@article{Drenckhahn2021, author = {Drenckhahn, Detlev}, title = {Zur Vegetation der Seedeiche der Nordseek{\"u}ste Schleswig-Holsteins - Implikationen f{\"u}r die Umsetzung des Generalplans K{\"u}stenschutz}, series = {Forum Geobotanicum}, volume = {10}, journal = {Forum Geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2021.0825a}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243795}, pages = {28-37}, year = {2021}, abstract = {Bis zum Jahr 2100 prognostiziert der Weltklimarat (IPCC 2021) einen Anstieg des Meeresspiegels von bis zu 63-101 cm gegen{\"u}ber heutigen Wasserst{\"a}nden. Im Rahmen des Generalplans K{\"u}stenschutz Schleswig-Holstein(GKSH) soll als Klimafolgeanpassung eine Erh{\"o}hung und Profil{\"a}nderung der meisten Nordseedeiche und Elbedeiche erfolgen (zusammen 363,3 km mit einer Vegetationsfl{\"a}che von 3.500 ha). Diese Maßnahmen werden mit einem vollst{\"a}ndigen Verlust der alten Deichvegetation einhergehen und zur Freisetzung von großen Mengen an CO₂ aus dem Bodenkohlenstoff f{\"u}hren. Die Seedeiche der Nordseek{\"u}ste (262 km) z{\"a}hlen zu den artenreichen, semi-nat{\"u}rlichen und von Schafen beweideten Grasl{\"a}ndern (Fl{\"a}che von 2600 ha) in Schleswig-Holstein mit bis zu 18 Gras- und 64 zweikeim-bl{\"a}ttrigen Bl{\"u}tenpflanzen und an die Vegetation gebundene 800-1000 Arten von Invertebraten (darunter 200 K{\"a}ferarten). Auf die Außenb{\"o}schung dringen Pflanzen der Salzwiesengesellschaften vor. Die steileren, w{\"a}rmeexponierten ({\"u}berwiegend nach Osten und S{\"u}den ausgerichtet) und durch Vertritt l{\"u}ckigen Innenb{\"o}schungen der Seedeiche sind wertvolle Refugien w{\"a}rmeliebender, konkurrenzschwacher Arten von Magerstandorten und Trittgesellschaften wie die folgenden mediterran-subatlantischen Arten: Knotenklettenkerbel (Torilis nodosa), Zwergklee/Armbl{\"u}tiger Klee (Trifolium micranthum) und Vogelfußklee (Trifolium ornithopodioides). F{\"u}r die Erhaltung beider Kleearten (die aktuelle Verbreitung wird dokumentiert) besitzt Schleswig-Holstein eine nationale und nordwest-europ{\"a}isch-kontinentale Verantwortlichkeit. Folgende Maßnahmen zum Schutz der reichhaltigen Deichvegetation und Teilen seiner Invertebratenfauna bei der Deichverst{\"a}rkung im Rahmen des GKSH werden vorgeschlagen: 1. Abheben der Grasnarbe mit Wurzelraum und zeitnahe Wiederverlegung der alten Grasnarbe (Soden) auf das neue Deichprofil; das ist auch wichtig zum Erhalt des Bodenkohlenstoffs (Klimaschutz). 2. Einsaat von neuen Deichprofilen mit Saatgut von artenreichen Deichabschnitten. 3. Aufnahme substanzieller Forschungsprogramme/Forschungsf{\"o}rderung zur {\"O}kologie der Seedeiche. Weiterhin sollte auf den Einsatz von Herbiziden auf Deichen zur Bek{\"a}mpfung von Disteln verzichtet werden.}, subject = {Seedeich}, language = {de} } @article{ReinersAsamFreyetal.2021, author = {Reiners, Philipp and Asam, Sarah and Frey, Corinne and Holzwarth, Stefanie and Bachmann, Martin and Sobrino, Jose and G{\"o}ttsche, Frank-M. and Bendix, J{\"o}rg and Kuenzer, Claudia}, title = {Validation of AVHRR Land Surface Temperature with MODIS and in situ LST — a TIMELINE thematic processor}, series = {Remote Sensing}, volume = {13}, journal = {Remote Sensing}, number = {17}, issn = {2072-4292}, doi = {10.3390/rs13173473}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246051}, year = {2021}, abstract = {Land Surface Temperature (LST) is an important parameter for tracing the impact of changing climatic conditions on our environment. Describing the interface between long- and shortwave radiation fluxes, as well as between turbulent heat fluxes and the ground heat flux, LST plays a crucial role in the global heat balance. Satellite-derived LST is an indispensable tool for monitoring these changes consistently over large areas and for long time periods. Data from the AVHRR (Advanced Very High-Resolution Radiometer) sensors have been available since the early 1980s. In the TIMELINE project, LST is derived for the entire operating period of AVHRR sensors over Europe at a 1 km spatial resolution. In this study, we present the validation results for the TIMELINE AVHRR daytime LST. The validation approach consists of an assessment of the temporal consistency of the AVHRR LST time series, an inter-comparison between AVHRR LST and in situ LST, and a comparison of the AVHRR LST product with concurrent MODIS (Moderate Resolution Imaging Spectroradiometer) LST. The results indicate the successful derivation of stable LST time series from multi-decadal AVHRR data. The validation results were investigated regarding different LST, TCWV and VA, as well as land cover classes. The comparisons between the TIMELINE LST product and the reference datasets show seasonal and land cover-related patterns. The LST level was found to be the most determinative factor of the error. On average, an absolute deviation of the AVHRR LST by 1.83 K from in situ LST, as well as a difference of 2.34 K from the MODIS product, was observed.}, language = {en} } @article{Hunfeld2021, author = {Hunfeld, Barbara}, title = {Die Lesbarkeit Jean Pauls}, series = {editio}, volume = {35}, journal = {editio}, number = {1}, issn = {0931-3079}, doi = {10.1515/editio-2021-0003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-247181}, pages = {53 -- 66}, year = {2021}, abstract = {In this article, the readability of the world that Jean Paul's literature tries to produce and the readability of Jean Paul's literature that the traditional edition wanted to ensure are intertwined with, firstly, the interwovenness of the primary work and parerga and, secondly, with the issue of the edition of his manuscripts. Jean Paul's autonomy aesthetics replaces the depiction of reality with the world as text; this is mirrored in his handwritings, the edition of which allows for insights into the mycelium of an 'alternate' classical literature.}, language = {de} } @article{ShanBoeckKelleretal.2021, author = {Shan, Junwen and B{\"o}ck, Thomas and Keller, Thorsten and Forster, Leonard and Blunk, Torsten and Groll, J{\"u}rgen and Teßmar, J{\"o}rg}, title = {TEMPO/TCC as a Chemo Selective Alternative for the Oxidation of Hyaluronic Acid}, series = {Molecules}, volume = {26}, journal = {Molecules}, number = {19}, issn = {1420-3049}, doi = {10.3390/molecules26195963}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248362}, year = {2021}, abstract = {Hyaluronic acid (HA)-based hydrogels are very commonly applied as cell carriers for different approaches in regenerative medicine. HA itself is a well-studied biomolecule that originates from the physiological extracellular matrix (ECM) of mammalians and, due to its acidic polysaccharide structure, offers many different possibilities for suitable chemical modifications which are necessary to control, for example, network formation. Most of these chemical modifications are performed using the free acid function of the polymer and, additionally, lead to an undesirable breakdown of the biopolymer's backbone. An alternative modification of the vicinal diol of the glucuronic acid is oxidation with sodium periodate to generate dialdehydes via a ring opening mechanism that can subsequently be further modified or crosslinked via Schiff base chemistry. Since this oxidation causes a structural destruction of the polysaccharide backbone, it was our intention to study a novel synthesis protocol frequently applied to selectively oxidize the C6 hydroxyl group of saccharides. On the basis of this TEMPO/TCC oxidation, we studied an alternative hydrogel platform based on oxidized HA crosslinked using adipic acid dihydrazide as the crosslinker.}, language = {en} } @article{SchlevogtBoekerMaussetal.2021, author = {Schlevogt, Bernhard and Boeker, Klaus H. W. and Mauss, Stefan and Klinker, Hartwig and Heyne, Renate and Link, Ralph and Simon, Karl-Georg and Sarrazin, Christoph and Serfert, Yvonne and Manns, Michael P. and Wedemeyer, Heiner}, title = {Weight gain after interferon-free treatment of chronic hepatitis C — results from the German Hepatitis C-Registry (DHC-R)}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {10}, issn = {2227-9059}, doi = {10.3390/biomedicines9101495}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248476}, year = {2021}, abstract = {Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term weight change of patients receiving interferon-free antiviral treatment for chronic hepatitis C. The German Hepatitis C-registry (DHC-R) is a national multicenter real-world cohort. A total of 5111 patients were followed prospectively after DAA treatment for up to 3 years. Weight change compared to baseline was analyzed at end of treatment and at years 1, 2, and 3 after completion of antiviral therapy. Regression analysis was performed to identify baseline predictors for weight change. While there was no relevant mean weight change (-0.2 kg, SD 4.3 kg) at the end of antiviral treatment, weight started to increase during long-term follow-up reaching +1.7 kg (SD 8.0 kg, p < 0.001) compared to baseline at 3 years (follow-up year 3, FU3) after completion of antiviral therapy. 48\%, 31\%, and 22\% of patients had a weight gain greater than 1, 3, and 5 kg at FU3, respectively. During follow-up, a body mass index (BMI) <30 proved to be the only consistent predictor for weight gain. DAA treatment is followed by a substantial weight gain (+3 kg or more) in one-third of the patients during long-term follow-up. Non-obese patients seemed to be most vulnerable to weight gain. The body compartment involved in weight gain as well as the mechanism of weight gain remain to be elucidated.}, language = {en} } @article{Feldhaus2021, author = {Feldhaus, Stephan}, title = {„Wir Nichtgnostiker": Die Hitler-Engelhardt-Parallele in Christian Krachts Imperium}, series = {arcadia}, volume = {56}, journal = {arcadia}, number = {2}, issn = {1613-0642}, doi = {10.1515/arcadia-2021-9028}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248935}, pages = {183 -- 203}, year = {2021}, abstract = {In 2012 Georg Diez provoked a literary scandal with his review of Christian Kracht's novel Imperium. Since then, almost ninety informed studies which show an ongoing academic interest in the book have been published. Many of these studies attempted to explain the apparently failing analogy between Hitler and Engelhardt that the novel claimed in an irritating manner. Nevertheless, none of them took an esoteric approach which Kracht himself suggested in an interview with Denis Scheck as a starting point for their analyses, although esoteric references seem to be an ignored constant in Kracht's oeuvre since Tristesse Royale. Hence, by tracing this esoteric intertextuality in the whole of Kracht's oeuvre and linking it to the references which Kracht makes to right-wing ideologies since Faserland, it will be shown that there actually does exist an analogy between Hitler and Engelhardt in Imperium which aims to deconstruct Hitler mythemes by ridiculizing Engelhardt. Furthermore, it will be demonstrated that the interrelations between Kracht's texts create a rhizomatic network of intertextuality that dissolves the boarders between external references and self-references.}, language = {de} } @article{KochPetzoldWesselyetal.2021, author = {Koch, Elias A. T. and Petzold, Anne and Wessely, Anja and Dippel, Edgar and Gesierich, Anja and Gutzmer, Ralf and Hassel, Jessica C. and Haferkamp, Sebastian and Hohberger, Bettina and K{\"a}hler, Katharina C. and Knorr, Harald and Kreuzberg, Nicole and Leiter, Ulrike and Loquai, Carmen and Meier, Friedegund and Meissner, Markus and Mohr, Peter and Pf{\"o}hler, Claudia and Rahimi, Farnaz and Schadendorf, Dirk and Schell, Beatrice and Schlaak, Max and Terheyden, Patrick and Thoms, Kai-Martin and Schuler-Thurner, Beatrice and Ugurel, Selma and Ulrich, Jens and Utikal, Jochen and Weichenthal, Michael and Ziller, Fabian and Berking, Carola and Heppt, Markus}, title = {Immune checkpoint blockade for metastatic uveal melanoma: patterns of response and survival according to the presence of hepatic and extrahepatic metastasis}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {13}, issn = {2072-6694}, doi = {10.3390/cancers13133359}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242603}, year = {2021}, abstract = {Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan-Meier method. Log-rank tests, χ\(^2\) tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95\% CI 13.4-23.7) and the median PFS, 2.8 months (95\% CI 2.5-3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8\% and to anti-PD-1 monotherapy 8.9\% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7\% vs. cohort B 16.7\%; p = 0.45). Adverse events (AE) occurred in 41.6\%. Severe AE were observed in 26.3\% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.}, language = {en} } @article{OpolkaMuellerFellaetal.2021, author = {Opolka, Alexander and M{\"u}ller, Dominik and Fella, Christian and Balles, Andreas and Mohr, J{\"u}rgen and Last, Arndt}, title = {Multi-lens array full-field X-ray microscopy}, series = {Applied Sciences}, volume = {11}, journal = {Applied Sciences}, number = {16}, issn = {2076-3417}, doi = {10.3390/app11167234}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244974}, year = {2021}, abstract = {X-ray full-field microscopy at laboratory sources for photon energies above 10 keV suffers from either long exposure times or low resolution. The photon flux is mainly limited by the objectives used, having a limited numerical aperture NA. We show that this can be overcome by making use of the cone-beam illumination of laboratory sources by imaging the same field of view (FoV) several times under slightly different angles using an array of X-ray lenses. Using this technique, the exposure time can be reduced drastically without any loss in terms of resolution. A proof-of-principle is given using an existing laboratory metal-jet source at the 9.25 keV Ga K\(_α\)-line and compared to a ray-tracing simulation of the setup.}, language = {en} } @article{BrunkhorstKanaanTrautmannSchreiberetal.2021, author = {Brunkhorst-Kanaan, Nathalie and Trautmann, Sandra and Schreiber, Yannick and Thomas, Dominique and Kittel-Schneider, Sarah and Gurke, Robert and Geisslinger, Gerd and Reif, Andreas and Tegeder, Irmgard}, title = {Sphingolipid and endocannabinoid profiles in adult attention deficit hyperactivity disorder}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {9}, issn = {2227-9059}, doi = {10.3390/biomedicines9091173}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246080}, year = {2021}, abstract = {Genes encoding endocannabinoid and sphingolipid metabolism pathways were suggested to contribute to the genetic risk towards attention deficit hyperactivity disorder (ADHD). The present pilot study assessed plasma concentrations of candidate endocannabinoids, sphingolipids and ceramides in individuals with adult ADHD in comparison with healthy controls and patients with affective disorders. Targeted lipid analyses of 23 different lipid species were performed in 71 mental disorder patients and 98 healthy controls (HC). The patients were diagnosed with adult ADHD (n = 12), affective disorder (major depression, MD n = 16 or bipolar disorder, BD n = 6) or adult ADHD with comorbid affective disorders (n = 37). Canonical discriminant analysis and CHAID analyses were used to identify major components that predicted the diagnostic group. ADHD patients had increased plasma concentrations of sphingosine-1-phosphate (S1P d18:1) and sphinganine-1-phosphate (S1P d18:0). In addition, the endocannabinoids, anandamide (AEA) and arachidonoylglycerol were increased. MD/BD patients had increased long chain ceramides, most prominently Cer22:0, but low endocannabinoids in contrast to ADHD patients. Patients with ADHD and comorbid affective disorders displayed increased S1P d18:1 and increased Cer22:0, but the individual lipid levels were lower than in the non-comorbid disorders. Sphingolipid profiles differ between patients suffering from ADHD and affective disorders, with overlapping patterns in comorbid patients. The S1P d18:1 to Cer22:0 ratio may constitute a diagnostic or prognostic tool.}, language = {en} } @article{DechHolzwarthAsametal.2021, author = {Dech, Stefan and Holzwarth, Stefanie and Asam, Sarah and Andresen, Thorsten and Bachmann, Martin and Boettcher, Martin and Dietz, Andreas and Eisfelder, Christina and Frey, Corinne and Gesell, Gerhard and Gessner, Ursula and Hirner, Andreas and Hofmann, Matthias and Kirches, Grit and Klein, Doris and Klein, Igor and Kraus, Tanja and Krause, Detmar and Plank, Simon and Popp, Thomas and Reinermann, Sophie and Reiners, Philipp and Roessler, Sebastian and Ruppert, Thomas and Scherbachenko, Alexander and Vignesh, Ranjitha and Wolfmueller, Meinhard and Zwenzner, Hendrik and Kuenzer, Claudia}, title = {Potential and challenges of harmonizing 40 years of AVHRR data: the TIMELINE experience}, series = {Remote Sensing}, volume = {13}, journal = {Remote Sensing}, number = {18}, issn = {2072-4292}, doi = {10.3390/rs13183618}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246134}, year = {2021}, abstract = {Earth Observation satellite data allows for the monitoring of the surface of our planet at predefined intervals covering large areas. However, there is only one medium resolution sensor family in orbit that enables an observation time span of 40 and more years at a daily repeat interval. This is the AVHRR sensor family. If we want to investigate the long-term impacts of climate change on our environment, we can only do so based on data that remains available for several decades. If we then want to investigate processes with respect to climate change, we need very high temporal resolution enabling the generation of long-term time series and the derivation of related statistical parameters such as mean, variability, anomalies, and trends. The challenges to generating a well calibrated and harmonized 40-year-long time series based on AVHRR sensor data flown on 14 different platforms are enormous. However, only extremely thorough pre-processing and harmonization ensures that trends found in the data are real trends and not sensor-related (or other) artefacts. The generation of European-wide time series as a basis for the derivation of a multitude of parameters is therefore an extremely challenging task, the details of which are presented in this paper.}, language = {en} } @article{HennigDjakovicDoelkenetal.2021, author = {Hennig, Thomas and Djakovic, Lara and D{\"o}lken, Lars and Whisnant, Adam W.}, title = {A Review of the Multipronged Attack of Herpes Simplex Virus 1 on the Host Transcriptional Machinery}, series = {Viruses}, volume = {13}, journal = {Viruses}, number = {9}, issn = {1999-4915}, doi = {10.3390/v13091836}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246165}, year = {2021}, abstract = {During lytic infection, herpes simplex virus (HSV) 1 induces a rapid shutoff of host RNA synthesis while redirecting transcriptional machinery to viral genes. In addition to being a major human pathogen, there is burgeoning clinical interest in HSV as a vector in gene delivery and oncolytic therapies, necessitating research into transcriptional control. This review summarizes the array of impacts that HSV has on RNA Polymerase (Pol) II, which transcribes all mRNA in infected cells. We discuss alterations in Pol II holoenzymes, post-translational modifications, and how viral proteins regulate specific activities such as promoter-proximal pausing, splicing, histone repositioning, and termination with respect to host genes. Recent technological innovations that have reshaped our understanding of previous observations are summarized in detail, along with specific research directions and technical considerations for future studies.}, language = {en} } @article{Dunkel2021, author = {Dunkel, Franz G.}, title = {Sieben neue Arten aus dem Schweizer Ranunculus auricomus-Komplex}, series = {Forum Geobotanicum}, volume = {10}, journal = {Forum Geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2021.0825}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243782}, pages = {1-27}, year = {2021}, abstract = {Die Arten des Schweizer Ranunculus-auricomus-Komplexes sind nur zu einem Teil bekannt. Zur vollst{\"a}ndigeren Erfassung des Komplexes wurden Exkursionen in die s{\"u}dwestliche und {\"o}stliche Schweiz unternommen. Es wurden sieben neue Arten entdeckt, die hier beschrieben und abgebildet sind. Ihre Taxonomie und Gef{\"a}hrdung wird diskutiert. R. chalarocarpus W. Koch ex Dunkel ist bereits bei Koch provisorisch erw{\"a}hnt, R. clavicornis Dunkel wird nun g{\"u}ltig beschrieben. Beide Arten sind aufgrund ihres Vorkommens in Auw{\"a}ldern und feuchten Laubw{\"a}ldern stark gef{\"a}hrdet, R. clavicornis sogar fast ausgestorben. Der neu beschriebene R. thurgoviae kommt im Osten der Schweiz vor (Kanton Thurgau). Die bislang bekannte Verbreitung von R. allobrogorum Dunkel, R. crenulatus Dunkel, R. genevensis Dunkel und R. lineatus ist fast vollst{\"a}ndig auf den Kanton Genf beschr{\"a}nkt. Die Arten des Ranunculus auricomus-Komplexes sind ein sensibler Indikator f{\"u}r Ver{\"a}nderungen der Vegetation und Umwelt und sollten diesbez{\"u}glich deutlich mehr Gewicht bekommen.