviews and/or skin prick testing, 238 (10.4\%) were eligible for a DBPCFC. Sixty-three foods were challenge-tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy-one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4\% (88 related to all 6105 participants of this follow-up) and 3.8\% (88 related to 2289 with completed eligibility assessment). Interpretation In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons.}, language = {en} } @article{ShuklaMannheim2020, author = {Shukla, A. and Mannheim, K.}, title = {Gamma-ray flares from relativistic magnetic reconnection in the jet of the quasar 3C 279}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-17912-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231328}, year = {2020}, abstract = {Spinning black holes in the centres of galaxies can release powerful magnetised jets. When the jets are observed at angles of less than a few degrees to the line-of-sight, they are called blazars, showing variable non-thermal emission across the electromagnetic spectrum from radio waves to gamma rays. It is commonly believed that shock waves are responsible for this dissipation of jet energy. Here we show that gamma-ray observations of the blazar 3C 279 with the space-borne telescope Fermi-LAT reveal a characteristic peak-in-peak variability pattern on time scales of minutes expected if the particle acceleration is instead due to relativistic magnetic reconnection. The absence of gamma-ray pair attenuation shows that particle acceleration takes place at a distance of ten thousand gravitational radii from the black hole where the fluid dynamical kink instability drives plasma turbulence.}, language = {en} } @article{MasotaVoggHelleretal.2020, author = {Masota, Nelson E. and Vogg, Gerd and Heller, Eberhard and Holzgrabe, Ulrike}, title = {Comparison of extraction efficiency and selectivity between low-temperature pressurized microwave-assisted extraction and prolonged maceration}, series = {Archiv der Pharmazie}, volume = {353}, journal = {Archiv der Pharmazie}, number = {10}, doi = {10.1002/ardp.202000147}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218529}, year = {2020}, abstract = {Extraction is a key step in studying compounds from plants and other natural sources. The common use of high temperatures in pressurized microwave-assisted extraction (PMAE) makes it unsuitable for the extraction of compounds with low or unknown thermal stability. This study aimed at determining the suitability of low-temperature, short-time PMAE in attaining yields comparable to those of prolonged maceration at room temperature. Additionally, we explored the phytochemical differences of the extracts from both techniques. Maceration at room temperature for 24 hr and PMAE at 40-45°C and 10 bar for 30 min were carried out on 18 samples from 14 plant species at a solvent-to-feeds ratio of 10. The PMAE yields of 16 out of 18 samples were within the proportions of 91-139.2\% as compared with the respective extracts from maceration. Varying numbers of nonmatching peaks were noted in MS chromatograms of five extract pairs, indicating selective extraction of some compounds. Low-temperature PMAE can attain reasonable extraction efficiency with the added value of sparing compounds of low thermal stability. The method can also enable the recovery of compounds distinct from those obtained by maceration.}, language = {en} } @inproceedings{OPUS4-21158, title = {Neue Materialien des Bayerischen Neolithikums 3. Tagung im Kloster Windberg vom 16. bis 18. November 2018}, editor = {Husty, Ludwig and Link, Thomas and Pechtl, Joachim}, edition = {1. Auflage}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, isbn = {978-3-95826-144-0}, issn = {2367-0681}, doi = {10.25972/WUP-978-3-95826-145-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211585}, pages = {257}, year = {2020}, abstract = {Vom 16. bis 18. November 2018 fand im Kloster Windberg bei Straubing zum dritten Mal nach 2014 eine Tagung unter dem Titel "Neue Materialien des Bayerischen Neolithikums" statt. Dabei wurden neue, bislang unpublizierte Fundkomplexe vorgestellt und diskutiert, die alle Phasen der Jungsteinzeit vom Altneolithikum bis zum Endneolithikum abdeckten und die aus verschiedenen Landesteilen des Freistaats Bayern stammen. Mit einer diachronen und Regionen {\"u}bergreifenden Betrachtung charakteristischer Inventare aus den verschiedenen Landschaftsr{\"a}umen und Zeitabschnitten wurde das Ziel verfolgt, neues Material zu erschließen und damit die arch{\"a}ologische Quellenbasis zu erweitern und der Neolithforschung in Bayern neue Impulse zu geben. Im vorliegenden Band werden sieben der Vortr{\"a}ge dieser Tagung sowie drei Beitr{\"a}ge der vorangegangenen Arbeitstreffen zusammengestellt.}, subject = {Bayern}, language = {de} } @article{McNeillZieglerRadtkeetal.2020, author = {McNeill, Rhiannon V. and Ziegler, Georg C. and Radtke, Franziska and Nieberler, Matthias and Lesch, Klaus‑Peter and Kittel‑Schneider, Sarah}, title = {Mental health dished up — the use of iPSC models in neuropsychiatric research}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, issn = {0300-9564}, doi = {10.1007/s00702-020-02197-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235666}, pages = {1547-1568}, year = {2020}, abstract = {Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006-2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient's own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease.}, language = {en} } @article{EndlichRichterMarxetal.2020, author = {Endlich, Darius and Richter, Tobias and Marx, Peter and Lenhard, Wolfgang and Moll, Kristina and Witzel, Bj{\"o}rn and Schulte-K{\"o}rne, Gerd}, title = {Spelling Error Detection : A Valid and Economical Task for Assessing Spelling Skills in Elementary-School Children}, series = {Zeitschrift f{\"u}r Entwicklungspsychologie und P{\"a}dagogische Psychologie}, volume = {52}, journal = {Zeitschrift f{\"u}r Entwicklungspsychologie und P{\"a}dagogische Psychologie}, number = {1-2}, issn = {0049-8637}, doi = {10.1026/0049-8637/a000227}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244665}, pages = {25-40}, year = {2020}, abstract = {The ability to spell words correctly is a key competence for educational and professional achievement. Economical procedures are essential to identifying children with spelling problems as early as possible. Given the strong evidence showing that reading and spelling are based on the same orthographic knowledge, error-detection tasks (EDTs) could be considered such an economical procedure. Although EDTs are widely used in English-speaking countries, the few studies in German-speaking countries investigated only pupils in secondary school. The present study investigated N = 1,513 children in elementary school. We predicted spelling competencies (measured by dictation or gap-fill dictation) based on an EDT via linear regression. Error-detection abilities significantly predicted spelling competencies (R² between .509 and .679), indicating a strong connection. Predictive values in identifying children with poor spelling abilities with an EDT proved to be sufficient. Error detection for the assessment of spelling skills is therefore a valid instrument for transparent languages as well.}, language = {en} } @article{AndreskaLueningschroerSendtner2020, author = {Andreska, Thomas and L{\"u}ningschr{\"o}r, Patrick and Sendtner, Michael}, title = {Regulation of TrkB cell surface expression — a mechanism for modulation of neuronal responsiveness to brain-derived neurotrophic factor}, series = {Cell and Tissue Research}, volume = {382}, journal = {Cell and Tissue Research}, doi = {10.1007/s00441-020-03224-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235055}, pages = {5-14}, year = {2020}, abstract = {Neurotrophin signaling via receptor tyrosine kinases is essential for the development and function of the nervous system in vertebrates. TrkB activation and signaling show substantial differences to other receptor tyrosine kinases of the Trk family that mediate the responses to nerve growth factor and neurotrophin-3. Growing evidence suggests that TrkB cell surface expression is highly regulated and determines the sensitivity of neurons to brain-derived neurotrophic factor (BDNF). This translocation of TrkB depends on co-factors and modulators of cAMP levels, N-glycosylation, and receptor transactivation. This process can occur in very short time periods and the resulting rapid modulation of target cell sensitivity to BDNF could represent a mechanism for fine-tuning of synaptic plasticity and communication in complex neuronal networks. This review focuses on those modulatory mechanisms in neurons that regulate responsiveness to BDNF via control of TrkB surface expression.}, language = {en} } @article{StengelVulinovicMeieretal.2020, author = {Stengel, Felix and Vulinovic, Franca and Meier, Britta and Gr{\"u}tz, Karen and Klein, Christine and Capetian, Philipp}, title = {Impaired differentiation of human induced neural stem cells by TOR1A overexpression}, series = {Molecular Biology Reports}, volume = {47}, journal = {Molecular Biology Reports}, doi = {10.25972/OPUS-24117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241177}, pages = {3993-4001}, year = {2020}, abstract = {DYT-TOR1A is the most common inherited dystonia caused by a three nucleotide (GAG) deletion (dE) in the TOR1A gene. Death early after birth and cortical anomalies of the full knockout in rodents underscore its developmental importance. We therefore explored the timed effects of TOR1A-wt and TOR1A-dE during differentiation in a human neural in vitro model. We used lentiviral tet-ON expression of TOR1A-wt and -dE in induced neural stem cells derived from healthy donors. Overexpression was induced during proliferation of neural precursors, during differentiation and after differentiation into mature neurons. Overexpression of both wildtype and mutated protein had no effect on the viability and cell number of neural precursors as well as mature neurons when initiated before or after differentiation. However, if induced during differentiation, overexpression of TOR1A-wt and -dE led to a pronounced reduction of mature neurons in a dose dependent manner. Our data underscores the importance of physiological expression levels of TOR1A as crucial for proper neuronal differentiation. We did not find evidence for a specific impact of the mutated TOR1A on neuronal maturation.