}, subject = {Ranunculus}, language = {de} } @article{Schierbaum2021, author = {Schierbaum, Sonja}, title = {Crusius {\"u}ber die Vern{\"u}nftigkeit des Wollens und die Rolle des Urteilens}, series = {Deutsche Zeitschrift f{\"u}r Philosophie}, volume = {69}, journal = {Deutsche Zeitschrift f{\"u}r Philosophie}, number = {4}, issn = {2192-1482}, doi = {10.1515/dzph-2021-0051}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245582}, pages = {607 -- 618}, year = {2021}, abstract = {In this paper, I consider the relevance of judgment for practical considerations by discussing Christian August Crusius's conception of rational desire. According to my interpretation of Crusius's distinction between rational and non-rational desire, we are responsible at least for our rational desires insofar as we can control them. And we can control our rational desires by judging whether what we want complies with our human nature. It should become clear that Crusius's conception of rational desire is normative in that we necessarily desire things that are compatible with our nature, such as our own perfection. Therefore, a desire is rational if the desired object is apt to satisfy the desires compatible with our nature. From a contemporary perspective, such a normative conception of rational desire might not appear very attractive; it is apt, however, to stimulate a debate on the normative criteria and the role of judgment for rational desire, which is the ultimate aim of this paper.}, language = {de} } @article{SchroerToussaintBachmannetal.2021, author = {Schroer, Guido and Toussaint, Val{\´e}rie and Bachmann, Stephanie and P{\"o}ppler, Ann-Christin and Gierlich, Christian Henning and Delidovich, Irina}, title = {Functional Phenylboronate Polymers for the Recovery of Diols, Sugar Alcohols, and Saccharides from Aqueous Solution}, series = {ChemSusChem}, volume = {14}, journal = {ChemSusChem}, number = {23}, doi = {10.1002/cssc.202002887}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239889}, pages = {5207 -- 5215}, year = {2021}, abstract = {The ongoing transition from fossil to renewable feedstocks demands new efficient processes for an economically viable production of biomass-derived commodities and fine chemicals. Novel energy- and material-efficient product purification and separation will play a crucial role due to altered product and feed composition. The present study comprises the synthesis and tests of cross-linked p-vinylphenylboronate polymers for the separation of 18 diols, sugar alcohols, and saccharides, which can be obtained during biomass processing. The separation was based on molecular recognition, that is, esterification of the phenylboronate with vicinal diols. A correlation of the molecular complexation constant, the polymer swelling, and the maximum adsorption capacity was found. The adsorption curves over time were recorded. Preliminary results on competitive adsorption of binary mixtures showed a high potential for the separation of substrates with significantly different complexation constants. Desorption tests implied easier desorption of substrates that only adsorb on the outer polymer shell.}, language = {en} } @article{ShityakovHayashiStoerketal.2021, author = {Shityakov, Sergey and Hayashi, Kentaro and St{\"o}rk, Stefan and Scheper, Verena and Lenarz, Thomas and F{\"o}rster, Carola Y.}, title = {The conspicuous link between ear, brain and heart - Could neurotrophin-treatment of age-related hearing loss help prevent Alzheimer's disease and associated amyloid cardiomyopathy?}, series = {Biomolecules}, volume = {11}, journal = {Biomolecules}, number = {6}, issn = {2218-273X}, doi = {10.3390/biom11060900}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241084}, year = {2021}, abstract = {Alzheimer's disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction and cognitive decline. While the deposition of amyloid β peptide (Aβ) and the formation of neurofibrillary tangles (NFTs) are the pathological hallmarks of AD-affected brains, the majority of cases exhibits a combination of comorbidities that ultimately lead to multi-organ failure. Of particular interest, it can be demonstrated that Aβ pathology is present in the hearts of patients with AD, while the formation of NFT in the auditory system can be detected much earlier than the onset of symptoms. Progressive hearing impairment may beget social isolation and accelerate cognitive decline and increase the risk of developing dementia. The current review discusses the concept of a brain-ear-heart axis by which Aβ and NFT inhibition could be achieved through targeted supplementation of neurotrophic factors to the cochlea and the brain. Such amyloid inhibition might also indirectly affect amyloid accumulation in the heart, thus reducing the risk of developing AD-associated amyloid cardiomyopathy and cardiovascular disease.}, language = {en} } @article{WeissHeinHewig2021, author = {Weiß, Martin and Hein, Grit and Hewig, Johannes}, title = {Between joy and sympathy: Smiling and sad recipient faces increase prosocial behavior in the dictator game}, series = {International Journal of Environmental Research and Public Health}, volume = {18}, journal = {International Journal of Environmental Research and Public Health}, number = {11}, doi = {10.3390/ijerph18116172}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241106}, year = {2021}, abstract = {In human interactions, the facial expression of a bargaining partner may contain relevant information that affects prosocial decisions. We were interested in whether facial expressions of the recipient in the dictator game influence dictators´ ehavior. To test this, we conducted an online study (n = 106) based on a modified version of a dictator game. The dictators allocated money between themselves and another person (recipient), who had no possibility to respond to the dictator. Importantly, before the allocation decision, the dictator was presented with the facial expression of the recipient (angry, disgusted, sad, smiling, or neutral). The results showed that dictators sent more money to recipients with sad or smiling facial expressions and less to recipients with angry or disgusted facial expressions compared with a neutral facial expression. Moreover, based on the sequential analysis of the decision and the interaction partner in the preceding trial, we found that decision-making depends upon previous interactions.}, language = {en} } @article{LillaKesslerWeilandetal.2021, author = {Lilla, Nadine and Kessler, Almuth F. and Weiland, Judith and Ernestus, Ralf-Ingo and Westermaier, Thomas}, title = {Case Report: A Case Series Using Natural Anatomical Gaps — Posterior Cervical Approach to Skull Base and Upper Craniocervical Meningiomas Without Bone Removal}, series = {Frontiers in Surgery}, volume = {8}, journal = {Frontiers in Surgery}, issn = {2296-875X}, doi = {10.3389/fsurg.2021.666699}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244613}, year = {2021}, abstract = {Background: Removal of anteriorly located tumors of the upper cervical spine and craniovertebral junction (CVJ) is a particular surgical challenge. Extensive approaches are associated with pain, restricted mobility of neck and head and, in case of foramen magnum and clivus tumors, with retraction of brainstem and cerebellum. Methods: Four symptomatic patients underwent resection of anteriorly located upper cervical and lower clivus meningiomas without laminotomy or craniotomy using a minimally invasive posterior approach. Distances of natural gaps between C0/C1, C1/C2, and C2/C3 were measured using preoperative CT scans and intraoperative lateral x-rays. Results: In all patients, safe and complete resection was conducted by the opening of the dura between C0/C1, C1/C2, and C2/C3, respectively. There were no surgical complications. Local pain was reported as very moderate by all patients and postoperative recovery was extremely fast. All tumors had a rather soft consistency, allowing mass reduction prior to removal of the tumor capsule and were well separable from lower cranial nerves and vascular structures. Conclusion: If tumor consistency is appropriate for careful mass reduction before removal of the tumor capsule and if tumor margins are not firmly attached to crucial structures, then upper cervical, foramen magnum, and lower clivus meningiomas can be safely and completely removed through natural gaps in the CVJ region. Both prerequisites usually become clear early during surgery. Thus, this tumor entity may be planned using this minimally invasive approach and may be extended if tumor consistency turns out to be less unfavorable for resection or if crucial structures cannot be easily separated from the tumor.}, language = {en} } @article{DekantLangerLuppetal.2021, author = {Dekant, Raphael and Langer, Michael and Lupp, Maria and Adaku Chilaka, Cynthia and Mally, Angela}, title = {In vitro and in vivo analysis of ochratoxin A-derived glucuronides and mercapturic acids as biomarkers of exposure}, series = {Toxins}, volume = {13}, journal = {Toxins}, number = {8}, issn = {2072-6651}, doi = {10.3390/toxins13080587}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245146}, year = {2021}, abstract = {Ochratoxin A (OTA) is a widespread food contaminant, with exposure estimated to range from 0.64 to 17.79 ng/kg body weight (bw) for average consumers and from 2.40 to 51.69 ng/kg bw per day for high consumers. Current exposure estimates are, however, associated with considerable uncertainty. While biomarker-based approaches may contribute to improved exposure assessment, there is yet insufficient data on urinary metabolites of OTA and their relation to external dose to allow reliable estimates of daily intake. This study was designed to assess potential species differences in phase II biotransformation in vitro and to establish a correlation between urinary OTA-derived glucuronides and mercapturic acids and external exposure in rats in vivo. In vitro analyses of OTA metabolism using the liver S9 of rats, humans, rabbits and minipigs confirmed formation of an OTA glucuronide but provided no evidence for the formation of OTA-derived mercapturic acids to support their use as biomarkers. Similarly, OTA-derived mercapturic acids were not detected in urine of rats repeatedly dosed with OTA, while indirect analysis using enzymatic hydrolysis of the urine samples prior to LC-MS/MS established a linear relationship between urinary glucuronide excretion and OTA exposure. These results support OTA-derived glucuronides but not mercapturic acids as metabolites suitable for biomonitoring.}, language = {en} } @article{ScheinerLimMeixneretal.2021, author = {Scheiner, Ricarda and Lim, Kayun and Meixner, Marina D. and Gabel, Martin S.}, title = {Comparing the appetitive learning performance of six European honeybee subspecies in a common apiary}, series = {Insects}, volume = {12}, journal = {Insects}, number = {9}, issn = {2075-4450}, doi = {10.3390/insects12090768}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245180}, year = {2021}, abstract = {The Western honeybee (Apis mellifera L.) is one of the most widespread insects with numerous subspecies in its native range. How far adaptation to local habitats has affected the cognitive skills of the different subspecies is an intriguing question that we investigate in this study. Naturally mated queens of the following five subspecies from different parts of Europe were transferred to Southern Germany: A. m. iberiensis from Portugal, A. m. mellifera from Belgium, A. m. macedonica from Greece, A. m. ligustica from Italy, and A. m. ruttneri from Malta. We also included the local subspecies A. m. carnica in our study. New colonies were built up in a common apiary where the respective queens were introduced. Worker offspring from the different subspecies were compared in classical olfactory learning performance using the proboscis extension response. Prior to conditioning, we measured individual sucrose responsiveness to investigate whether possible differences in learning performances were due to differential responsiveness to the sugar water reward. Most subspecies did not differ in their appetitive learning performance. However, foragers of the Iberian honeybee, A. m. iberiensis, performed significantly more poorly, despite having a similar sucrose responsiveness. We discuss possible causes for the poor performance of the Iberian honeybees, which may have been shaped by adaptation to the local habitat.}, language = {en} } @article{LauruschkatEtterSchnacketal.2021, author = {Lauruschkat, Chris D. and Etter, Sonja and Schnack, Elisabeth and Ebel, Frank and Sch{\"a}uble, Sascha and Page, Lukas and R{\"u}mens, Dana and Dragan, Mariola and Schlegel, Nicolas and Panagiotou, Gianni and Kniemeyer, Olaf and Brakhage, Axel A. and Einsele, Hermann and Wurster, Sebastian and Loeffler, Juergen}, title = {Chronic occupational mold exposure drives expansion of Aspergillus-reactive type 1 and type 2 T-helper cell responses}, series = {Journal of Fungi}, volume = {7}, journal = {Journal of Fungi}, number = {9}, issn = {2309-608X}, doi = {10.3390/jof7090698}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245202}, year = {2021}, abstract = {Occupational mold exposure can lead to Aspergillus-associated allergic diseases including asthma and hypersensitivity pneumonitis. Elevated IL-17 levels or disbalanced T-helper (Th) cell expansion were previously linked to Aspergillus-associated allergic diseases, whereas alterations to the Th cell repertoire in healthy occupationally exposed subjects are scarcely studied. Therefore, we employed functional immunoassays to compare Th cell responses to A. fumigatus antigens in organic farmers, a cohort frequently exposed to environmental molds, and non-occupationally exposed controls. Organic farmers harbored significantly higher A. fumigatus-specific Th-cell frequencies than controls, with comparable expansion of Th1- and Th2-cell frequencies but only slightly elevated Th17-cell frequencies. Accordingly, Aspergillus antigen-induced Th1 and Th2 cytokine levels were strongly elevated, whereas induction of IL-17A was minimal. Additionally, increased levels of some innate immune cell-derived cytokines were found in samples from organic farmers. Antigen-induced cytokine release combined with Aspergillus-specific Th-cell frequencies resulted in high classification accuracy between organic farmers and controls. Aspf22, CatB, and CipC elicited the strongest differences in Th1 and Th2 responses between the two cohorts, suggesting these antigens as potential candidates for future bio-effect monitoring approaches. Overall, we found that occupationally exposed agricultural workers display a largely balanced co-expansion of Th1 and Th2 immunity with only minor changes in Th17 responses.}, language = {en} } @article{TeichmannWicke2021, author = {Teichmann, Christoph and Wicke, Hartmut}, title = {Zukunftsmodell „Hybride Hauptversammlung"}, series = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, volume = {50}, journal = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, number = {2}, issn = {1612-7048}, doi = {10.1515/zgr-2021-0007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244820}, pages = {173 -- 200}, year = {2021}, abstract = {Die Corona-Pandemie hat dem Aktienrecht einen unerwarteten Modernisierungsschub verliehen. Der Gesetzgeber schuf in Windeseile eine zeitlich begrenzte rechtliche Grundlage f{\"u}r die rein virtuelle Hauptversammlung. Die Gesellschaften haben diese neue rechtliche und technische Herausforderung gut gemeistert. Das legt die Frage nahe, ob der Gesetzgeber nicht auch f{\"u}r die Zukunft eine rein virtuelle Hauptversammlung in rechtlich abgesicherter Form erm{\"o}glichen sollte. Dabei m{\"u}ssen die Rechte der Aktion{\"a}re umfassend gewahrt bleiben. Zugleich sollten die Defizite der Hauptversammlungskultur behoben werden, die heute nur noch in Grenzen als Forum der freien Diskussion zwischen Aktion{\"a}ren und Unternehmensleitung angesehen werden kann. Das Beste aus zwei Welten liegt nach der hier entfalteten Konzeption in einer hybriden Versammlung, die eine Pr{\"a}senzversammlung mit qualifizierten Teilnahmevoraussetzungen und eine elektronische Teilnahme aller {\"u}brigen Aktion{\"a}re erm{\"o}glicht.}, language = {de} } @article{OpitzSchuwerkPaulusetal.2021, author = {Opitz, Timm and Schuwerk, Tobias and Paulus, Markus and Kloo, Daniela and Osterhaus, Christopher and Lesch, Klaus-Peter and Sodian, Beate}, title = {No links between genetic variation and developing theory of mind: A preregistered replication attempt of candidate gene studies}, series = {Developmental Science}, volume = {24}, journal = {Developmental Science}, number = {5}, doi = {10.1111/desc.13100}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238812}, year = {2021}, abstract = {Genetic variability is being discussed as a source of inter-individual differences in Theory of Mind development. Previous studies documented an association between variations in DRD4 VNTR 48 bp, OXTR rs53576, COMT rs4680, and Theory of Mind task performance. As empirical evidence on these associations is sparse, we conducted a preregistered replication attempt of a study reporting a link between DRD4 VNTR 48 bp and false belief understanding in 50-month-old children [Lackner, C., Sabbagh, M. A., Hallinan, E., Liu, X., \& Holden, J. J. (2012). Developmental Science, 15(2), 272-280.]. Additionally, we attempted a replication of studies on the role of OXTR rs53576 and COMT rs4680 in Theory of Mind. In both replication attempts, we did not find any evidence for associations between the sampled genetic markers and Theory of Mind ability in a series of analyses. Extending the replication attempt of Lackner et al., we employed longitudinal data from several tasks and measurement points, which allowed us to run follow-up robustness checks with more reliable scores. These extensive analyses corroborated our null finding. This comprehensive non-replication is important to balance current research on genetic markers of Theory of Mind. In a combined evaluation of our own and previous studies, we point to substantial methodological issues that research on the genetic basis of Theory of Mind development faces. We conclude that these limitations currently prevent firm conclusions on genetic influences on Theory of Mind development.}, language = {en} } @article{LauererTiedemannPolaketal.2021, author = {Lauerer, Elias and Tiedemann, Elena and Polak, Thomas and Simmenroth, Anne}, title = {Can smoking cessation be taught online? A prospective study comparing e-learning and role-playing in medical education}, series = {International Journal of Medical Education}, volume = {12}, journal = {International Journal of Medical Education}, doi = {10.5116/ijme.5ff9.bccc}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230056}, pages = {12-21}, year = {2021}, abstract = {Objectives: We compared the effect of different didactic formats - e - learning and role-playing - on medical students' knowledge and counselling skills in smoking cessation training. Methods: At a German medical school, 145 third-year students were randomly allocated to attend an online course with video examples or an attendance course with role-playing. Students were trained in smoking cessation counselling according to the 5A's (ask, advise, assess, assist, arrange) for approximately 90 minutes. Practical skills were measured in an objective structured clinical examination (OSCE) and represent the primary endpoint of this prospective comparative study. Additionally, changes in theoretic knowledge were assessed by pre - and post - interventional questionnaires and a final written exam. Results: In the OSCE, overall scores were higher in the attendance group (Mdn=70.8 \% vs. 62.8 \%; U=119; p=.087, n=36), but a statistical advantage was only found in one single counselling sequence ("Assist": Mdn=66.7 \% vs. 51.4 \%; p = .049) and the rating of the standardised patients (M=4.7 vs. 4.2 out of 5 points, t(27.836)=2.0, p=.028). Students' results (n=130) from self-assessment and written exams suggest that both approaches are equally well suited to increase theoretical knowledge. The online course was more time efficient (90 vs. 73 minutes). Conclusions: Seminar and web-based training seem equally well suited for transferring knowledge and skills on tobacco cessation counselling. Considering their particular strengths, these two teaching approaches could be combined.}, language = {en} } @article{AntonRoessler2021, author = {Anton, Sylvia and R{\"o}ssler, Wolfgang}, title = {Plasticity and modulation of olfactory circuits in insects}, series = {Cell and Tissue Research}, volume = {383}, journal = {Cell and Tissue Research}, issn = {0302-766X}, doi = {10.1007/s00441-020-03329-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235820}, pages = {149-164}, year = {2021}, abstract = {Olfactory circuits change structurally and physiologically during development and adult life. This allows insects to respond to olfactory cues in an appropriate and adaptive way according to their physiological and behavioral state, and to adapt to their specific abiotic and biotic natural environment. We highlight here findings on olfactory plasticity and modulation in various model and non-model insects with an emphasis on moths and social Hymenoptera. Different categories of plasticity occur in the olfactory systems of insects. One type relates to the reproductive or feeding state, as well as to adult age. Another type of plasticity is context-dependent and includes influences of the immediate sensory and abiotic environment, but also environmental conditions during postembryonic development, periods of adult behavioral maturation, and short- and long-term sensory experience. Finally, plasticity in olfactory circuits is linked to associative learning and memory formation. The vast majority of the available literature summarized here deals with plasticity in primary and secondary olfactory brain centers, but also peripheral modulation is treated. The described molecular, physiological, and structural neuronal changes occur under the influence of neuromodulators such as biogenic amines, neuropeptides, and hormones, but the mechanisms through which they act are only beginning to be analyzed.}, language = {en} } @article{FreimannDierkesPetermannetal.2021, author = {Freimann, A. and Dierkes, M. and Petermann, T. and Liman, C. and Kempf, F. and Schilling, K.}, title = {ESTNeT: a discrete event simulator for space-terrestrial networks}, series = {CEAS Space Journal}, volume = {13}, journal = {CEAS Space Journal}, issn = {1868-2502}, doi = {10.1007/s12567-020-00316-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235835}, pages = {39-49}, year = {2021}, abstract = {The capabilities of small satellites have improved significantly in recent years. Specifically multi-satellite systems become increasingly popular, since they allow the support of new applications. The development and testing of these multi-satellite systems is a new challenge for engineers and requires the implementation of appropriate development and testing environments. In this paper, a modular network simulation framework for space-terrestrial systems is presented. It enables discrete event simulations for the development and testing of communication protocols, as well as mission-based analysis of other satellite system aspects, such as power supply and attitude control. ESTNeT is based on the discrete event simulator OMNeT++ and will be released under an open source license.}, language = {en} } @article{StrzalkowskaStrzalkowskiAlYousefetal.2021, author = {Strzalkowska, A. and Strzalkowski, P. and Al Yousef, Y. and Grehn, F. and Hillenkamp, J. and Loewen, Nils A.}, title = {Exact matching of trabectome-mediated ab interno trabeculectomy to conventional trabeculectomy with mitomycin C followed for 2 years}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {259}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, issn = {0721-832X}, doi = {10.1007/s00417-020-05031-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235224}, pages = {963-970}, year = {2021}, abstract = {Purpose We used exact matching for a highly balanced comparison of ab interno trabeculectomy (AIT) with the trabectome to trabeculectomy with mitomycin C (TRAB). Methods A total of 5485 patients who underwent AIT were exact-matched to 196 TRAB patients by baseline intraocular pressure (IOP), number of glaucoma medications, and glaucoma type. Nearest-neighbor-matching was applied to age. Success was defined as a final IOP of less than 21 mmHg, IOP reduction of at least 20\% reduction from baseline, and no secondary surgical interventions. Outcomes were measured at 1, 3, 6, 12, 18, and 24 months. Results A total of 165 AIT could be matched to 165 TRAB. The mean baseline IOP was 22.3 ± 5.6 mmHg, and the baseline number of glaucoma medications was 2.7 ± 1.1 in both groups. At 24 months, IOP was reduced to 15.8 ± 5.2 mmHg in AIT and 12.4 ± 4.7 mmHg in TRAB. IOP was lower than baseline at all visits (p < 0.01) and lower in TRAB than AIT (p < 0.01). Glaucoma medications were reduced to 2.1 ± 1.3 in AIT and 0.2 ± 0.8 in TRAB. Compared to baseline, patients used fewer drops postoperatively (p < 0.01) and more infrequently in TRAB than in AIT (p > 0.01). Secondary surgical interventions had the highest impact on success and became necessary in 15 AIT and 59 TRAB patients. Thirty-two challenging events occurred in TRAB and none in AIT. Conclusion Both AIT and TRAB reduced IOP and medications. This reduction was more significant in TRAB but at the expense of four times as many secondary interventions.}, language = {en} } @article{WeichWernerBucketal.2021, author = {Weich, Alexander and Werner, Rudolf A. and Buck, Andreas K. and Hartrampf, Philipp E. and Serfling, Sebastian E. and Scheurlen, Michael and Wester, Hans-J{\"u}rgen and Meining, Alexander and Kircher, Stefan and Higuchi, Takahiro and Pomper, Martin G. and Rowe, Steven P. and Lapa, Constantin and Kircher, Malte}, title = {CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas}, series = {Diagnostics}, volume = {11}, journal = {Diagnostics}, number = {4}, issn = {2075-4418}, doi = {10.3390/diagnostics11040605}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234231}, year = {2021}, abstract = {We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-na{\"i}ve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.}, language = {en} } @article{BachmannSchrederEngelhardtetal.2021, author = {Bachmann, Friederike and Schreder, Martin and Engelhardt, Monika and Langer, Christian and Wolleschak, Denise and M{\"u}gge, Lars Olof and D{\"u}rk, Heinz and Sch{\"a}fer-Eckart, Kerstin and Blau, Igor Wolfgang and Gramatzki, Martin and Liebisch, Peter and Grube, Matthias and Metzler, Ivana v. and Bassermann, Florian and Metzner, Bernd and R{\"o}llig, Christoph and Hertenstein, Bernd and Khandanpour, Cyrus and Dechow, Tobias and Hebart, Holger and Jung, Wolfram and Theurich, Sebastian and Maschmeyer, Georg and Salwender, Hans and Hess, Georg and Bittrich, Max and Rasche, Leo and Brioli, Annamaria and Eckardt, Kai-Uwe and Straka, Christian and Held, Swantje and Einsele, Hermann and Knop, Stefan}, title = {Kinetics of renal function during induction in newly diagnosed multiple myeloma: results of two prospective studies by the German Myeloma Study Group DSMM}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {6}, issn = {2072-6694}, doi = {10.3390/cancers13061322}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234139}, year = {2021}, abstract = {Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3\% at baseline to 1.9\% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49\% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined "renal complete response (CRrenal)" was achieved in 17/25 (68\%) pts after VCD, 12/19 (63\%) after RAD, and 14/27 (52\%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment "renal fitness" in the latter group.}, language = {en} } @article{EgenolfAltenschildescheKressetal.2021, author = {Egenolf, Nadine and Altenschildesche, Caren Meyer zu and Kreß, Luisa and Eggermann, Katja and Namer, Barbara and Gross, Franziska and Klitsch, Alexander and Malzacher, Tobias and Kampik, Daniel and Malik, Rayaz A. and Kurth, Ingo and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan}, title = {Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study}, series = {Therapeutic Advances in Neurological Disorders}, volume = {14}, journal = {Therapeutic Advances in Neurological Disorders}, issn = {1756-2864}, doi = {10.1177/17562864211004318}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232019}, year = {2021}, abstract = {Background and aims: Small fiber neuropathy (SFN) is increasingly suspected in patients with pain of uncertain origin, and making the diagnosis remains a challenge lacking a diagnostic gold standard. Methods: In this case-control study, we prospectively recruited 86 patients with a medical history and clinical phenotype suggestive of SFN. Patients underwent neurological examination, quantitative sensory testing (QST), and distal and proximal skin punch biopsy, and were tested for pain-associated gene loci. Fifty-five of these patients additionally underwent pain-related evoked potentials (PREP), corneal confocal microscopy (CCM), and a quantitative sudomotor axon reflex test (QSART). Results: Abnormal distal intraepidermal nerve fiber density (IENFD) (60/86, 70\%) and neurological examination (53/86, 62\%) most frequently reflected small fiber disease. Adding CCM and/or PREP further increased the number of patients with small fiber impairment to 47/55 (85\%). Genetic testing revealed potentially pathogenic gene variants in 14/86 (16\%) index patients. QST, QSART, and proximal IENFD were of lower impact. Conclusion: We propose to diagnose SFN primarily based on the results of neurological examination and distal IENFD, with more detailed phenotyping in specialized centers.}, language = {en} } @article{KunzHirthSchweitzeretal.2021, author = {Kunz, Felix and Hirth, Matthias and Schweitzer, Tilmann and Linz, Christian and Goetz, Bernhard and Stellzig-Eisenhauer, Angelika and Borchert, Kathrin and B{\"o}hm, Hartmut}, title = {Subjective perception of craniofacial growth asymmetries in patients with deformational plagiocephaly}, series = {Clinical Oral Investigations}, volume = {25}, journal = {Clinical Oral Investigations}, issn = {1432-6981}, doi = {10.1007/s00784-020-03417-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232803}, pages = {525-537}, year = {2021}, abstract = {Objectives The present investigation aimed to evaluate the subjective perception of deformational cranial asymmetries by different observer groups and to compare these subjective perceptions with objective parameters. Materials and methods The 3D datasets of ten infants with different severities of deformational plagiocephaly (DP) were presented to 203 observers, who had been subdivided into five different groups (specialists, pediatricians, medical doctors (not pediatricians), parents of infants with DP, and laypersons). The observers rated their subjective perception of the infants' cranial asymmetries using a 4-point Likert-type scale. The ratings from the observer groups were compared with one another using a multilevel modelling linear regression analysis and were correlated with four commonly used parameters to objectively quantify the cranial asymmetries. Results No significant differences were found between the ratings of the specialists and those of the parents of infants with DP, but both groups provided significantly more asymmetric ratings than did pediatricians, medical doctors, or laypersons. Moreover, the subjective perception of cranial asymmetries correlated significantly with commonly used parameters for objectively quantifying cranial asymmetries. Conclusions Our results demonstrate that different observer groups perceive the severity of cranial asymmetries differently. Pediatricians' more moderate perception of cranial asymmetries may reduce the likelihood of parents to seek therapeutic interventions for their infants. Moreover, we identified some objective symmetry-related parameters that correlated strongly with the observers' subjective perceptions. Clinical relevance Knowledge about these findings is important for clinicians when educating parents of infants with DP about the deformity.}, language = {en} } @article{MerzMerzKirchneretal.2021, author = {Merz, Viktor and Merz, Julia and Kirchner, Maximilian and Lenhart, Julian and Marder, Todd B. and Krueger, Anke}, title = {Pyrene-Based "Turn-Off" Probe with Broad Detection Range for Cu\(^{2+}\), Pb\(^{2+}\) and Hg\(^{2+}\) Ions}, series = {Chemistry—A European Journal}, volume = {27}, journal = {Chemistry—A European Journal}, number = {31}, doi = {10.1002/chem.202100594}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256803}, pages = {8118-8126}, year = {2021}, abstract = {Detection of metals in different environments with high selectivity and specificity is one of the prerequisites of the fight against environmental pollution with these elements. Pyrenes are well suited for the fluorescence sensing in different media. The applied sensing principle typically relies on the formation of intra- and intermolecular excimers, which is however limiting the sensitivity range due to masking of e. g. quenching effects by the excimer emission. Herein we report a highly selective, structurally rigid chemical sensor based on the monomer fluorescence of pyrene moieties bearing triazole groups. This sensor can quantitatively detect Cu\(^{2+}\), Pb\(^{2+}\) and Hg\(^{2+}\) in organic solvents over a broad concentrations range, even in the presence of ubiquitous ions such as Na\(^{+}\), K\(^{+}\), Ca\(^{2+}\) and Mg\(^{2+}\). The strongly emissive sensor's fluorescence with a long lifetime of 165 ns is quenched by a 1 : 1 complex formation upon addition of metal ions in acetonitrile. Upon addition of a tenfold excess of the metal ion to the sensor, agglomerates with a diameter of about 3 nm are formed. Due to complex interactions in the system, conventional linear correlations are not observed for all concentrations. Therefore, a critical comparison between the conventional Job plot interpretation, the method of Benesi-Hildebrand, and a non-linear fit is presented. The reported system enables the specific and robust sensing of medically and environmentally relevant ions in the health-relevant nM range and could be used e. g. for the monitoring of the respective ions in waste streams.}, language = {en} } @article{AnkenbrandLohrSchloetelburgetal.2021, author = {Ankenbrand, Markus Johannes and Lohr, David and Schl{\"o}telburg, Wiebke and Reiter, Theresa and Wech, Tobias and Schreiber, Laura Maria}, title = {Deep learning-based cardiac cine segmentation: Transfer learning application to 7T ultrahigh-field MRI}, series = {Magnetic Resonance in Medicine}, volume = {86}, journal = {Magnetic Resonance in Medicine}, number = {4}, doi = {10.1002/mrm.28822}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257604}, pages = {2179-2191}, year = {2021}, abstract = {Purpose Artificial neural networks show promising performance in automatic segmentation of cardiac MRI. However, training requires large amounts of annotated data and generalization to different vendors, field strengths, sequence parameters, and pathologies is limited. Transfer learning addresses this challenge, but specific recommendations regarding type and amount of data required is lacking. In this study, we assess data requirements for transfer learning to experimental cardiac MRI at 7T where the segmentation task can be challenging. In addition, we provide guidelines, tools, and annotated data to enable transfer learning approaches by other researchers and clinicians. Methods A publicly available segmentation model was used to annotate a publicly available data set. This labeled data set was subsequently used to train a neural network for segmentation of left ventricle and myocardium in cardiac cine MRI. The network is used as starting point for transfer learning to 7T cine data of healthy volunteers (n = 22; 7873 images) by updating the pre-trained weights. Structured and random data subsets of different sizes were used to systematically assess data requirements for successful transfer learning. Results Inconsistencies in the publically available data set were corrected, labels created, and a neural network trained. On 7T cardiac cine images the model pre-trained on public imaging data, acquired at 1.5T and 3T, achieved DICE\(_{LV}\) = 0.835 and DICE\(_{MY}\) = 0.670. Transfer learning using 7T cine data and ImageNet weight initialization improved model performance to DICE\(_{LV}\) = 0.900 and DICE\(_{MY}\) = 0.791. Using only end-systolic and end-diastolic images reduced training data by 90\%, with no negative impact on segmentation performance (DICE\(_{LV}\) = 0.908, DICE\(_{MY}\) = 0.805). Conclusions This work demonstrates and quantifies the benefits of transfer learning for cardiac cine image segmentation. We provide practical guidelines for researchers planning transfer learning projects in cardiac MRI and make data, models, and code publicly available.}, language = {en} } @article{MoraisPasechnikPorod2021, author = {Morais, Ant{\´o}nio P. and Pasechnik, Roman and Porod, Werner}, title = {Grand Unified origin of gauge interactions and families replication in the Standard Model}, series = {Universe}, volume = {7}, journal = {Universe}, number = {12}, issn = {2218-1997}, doi = {10.3390/universe7120461}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250237}, year = {2021}, abstract = {The tremendous phenomenological success of the Standard Model (SM) suggests that its flavor structure and gauge interactions may not be arbitrary but should have a fundamental first-principle explanation. In this work, we explore how the basic distinctive properties of the SM dynamically emerge from a unified New Physics framework tying together both flavor physics and Grand Unified Theory (GUT) concepts. This framework is suggested by a novel anomaly-free supersymmetric chiral E\(_6\)×SU(2)\(_F\)×U(1)\(_F\) GUT containing the SM. Among the most appealing emergent properties of this theory is the Higgs-matter unification with a highly-constrained massless chiral sector featuring two universal Yukawa couplings close to the GUT scale. At the electroweak scale, the minimal SM-like effective field theory limit of this GUT represents a specific flavored three-Higgs doublet model consistent with the observed large hierarchies in the quark mass spectra and mixing already at tree level.}, language = {en} } @article{WagenbrennerMayerWagnerRudertetal.2021, author = {Wagenbrenner, Mike and Mayer-Wagner, Susanne and Rudert, Maximilian and Holzapfel, Boris Michael and Weissenberger, Manuel}, title = {Combinations of hydrogels and mesenchymal stromal cells (MSCs) for cartilage tissue engineering — a review of the literature}, series = {Gels}, volume = {7}, journal = {Gels}, number = {4}, issn = {2310-2861}, doi = {10.3390/gels7040217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250177}, year = {2021}, abstract = {Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering.}, language = {en} } @article{HocheFlockMiaoetal.2021, author = {Hoche, Joscha and Flock, Marco and Miao, Xincheng and Philipp, Luca Nils and Wenzel, Michael and Fischer, Ingo and Mitric, Roland}, title = {Excimer formation dynamics in the isolated tetracene dimer}, series = {Chemical Science}, volume = {12}, journal = {Chemical Science}, number = {36}, doi = {10.1039/D1SC03214C}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251559}, pages = {11965 -- 11975}, year = {2021}, abstract = {The understanding of excimer formation and its interplay with the singlet-correlated triplet pair state \(^{1}\)(TT) is of high significance for the development of efficient organic electronics. Here, we study the photoinduced dynamics of the tetracene dimer in the gas phase by time-resolved photoionisation and photoion imaging experiments as well as nonadiabatic dynamics simulations in order to obtain mechanistic insight into the excimer formation dynamics. The experiments are performed using a picosecond laser system for excitation into the S\(_{2}\) state and reveal a biexponential time dependence. The time constants, obtained as a function of excess energy, lie in the range between ≈10 ps and 100 ps and are assigned to the relaxation of the excimer on the S\(_{1}\) surface and to its deactivation to the ground state. Simulations of the quantum-classical photodynamics are carried out in the frame of the semi-empirical CISD and TD-lc-DFTB methods. Both theoretical approaches reveal a dominating relaxation pathway that is characterised by the formation of a perfectly stacked excimer. TD-lc-DFTB simulations have also uncovered a second relaxation channel into a less stable dimer conformation in the S\(_{1}\) state. Both methods have consistently shown that the electronic and geometric relaxation to the excimer state is completed in less than 10 ps. The inclusion of doubly excited states in the CISD dynamics and their diabatisation further allowed to observe a transient population of the \(^{1}\)(TT) state, which, however, gets depopulated on a timescale of 8 ps, leading finally to the trapping in the excimer minimum.