}, language = {en} } @article{ReinersDrozdYamashita2020, author = {Reiners, Christoph and Drozd, Valentina and Yamashita, Shunichi}, title = {Hypothyroidism after radiation exposure: brief narrative review}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, issn = {0300-9564}, doi = {10.1007/s00702-020-02260-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235653}, pages = {1455-1466}, year = {2020}, abstract = {The thyroid gland is among the organs at the greatest risk of cancer from ionizing radiation. Epidemiological evidence from survivors of radiation therapy, atomic bombing, and the Chernobyl reactor accident, clearly shows that radiation exposure in childhood can cause thyroid cancer and benign thyroid nodules. Radiation exposure also may induce hypothyroidism and autoimmune reactions against the thyroid, but these effects are less well-documented. The literature includes only a few, methodologically weak animal studies regarding genetic/molecular mechanisms underlying hypothyroidism and thyroid autoimmunity after radiation exposure. Rather, evidence about radiation-induced hypothyroidism and thyroid autoimmunity derives mainly from follow-up studies in patients treated with external beam radiotherapy (EBRT) or iodine-131, and from epidemiological studies in the atomic bombing or nuclear accident survivors. Historically, hypothyroidism after external irradiation of the thyroid in adulthood was considered not to develop below a 10-20 Gy dose threshold. Newer data suggest a 10 Gy threshold after EBRT. By contrast, data from patients after iodine-131 "internal radiation therapy" of Graves´ disease indicate that hypothyroidism rarely occurs below thyroid doses of 50 Gy. Studies in children affected by the Chernobyl accident indicate that the dose threshold for hypothyroidism may be considerably lower, 3-5 Gy, aligning with observations in A-bomb survivors exposed as children. The reasons for these dose differences in radiosensitivity are not fully understood. Other important questions about the development of hypothyroidism after radiation exposure e.g., in utero, about the interaction between autoimmunity and hypofunction, and about the different effects of internal and external irradiation still must be answered.}, language = {en} } @article{CaoChenHaendel2020, author = {Cao, Liyu and Chen, Xinyu and Haendel, Barbara F.}, title = {Overground Walking Decreases Alpha Activity and Entrains Eye Movements in Humans}, series = {Frontiers in Human Neuroscience}, volume = {14}, journal = {Frontiers in Human Neuroscience}, issn = {1662-5161}, doi = {10.3389/fnhum.2020.561755}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219872}, year = {2020}, abstract = {Experiments in animal models have shown that running increases neuronal activity in early visual areas in light as well as in darkness. This suggests that visual processing is influenced by locomotion independent of visual input. Combining mobile electroencephalography, motion- and eye-tracking, we investigated the influence of overground free walking on cortical alpha activity (~10 Hz) and eye movements in healthy humans. Alpha activity has been considered a valuable marker of inhibition of sensory processing and shown to negatively correlate with neuronal firing rates. We found that walking led to a decrease in alpha activity over occipital cortex compared to standing. This decrease was present during walking in darkness as well as during light. Importantly, eye movements could not explain the change in alpha activity. Nevertheless, we found that walking and eye related movements were linked. While the blink rate increased with increasing walking speed independent of light or darkness, saccade rate was only significantly linked to walking speed in the light. Pupil size, on the other hand, was larger during darkness than during light, but only showed a modulation by walking in darkness. Analyzing the effect of walking with respect to the stride cycle, we further found that blinks and saccades preferentially occurred during the double support phase of walking. Alpha power, as shown previously, was lower during the swing phase than during the double support phase. We however could exclude the possibility that the alpha modulation was introduced by a walking movement induced change in electrode impedance. Overall, our work indicates that the human visual system is influenced by the current locomotion state of the body. This influence affects eye movement pattern as well as neuronal activity in sensory areas and might form part of an implicit strategy to optimally extract sensory information during locomotion.