}, language = {en} } @article{Klein2021, author = {Klein, Wolf Peter}, title = {Vorlesung und H{\"o}rsaal als Symptomw{\"o}rter f{\"u}r Geschichte und Gegenwart der deutschen Sprache}, series = {Zeitschrift f{\"u}r germanistische Linguistik}, volume = {49}, journal = {Zeitschrift f{\"u}r germanistische Linguistik}, number = {3}, issn = {1613-0626}, doi = {10.1515/zgl-2021-2039}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250810}, pages = {556 -- 595}, year = {2021}, abstract = {The article starts with the etymology of the words Vorlesung („lecture") and H{\"o}rsaal ("lecture hall"). On the one hand, it turns out that the two expressions are deeply anchored in the history of the old Latin scientific language. They transmit Latin structures and perspectives in German neologisms. On the other hand, the two words arose exactly at the time when the sciences were moving from Latin to German, thus distancing themselves from the traditional forms of Latin scholarship. In this light, they exemplify an epochal change in the history of the German language, but at the same time they represent a great European continuity. Against this background, the two words can be interpreted as symptomatic words associated with the Enlightenment's confident outlook on the future relationship between science and society. Further corpus linguistic surveys also show how productively the two words appear in word formation processes. In particular, these surveys show by way of example that and how German standard language has benefited from the emergence of German academic language.}, language = {de} } @article{StrekalovaVeniaminovaSvirinetal.2021, author = {Strekalova, Tatyana and Veniaminova, Ekaterina and Svirin, Evgeniy and Kopeikina, Ekaterina and Veremeyko, Tatyana and Yung, Amanda W. Y. and Proshin, Andrey and Tan, Shawn Zheng Kai and Khairuddin, Sharafuddin and Lim, Lee Wei and Lesch, Klaus-Peter and Walitza, Susanne and Anthony, Daniel C. and Ponomarev, Eugene D.}, title = {Sex-specific ADHD-like behaviour, altered metabolic functions, and altered EEG activity in sialyltransferase ST3GAL5-deficient mice}, series = {Biomolecules}, volume = {11}, journal = {Biomolecules}, number = {12}, issn = {2218-273X}, doi = {10.3390/biom11121759}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250071}, year = {2021}, abstract = {A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5\(^{-/-}\)) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5\(^{-/-}\) mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5\(^{-/-}\) mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5\(^{-/-}\) mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5\(^{-/-}\) mice. Together, St3gal5\(^{-/-}\) mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.}, language = {en} } @article{FussOtherHeinzeetal.2021, author = {Fuss, Carmina Teresa and Other, Katharina and Heinze, Britta and Landwehr, Laura-Sophie and Wiegering, Armin and Kalogirou, Charis and Hahner, Stefanie and Fassnacht, Martin}, title = {Expression of the chemokine receptor CCR7 in the normal adrenal gland and adrenal tumors and its correlation with clinical outcome in adrenocortical carcinoma}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {22}, issn = {2072-6694}, doi = {10.3390/cancers13225693}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250112}, year = {2021}, abstract = {Background: The chemokine receptor CCR7 is crucial for an intact immune function, but its expression is also associated with clinical outcome in several malignancies. No data exist on the expression of CCR7 in adrenocortical tumors. Methods: CCR7 expression was investigated by qRT-PCR and immunohistochemistry in 4 normal adrenal glands, 59 adrenocortical adenomas, and 181 adrenocortical carcinoma (ACC) samples. Results: CCR7 is highly expressed in the outer adrenocortical zones and medulla. Aldosterone-producing adenomas showed lower CCR7 protein levels (H-score 1.3 ± 1.0) compared to non-functioning (2.4 ± 0.5) and cortisol-producing adenomas (2.3 ± 0.6), whereas protein expression was variable in ACC (1.8 ± 0.8). In ACC, CCR7 protein expression was significantly higher in lymph node metastases (2.5 ± 0.5) compared to primary tumors (1.8±0.8) or distant metastases (2.0 ± 0.4; p < 0.01). mRNA levels of CCR7 were not significantly different between ACCs, normal adrenals, and adrenocortical adenomas. In contrast to other tumor entities, neither CCR7 protein nor mRNA expression significantly impacted patients' survival. Conclusion: We show that CCR7 is expressed on mRNA and protein level across normal adrenals, benign adrenocortical tumors, as well as ACCs. Given that CCR7 did not influence survival in ACC, it is probably not involved in tumor progression, but it could play a role in adrenocortical homeostasis.}, language = {en} } @article{Koelligan2021, author = {K{\"o}lligan, Daniel}, title = {Murmur, heat and bonds - on some words of magic and healing}, series = {Indogermanische Forschungen}, volume = {126}, journal = {Indogermanische Forschungen}, number = {1}, issn = {1613-0405}, doi = {10.1515/if-2021-006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250976}, pages = {107 -- 134}, year = {2021}, abstract = {The paper argues that a) Germanic *tauf/ƀra- (Germ. Zauber, etc.) is related to a root PIE *deu̯p- 'beat; make a hollow sound, resound' found in Greek δοῦπος 'thud', etc., b) Greek φάρμακον goes back to the root PIE *gʷʰer- 'heat' (Gk. θερμός, etc.) implying healing by fomentation, and c) Armenian hiwand 'sick', borrowed from Iranian, to PIE *sh₂ei̯- 'bind' relying on the notion of disease as a supernatural bond.}, language = {en} } @article{Koelligan2021, author = {K{\"o}lligan, Daniel}, title = {A note on Vedic cīti-}, series = {Indogermanische Forschungen}, volume = {126}, journal = {Indogermanische Forschungen}, number = {1}, issn = {1613-0405}, doi = {10.1515/if-2021-007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250986}, pages = {135 -- 140}, year = {2021}, abstract = {Vedic cīti-, attested in the Atharvaveda, is argued to be related to Av. ṣ̌āitī-, OP šiyāti- 'happiness' built to PIE *kʷi̯eh₁- 'to (come to) rest'.}, language = {en} } @article{TamihardjaLutyjKraftetal.2021, author = {Tamihardja, J{\"o}rg and Lutyj, Paul and Kraft, Johannes and Lisowski, Dominik and Weick, Stefan and Flentje, Michael and Polat, B{\"u}lent}, title = {Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis}, series = {Frontiers in Oncology}, volume = {11}, journal = {Frontiers in Oncology}, issn = {2234-943X}, doi = {10.3389/fonc.2021.764536}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250992}, year = {2021}, abstract = {Purpose Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer. Methods 338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90\%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1\%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition. Results Median follow-up was 101.8 months. 15 (4.4\%)/115 (34.0\%)/208 (61.5\%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7\% and 75.9\% for all patients. The estimated 5-year bRFS was 93.3\%, 93.4\% and 79.5\% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5\% and 70.0\%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3\% and 5.0\% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6\%/0.3\%. Conclusions Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.}, language = {en} } @article{StrilciucVecseiBoeringetal.2021, author = {Strilciuc, Stefan and V{\´e}csei, L{\´a}szl{\´o} and Boering, Dana and Pražnikar, Aleš and Kaut, Oliver and Riederer, Peter and Battistin, Leontino}, title = {Safety of Cerebrolysin for neurorecovery after acute ischemic stroke: a systematic review and meta-analysis of twelve randomized-controlled trials}, series = {Pharmaceuticals}, volume = {14}, journal = {Pharmaceuticals}, number = {12}, issn = {1424-8247}, doi = {10.3390/ph14121297}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252403}, year = {2021}, abstract = {We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed, and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis were conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95\% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p > 0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.}, language = {en} } @article{NguemeniHiewKoegleretal.2021, author = {Nguemeni, Carine and Hiew, Shawn and K{\"o}gler, Stefanie and Homola, Gy{\"o}rgy A. and Volkmann, Jens and Zeller, Daniel}, title = {Split-belt training but not cerebellar anodal tDCS improves stability control and reduces risk of fall in patients with multiple sclerosis}, series = {Brain Sciences}, volume = {12}, journal = {Brain Sciences}, number = {1}, issn = {2076-3425}, doi = {10.3390/brainsci12010063}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252179}, year = {2021}, abstract = {The objective of this study was to examine the therapeutic potential of multiple sessions of training on a split-belt treadmill (SBT) combined with cerebellar anodal transcranial direct current stimulation (tDCS) on gait and balance in People with Multiple Sclerosis (PwMS). Twenty-two PwMS received six sessions of anodal (PwMS\(_{real}\), n = 12) or sham (PwMS\(_{sham}\), n = 10) tDCS to the cerebellum prior to performing the locomotor adaptation task on the SBT. To evaluate the effect of the intervention, functional gait assessment (FGA) scores and distance walked in 2 min (2MWT) were measured at the baseline (T0), day 6 (T5), and at the 4-week follow up (T6). Locomotor performance and changes of motor outcomes were similar in PwMS\(_{real}\) and PwMS\(_{sham}\) independently from tDCS mode applied to the cerebellum (anodal vs. sham, on FGA, p = 0.23; and 2MWT, p = 0.49). When the data were pooled across the groups to investigate the effects of multiple sessions of SBT training alone, significant improvement of gait and balance was found on T5 and T6, respectively, relative to baseline (FGA, p < 0.001 for both time points). The FGA change at T6 was significantly higher than at T5 (p = 0.01) underlining a long-lasting improvement. An improvement of the distance walked during the 2MWT was also observed on T5 and T6 relative to T0 (p = 0.002). Multiple sessions of SBT training resulted in a lasting improvement of gait stability and endurance, thus potentially reducing the risk of fall as measured by FGA and 2MWT. Application of cerebellar tDCS during SBT walking had no additional effect on locomotor outcomes.}, language = {en} } @article{KhareDeslauriersMorinetal.2021, author = {Khare, Siddhartha and Deslauriers, Annie and Morin, Hubert and Latifi, Hooman and Rossi, Sergio}, title = {Comparing time-lapse PhenoCams with satellite observations across the boreal forest of Quebec, Canada}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {1}, issn = {2072-4292}, doi = {10.3390/rs14010100}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252213}, year = {2021}, abstract = {Intercomparison of satellite-derived vegetation phenology is scarce in remote locations because of the limited coverage area and low temporal resolution of field observations. By their reliable near-ground observations and high-frequency data collection, PhenoCams can be a robust tool for intercomparison of land surface phenology derived from satellites. This study aims to investigate the transition dates of black spruce (Picea mariana (Mill.) B.S.P.) phenology by comparing fortnightly the MODIS normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI) extracted using the Google Earth Engine (GEE) platform with the daily PhenoCam-based green chromatic coordinate (GCC) index. Data were collected from 2016 to 2019 by PhenoCams installed in six mature stands along a latitudinal gradient of the boreal forests of Quebec, Canada. All time series were fitted by double-logistic functions, and the estimated parameters were compared between NDVI, EVI, and GCC. The onset of GCC occurred in the second week of May, whereas the ending of GCC occurred in the last week of September. We demonstrated that GCC was more correlated with EVI (R\(^2\) from 0.66 to 0.85) than NDVI (R\(^2\) from 0.52 to 0.68). In addition, the onset and ending of phenology were shown to differ by 3.5 and 5.4 days between EVI and GCC, respectively. Larger differences were detected between NDVI and GCC, 17.05 and 26.89 days for the onset and ending, respectively. EVI showed better estimations of the phenological dates than NDVI. This better performance is explained by the higher spectral sensitivity of EVI for multiple canopy leaf layers due to the presence of an additional blue band and an optimized soil factor value. Our study demonstrates that the phenological observations derived from PhenoCam are comparable with the EVI index. We conclude that EVI is more suitable than NDVI to assess phenology in evergreen species of the northern boreal region, where PhenoCam data are not available. The EVI index could be used as a reliable proxy of GCC for monitoring evergreen species phenology in areas with reduced access, or where repeated data collection from remote areas are logistically difficult due to the extreme weather.}, language = {en} } @article{Dosoo2021, author = {Dosoo, Korshi}, title = {Healing traditions in Coptic magical texts}, series = {Trends in Classics}, volume = {13}, journal = {Trends in Classics}, number = {1}, issn = {1866-7473}, doi = {10.1515/tc-2021-0003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251219}, pages = {44 -- 94}, year = {2021}, abstract = {Within the 'market of healing' of Christian Egypt (here broadly considered as the fourth through twelfth centuries CE), 'magical' practitioners represent an elusive yet recurrent category. This article explores the evidence for magical healing from three perspectives - first, literary texts which situate 'magicians' in competition with medical and ecclesiastical healing; second, the papyrological evidence of Coptic-language magical texts, which provide evidence for concepts of disease, wellness, and their mediation; and finally confronting the question of how these healing traditions might be understood within the methodologically materialistic framework of academic history, using the concepts of placebo and healing as a performance.}, language = {en} } @article{SchmidtJakubietzGilbertetal.2021, author = {Schmidt, Karsten and Jakubietz, Michael Georg and Gilbert, Fabian and Fenwick, Annabel and Meffert, Reiner Heribert and Jakubietz, Rafael Gregor}, title = {Muscle cuff in distal pedicled adipofascial sural artery flaps: a retrospective case control study}, series = {PRS Global Open}, volume = {9}, journal = {PRS Global Open}, number = {3}, doi = {10.1097/GOX.0000000000003464}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259875}, year = {2021}, abstract = {Background: Amputation after open tibial fracture occurs in 3\% of cases. The rate increases when flap reconstruction is required. The standard care involves microsurgical tissue transfer although the pedicled reverse sural artery adipofascial flap (PRSAF) is a local alternative in patients endangered by a prolonged operative time. Incorporation of a gastrocnemius muscle cuff in this flap can be used to fill dead space and increase healing potential. Literature shows superior survival rates for both PRSAF and inclusion of a muscle cuff in comparison with the cutaneous version. The aim of the study was to compare the outcome of the PRSAF and the musculoadipofascial version (PRSMAF). We hypothesize that the PRSMAF provides similar lap viability and flap-related complication rates as does the adipofascial version. The muscle component may reduce the long-term osteomyelitis rate. Methods: Patients were evaluated retrospectively after reconstruction with either PRSAF or PRSMAF. Preoperative osteomyelitis, flap survival, complications and osteomyelitis clearance were analyzed. Results: The study shows preliminary results supporting the potential use of the PRSMAF. We compare either 23 PRSMAF or 20 PRSAF flaps. We found no statistically significant differences in flap survival or in complication rate. Conclusions: Although the anatomical situation may sometimes dictate the use of a free flap, a technically less-complicated option may in some cases offer a viable alternative. This study shows that the PRSMAF can serve as an alternative for complex bone defects in the limb, though it does not provide statistical improvement to the PRSAF.}, language = {en} } @article{HojsgaardSchartl2021, author = {Hojsgaard, Diego and Schartl, Manfred}, title = {Skipping sex: A nonrecombinant genomic assemblage of complementary reproductive modules}, series = {BioEssays}, volume = {43}, journal = {BioEssays}, number = {1}, doi = {10.1002/bies.202000111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225818}, year = {2021}, abstract = {The unusual occurrence and developmental diversity of asexual eukaryotes remain a puzzle. De novo formation of a functioning asexual genome requires a unique assembly of sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and to affect discrete components of sexuality and produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, that is, a nonrecombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.}, language = {en} } @article{BousquetAntoBachertetal.2021, author = {Bousquet, Jean and Anto, Josep M. and Bachert, Claus and Haahtela, Tari and Zuberbier, Torsten and Czarlewski, Wienczyslawa and Bedbrook, Anna and Bosnic-Anticevich, Sinthia and Walter Canonica, G. and Cardona, Victoria and Costa, Elisio and Cruz, Alvaro A. and Erhola, Marina and Fokkens, Wytske J. and Fonseca, Joao A. and Illario, Maddalena and Ivancevich, Juan-Carlos and Jutel, Marek and Klimek, Ludger and Kuna, Piotr and Kvedariene, Violeta and Le, LTT and Larenas-Linnemann, D{\´e}sir{\´e}e E. and Laune, Daniel and Louren{\c{c}}o, Olga M. and Mel{\´e}n, Erik and Mullol, Joaquim and Niedoszytko, Marek and Odemyr, Mika{\"e}la and Okamoto, Yoshitaka and Papadopoulos, Nikos G. and Patella, Vincenzo and Pfaar, Oliver and Pham-Thi, Nh{\^a}n and Rolland, Christine and Samolinski, Boleslaw and Sheikh, Aziz and Sofiev, Mikhail and Suppli Ulrik, Charlotte and Todo-Bom, Ana and Tomazic, Peter-Valentin and Toppila-Salmi, Sanna and Tsiligianni, Ioanna and Valiulis, Arunas and Valovirta, Erkka and Ventura, Maria-Teresa and Walker, Samantha and Williams, Sian and Yorgancioglu, Arzu and Agache, Ioana and Akdis, Cezmi A. and Almeida, Rute and Ansotegui, Ignacio J. and Annesi-Maesano, Isabella and Arnavielhe, Sylvie and Basaga{\~n}a, Xavier and D. Bateman, Eric and B{\´e}dard, Annabelle and Bedolla-Barajas, Martin and Becker, Sven and Bennoor, Kazi S. and Benveniste, Samuel and Bergmann, Karl C. and Bewick, Michael and Bialek, Slawomir and E. Billo, Nils and Bindslev-Jensen, Carsten and Bjermer, Leif and Blain, Hubert and Bonini, Matteo and Bonniaud, Philippe and Bosse, Isabelle and Bouchard, Jacques and Boulet, Louis-Philippe and Bourret, Rodolphe and Boussery, Koen and Braido, Fluvio and Briedis, Vitalis and Briggs, Andrew and Brightling, Christopher E. and Brozek, Jan and Brusselle, Guy and Brussino, Luisa and Buhl, Roland and Buonaiuto, Roland and Calderon, Moises A. and Camargos, Paulo and Camuzat, Thierry and Caraballo, Luis and Carriazo, Ana-Maria and Carr, Warner and Cartier, Christine and Casale, Thomas and Cecchi, Lorenzo and Cepeda Sarabia, Alfonso M. and H. Chavannes, Niels and Chkhartishvili, Ekaterine and Chu, Derek K. and Cingi, Cemal and Correia de Sousa, Jaime and Costa, David J. and Courbis, Anne-Lise and Custovic, Adnan and Cvetkosvki, Biljana and D'Amato, Gennaro and da Silva, Jane and Dantas, Carina and Dokic, Dejan and Dauvilliers, Yves and De Feo, Giulia and De Vries, Govert and Devillier, Philippe and Di Capua, Stefania and Dray, Gerard and Dubakiene, Ruta and Durham, Stephen R. and Dykewicz, Mark and Ebisawa, Motohiro and Gaga, Mina and El-Gamal, Yehia and Heffler, Enrico and Emuzyte, Regina and Farrell, John and Fauquert, Jean-Luc and Fiocchi, Alessandro and Fink-Wagner, Antje and Fontaine, Jean-Fran{\c{c}}ois and Fuentes Perez, Jos{\´e} M. and Gemicioğlu, Bilun and Gamkrelidze, Amiran and Garcia-Aymerich, Judith and Gevaert, Philippe and Gomez, Ren{\´e} Maximiliano and Gonz{\´a}lez Diaz, Sandra and Gotua, Maia and Guldemond, Nick A. and Guzm{\´a}n, Maria-Antonieta and Hajjam, Jawad and Huerta Villalobos, Yunuen R. and Humbert, Marc and Iaccarino, Guido and Ierodiakonou, Despo and Iinuma, Tomohisa and Jassem, Ewa and Joos, Guy and Jung, Ki-Suck and Kaidashev, Igor and Kalayci, Omer and Kardas, Przemyslaw and Keil, Thomas and Khaitov, Musa and Khaltaev, Nikolai and Kleine-Tebbe, Jorg and Kouznetsov, Rostislav and Kowalski, Marek L. and Kritikos, Vicky and Kull, Inger and La Grutta, Stefania and Leonardini, Lisa and Ljungberg, Henrik and Lieberman, Philip and Lipworth, Brian and Lodrup Carlsen, Karin C. and Lopes-Pereira, Catarina and Loureiro, Claudia C. and Louis, Renaud and Mair, Alpana and Mahboub, Bassam and Makris, Micha{\"e}l and Malva, Joao and Manning, Patrick and Marshall, Gailen D. and Masjedi, Mohamed R. and Maspero, Jorge F. and Carreiro-Martins, Pedro and Makela, Mika and Mathieu-Dupas, Eve and Maurer, Marcus and De Manuel Keenoy, Esteban and Melo-Gomes, Elisabete and Meltzer, Eli O. and Menditto, Enrica and Mercier, Jacques and Micheli, Yann and Miculinic, Neven and Mihaltan, Florin and Milenkovic, Branislava and Mitsias, Dimitirios I. and Moda, Giuliana and Mogica-Martinez, Maria-Dolores and Mohammad, Yousser and Montefort, Steve and Monti, Ricardo and Morais-Almeida, Mario and M{\"o}sges, Ralph and M{\"u}nter, Lars and Muraro, Antonella and Murray, Ruth and Naclerio, Robert and Napoli, Luigi and Namazova-Baranova, Leyla and Neffen, Hugo and Nekam, Kristoff and Neou, Angelo and Nordlund, Bj{\"o}rn and Novellino, Ettore and Nyembue, Dieudonn{\´e} and O'Hehir, Robyn and Ohta, Ken and Okubo, Kimi and Onorato, Gabrielle L. and Orlando, Valentina and Ouedraogo, Solange and Palamarchuk, Julia and Pali-Sch{\"o}ll, Isabella and Panzner, Peter and Park, Hae-Sim and Passalacqua, Gianni and P{\´e}pin, Jean-Louis and Paulino, Ema and Pawankar, Ruby and Phillips, Jim and Picard, Robert and Pinnock, Hilary and Plavec, Davor and Popov, Todor A. and Portejoie, Fabienne and Price, David and Prokopakis, Emmanuel P. and Psarros, Fotis and Pugin, Benoit and Puggioni, Francesca and Quinones-Delgado, Pablo and Raciborski, Filip and Rajabian-S{\"o}derlund, Rojin and Regateiro, Frederico S. and Reitsma, Sietze and Rivero-Yeverino, Daniela and Roberts, Graham and Roche, Nicolas and Rodriguez-Zagal, Erendira and Rolland, Christine and Roller-Wirnsberger, Regina E. and Rosario, Nelson and Romano, Antonino and Rottem, Menachem and Ryan, Dermot and Salim{\"a}ki, Johanna and Sanchez-Borges, Mario M. and Sastre, Joaquin and Scadding, Glenis K. and Scheire, Sophie and Schmid-Grendelmeier, Peter and Sch{\"u}nemann, Holger J. and Sarquis Serpa, Faradiba and Shamji, Mohamed and Sisul, Juan-Carlos and Sofiev, Mikhail and Sol{\´e}, Dirceu and Somekh, David and Sooronbaev, Talant and Sova, Milan and Spertini, Fran{\c{c}}ois and Spranger, Otto and Stellato, Cristiana and Stelmach, Rafael and Thibaudon, Michel and To, Teresa and Toumi, Mondher and Usmani, Omar and Valero, Antonio A. and Valenta, Rudolph and Valentin-Rostan, Marylin and Pereira, Marilyn Urrutia and van der Kleij, Rianne and Van Eerd, Michiel and Vandenplas, Olivier and Vasankari, Tuula and Vaz Carneiro, Antonio and Vezzani, Giorgio and Viart, Fr{\´e}d{\´e}ric and Viegi, Giovanni and Wallace, Dana and Wagenmann, Martin and Wang, De Yun and Waserman, Susan and Wickman, Magnus and Williams, Dennis M. and Wong, Gary and Wroczynski, Piotr and Yiallouros, Panayiotis K. and Yusuf, Osman M. and Zar, Heather J. and Zeng, St{\´e}phane and Zernotti, Mario E. and Zhang, Luo and Shan Zhong, Nan and Zidarn, Mihaela}, title = {ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice}, series = {Allergy}, volume = {76}, journal = {Allergy}, number = {1}, doi = {10.1111/all.14422}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228339}, pages = {168 -- 190}, year = {2021}, abstract = {Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.}, language = {en} } @article{DohrnIhneHegenbartetal.2021, author = {Dohrn, Maike F. and Ihne, Sandra and Hegenbart, Ute and Medina, Jessica and Z{\"u}chner, Stephan L. and Coelho, Teresa and Hahn, Katrin}, title = {Targeting transthyretin - Mechanism-based treatment approaches and future perspectives in hereditary amyloidosis}, series = {Journal of Neurochemistry}, volume = {156}, journal = {Journal of Neurochemistry}, number = {6}, doi = {10.1111/jnc.15233}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224481}, pages = {802 -- 818}, year = {2021}, abstract = {The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate-limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence-specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac-conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood-brain barrier, but its half-life is short and liver failure a potential side effect. Amyloid-directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR-amyloidosis has become a model disease for pathophysiology-based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood-brain barrier permeability.}, language = {en} } @article{FlentjeRichter2021, author = {Flentje, Michael and Richter, J{\"u}rgen}, title = {Professor Dr. Werner Bohndorf gestorben}, series = {Strahlentherapie und Onkologie}, volume = {197}, journal = {Strahlentherapie und Onkologie}, number = {7}, issn = {1439-099X}, doi = {10.1007/s00066-021-01792-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264838}, pages = {664-665}, year = {2021}, abstract = {Kein Abstract verf{\"u}gbar.}, language = {de} } @article{LinsenmannCattaneoMaerzetal.2021, author = {Linsenmann, Thomas and Cattaneo, Andrea and M{\"a}rz, Alexander and Weiland, Judith and Stetter, Christian and Nickl, Robert and Westermaier, Thomas}, title = {Combined frameless stereotactical biopsy and intraoperative cerebral angiography by 3D-rotational fluoroscopy with intravenous contrast administration: a feasibility study}, series = {BMC Medical Imaging}, volume = {21}, journal = {BMC Medical Imaging}, doi = {10.1186/s12880-021-00622-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270370}, year = {2021}, abstract = {Background Mobile 3-dimensional fluoroscopes are an integral part of modern neurosurgical operating theatres and can also be used in combination with free available image post processing to depict cerebral vessels. In preparation of stereotactic surgery, preoperative Computed Tomography (CT) may be required for image fusion. Contrast CT may be of further advantage for image fusion as it regards the vessel anatomy in trajectory planning. Time-consuming in-hospital transports are necessary for this purpose. Mobile 3D-fluoroscopes may be used to generate a CT equal preoperative data set without an in-hospital transport. This study was performed to determine the feasibility and image quality of intraoperative 3-dimensional fluoroscopy with intravenous contrast administration in combination with stereotactical procedures. Methods 6 patients were included in this feasibility study. After fixation in a radiolucent Mayfield clamp a rotational fluoroscopy scan was performed with 50 mL iodine contrast agent. The image data sets were merged with the existing MRI images at a planning station and visually evaluated by two observer. The operation times were compared between the frame-based and frameless systems ("skin-to-skin" and "OR entry to exit"). Results The procedure proves to be safe. The entire procedure from fluoroscope positioning to the transfer to the planning station took 5-6 min with an image acquisition time of 24 s. In 5 of 6 cases, the fused imaging was able to reproduce the vascular anatomy accurately and in good quality. Both time end-points were significantly shorter compared to frame-based interventions. Conclusion The images could easily be transferred to the planning and navigation system and were successfully merged with the MRI data set. The procedure can be completely integrated into the surgical workflow. Preoperative CT imaging or transport under anaesthesia may even be replaced by this technique in the future. Furthermore, hemorrhages can be successfully visualized intraoperatively and might prevent time delays in emergencies.}, language = {en} } @article{KannBlessmannWinkelmannetal.2021, author = {Kann, Simone and Blessmann, Joerg and Winkelmann, Yvonne and Hansen, Jessica and Maya Amaya, Leonardo J. and Rivera Salcedo, Gadith E. and Halas, Hussein El and Schmidt-Chanasit, Jonas and Keoviengkhone, Latdamone and Sopraseuth, Vatsana and Deschermeier, Christina and Mika, Angela}, title = {Dengue virus detection in Lao PDR and Colombia: Comparative evaluation of PCR tests}, series = {Tropical Medicine \& International Health}, volume = {26}, journal = {Tropical Medicine \& International Health}, number = {10}, doi = {10.1111/tmi.13670}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262703}, pages = {1296 -- 1302}, year = {2021}, abstract = {Objectives Dengue virus (DENV) detection by polymerase chain reaction (PCR) facilitates diagnosis of dengue fever, which is the most frequent arboviral disease globally. Two studies were performed in countries with high dengue incidence, to assess the diagnostic performance of different PCR techniques. Methods/Results Two hundred and seventy-nine acute phase blood samples from febrile patients were analyzed for DENV by the RealStar Dengue RT-PCR kit (Altona Diagnostics) as gold standard in comparison with the Tropical Fever Core multiplex PCR (Fast Track Diagnostics). In total, 102 samples collected in Savannakhet Province (Lao PDR, Southeast Asia) in 2013 and 35 samples from Valledupar (Colombia, South America) tested positive for DENV by RealStar RT-PCR. In comparison, the Tropical Fever Core multiplex PCR detected 65.0\% (65/102) and 68.6\% (24/35) of these samples as positive for DENV in Savannakhet and Valledupar, respectively. Diagnostic sensitivity of the multiplex PCR strongly correlated with viral load. A subset of DENV PCR-confirmed samples was additionally tested by BNITM in house Dengue Type RT-PCR in comparison with two commercial test kits (RealStar Dengue Type RT-PCR [Altona Diagnostics], Dengue differentiation PCR [Fast Track Diagnostics]). The leading dengue serotype in Savannakhet was DENV-3 (58\% [29/50]), while DENV-1 (53.8\% [14/26]) was the predominant serotype found in samples collected in Valledupar by BNITM-type PCR. However, three DENV serotypes were circulating in Valledupar and in Savannakhet. In 2015, additional studies found predominantly DENV-4 (71\% [12/17]) in Savannakhet. Conclusions Both studies emphasized that routine diagnostics in both regions will benefit from an expanded use of highly sensitive pan-dengue PCRs.}, language = {en} } @article{Freitag‐WolfMunzJungeetal.2021, author = {Freitag-Wolf, Sandra and Munz, Matthias and Junge, Olaf and Graetz, Christian and Jockel-Schneider, Yvonne and Staufenbiel, Ingmar and Bruckmann, Corinna and Lieb, Wolfgang and Franke, Andre and Loos, Bruno G. and Jepsen, S{\o}ren and Dommisch, Henrik and Schaefer, Arne S.}, title = {Sex-specific genetic factors affect the risk of early-onset periodontitis in Europeans}, series = {Journal of Clinical Periodontology}, volume = {48}, journal = {Journal of Clinical Periodontology}, number = {11}, doi = {10.1111/jcpe.13538}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262445}, pages = {1404 -- 1413}, year = {2021}, abstract = {Aims Various studies have reported that young European women are more likely to develop early-onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the increased prevalence and severity. Materials and methods Using the case-only design, we tested for differences in genetic effects between men and women in 896 North-West European early-onset cases, using imputed genotypes from the OmniExpress genotyping array. Population-representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population. Results In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13). Conclusions Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter-sex phenotypic variation in early-onset periodontitis.}, language = {en} } @article{KarimiFreundWageretal.2021, author = {Karimi, Sohail M. and Freund, Matthias and Wager, Brittney M. and Knoblauch, Michael and Fromm, J{\"o}rg and M. Mueller, Heike and Ache, Peter and Krischke, Markus and Mueller, Martin J. and M{\"u}ller, Tobias and Dittrich, Marcus and Geilfus, Christoph-Martin and Alfaran, Ahmed H. and Hedrich, Rainer and Deeken, Rosalia}, title = {Under salt stress guard cells rewire ion transport and abscisic acid signaling}, series = {New Phytologist}, volume = {231}, journal = {New Phytologist}, number = {3}, doi = {10.1111/nph.17376}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259635}, pages = {1040-1055}, year = {2021}, abstract = {Soil salinity is an increasingly global problem which hampers plant growth and crop yield. Plant productivity depends on optimal water-use efficiency and photosynthetic capacity balanced by stomatal conductance. Whether and how stomatal behavior contributes to salt sensitivity or tolerance is currently unknown. This work identifies guard cell-specific signaling networks exerted by a salt-sensitive and salt-tolerant plant under ionic and osmotic stress conditions accompanied by increasing NaCl loads. We challenged soil-grown Arabidopsis thaliana and Thellungiella salsuginea plants with short- and long-term salinity stress and monitored genome-wide gene expression and signals of guard cells that determine their function. Arabidopsis plants suffered from both salt regimes and showed reduced stomatal conductance while Thellungiella displayed no obvious stress symptoms. The salt-dependent gene expression changes of guard cells supported the ability of the halophyte to maintain high potassium to sodium ratios and to attenuate the abscisic acid (ABA) signaling pathway which the glycophyte kept activated despite fading ABA concentrations. Our study shows that salinity stress and even the different tolerances are manifested on a single cell level. Halophytic guard cells are less sensitive than glycophytic guard cells, providing opportunities to manipulate stomatal behavior and improve plant productivity.}, language = {en} } @article{Lemm2021, author = {Lemm, Lukas}, title = {Is there a decline of democracy in the EU between 2004 and 2016? The relevance of data selection: a replication study of Smolka (2021) and comparison of democracy measures}, series = {Zeitschrift f{\"u}r Vergleichende Politikwissenschaft}, volume = {15}, journal = {Zeitschrift f{\"u}r Vergleichende Politikwissenschaft}, number = {3}, issn = {1865-2654}, doi = {10.1007/s12286-021-00502-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270107}, pages = {375-400}, year = {2021}, abstract = {Is there a Decline of Democracy? Democracy measurement provides the basis for answering this question. However, there are different measurement tools based on different meanings of democracy that have been shown to vary in their concept validity. Therefore, it is relevant to examine whether the results of the different measurement tools converge or diverge with respect to a potential decline of democracy. Smolka (2021) finds a decline of democracy for new and old EU states based on standardized data from the Democracy Barometer. A re-analysis using the original data of the Democracy Barometer and the Democracy Matrix can hardly replicate these results. A comparison of further measurements shows that the instruments diverge rather than converge. I therefore conclude with some thoughts on overcoming the selection problem that arises in light of these contrasts.}, language = {en} } @article{SchmittEguWalteretal.2021, author = {Schmitt, T. and Egu, D.T. and Walter, E. and Sigmund, A.M. and Eichkorn, R. and Yazdi, A. and Schmidt, E. and S{\´a}rdy, M. and Eming, R. and Goebeler, M. and Waschke, J.}, title = {Ca\(^{2+}\) signalling is critical for autoantibody-induced blistering of human epidermis in pemphigus}, series = {British Journal of Dermatology}, volume = {185}, journal = {British Journal of Dermatology}, number = {3}, doi = {10.1111/bjd.20091}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262810}, pages = {595 -- 604}, year = {2021}, abstract = {Background Pemphigus is a severe bullous autoimmune skin disease. Pemphigus foliaceus (PF) is characterized by antidesmoglein (Dsg) 1 IgG causing epidermal blistering; mucosal pemphigus vulgaris (mPV) by anti-Dsg3 IgG inducing erosions in the mucosa; and mucocutaneous pemphigus vulgaris (PV) by affecting both, with autoantibodies targeting Dsg1 and Dsg3. Objectives To characterize the Ca\(^{2+}\) flux pathway and delineate its importance in pemphigus pathogenesis and clinical phenotypes caused by different antibody profiles. Methods Immunoprecipitation, Ca\(^{2+}\) flux analysis, Western blotting, immunofluorescence staining, dissociation assays and a human skin ex vivo model were used. Results PV IgG and PF IgG, but neither Dsg3-specific monoclonal antibody (AK23) nor mPV IgG, caused Ca\(^{2+}\) influx in primary human keratinocytes. Phosphatidylinositol 4-kinase α interacts with Dsg1 but not with Dsg3. Its downstream target - phospholipase-C-γ1 (PLC) - was activated by PV IgG and PF IgG but not AK23 or mPV IgG. PLC releases inositol 1,4,5-trisphosphate (IP3) causing IP3 receptor (IP3R) activation and Ca2+ flux from the endoplasmic reticulum into the cytosol, which stimulates Ca2+ release-activated channels (CRAC)-mediated Ca\(^{2+}\) influx. Inhibitors against PLC, IP3R and CRAC effectively blocked PV IgG and PF IgG-induced Ca\(^{2+}\) influx; ameliorated alterations of Dsg1 and Dsg3 localization, and reorganization of keratin and actin filaments; and inhibited loss of cell adhesion in vitro. Finally, inhibiting PLC or IP3R was protective against PV IgG-induced blister formation and redistribution of Dsg1 and Dsg3 in human skin ex vivo. Conclusions Ca2+-mediated signalling is important for epidermal blistering and dependent on the autoantibody profile, which indicates different roles for signalling complexes organized by Dsg1 and Dsg3. Interfering with PLC and Ca\(^{2+}\) signalling may be a promising approach to treat epidermal manifestations of pemphigus.}, language = {en} } @article{Dittmann2021, author = {Dittmann, Lara A.}, title = {Sprach- und Kommunikationsnuancen in literarischen Interspeziesbegegnungen - Juan Ram{\´o}n Jim{\´e}nezʼ Platero y yo (1914/1917) und Thomas Manns Herr und Hund (1919)}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {7}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2364-6705}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305658}, pages = {55-71}, year = {2021}, abstract = {The encounter with non-human animals has always been a major preoccupation in the (philosophical) quest of understanding the human (condition). Of course, they are not only present in literary texts, but also in other media such as music and art. We consider ourselves aware of their selves, natures and skills as well as their sensory perceptions. Indeed, the ways we interact with non-human animals in everyday life and in the fictional world, how we perceive, think and talk about them as well as how we communicate with them are often related to our own self-perceptions in the social collective and in social-historical discourse. If we take a closer look at literary interspecies relations, we can detect clear shades in language and communication. Based on the approaches of Human-Animal Studies, this article deals with those nuances regarding animal-human encounters in Juan Ram{\´o}n Jim{\´e}nez' Platero y yo (1914/1917) and Thomas Mann's Herr und Hund (1919) in a comparative perspective. In addition to this, a special focus is placed on the effect these elements can have on (inter)acting literary subjects as well as on extra-textual recipients.}, language = {de} } @article{Henk2021, author = {Henk, Lars Thorben}, title = {«We're on the road to nowhere» - Felwine Sarrs narrativer Weg in die Afrotopie}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {7}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2364-6705}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305662}, pages = {73-90}, year = {2021}, abstract = {According to the Senegalesian scholar Felwine Sarr who conceives an African utopia in his programmatic essay Afrotopia (2016), this Afrotopos has already germinated in contemporary African literature. However, it still needs to be enquired to what extent the narrated topos of the street in Sarr's own anthology 105 Rue Carnot (2011) has already realized the Afrotopos. In order to respond to this question, we would like to mobilise Michel Foucault's concept of heterotopia, which elaborates on the interactions between truth production/knowledge, power and space, and permits us to conceive of «les lieux utopiques» (Foucault 2005: 40) as actually locatable on the map and real other places outside of all places (cf. Foucault 1994: 755). Thus, in the street, a different relationship between global North and South is founded, which becomes legible as an African «utopie localis{\´e}e» (Foucault 2005: 41) that Sarr calls for in Afrotopia (2016).