}, language = {en} } @article{WertgenRichter2020, author = {Wertgen, Andreas G. and Richter, Tobias}, title = {Source credibility modulates the validation of implausible information}, series = {Memory \& Cognition}, volume = {48}, journal = {Memory \& Cognition}, issn = {0090-502X}, doi = {10.3758/s13421-020-01067-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234825}, pages = {1359-1375}, year = {2020}, abstract = {Validation of text information as a general mechanism for detecting inconsistent or false information is an integral part of text comprehension. This study examined how the credibility of the information source affects validation processes. Two experiments investigated combined effects of source credibility and plausibility of information during validation with explicit (ratings) and implicit (reading times) measurements. Participants read short stories with a high-credible versus low-credible person that stated a consistent or inconsistent assertion with general world knowledge. Ratings of plausibility and ratings of source credibility were lower when a credible source stated a world-knowledge inconsistent assertion compared with a low-credible source. Reading times on target sentences and on spillover sentences were slower when a credible source stated an assertion inconsistent with world knowledge compared with a low-credible source, suggesting that source information modulated the validation of implausible information. These results show that source credibility modulates validation and suggest a bidirectional relationship of perceived plausibility and source credibility in the reading process.}, language = {en} } @article{LapuenteArandjelovicKuehletal.2020, author = {Lapuente, Juan and Arandjelovic, Mimi and K{\"u}hl, Hjalmar and Dieguez, Paula and Boesch, Christophe and Linsenmair, K. Eduard}, title = {Sustainable Peeling of Kapok Tree (Ceiba pentandra) Bark by the Chimpanzees (Pan troglodytes verus) of Como{\´e} National Park, Ivory Coast}, series = {International Journal of Primatology}, volume = {41}, journal = {International Journal of Primatology}, issn = {0164-0291}, doi = {10.1007/s10764-020-00152-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232581}, pages = {962-988}, year = {2020}, abstract = {Primates often consume either bark or cambium (inner bark) as a fallback food tocomplete their diet during periods of food scarcity. Wild chimpanzees exhibit greatbehavioral diversity across Africa, as studies of new populations frequently reveal.Since 2014, we have been using a combination of camera traps and indirect signs tostudy the ecology and behavior of wild chimpanzees (Pan troglodytes verus) in Como{\´e}National Park, Ivory Coast, to document and understand the behavioral adaptations thathelp them to survive in a savanna-forest mosaic landscape. We found that Como{\´e}chimpanzees peel the bark of the buttresses of kapok tree (Ceiba pentandra) trees to eatthe cambium underneath. Individuals of all sex/age classes across at least six neigh-boring communities peeled the bark, but only during the late rainy season andbeginning of the dry season, when cambium may represent an important fallback food.Baboons (Papio anubis) also target the same trees but mainly eat the bark itself. Mostof the bark-peeling wounds onCeibatrees healed completely within 2 years, seeminglywithout any permanent damage. We recorded chimpanzees visiting trees in early stagesof wound recovery but leaving them unpeeled. Only 6\% of peeled trees (N= 53) werereexploited after a year, suggesting that chimpanzees waited for the rest of the trees toregrow the bark fully before peeling them again, thus using them sustainably. Manyhuman groups of hunter-gatherers and herders exploited cambium sustainably in thepast. The observation that similar sustainable bark-peeling behavior evolved in bothchimpanzees and humans suggests that it has an important adaptive value in harshenvironments when other food sources become seasonally scarce, by avoiding thedepletion of the resource and keeping it available for periods of scarcity.}, language = {en} } @article{GesellNiklasSchmiedeleretal.2020, author = {Gesell, Nathalie and Niklas, Frank and Schmiedeler, Sandra and Segerer, Robin}, title = {Mindfulness and romantic relationship outcomes: the mediating role of conflict resolution styles and closeness}, series = {Mindfulness}, volume = {11}, journal = {Mindfulness}, issn = {1868-8527}, doi = {10.1007/s12671-020-01449-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235080}, pages = {2314-2324}, year = {2020}, abstract = {Objectives The association of mindfulness and romantic relationship outcomes such as partnership quality and satisfaction is well-established; however, the mechanisms of action are not yet clear. The current study tested conflict resolution styles and closeness as possible mediating factors. We hypothesized that trait mindfulness would increase the use of constructive conflict resolution styles (positive problem solving), decrease the use of destructive styles (conflict engagement, withdrawal, and compliance), and promote feelings of closeness between partners, which in turn would predict positive relationship outcomes (namely partnership quality, partnership satisfaction, and sexual satisfaction). Methods A total of 209 individuals (86\% German, 76\% female, mean age = 32 years) living in a relationship (31\% married) participated in an online questionnaire. Results Mediation analyses revealed that positive problem solving mediated the association between mindfulness and partnership quality with b = .09 (95\% CI = .03-.17), mindfulness and partnership satisfaction with b = .07 (95\% CI = .02-.13), and mindfulness and sexual satisfaction with b = .04 (95\% CI = .00-.10). Furthermore, a mediating role of withdrawal and closeness was shown for individual relationship outcomes. Conclusions Findings suggest that more positive problem solving, less withdrawal, and more closeness are mechanisms by which mindfulness is associated with positive relationship outcomes. The results of our study thus broaden our understanding of the processes that underlie fulfilling romantic relationships and, in turn, underline the positive effects of mindfulness.}, language = {en} } @article{GuesgenAngerHaueretal.2020, author = {G{\"u}sgen, C. and Anger, F. and Hauer, T. and Willms, A. and Buhr, H. J. and Germer, C.-T. and Schwab, R. and Lock, J. F.}, title = {Fortbildung von Allgemein- und Viszeralchirurgen in der lebensrettenden Notfallchirurgie. Ergebnisse einer Umfrage unter Operationskursteilnehmern}, series = {Der Chirurg}, volume = {91}, journal = {Der Chirurg}, organization = {Chirurgische ArbeitsgemeinschaftMilit{\"a}r- und Notfallchirurgie (CAMIN) der Deutschen Gesellschaft f{\"u}r Allgemein- und Viszeralchirurgie (DGAV)}, issn = {0009-4722}, doi = {10.1007/s00104-020-01170-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235246}, pages = {1044-1052}, year = {2020}, abstract = {Hintergrund Die geringe Anzahl operativ zu versorgender K{\"o}rperh{\"o}hlenverletzungen erfordert ein Umdenken in der chirurgischen Aus- und Weiterbildung. Ein entsprechendes Kursformat wird seit 2014 {\"u}ber die DGAV angeboten. Um Berechtigung, Bedarf, Nutzen und Erfolg eines solchen Kursformates zu erheben, erfolgte eine Evaluation durch die bisherigen Kursteilnehmer. Material und Methoden Kursevaluation und zus{\"a}tzliche Onlinebefragung der bisherigen Kursteilnehmer hinsichtlich Alter, Geschlecht, Ausbildungsstand, Fachrichtung, Versorgungsstufe des Krankenhauses, notfallchirurgischer Erfahrungen, der H{\"a}ufigkeit chirurgischer Notfallversorgungen, Teilnahme an anderen Kursformaten, Erfahrungen nach der Kursteilnahme, Einsch{\"a}tzung der aktuellen Fort- und Weiterbildungssituation und Finanzierung solcher Kurse. Ergebnisse Insgesamt 142 Kursteilnehmer evaluierten ihre Kursteilnahme, zus{\"a}tzlich beantworteten 83 den Onlinefragebogen. {\"U}ber 90 \% berichteten von einem nachhaltigen positiven Einfluss des Kurses auf ihr notfallchirurgisches Handeln. Mehr als die H{\"a}lfte konnte von konkreten Notfallsituationen berichten, die sie aufgrund der Kursteilnahme besser bew{\"a}ltigen konnten. In der Notfallversorgung erfahrene Chirurgen bewerteten den eigenen Lernerfolg durch die Kursteilnahme signifikant h{\"a}ufiger positiv als ihre weniger erfahrenen Kollegen. Keinen Einfluss auf den Lernerfolg hatten eine Ober- oder Chefarztposition, die Versorgungsstufe des Krankenhauses, das Alter oder Geschlecht der Teilnehmer. Die Mehrheit der antwortenden Chirurgen bef{\"u}rwortet die Integration eines solchen Kursformates in die chirurgische Weiterbildung und fordert hierzu eine finanzielle Unterst{\"u}tzung. Schlussfolgerung Kursformate, in denen notfallchirurgische Strategien und F{\"a}higkeiten vermittelt werden, sind etabliert und werden sehr positiv evaluiert. Die Fort- und Weiterbildung in notfallchirurgischen F{\"a}higkeiten und Kenntnissen liegt im gesellschaftlichen Interesse und zumindest anteilig auch in ihrer Verantwortung.}, language = {de} } @article{JuergensBieniussaVoelkeretal.2020, author = {Juergens, Lukas and Bieniussa, Linda and Voelker, Johannes and Hagen, Rudolf and Rak, Kristen}, title = {Spatio-temporal distribution of tubulin-binding cofactors and posttranslational modifications of tubulin in the cochlea of mice}, series = {Histochemistry and Cell Biology}, volume = {154}, journal = {Histochemistry and Cell Biology}, issn = {0948-6143}, doi = {10.1007/s00418-020-01905-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234852}, pages = {671-681}, year = {2020}, abstract = {The five tubulin-binding cofactors (TBC) are involved in tubulin synthesis and the formation of microtubules. Their importance is highlighted by various diseases and syndromes caused by dysfunction or mutation of these proteins. Posttranslational modifications (PTMs) of tubulin promote different characteristics, including stability-creating subpopulations of tubulin. Cell- and time-specific distribution of PTMs has only been investigated in the organ of Corti in gerbils. The aim of the presented study was to investigate the cell type-specific and time-specific expression patterns of TBC proteins and PTMs for the first time in murine cochleae over several developmental stages. For this, murine cochleae were investigated at the postnatal (P) age P1, P7 and P14 by immunofluorescence analysis. The investigations revealed several profound interspecies differences in the distribution of PTMs between gerbil and mouse. Furthermore, this is the first study to describe the spatio-temporal distribution of TBCs in any tissue ever showing a volatile pattern of expression. The expression analysis of TBC proteins and PTMs of tubulin reveals that these proteins play a role in the physiological development of the cochlea and might be essential for hearing.}, language = {en} } @book{Reuter2020, author = {Reuter, Oliver M.}, title = {Erfahrungsverankerte Rezeption : Eine Methode zur Verzahnung von Produktion und Rezeption}, edition = {1. Auflage}, publisher = {kopaed}, isbn = {978-3-86736-580-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-345281}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {210}, year = {2020}, abstract = {Eine Rezeption auf den von Kindern und Jugendlichen selbst gemachten Erfahrungen aufzubauen, ist das zentrale Anliegen der ausgef{\"u}hrten Methode zur Verschr{\"a}nkung von produktiven und rezeptiven Anteilen im Kunstunterricht. Indem vor der Rezeption eine bildnerische Praxis stattfindet, k{\"o}nnen Ideen und Vorstellungen selbst{\"a}ndig und individuell entwickelt und in Bilder {\"u}bersetzt werden. Bei der erfahrungsverankerten Vermittlung basiert die Rezeption auf einer Schnittmenge zwischen eigenen Handlungen im bildnerischen oder darstellenden Prozess und zentralen Aspekten des Werks. Solche Referenzpunkte zwischen der Produktion und der Rezeption k{\"o}nnen im Material, im Thema, in der Gattung, im bildnerischen Verfahren oder in einer k{\"u}nstlerischen Strategie ausfindig gemacht werden. Sie dienen dazu, Einsichten, Einstellungen, Kenntnisse und Wissen aus der Produktion in die Rezeption mitzunehmen. Somit ist die Methode der erfahrungsverankerten Rezeption gleichermaßen geeignet f{\"u}r die Vermittlung historischer wie f{\"u}r zeitgen{\"o}ssischer Kunst. Nach der Darlegung und Konturierung der Konzeption zeigt die Publikation Wege auf, die erfahrungsverankerte Rezeption in Unterricht zu {\"u}berf{\"u}hren. Exemplarische Unterrichtsskizzen illustrieren die Umsetzung im Kunstunterricht.}, subject = {Erfahrung}, language = {de} } @article{HerrmannAdamNotzetal.2020, author = {Herrmann, Johannes and Adam, Elisabeth Hannah and Notz, Quirin and Helmer, Philipp and Sonntagbauer, Michael and Ungemach-Papenberg, Peter and Sanns, Andreas and Zausig, York and Steinfeldt, Thorsten and Torje, Iuliu and Schmid, Benedikt and Schlesinger, Tobias and Rolfes, Caroline and Reyher, Christian and Kredel, Markus and Stumpner, Jan and Brack, Alexander and Wurmb, Thomas and Gill-Schuster, Daniel and Kranke, Peter and Weismann, Dirk and Klinker, Hartwig and Heuschmann, Peter and R{\"u}cker, Viktoria and Frantz, Stefan and Ertl, Georg and Muellenbach, Ralf Michael and Mutlak, Haitham and Meybohm, Patrick and Zacharowski, Kai and Lotz, Christopher}, title = {COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study}, series = {Frontiers in Medicine}, volume = {7}, journal = {Frontiers in Medicine}, issn = {2296-858X}, doi = {10.3389/fmed.2020.599533}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219834}, year = {2020}, abstract = {Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0\%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5\%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3\%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.}, language = {en} } @article{GabbertDillingMeybohmetal.2020, author = {Gabbert, Lydia and Dilling, Christina and Meybohm, Patrick and Burek, Malgorzata}, title = {Deletion of Protocadherin Gamma C3 Induces Phenotypic and Functional Changes in Brain Microvascular Endothelial Cells In Vitro}, series = {Frontiers in Pharmacology}, volume = {11}, journal = {Frontiers in Pharmacology}, issn = {1663-9812}, doi = {10.3389/fphar.2020.590144}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219828}, year = {2020}, abstract = {Inflammation of the central nervous system (CNS) is associated with diseases such as multiple sclerosis, stroke and neurodegenerative diseases. Compromised integrity of the blood-brain barrier (BBB) and increased migration of immune cells into the CNS are the main characteristics of brain inflammation. Clustered protocadherins (Pcdhs) belong to a large family of cadherin-related molecules. Pcdhs are highly expressed in the CNS in neurons, astrocytes, pericytes and epithelial cells of the choroid plexus and, as we have recently demonstrated, in brain microvascular endothelial cells (BMECs). Knockout of a member of the Pcdh subfamily, PcdhgC3, resulted in significant changes in the barrier integrity of BMECs. Here we characterized the endothelial PcdhgC3 knockout (KO) cells using paracellular permeability measurements, proliferation assay, wound healing assay, inhibition of signaling pathways, oxygen/glucose deprivation (OGD) and a pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) treatment. PcdhgC3 KO showed an increased paracellular permeability, a faster proliferation rate, an altered expression of efflux pumps, transporters, cellular receptors, signaling and inflammatory molecules. Serum starvation led to significantly higher phosphorylation of extracellular signal-regulated kinases (Erk) in KO cells, while no changes in phosphorylated Akt kinase levels were found. PcdhgC3 KO cells migrated faster in the wound healing assay and this migration was significantly inhibited by respective inhibitors of the MAPK-, β-catenin/Wnt-, mTOR- signaling pathways (SL327, XAV939, or Torin 2). PcdhgC3 KO cells responded stronger to OGD and TNFα by significantly higher induction of interleukin 6 mRNA than wild type cells. These results suggest that PcdhgC3 is involved in the regulation of major signaling pathways and the inflammatory response of BMECs.