}, language = {de} } @article{Kneifel2021, author = {Kneifel, Malte}, title = {Futur-Formen und ihre Funktionen im Portugu{\^e}s Arcaico}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {7}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2364-6705}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305673}, pages = {91-109}, year = {2021}, abstract = {This article aims to trace the development of different verb forms that express future tense of Old Portuguese from the 13th to the 15th century by analyzing a historical text corpus. During this period, Portuguese future tense could be expressed through one synthetical as well as two analytical morphological verb constructions. Adapting an analytic model formerly employed by the Mexican researcher Concepci{\´o}n Company Company for an investigation of similar future tense forms in Old Spanish, this article seeks to point out that the use of the different verb forms in Portuguese followed distinct functions regarding aspects of both information structure as well as modality.}, language = {de} } @article{Klamp2021, author = {Klamp, Yannic}, title = {Alma und {\´a}nima in spanisch-zapotekischen Evangelisierungswerken: die Translation des Konzepts Seele im kolonialen Missionskontext (Neu-Spanien, 16.-18. Jh.)}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {7}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2364-6705}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305681}, pages = {111-130}, year = {2021}, abstract = {The arrival of the Spanish in present-day Oaxaca, Mexico, led to manifold communicative challenges and was the origin of the first written documents in the local indigenous languages. This paper focuses on Spanish-Zapotec translations produced by Christian missionaries during the colonial period. In this context, it aims to investigate the expression of the concept of soul in their catechisms and confesionarios by analyzing chronologically how different authors apply the Spanish synonyms alma and {\´a}nima. On the one hand, we can observe some similar tendencies in central Mexican documents for the early colonial period so that we can assume that the corpus was influenced by Nahuatl translations. On the other hand, there is an independent development in Spanish-Zapotec translations not only regarding the target text but also the source text.}, language = {de} } @article{Scholz2021, author = {Scholz, Janek}, title = {S{\´e}rgio Zimbas Covid-19-Karikaturen im Kontext {\"o}ffentlicher Gesundheitsf{\"u}rsorge in Mosambik}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {7}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2364-6705}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305692}, pages = {133-155}, year = {2021}, abstract = {The article deals with the educational comics of the Mozambican artist S{\´e}rgio Zimba, especially in the context of the current pandemic situation caused by Covid-19. First, comics from and comic research on Africa will be presented, especially in their repercussion within the German-language comics landscape. This will be followed by a discussion of the special situation in lusophone Africa, exemplified and illustrated by the works of the Mozambican cartoonist S{\´e}rgio Zimba. The article closes with a brief comparison of Zimba's work with the cartoons of S{\´e}rgio Pi{\c{c}}arra from Angola, to better classify the artist's work.}, language = {de} } @article{Christmann2021, author = {Christmann, Tim}, title = {Grenzerfahrung, Grenz{\"u}berschreitung, Grenz{\"u}berwindung: Das Falkland/Malvinas Malvinas-Trauma in Lola Arias' Film Teatro de Guerra (2018)}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {7}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2364-6705}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305577}, pages = {17-33}, year = {2021}, abstract = {This article will examine the cinematic approach to the trauma of the Falklands/Malvinas War in Lola Ariasʼ film Teatro de Guerra (AR/ES, 2018). The armed conflict between Ar-gentina and Great Britain in 1982 can be understood as a traumatic liminal experience, whose artistic reception pushes conventional aesthetics to their limits and calls for innova-tive representational strategies. Based on a cultural studies approach to the Falklands/Mal-vinas War as a collective trauma, this contribution will highlight selected moments of aes-thetic border crossing in Teatro de Guerra, by which the film succeeds in transcending boundaries between former enemies of the war.}, language = {de} } @article{deCringis2021, author = {de Cringis, Patricia}, title = {100 Jahre Vokalschw{\"a}chung in den tierras altas: historische Perspektiven eines (zu) wenig beachteten Aussprachemerkmal}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {7}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2364-6705}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305638}, pages = {35-52}, year = {2021}, abstract = {This paper deals with the origin of the hundred-year old theory of tierras bajas and tierras altas, focusing on the description of vowel weakening within that theory developed in 1921 by Henr{\´i}quez Ure{\~n}a. I argue that the early conception of vowel weakening and its dialectal distribution has strongly influenced the kind of research we have been conducting about this phonetic feature to this day. The aim of this study therefore, is to sharpen our understanding of the former zeitgeist of research and to stimulate further big data-based studies on vowel weakening overcoming the traditional dialectal division of tierras bajas and tierras altas.}, language = {de} } @article{SbieraKircherAltierietal.2021, author = {Sbiera, Iuliu and Kircher, Stefan and Altieri, Barbara and Fassnacht, Martin and Kroiss, Matthias and Sbiera, Silviu}, title = {Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {7}, issn = {2072-6694}, doi = {10.3390/cancers13071736}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236486}, year = {2021}, abstract = {A clinically relevant proportion of adrenocortical carcinoma (ACC) cases shows a tendency to metastatic spread. The objective was to determine whether the epithelial to mesenchymal transition (EMT), a mechanism associated with metastasizing in several epithelial cancers, might play a crucial role in ACC. 138 ACC, 29 adrenocortical adenomas (ACA), three normal adrenal glands (NAG), and control tissue samples were assessed for the expression of epithelial (E-cadherin and EpCAM) and mesenchymal (N-cadherin, SLUG and SNAIL) markers by immunohistochemistry. Using real-time RT-PCR we quantified the alternative isoform splicing of FGFR 2 and 3, another known indicator of EMT. We also assessed the impact of these markers on clinical outcome. Results show that both normal and neoplastic adrenocortical tissues lacked expression of epithelial markers but strongly expressed mesenchymal markers N-cadherin and SLUG. FGFR isoform splicing confirmed higher similarity of adrenocortical tissues to mesenchymal compared to epithelial tissues. In ACC, higher SLUG expression was associated with clinical markers indicating aggressiveness, while N-cadherin expression inversely associated with these markers. In conclusion, we could not find any indication of EMT as all adrenocortical tissues lacked expression of epithelial markers and exhibited closer similarity to mesenchymal tissues. However, while N-cadherin might play a positive role in tissue structure upkeep, SLUG seems to be associated with a more aggressive phenotype.}, language = {en} } @article{RajendranBoettigerDentzienetal.2021, author = {Rajendran, Ranjithkumar and B{\"o}ttiger, Gregor and Dentzien, Niklas and Rajendran, Vinothkumar and Sharifi, Bischand and Erg{\"u}n, S{\"u}leyman and Stadelmann, Christine and Karnati, Srikanth and Berghoff, Martin}, title = {Effects of FGFR tyrosine kinase inhibition in OLN-93 oligodendrocytes}, series = {Cells}, volume = {10}, journal = {Cells}, number = {6}, issn = {2073-4409}, doi = {10.3390/cells10061318}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239600}, year = {2021}, abstract = {Fibroblast growth factor (FGF) signaling is involved in the pathogenesis of multiple sclerosis (MS). Data from neuropathology studies suggest that FGF signaling contributes to the failure of remyelination in MS. In MOG\(_{35-55}\)-induced EAE, oligodendrocyte-specific deletion of FGFR1 and FGFR2 resulted in a less severe disease course, reduced inflammation, myelin and axon degeneration and changed FGF/FGFR and BDNF/TrkB signaling. Since signaling cascades in oligodendrocytes could not be investigated in the EAE studies, we here aimed to characterize FGFR-dependent oligodendrocyte-specific signaling in vitro. FGFR inhibition was achieved by application of the multi-kinase-inhibitor dovitinib and the FGFR1/2/3-inhibitor AZD4547. Both substances are potent inhibitors of FGF signaling; they are effective in experimental tumor models and patients with malignancies. Effects of FGFR inhibition in oligodendrocytes were studied by immunofluorescence microscopy, protein and gene analyses. Application of the tyrosine kinase inhibitors reduced FGFR1, phosphorylated ERK and Akt expression, and it enhanced BDNF and TrkB expression. Furthermore, the myelin proteins CNPase and PLP were upregulated by FGFR inhibition. In summary, inhibition of FGFR signaling in oligodendrocytes can be achieved by application of tyrosine kinase inhibitors. Decreased phosphorylation of ERK and Akt is associated with an upregulation of BDNF/TrkB signaling, which may be responsible for the increased production of myelin proteins. Furthermore, these data suggest that application of FGFR inhibitors may have the potential to promote remyelination in the CNS.}, language = {en} } @article{LeistnerHolzgrabe2021, author = {Leistner, Adrian and Holzgrabe, Ulrike}, title = {Impurity Profiling of Baclofen Using Gradient HPLC-UV Method}, series = {Chromatographia}, volume = {84}, journal = {Chromatographia}, number = {10}, issn = {1612-1112}, doi = {10.1007/s10337-021-04079-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268921}, pages = {927-935}, year = {2021}, abstract = {The GABA\(_{B}\) receptor agonist baclofen is a medication commonly used for the treatment of muscle spasticity. It is an amino acid and related to the neurotransmitter GABA. In this study, we developed a new, gradient high-performance liquid chromatography (HPLC) method for the impurity assessment of baclofen, which is appropriate for pharmacopoeial purposes. Since the impurities related to the synthesis pathway are acids, zwitterionic, or neutral, the method development is challenging. However, the separation of all components was achieved on a C18 stationary phase using a water-acetonitrile-trifluoroacetic acid gradient. A limit of detection (LOD) of at least 0.02\% was registered for all specified impurities. Additionally, CAD detection was performed to detect potential impurities lacking off a chromophore. The baclofen batches analyzed are far more pure than expected. All impurities were found below the specification limit, and thus, they can be regarded as unspecified. Moreover, the required runtime could be significantly reduced compared to the current USP or Ph. Eur. method.}, language = {en} } @article{ElMoualiGerovacMineikaitėetal.2021, author = {El Mouali, Youssef and Gerovac, Milan and Mineikaitė, Raminta and Vogel, J{\"o}rg}, title = {In vivo targets of Salmonella FinO include a FinP-like small RNA controlling copy number of a cohabitating plasmid}, series = {Nucleic Acids Research}, volume = {49}, journal = {Nucleic Acids Research}, number = {9}, doi = {10.1093/nar/gkab281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261072}, pages = {5319-5335}, year = {2021}, abstract = {FinO-domain proteins represent an emerging family of RNA-binding proteins (RBPs) with diverse roles in bacterial post-transcriptional control and physiology. They exhibit an intriguing targeting spectrum, ranging from an assumed single RNA pair (FinP/traJ) for the plasmid-encoded FinO protein, to transcriptome-wide activity as documented for chromosomally encoded ProQ proteins. Thus, the shared FinO domain might bear an unusual plasticity enabling it to act either selectively or promiscuously on the same cellular RNA pool. One caveat to this model is that the full suite of in vivo targets of the assumedly highly selective FinO protein is unknown. Here, we have extensively profiled cellular transcripts associated with the virulence plasmid-encoded FinO in Salmonella enterica. While our analysis confirms the FinP sRNA of plasmid pSLT as the primary FinO target, we identify a second major ligand: the RepX sRNA of the unrelated antibiotic resistance plasmid pRSF1010. FinP and RepX are strikingly similar in length and structure, but not in primary sequence, and so may provide clues to understanding the high selectivity of FinO-RNA interactions. Moreover, we observe that the FinO RBP encoded on the Salmonella virulence plasmid controls the replication of a cohabitating antibiotic resistance plasmid, suggesting cross-regulation of plasmids on the RNA level.}, language = {en} } @article{GrunzPennigFieberetal.2021, author = {Grunz, Jan-Peter and Pennig, Lenhard and Fieber, Tabea and Gietzen, Carsten Herbert and Heidenreich, Julius Frederik and Huflage, Henner and Gruschwitz, Philipp and Kuhl, Philipp Josef and Petritsch, Bernhard and Kosmala, Aleksander and Bley, Thorsten Alexander and Gassenmaier, Tobias}, title = {Twin robotic x-ray system in small bone and joint trauma: Impact of cone-beam computed tomography on treatment decisions}, series = {European Radiology}, volume = {31}, journal = {European Radiology}, issn = {0938-7994}, doi = {10.1007/s00330-020-07563-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235233}, pages = {3600-3609}, year = {2021}, abstract = {Objectives Trauma evaluation of extremities can be challenging in conventional radiography. A multi-use x-ray system with cone-beam CT (CBCT) option facilitates ancillary 3-D imaging without repositioning. We assessed the clinical value of CBCT scans by analyzing the influence of additional findings on therapy. Methods Ninety-two patients underwent radiography and subsequent CBCT imaging with the twin robotic scanner (76 wrist/hand/finger and 16 ankle/foot/toe trauma scans). Reports by on-call radiologists before and after CBCT were compared regarding fracture detection, joint affliction, comminuted injuries, and diagnostic confidence. An orthopedic surgeon recommended therapy based on reported findings. Surgical reports (N = 52) and clinical follow-up (N = 85) were used as reference standard. Results CBCT detected more fractures (83/64 of 85), joint involvements (69/53 of 71), and multi-fragment situations (68/50 of 70) than radiography (all p < 0.001). Six fractures suspected in radiographs were ruled out by CBCT. Treatment changes based on additional information from CBCT were recommended in 29 patients (31.5\%). While agreement between advised therapy before CBCT and actual treatment was moderate (κ = 0.41 [95\% confidence interval 0.35-0.47]; p < 0.001), agreement after CBCT was almost perfect (κ = 0.88 [0.83-0.93]; p < 0.001). Diagnostic confidence increased considerably for CBCT studies (p < 0.001). Median effective dose for CBCT was 4.3 μSv [3.3-5.3 μSv] compared to 0.2 μSv [0.1-0.2 μSv] for radiography. Conclusions CBCT provides advantages for the evaluation of acute small bone and joint trauma by detecting and excluding extremity fractures and fracture-related findings more reliably than radiographs. Additional findings induced therapy change in one third of patients, suggesting substantial clinical impact.}, language = {en} } @article{EssigBabilonVollmuthetal.2021, author = {Essig, Fabian and Babilon, Lilith and Vollmuth, Christoph and Kollikowski, Alexander M. and Pham, Mirko and Solymosi, L{\´a}szl{\´o} and Haeusler, Karl Georg and Kraft, Peter and Stoll, Guido and Schuhmann, Michael K.}, title = {High mobility group box 1 protein in cerebral thromboemboli}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {20}, issn = {1422-0067}, doi = {10.3390/ijms222011276}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265568}, year = {2021}, abstract = {High-mobility group box 1 protein (HMGB1) is a damage-associated molecular pattern (DAMP) involved in neutrophil extracellular trap (NET) formation and thrombosis. NETs are regularly found in cerebral thromboemboli. We here analyzed associated HMGB1 expression in human thromboemboli retrieved via mechanical thrombectomy from 37 stroke patients with large vessel occlusion. HMGB1 was detected in all thromboemboli, accounting for 1.7\% (IQR 0.6-6.2\%) of the total thromboemboli area and was found to be colocalized with neutrophils and NETs and in spatial proximity to platelets. Correlation analysis revealed that the detection of HMGB1 was strongly related to the number of neutrophils (r = 0.58, p = 0.0002) and platelets (r = 0.51, p = 0.001). Our results demonstrate that HMGB1 is a substantial constituent of thromboemboli causing large vessel occlusion stroke.}, language = {en} } @article{GrassingerFlorenMuelleretal.2021, author = {Grassinger, Julia Maria and Floren, Andreas and M{\"u}ller, Tobias and Cerezo-Echevarria, Argi{\~n}e and Beitzinger, Christoph and Conrad, David and T{\"o}rner, Katrin and Staudacher, Marlies and Aupperle-Lellbach, Heike}, title = {Digital lesions in dogs: a statistical breed analysis of 2912 cases}, series = {Veterinary Sciences}, volume = {8}, journal = {Veterinary Sciences}, number = {7}, issn = {2306-7381}, doi = {10.3390/vetsci8070136}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242690}, year = {2021}, abstract = {Breed predispositions to canine digital neoplasms are well known. However, there is currently no statistical analysis identifying the least affected breeds. To this end, 2912 canine amputated digits submitted from 2014-2019 to the Laboklin GmbH \& Co. KG for routine diagnostics were statistically analyzed. The study population consisted of 155 different breeds (most common: 634 Mongrels, 411 Schnauzers, 197 Labrador Retrievers, 93 Golden Retrievers). Non-neoplastic processes were present in 1246 (43\%), tumor-like lesions in 138 (5\%), and neoplasms in 1528 cases (52\%). Benign tumors (n = 335) were characterized by 217 subungual keratoacanthomas, 36 histiocytomas, 35 plasmacytomas, 16 papillomas, 12 melanocytomas, 9 sebaceous gland tumors, 6 lipomas, and 4 bone tumors. Malignant neoplasms (n = 1193) included 758 squamous cell carcinomas (SCC), 196 malignant melanomas (MM), 76 soft tissue sarcomas, 52 mast cell tumors, 37 non-specified sarcomas, 29 anaplastic neoplasms, 24 carcinomas, 20 bone tumors, and 1 histiocytic sarcoma. Predisposed breeds for SCC included the Schnauzer (log OR = 2.61), Briard (log OR = 1.78), Rottweiler (log OR = 1.54), Poodle (log OR = 1.40), and Dachshund (log OR = 1.30). Jack Russell Terriers (log OR = -2.95) were significantly less affected by SCC than Mongrels. Acral MM were significantly more frequent in Rottweilers (log OR = 1.88) and Labrador Retrievers (log OR = 1.09). In contrast, Dachshunds (log OR = -2.17), Jack Russell Terriers (log OR = -1.88), and Rhodesian Ridgebacks (log OR = -1.88) were rarely affected. This contrasted with the well-known predisposition of Dachshunds and Rhodesian Ridgebacks to oral and cutaneous melanocytic neoplasms. Further studies are needed to explain the underlying reasons for breed predisposition or "resistance" to the development of specific acral tumors and/or other sites.