}, language = {en} } @article{LotzMuellenbachMeybohmetal.2020, author = {Lotz, C. and Muellenbach, R. M. and Meybohm, P. and Rolfes, C. and Reyher, C.}, title = {Pr{\"a}klinisches Management bei Herz-Kreislauf-Stillstand - extrakorporale kardiopulmonale Reanimation}, series = {Der Anaesthesist}, volume = {69}, journal = {Der Anaesthesist}, issn = {0003-2417}, doi = {10.1007/s00101-020-00787-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232525}, pages = {404-413}, year = {2020}, abstract = {Hintergrund Die {\"U}berlebenschancen nach pr{\"a}klinischem Herz-Kreislauf-Stillstand sind weiterhin sehr gering. Trotz intensiver Bem{\"u}hungen bleibt das Outcome seit vielen Jahren weitestgehend konstant. Neue Technologien wie die extrakorporale kardiopulmonale Reanimation (eCPR) k{\"o}nnen in bestimmten Situationen m{\"o}glicherweise das {\"U}berleben mit gutem neurologischen Outcome signifikant verbessern. Fragestellung Beeinflusst die sofortige Reperfusion und Reoxygenierung des K{\"o}rpers mittels eCPR das {\"U}berleben nach Herz-Kreislauf-Stillstand? Bedarf es einer Erweiterung der „chain of survival" um die eCPR? Material und Methoden Diskussion aktueller Studienergebnisse und Leitlinienempfehlungen. Ergebnisse Die {\"U}berlebensraten nach pr{\"a}klinischem Herz-Kreislauf-Stillstand sind weltweit seit vielen Jahren unver{\"a}ndert bei 10-30 \%. Trotz geringer Fallzahlen zeigen neuere retrospektive Studien, dass durch die eCPR eine Verbesserung des Outcome erzielt werden kann. In selektionierten Patientenkollektiven ist ein {\"U}berleben mit gutem neurologischen Outcome von 38 \% m{\"o}glich. Schlussfolgerung Ob und mit welcher Lebensqualit{\"a}t ein Herz-Kreislauf-Stillstand {\"u}berlebt werden kann, ist von vielen unterschiedlichen Faktoren abh{\"a}ngig. Der Faktor Zeit, also die Vermeidung einer „No-flow-Phase" und die Reduktion der „Low-flow-Phase", ist von zentraler Bedeutung. Durch die sofortige Wiederherstellung von Zirkulation und Sauerstoffversorgung kann durch die eCPR das {\"U}berleben signifikant verbessert werden. Große kontrollierte, randomisierte Studien hierzu fehlen jedoch bisher.}, language = {de} } @article{LotzNotzKrankeetal.2020, author = {Lotz, Christopher and Notz, Quirin and Kranke, Peter and Kredel, Markus and Meybohm, Patrick}, title = {Unconventional approaches to mechanical ventilation - step-by-step through the COVID-19 crisis}, series = {Critical Care}, volume = {24}, journal = {Critical Care}, doi = {10.1186/s13054-020-02954-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229868}, year = {2020}, abstract = {No abstract available.}, language = {en} } @article{AverdunkBernhagenFehnleetal.2020, author = {Averdunk, Luisa and Bernhagen, J{\"u}rgen and Fehnle, Karl and Surowy, Harald and L{\"u}decke, Hermann-Josef and Mucha, S{\"o}ren and Meybohm, Patrick and Wieczorek, Dagmar and Leng, Lin and Marx, Gernot and Leaf, David E. and Zarbock, Alexander and Zacharowski, Kai and Bucala, Richard and Stoppe, Christian}, title = {The Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms (rs3063368, rs755622) predict acute kidney injury and death after cardiac surgery}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {9}, issn = {2077-0383}, doi = {10.3390/jcm9092936}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213126}, year = {2020}, abstract = {Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT\(_{5-7}\) (rs5844572/rs3063368,"-794") and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT\(_7\)) had a significantly higher risk of acute kidney injury (AKI) compared to others (23\% vs. 13\%; OR 2.01 (1.40-2.88), p = 0.0001). Carriers of CATT\(_7\) were also at higher risk of death (1.8\% vs. 0.4\%; OR 5.12 (0.99-33.14), p = 0.026). The GC genotype was associated with AKI (20\% vs. GG/CC:13\%, OR 1.71 (1.20-2.43), p = 0.003). Multivariate analyses identified CATT\(_7\) predictive for AKI (OR 2.13 (1.46-3.09), p < 0.001) and death (OR 5.58 (1.29-24.04), p = 0.021). CATT\(_7\) was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT\(_7\) allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.