}, language = {en} } @article{RappVanDijckLaugwitzetal.2021, author = {Rapp, Christina K. and Van Dijck, Ine and Laugwitz, Lucia and Boon, Mieke and Briassoulis, George and Ilia, Stavroula and Kammer, Birgit and Reu, Simone and Hornung, Stefanie and Buchert, Rebecca and Sofan, Linda and Froukh, Tawfiq and Witters, Peter and Rymen, Daisy and Haack, Tobias B. and Proesmans, Marijke and Griese, Matthias}, title = {Expanding the phenotypic spectrum of FINCA (fibrosis, neurodegeneration, and cerebral angiomatosis) syndrome beyond infancy}, series = {Clinical Genetics}, volume = {100}, journal = {Clinical Genetics}, number = {4}, doi = {10.1111/cge.14016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262732}, pages = {453 -- 461}, year = {2021}, abstract = {Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA, MIM\#618278) is a rare clinical condition caused by bi-allelic variants in NHL repeat containing protein 2 (NHLRC2, MIM*618277). Pulmonary disease may be the presenting sign and the few patients reported so far, all deceased in early infancy. Exome sequencing was performed on patients with childhood interstitial lung disease (chILD) and additional neurological features. The chILD-EU register database and an in-house database were searched for patients with NHLRC2 variants and clinical features overlapping FINCA syndrome. Six patients from three families were identified with bi-allelic variants in NHLRC2. Two of these children died before the age of two while four others survived until childhood. Interstitial lung disease was pronounced in almost all patients during infancy and stabilized over the course of the disease with neurodevelopmental delay (NDD) evolving as the key clinical finding. We expand the phenotype of FINCA syndrome to a multisystem disorder with variable severity. FINCA syndrome should also be considered in patients beyond infancy with NDD and a history of distinct interstitial lung disease. Managing patients in registers for rare diseases helps identifying new diagnostic entities and advancing care for these patients.}, language = {en} } @article{MonteagudoMartinezLeandroGarciaetal.2021, author = {Monteagudo, Mar{\´i}a and Mart{\´i}nez, Paula and Leandro-Garc{\´i}a, Luis J. and Mart{\´i}nez-Montes, {\´A}ngel M. and Calsina, Bruna and Pulgar{\´i}n-Alfaro, Marta and D{\´i}az-Talavera, Alberto and Mellid, Sara and Let{\´o}n, Roc{\´i}o and Gil, Eduardo and P{\´e}rez-Mart{\´i}nez, Manuel and Meg{\´i}as, Diego and Torres-Ruiz, Ra{\´u}l and Rodriguez-Perales, Sandra and Gonz{\´a}lez, Patricia and Caleiras, Eduardo and Jim{\´e}nez-Villa, Scherezade and Roncador, Giovanna and {\´A}lvarez-Escol{\´a}, Cristina and Regojo, Rita M. and Calatayud, Mar{\´i}a and Guadalix, Sonsoles and Curr{\´a}s-Freixes, Maria and Rapizzi, Elena and Canu, Letizia and N{\"o}lting, Svenja and Remde, Hanna and Fassnacht, Martin and Bechmann, Nicole and Eisenhofer, Graeme and Mannelli, Massimo and Beuschlein, Felix and Quinkler, Marcus and Rodr{\´i}guez-Antona, Cristina and Casc{\´o}n, Alberto and Blasco, Mar{\´i}a A. and Montero-Conde, Cristina and Robledo, Mercedes}, title = {Analysis of telomere maintenance related genes reveals NOP10 as a new metastatic-risk marker in pheochromocytoma/paraganglioma}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {19}, issn = {2072-6694}, doi = {10.3390/cancers13194758}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246321}, year = {2021}, abstract = {One of the main problems we face with PPGL is the lack of molecular markers capable of predicting the development of metastases in patients. Telomere-related genes, such as TERT and ATRX, have been recently described in PPGL, supporting the association between the activation of immortalization mechanisms and disease progression. However, the contribution of other genes involving telomere preservation machinery has not been previously investigated. In this work, we aimed to analyze the prognostic value of a comprehensive set of genes involved in telomere maintenance. For this study, we collected 165 PPGL samples (97 non-metastatic/63 metastatic), genetically characterized, in which the expression of 29 genes of interest was studied by NGS. Three of the 29 genes studied, TERT, ATRX and NOP10, showed differential expression between metastatic and non-metastatic cases, and alterations in these genes were associated with a shorter time to progression, independent of SDHB-status. We studied telomere length by Q-FISH in patient samples and in an in vitro model. NOP10 overexpressing tumors displayed an intermediate-length telomere phenotype without ALT, and in vitro results suggest that NOP10 has a role in telomerase-dependent telomere maintenance. We also propose the implementation of NOP10 IHC to better stratify PPGL patients.}, language = {en} } @article{SchuchForstnerRappetal.2021, author = {Schuch, Luise A. and Forstner, Maria and Rapp, Christina K. and Li, Yang and Smith, Desiree E. C. and Mendes, Marisa I. and Delhommel, Florent and Sattler, Michael and Emiralioğlu, Nagehan and Taskiran, Ekim Z. and Orhan, Diclehan and Kiper, Nural and Rohlfs, Meino and Jeske, Tim and Hastreiter, Maximilian and Gerstlauer, Michael and Torrent-Vernetta, Alba and Moreno-Gald{\´o}, Antonio and Kammer, Birgit and Brasch, Frank and Reu-Hofer, Simone and Griese, Matthias}, title = {FARS1-related disorders caused by bi-allelic mutations in cytosolic phenylalanyl-tRNA synthetase genes: Look beyond the lungs!}, series = {Clinical Genetics}, volume = {99}, journal = {Clinical Genetics}, number = {6}, doi = {10.1111/cge.13943}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238827}, pages = {789 -- 801}, year = {2021}, abstract = {Aminoacyl-tRNA synthetases (ARSs) catalyze the first step of protein biosynthesis (canonical function) and have additional (non-canonical) functions outside of translation. Bi-allelic pathogenic variants in genes encoding ARSs are associated with various recessive mitochondrial and multisystem disorders. We describe here a multisystem clinical phenotype based on bi-allelic mutations in the two genes (FARSA, FARSB) encoding distinct subunits for tetrameric cytosolic phenylalanyl-tRNA synthetase (FARS1). Interstitial lung disease with cholesterol pneumonitis on histology emerged as an early characteristic feature and significantly determined disease burden. Additional clinical characteristics of the patients included neurological findings, liver dysfunction, and connective tissue, muscular and vascular abnormalities. Structural modeling of newly identified missense mutations in the alpha subunit of FARS1, FARSA, showed exclusive mapping to the enzyme's conserved catalytic domain. Patient-derived mutant cells displayed compromised aminoacylation activity in two cases, while remaining unaffected in another. Collectively, these findings expand current knowledge about the human ARS disease spectrum and support a loss of canonical and non-canonical function in FARS1-associated recessive disease.}, language = {en} } @article{FicklThereseKroegerDietrichetal.2021, author = {Fickl, Stefan and Therese Kr{\"o}ger, Annika and Dietrich, Thomas and Kebschull, Moritz}, title = {Influence of soft tissue augmentation procedures around dental implants on marginal bone level changes-A systematic review}, series = {Clinical Oral Implants Research}, volume = {32}, journal = {Clinical Oral Implants Research}, number = {S21}, doi = {10.1111/clr.13829}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258394}, pages = {108-137}, year = {2021}, abstract = {Objectives This systematic review assessed the influence of soft tissue augmentation procedures on marginal bone level changes in partial or fully edentulous patients. Material and Methods We identified three relevant PICO questions related to soft tissue augmentation procedures and conducted a systematic search of four major electronic databases for clinical studies in systemically healthy patients receiving at least one dental implant and a minimum follow-up of one year after implant placement. The primary outcome was mean difference in marginal bone levels, and secondary outcomes were clinical and patient-related outcomes such as thickness of peri-implant mucosa, bleeding indices, and Pink Esthetic Score. Results We identified 20 publications reporting on 16 relevant comparisons. Studies varied considerably and thus only two meta-analyses could be performed. This systematic review showed that: Soft tissue augmentation either for augmentation of keratinized mucosa or soft tissue volume inconsistently had an effect on marginal bone level changes when compared to no soft tissue augmentation, but consistently improved secondary outcomes. The combination soft and hard tissue augmentation showed no statistically significant difference in terms of marginal bone level changes when compared to hard tissue augmentation alone, but resulted in less marginal soft tissue recession as shown by a meta-analysis. Soft or hard tissue augmentation performed as contour augmentations resulted in comparable marginal bone level changes. Conclusions Peri-implant soft and hard tissues seem to have a bidirectional relationship: "Bone stands hard, but soft tissue is the guard".}, language = {en} } @article{WelkerKerstenMuelleretal.2021, author = {Welker, Armin and Kersten, Christian and M{\"u}ller, Christin and Madhugiri, Ramakanth and Zimmer, Collin and M{\"u}ller, Patrick and Zimmermann, Robert and Hammerschmidt, Stefan and Maus, Hannah and Ziebuhr, John and Sotriffer, Christoph and Schirmeister, Tanja}, title = {Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2}, series = {ChemMedChem}, volume = {16}, journal = {ChemMedChem}, number = {2}, doi = {10.1002/cmdc.202000548}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225700}, pages = {340 -- 354}, year = {2021}, abstract = {Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL\(^{pro}\)) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL\(^{pro}\). Moreover, we report the discovery of isoindolines as a new class of potent PL\(^{pro}\) inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL\(^{pro}\) are valuable starting points for the development of new pan-coronaviral inhibitors.}, language = {en} } @article{LohPoigneeWamseretal.2021, author = {Loh, Frank and Poign{\´e}e, Fabian and Wamser, Florian and Leidinger, Ferdinand and Hoßfeld, Tobias}, title = {Uplink vs. Downlink: Machine Learning-Based Quality Prediction for HTTP Adaptive Video Streaming}, series = {Sensors}, volume = {21}, journal = {Sensors}, number = {12}, issn = {1424-8220}, doi = {10.3390/s21124172}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241121}, year = {2021}, abstract = {Streaming video is responsible for the bulk of Internet traffic these days. For this reason, Internet providers and network operators try to make predictions and assessments about the streaming quality for an end user. Current monitoring solutions are based on a variety of different machine learning approaches. The challenge for providers and operators nowadays is that existing approaches require large amounts of data. In this work, the most relevant quality of experience metrics, i.e., the initial playback delay, the video streaming quality, video quality changes, and video rebuffering events, are examined using a voluminous data set of more than 13,000 YouTube video streaming runs that were collected with the native YouTube mobile app. Three Machine Learning models are developed and compared to estimate playback behavior based on uplink request information. The main focus has been on developing a lightweight approach using as few features and as little data as possible, while maintaining state-of-the-art performance.}, language = {en} } @article{LiaqatSednevStilleretal.2021, author = {Liaqat, Anam and Sednev, Maksim V. and Stiller, Carina and H{\"o}bartner, Claudia}, title = {RNA-cleaving deoxyribozymes differentiate methylated cytidine isomers in RNA}, series = {Angewandte Chemie International Edition}, volume = {60}, journal = {Angewandte Chemie International Edition}, doi = {10.1002/anie.202106517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256519}, pages = {19058-19062}, year = {2021}, abstract = {Deoxyribozymes are emerging as modification-specific endonucleases for the analysis of epigenetic RNA modifications. Here, we report RNA-cleaving deoxyribozymes that differentially respond to the presence of natural methylated cytidines, 3-methylcytidine (m\(^3\)C), N\(^4\)-methylcytidine (m\(^4\)C), and 5-methylcytidine (m\(^5\)C), respectively. Using in vitro selection, we found several DNA catalysts, which are selectively activated by only one of the three cytidine isomers, and display 10- to 30-fold accelerated cleavage of their target m\(^3\)C-, m\(^4\)C- or m\(^5\)C-modified RNA. An additional deoxyribozyme is strongly inhibited by any of the three methylcytidines, but effectively cleaves unmodified RNA. The mXC-detecting deoxyribozymes are programmable for the interrogation of natural RNAs of interest, as demonstrated for human mitochondrial tRNAs containing known m\(^3\)C and m\(^5\)C sites. The results underline the potential of synthetic functional DNA to shape highly selective active sites.}, language = {en} } @article{HalbigLatoschik2021, author = {Halbig, Andreas and Latoschik, Marc Erich}, title = {A systematic review of physiological measurements, factors, methods, and applications in virtual reality}, series = {Frontiers in Virtual Reality}, volume = {2}, journal = {Frontiers in Virtual Reality}, doi = {10.3389/frvir.2021.694567}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260503}, year = {2021}, abstract = {Measurements of physiological parameters provide an objective, often non-intrusive, and (at least semi-)automatic evaluation and utilization of user behavior. In addition, specific hardware devices of Virtual Reality (VR) often ship with built-in sensors, i.e. eye-tracking and movements sensors. Hence, the combination of physiological measurements and VR applications seems promising. Several approaches have investigated the applicability and benefits of this combination for various fields of applications. However, the range of possible application fields, coupled with potentially useful and beneficial physiological parameters, types of sensor, target variables and factors, and analysis approaches and techniques is manifold. This article provides a systematic overview and an extensive state-of-the-art review of the usage of physiological measurements in VR. We identified 1,119 works that make use of physiological measurements in VR. Within these, we identified 32 approaches that focus on the classification of characteristics of experience, common in VR applications. The first part of this review categorizes the 1,119 works by field of application, i.e. therapy, training, entertainment, and communication and interaction, as well as by the specific target factors and variables measured by the physiological parameters. An additional category summarizes general VR approaches applicable to all specific fields of application since they target typical VR qualities. In the second part of this review, we analyze the target factors and variables regarding the respective methods used for an automatic analysis and, potentially, classification. For example, we highlight which measurement setups have been proven to be sensitive enough to distinguish different levels of arousal, valence, anxiety, stress, or cognitive workload in the virtual realm. This work may prove useful for all researchers wanting to use physiological data in VR and who want to have a good overview of prior approaches taken, their benefits and potential drawbacks.}, language = {en} } @article{LenschowFussKircheretal.2021, author = {Lenschow, Christina and Fuss, Carmina Teresa and Kircher, Stefan and Buck, Andreas and Kickuth, Ralph and Reibetanz, Joachim and Wiegering, Armin and Stenzinger, Albrecht and H{\"u}bschmann, Daniel and Germer, Christoph Thomas and Fassnacht, Martin and Fr{\"o}hling, Stefan and Schlegel, Nicolas and Kroiss, Matthias}, title = {Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management}, series = {Frontiers in Endocrinology}, volume = {12}, journal = {Frontiers in Endocrinology}, issn = {1664-2392}, doi = {10.3389/fendo.2021.643328}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233362}, year = {2021}, abstract = {Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1\% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.}, language = {en} } @article{RadeloffWeissHagenetal.2021, author = {Radeloff, Katrin and Weiss, Dorothee and Hagen, Rudolf and Kleinsasser, Norbert and Radeloff, Andreas}, title = {Differentiation behaviour of adipose-derived stromal cells (ASCs) seeded on polyurethane-fibrin scaffolds in vitro and in vivo}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {8}, issn = {2227-9059}, doi = {10.3390/biomedicines9080982}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245030}, year = {2021}, abstract = {Adipose-derived stromal cells (ASCs) are a promising cell source for tissue engineering and regenerative medicine approaches for cartilage replacement. For chondrogenic differentiation, human (h)ASCs were seeded on three-dimensional polyurethane (PU) fibrin composites and induced with a chondrogenic differentiation medium containing TGF-ß3, BMP-6, and IGF-1 in various combinations. In addition, in vitro predifferentiated cell-seeded constructs were implanted into auricular cartilage defects of New Zealand White Rabbits for 4 and 12 weeks. Histological, immunohistochemical, and RT-PCR analyses were performed on the constructs maintained in vitro to determine extracellular matrix (ECM) deposition and expression of specific cartilage markers. Chondrogenic differentiated constructs showed a uniform distribution of cells and ECM proteins. RT-PCR showed increased gene expression of collagen II, collagen X, and aggrecan and nearly stable expression of SOX-9 and collagen I. Rabbit (r)ASC-seeded PU-fibrin composites implanted in ear cartilage defects of New Zealand White Rabbits showed deposition of ECM with structures resembling cartilage lacunae by Alcian blue staining. However, extracellular calcium deposition became detectable over the course of 12 weeks. RT-PCR showed evidence of endochondral ossification during the time course with the expression of specific marker genes (collagen X and RUNX-2). In conclusion, hASCs show chondrogenic differentiation capacity in vitro with the expression of specific marker genes and deposition of cartilage-specific ECM proteins. After implantation of predifferentiated rASC-seeded PU-fibrin scaffolds into a cartilage defect, the constructs undergo the route of endochondral ossification.}, language = {en} } @article{GernertKieselFroehlichetal.2021, author = {Gernert, Michael and Kiesel, Matthias and Fr{\"o}hlich, Matthias and Renner, Regina and Strunz, Patrick-Pascal and Portegys, Jan and Tony, Hans-Peter and Schmalzing, Marc and Schwaneck, Eva Christina}, title = {High Prevalence of Genital Human Papillomavirus Infection in Patients With Primary Immunodeficiencies}, series = {Frontiers in Immunology}, volume = {12}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2021.789345}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250273}, year = {2021}, abstract = {Background Genital human papillomavirus (HPV)-infections are common in the general population and are responsible for relevant numbers of epithelial malignancies. Much data on the HPV-prevalence is available for secondary immunodeficiencies, especially for patients with human immunodeficiency virus (HIV)-infection. Little is known about the genital HPV-prevalence in patients with primary immunodeficiencies (PIDs). Methods We performed a cross-sectional study of patients with PIDs and took genital swabs from male and female patients, which were analyzed with polymerase chain reaction for the presence of HPV-DNA. Clinical and laboratory data was collected to identify risk factors. Results 28 PID patients were included in this study. 10 of 28 (35.7\%) had HPV-DNA in their genital swabs. 6 patients had high-risk HPV-types (21.4\%). Most patients had asymptomatic HPV-infections, as genital warts were rare (2 of 28 patients) and HPV-associated malignancy was absent. Differences in the HPV-positivity regarding clinical PID-diagnosis, duration of PID, age, sex, immunosuppression, immunoglobulin replacement, or circumcision in males were not present. HPV-positive PID patients had higher numbers of T cells (CD3\(^+\)), of cytotoxic T cells (CD3\(^+\)/CD8\(^+\)), of transitional B cells (CD19\(^+\)/CD38\(^{++}\)/CD10\(^+\)/IgD\(^+\)), and of plasmablasts (CD19\(^+\)/CD38\(^+\)/CD27\(^{++}\)/IgD\(^-\)) compared to HPV-negative. Conclusion PID patients exhibit a high rate of genital HPV-infections with a high rate of high-risk HPV-types. Regular screening for symptomatic genital HPV-infection and HPV-associated malignancy in PID patients seems recommendable.