}, language = {en} } @article{CurtazSchmittHerbertetal.2020, author = {Curtaz, Carolin J. and Schmitt, Constanze and Herbert, Saskia-Laureen and Feldheim, Jonas and Schlegel, Nicolas and Gosselet, Fabien and Hagemann, Carsten and Roewer, Norbert and Meybohm, Patrick and W{\"o}ckel, Achim and Burek, Malgorzata}, title = {Serum-derived factors of breast cancer patients with brain metastases alter permeability of a human blood-brain barrier model}, series = {Fluids and Barriers of the CNS}, volume = {17}, journal = {Fluids and Barriers of the CNS}, doi = {10.1186/s12987-020-00192-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229940}, year = {2020}, abstract = {Background The most threatening metastases in breast cancer are brain metastases, which correlate with a very poor overall survival, but also a limited quality of life. A key event for the metastatic progression of breast cancer into the brain is the migration of cancer cells across the blood-brain barrier (BBB). Methods We adapted and validated the CD34\(^+\) cells-derived human in vitro BBB model (brain-like endothelial cells, BLECs) to analyse the effects of patient serum on BBB properties. We collected serum samples from healthy donors, breast cancer patients with primary cancer, and breast cancer patients with, bone, visceral or cerebral metastases. We analysed cytokine levels in these sera utilizing immunoassays and correlated them with clinical data. We used paracellular permeability measurements, immunofluorescence staining, Western blot and mRNA analysis to examine the effects of patient sera on the properties of BBB in vitro. Results The BLECs cultured together with brain pericytes in transwells developed a tight monolayer with a correct localization of claudin-5 at the tight junctions (TJ). Several BBB marker proteins such as the TJ proteins claudin-5 and occludin, the glucose transporter GLUT-1 or the efflux pumps PG-P and BCRP were upregulated in these cultures. This was accompanied by a reduced paracellular permeability for fluorescein (400 Da). We then used this model for the treatment with the patient sera. Only the sera of breast cancer patients with cerebral metastases had significantly increased levels of the cytokines fractalkine (CX3CL1) and BCA-1 (CXCL13). The increased levels of fractalkine were associated with the estrogen/progesterone receptor status of the tumour. The treatment of BLECs with these sera selectively increased the expression of CXCL13 and TJ protein occludin. In addition, the permeability of fluorescein was increased after serum treatment. Conclusion We demonstrate that the CD34\(^+\) cell-derived human in vitro BBB model can be used as a tool to study the molecular mechanisms underlying cerebrovascular pathologies. We showed that serum from patients with cerebral metastases may affect the integrity of the BBB in vitro, associated with elevated concentrations of specific cytokines such as CX3CL1 and CXCL13.}, language = {en} } @article{SchlesingerWeissbrichWedekinketal.2020, author = {Schlesinger, Tobias and Weißbrich, Benedikt and Wedekink, Florian and Notz, Quirin and Herrmann, Johannes and Krone, Manuel and Sitter, Magdalena and Schmid, Benedikt and Kredel, Markus and Stumpner, Jan and D{\"o}lken, Lars and Wischhusen, J{\"o}rg and Kranke, Peter and Meybohm, Patrick and Lotz, Christpher}, title = {Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study}, series = {PLoS One}, volume = {15, 2020}, journal = {PLoS One}, number = {11}, doi = {10.1371/journal.pone.0242917}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231348}, year = {2020}, abstract = {Background The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). Methods This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay. Results Most patients (91\%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30\%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100\% of the cases, oropharyngeal swabs only in 77\%. Blood samples were positive in 26\% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009). Conclusions COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity.}, language = {en} } @article{FlemmingHankirErnestusetal.2020, author = {Flemming, S. and Hankir, M. and Ernestus, R.-I. and Seyfried, F. and Germer, C.-T. and Meybohm, P. and Wurmb, T. and Vogel, U. and Wiegering, A.}, title = {Surgery in times of COVID-19 — recommendations for hospital and patient management}, series = {Langenbeck's Archives of Surgery}, volume = {405}, journal = {Langenbeck's Archives of Surgery}, issn = {1435-2443}, doi = {10.1007/s00423-020-01888-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231766}, pages = {359-364}, year = {2020}, abstract = {Background The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeonshave had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards. Purpose To provide a detailed set of guidelines developed in a surgical ward at University Hospital Wuerzburg to safelyaccommodate the exponentially rising cases of SARS-CoV-2 infected patients without compromising the care of emergencysurgery and oncological patients or jeopardizing the well-being of hospital staff. Conclusions The dynamic prioritization of SARS-CoV-2 infected and surgical patient groups is key to preserving life whilemaintaining high surgical standards. Strictly segregating patient groups in emergency rooms, non-intensive care wards andoperating areas prevents viral spread while adequately training and carefully selecting hospital staff allow them to confidentlyand successfully undertake their respective clinical duties.}, language = {en} }