}, language = {en} } @article{HendricksLenschowKroissetal.2021, author = {Hendricks, Anne and Lenschow, Christina and Kroiss, Matthias and Buck, Andreas and Kickuth, Ralph and Germer, Christoph-Thomas and Schlegel, Nicolas}, title = {Evaluation of diagnostic efficacy for localization of parathyroid adenoma in patients with primary hyperparathyroidism undergoing repeat surgery}, series = {Langenbeck's Archives of Surgery}, volume = {406}, journal = {Langenbeck's Archives of Surgery}, number = {5}, issn = {1435-2451}, doi = {10.1007/s00423-021-02191-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267520}, pages = {1615-1624}, year = {2021}, abstract = {Purpose Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse. Methods A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated. Results Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24-48h after surgery and was achieved in 26/28 patients (92.9\%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100\%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80\%. Conclusion These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT.}, language = {en} } @article{GhanawiHennleinZareetal.2021, author = {Ghanawi, Hanaa and Hennlein, Luisa and Zare, Abdolhossein and Bader, Jakob and Salehi, Saeede and Hornburg, Daniel and Ji, Changhe and Sivadasan, Rajeeve and Drepper, Carsten and Meissner, Felix and Mann, Matthias and Jablonka, Sibylle and Briese, Michael and Sendtner, Michael}, title = {Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin}, series = {Nucleic Acids Research}, volume = {49}, journal = {Nucleic Acids Research}, number = {21}, doi = {10.1093/nar/gkab1120}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265687}, pages = {12284-12305}, year = {2021}, abstract = {Neurons critically rely on the functions of RNA-binding proteins to maintain their polarity and resistance to neurotoxic stress. HnRNP R has a diverse range of post-transcriptional regulatory functions and is important for neuronal development by regulating axon growth. Hnrnpr pre-mRNA undergoes alternative splicing giving rise to a full-length protein and a shorter isoform lacking its N-terminal acidic domain. To investigate functions selectively associated with the full-length hnRNP R isoform, we generated a Hnrnpr knockout mouse (Hnrnpr\(^{tm1a/tm1a}\)) in which expression of full-length hnRNP R was abolished while production of the truncated hnRNP R isoform was retained. Motoneurons cultured from Hnrnpr\(^{tm1a/tm1a}\) mice did not show any axonal growth defects but exhibited enhanced accumulation of double-strand breaks and an impaired DNA damage response upon exposure to genotoxic agents. Proteomic analysis of the hnRNP R interactome revealed the multifunctional protein Yb1 as a top interactor. Yb1-depleted motoneurons were defective in DNA damage repair. We show that Yb1 is recruited to chromatin upon DNA damage where it interacts with gamma-H2AX, a mechanism that is dependent on full-length hnRNP R. Our findings thus suggest a novel role of hnRNP R in maintaining genomic integrity and highlight the function of its N-terminal acidic domain in this context.}, language = {en} } @article{GuptaSrivastavaMinochaetal.2021, author = {Gupta, Shishir K. and Srivastava, Mugdha and Minocha, Rashmi and Akash, Aman and Dangwal, Seema and Dandekar, Thomas}, title = {Alveolar regeneration in COVID-19 patients: a network perspective}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {20}, issn = {1422-0067}, doi = {10.3390/ijms222011279}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284307}, year = {2021}, abstract = {A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.}, language = {en} } @article{SuratVogelWiegeringetal.2021, author = {Surat, G{\"u}zin and Vogel, Ulrich and Wiegering, Armin and Germer, Christoph-Thomas and Lock, Johan Friso}, title = {Defining the scope of antimicrobial stewardship interventions on the prescription quality of antibiotics for surgical intra-abdominal infections}, series = {Antibiotics}, volume = {10}, journal = {Antibiotics}, number = {1}, issn = {2079-6382}, doi = {10.3390/antibiotics10010073}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223034}, year = {2021}, abstract = {Background: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications. Methods: A single-center quality improvement study with retrospective evaluation of the impact of antimicrobial stewardship measures on optimizing antibacterial use in intra-abdominal infections requiring emergency surgery was performed. The study was conducted in a tertiary hospital in Germany from January 1, 2016, to January 30, 2020, three years after putting a set of antimicrobial stewardship standards into effect. Results: 767 patients were analyzed (n = 495 in 2016 and 2017, the baseline period; n = 272 in 2018, the antimicrobial stewardship period). The total days of therapy per 100 patient days declined from 47.0 to 42.2 days (p = 0.035). The rate of patients receiving postoperative therapy decreased from 56.8\% to 45.2\% (p = 0.002), comparing both periods. There was a significant decline in the rate of inappropriate indications (17.4\% to 8.1 \%, p = 0.015) as well as a significant change from broad-spectrum to narrow-spectrum antibiotic use (28.8\% to 6.5\%, p ≤ 0.001) for postoperative therapy. The significant decline in antibiotic use did not affect either clinical outcomes or the rate of postoperative wound complications. Conclusions: Postoperative antibiotic use for intra-abdominal infections could be significantly reduced by antimicrobial stewardship interventions. The identification of inappropriate indications remains a key target for antimicrobial stewardship programs.}, language = {en} } @article{GloegglerHellmannVonMansteinetal.2021, author = {Gl{\"o}ggler, Julia C. and Hellmann, Daniel and Von Manstein, Maja and J{\"a}ger, Rudolph and Repky, Stefan and Beyersmann, Jan and Lapatki, Bernd G.}, title = {Motor learning might contribute to a therapeutic anterior shift of the habitual mandibular position—An exploratory study}, series = {Journal of Oral Rehabilitation}, volume = {48}, journal = {Journal of Oral Rehabilitation}, number = {8}, doi = {10.1111/joor.13183}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262644}, pages = {891 -- 900}, year = {2021}, abstract = {Background Passive mandibular advancement with functional appliances is commonly used to treat juvenile patients with mandibular retrognathism. Objective The aim of this study was to investigate whether active repetitive training of the mandible into an anterior position would result in a shift of the habitual mandibular position (HMP). Methods Twenty adult healthy subjects were randomly assigned to one of two groups: a training group receiving six supervised functional training sessions of 10 min each and a control group without training. Bonded lateral biteplates disengaged occlusion among both groups throughout the 15-day experiment. Customised registration-training appliances consisted of a maxillary component with an anterior plane and a mandibular component with an attached metal sphere. Training sessions consisted of repeated mouth-opening/closing cycles (frequency: 30/min) to hit an anteriorly positioned hemispherical target notch with this metal sphere. The HMP was registered at defined times during the experiment. Results The HMP in the training group showed a statistically significant anterior shift of 1.6 mm (interquartile range [IQR]: 1.2 mm), compared with a significant posterior shift of -0.8 mm (IQR: 2.8 mm) in the control group (p < .05). Although the anterior shift among the training group showed a partial relapse 4 days after the first training block, it then advanced slightly in the 4-day interval after the second training block, which might indicate neuroplasticity of the masticatory motor system. Conclusions Motor learning by repetitive training of the mandible into an anterior position might help to improve the results of functional appliance therapy among patients with mandibular retrognathism.}, language = {en} } @article{DietzKudsiGarciaUrenaetal.2021, author = {Dietz, Ulrich A. and Kudsi, O. Yusef and Garcia-Ure{\~n}a, Miguel and Baur, Johannes and Ramser, Michaela and Maksimovic, Sladjana and Keller, Nicola and D{\"o}rfer, J{\"o}rg and Eisner, Lukas and Wiegering, Armin}, title = {Robotische Hernienchirurgie III: Robotische Inzisionalhernienversorgung mit „transversus abdominis release" (r-TAR). Videobeitrag und Ergebnisse einer Kohortenstudie}, series = {Der Chirurg}, volume = {92}, journal = {Der Chirurg}, number = {10}, doi = {10.1007/s00104-021-01480-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265172}, pages = {936-947}, year = {2021}, abstract = {Das Prinzip der gezielten Trennung bzw. Schw{\"a}chung einzelner Komponenten der Bauchdecke zur Spannungsentlastung der Medianlinie bei großen abdominellen Rekonstruktionen ist seit {\"u}ber 30 Jahren als anteriore Komponentenseparation (aKS) bekannt und ein etabliertes Verfahren. Auf der Suche nach Alternativen mit geringerer Komplikationsrate wurde die posteriore Komponentenseparation (pKS) entwickelt; der „transversus abdominis release" (TAR) ist eine nervenschonende Modifikation der pKS. Mit den ergonomischen Ressourcen der Robotik (z. B. abgewinkelte Instrumente) kann der TAR minimal-invasiv durchgef{\"u}hrt werden (r-TAR): Bruchl{\"u}cken von bis zu 14 cm lassen sich verschließen und ein großes extraperitoneales Netz implantieren. In diesem Videobeitrag wird die Versorgung großer Inzisionalhernien in der r‑TAR-Technik pr{\"a}sentiert. Exemplarisch werden die Ergebnisse einer Kohortenstudie an 13 konsekutiven Patienten vorgestellt. Der Eingriff ist anspruchsvoll, die eigenen Ergebnisse sind - wie auch die Berichte aus der Literatur - ermutigend. Der r‑TAR entwickelt sich zur K{\"o}nigsdisziplin der Bauchdeckenrekonstruktion.}, language = {de} } @article{ZwirnerAndersBohnertetal.2021, author = {Zwirner, Johann and Anders, Sven and Bohnert, Simone and Burkhardt, Ralph and Da Broi, Ugo and Hammer, Niels and Pohlers, Dirk and Tse, Rexson and Ondruschka, Benjamin}, title = {Screening for fatal traumatic brain injuries in cerebrospinal fluid using blood-validated CK and CK-MB immunoassays}, series = {Biomolecules}, volume = {11}, journal = {Biomolecules}, number = {7}, issn = {2218-273X}, doi = {10.3390/biom11071061}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242769}, year = {2021}, abstract = {A single, specific, sensitive biochemical biomarker that can reliably diagnose a traumatic brain injury (TBI) has not yet been found, but combining different biomarkers would be the most promising approach in clinical and postmortem settings. In addition, identifying new biomarkers and developing laboratory tests can be time-consuming and economically challenging. As such, it would be efficient to use established clinical diagnostic assays for postmortem biochemistry. In this study, postmortem cerebrospinal fluid samples from 45 lethal TBI cases and 47 controls were analyzed using commercially available blood-validated assays for creatine kinase (CK) activity and its heart-type isoenzyme (CK-MB). TBI cases with a survival time of up to two hours showed an increase in both CK and CK-MB with moderate (CK-MB: AUC = 0.788, p < 0.001) to high (CK: AUC = 0.811, p < 0.001) diagnostic accuracy. This reflected the excessive increase of the brain-type CK isoenzyme (CK-BB) following a TBI. The results provide evidence that CK immunoassays can be used as an adjunct quantitative test aid in diagnosing acute TBI-related fatalities.}, language = {en} } @article{LauruschkatPageWhiteetal.2021, author = {Lauruschkat, Chris D. and Page, Lukas and White, P. Lewis and Etter, Sonja and Davies, Helen E. and Duckers, Jamie and Ebel, Frank and Schnack, Elisabeth and Backx, Matthijs and Dragan, Mariola and Schlegel, Nicolas and Kniemeyer, Olaf and Brakhage, Axel A. and Einsele, Hermann and Loeffler, Juergen and Wurster, Sebastian}, title = {Development of a simple and robust whole blood assay with dual co-stimulation to quantify the release of T-cellular signature cytokines in response to Aspergillus fumigatus antigens}, series = {Journal of Fungi}, volume = {7}, journal = {Journal of Fungi}, number = {6}, issn = {2309-608X}, doi = {10.3390/jof7060462}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241025}, year = {2021}, abstract = {Deeper understanding of mold-induced cytokine signatures could promote advances in the diagnosis and treatment of invasive mycoses and mold-associated hypersensitivity syndromes. Currently, most T-cellular immunoassays in medical mycology require the isolation of mononuclear cells and have limited robustness and practicability, hampering their broader applicability in clinical practice. Therefore, we developed a simple, cost-efficient whole blood (WB) assay with dual α-CD28 and α-CD49d co-stimulation to quantify cytokine secretion in response to Aspergillus fumigatus antigens. Dual co-stimulation strongly enhanced A. fumigatus-induced release of T-cellular signature cytokines detectable by enzyme-linked immunosorbent assay (ELISA) or a multiplex cytokine assay. Furthermore, T-cell-dependent activation and cytokine response of innate immune cells was captured by the assay. The protocol consistently showed little technical variation and high robustness to pre-analytic delays of up to 8 h. Stimulation with an A. fumigatus lysate elicited at least 7-fold greater median concentrations of key T-helper cell signature cytokines, including IL-17 and the type 2 T-helper cell cytokines IL-4 and IL-5 in WB samples from patients with Aspergillus-associated lung pathologies versus patients with non-mold-related lung diseases, suggesting high discriminatory power of the assay. These results position WB-ELISA with dual co-stimulation as a simple, accurate, and robust immunoassay for translational applications, encouraging further evaluation as a platform to monitor host immunity to opportunistic pathogens.}, language = {en} } @article{KuckaWajant2021, author = {Kucka, Kirstin and Wajant, Harald}, title = {Receptor Oligomerization and Its Relevance for Signaling by Receptors of the Tumor Necrosis Factor Receptor Superfamily}, series = {Frontiers in Cell and Developmental Biology}, volume = {8}, journal = {Frontiers in Cell and Developmental Biology}, issn = {2296-634X}, doi = {10.3389/fcell.2020.615141}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227180}, year = {2021}, abstract = {With the exception of a few signaling incompetent decoy receptors, the receptors of the tumor necrosis factor receptor superfamily (TNFRSF) are signaling competent and engage in signaling pathways resulting in inflammation, proliferation, differentiation, and cell migration and also in cell death induction. TNFRSF receptors (TNFRs) become activated by ligands of the TNF superfamily (TNFSF). TNFSF ligands (TNFLs) occur as trimeric type II transmembrane proteins but often also as soluble ligand trimers released from the membrane-bound form by proteolysis. The signaling competent TNFRs are efficiently activated by the membrane-bound TNFLs. The latter recruit three TNFR molecules, but there is growing evidence that this is not sufficient to trigger all aspects of TNFR signaling; rather, the formed trimeric TNFL-TNFR complexes have to cluster secondarily in the cell-to-cell contact zone for full TNFR activation. With respect to their response to soluble ligand trimers, the signaling competent TNFRs can be subdivided into two groups. TNFRs of one group, designated as category I TNFRs, are robustly activated by soluble ligand trimers. The receptors of a second group (category II TNFRs), however, failed to become properly activated by soluble ligand trimers despite high affinity binding. The limited responsiveness of category II TNFRs to soluble TNFLs can be overcome by physical linkage of two or more soluble ligand trimers or, alternatively, by anchoring the soluble ligand molecules to the cell surface or extracellular matrix. This suggests that category II TNFRs have a limited ability to promote clustering of trimeric TNFL-TNFR complexes outside the context of cell-cell contacts. In this review, we will focus on three aspects on the relevance of receptor oligomerization for TNFR signaling: (i) the structural factors which promote clustering of free and liganded TNFRs, (ii) the signaling pathway specificity of the receptor oligomerization requirement, and (iii) the consequences for the design and development of TNFR agonists.}, language = {en} } @article{CarolusWienrichToerkeetal.2021, author = {Carolus, Astrid and Wienrich, Carolin and T{\"o}rke, Anna and Friedel, Tobias and Schwietering, Christian and Sperzel, Mareike}, title = {'Alexa, I feel for you!' Observers' empathetic reactions towards a conversational agent}, series = {Frontiers in Computer Science}, volume = {3}, journal = {Frontiers in Computer Science}, doi = {10.3389/fcomp.2021.682982}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258807}, year = {2021}, abstract = {Conversational agents and smart speakers have grown in popularity offering a variety of options for use, which are available through intuitive speech operation. In contrast to the standard dyad of a single user and a device, voice-controlled operations can be observed by further attendees resulting in new, more social usage scenarios. Referring to the concept of 'media equation' and to research on the idea of 'computers as social actors,' which describes the potential of technology to trigger emotional reactions in users, this paper asks for the capacity of smart speakers to elicit empathy in observers of interactions. In a 2 × 2 online experiment, 140 participants watched a video of a man talking to an Amazon Echo either rudely or neutrally (factor 1), addressing it as 'Alexa' or 'Computer' (factor 2). Controlling for participants' trait empathy, the rude treatment results in participants' significantly higher ratings of empathy with the device, compared to the neutral treatment. The form of address had no significant effect. Results were independent of the participants' gender and usage experience indicating a rather universal effect, which confirms the basic idea of the media equation. Implications for users, developers and researchers were discussed in the light of (future) omnipresent voice-based technology interaction scenarios.}, language = {en} } @article{KumarKhamzinaKnoefeletal.2021, author = {Kumar, Navneet and Khamzina, Asia and Kn{\"o}fel, Patrick and Lamers, John P. A. and Tischbein, Bernhard}, title = {Afforestation of degraded croplands as a water-saving option in irrigated region of the Aral Sea Basin}, series = {Water}, volume = {13}, journal = {Water}, number = {10}, issn = {2073-4441}, doi = {10.3390/w13101433}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239626}, year = {2021}, abstract = {Climate change is likely to decrease surface water availability in Central Asia, thereby necessitating land use adaptations in irrigated regions. The introduction of trees to marginally productive croplands with shallow groundwater was suggested for irrigation water-saving and improving the land's productivity. Considering the possible trade-offs with water availability in large-scale afforestation, our study predicted the impacts on water balance components in the lower reaches of the Amudarya River to facilitate afforestation planning using the Soil and Water Assessment Tool (SWAT). The land-use scenarios used for modeling analysis considered the afforestation of 62\% and 100\% of marginally productive croplands under average and low irrigation water supply identified from historical land-use maps. The results indicate a dramatic decrease in the examined water balance components in all afforestation scenarios based largely on the reduced irrigation demand of trees compared to the main crops. Specifically, replacing current crops (mostly cotton) with trees on all marginal land (approximately 663 km\(^2\)) in the study region with an average water availability would save 1037 mln m\(^3\) of gross irrigation input within the study region and lower the annual drainage discharge by 504 mln m\(^3\). These effects have a considerable potential to support irrigation water management and enhance drainage functions in adapting to future water supply limitations.}, language = {en} } @article{ZechScherfClavelDanielsetal.2021, author = {Zech, Linda D. and Scherf-Clavel, Maike and Daniels, Christine and Schwab, Michael and Deckert, J{\"u}rgen and Unterecker, Stefan and Herr, Alexandra S.}, title = {Patients with higher vitamin D levels show stronger improvement of self-reported depressive symptoms in psychogeriatric day-care setting}, series = {Journal of Neural Transmission}, volume = {128}, journal = {Journal of Neural Transmission}, number = {8}, issn = {1435-1463}, doi = {10.1007/s00702-021-02385-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268525}, pages = {1233-1238}, year = {2021}, abstract = {Depression is a common psychiatric disorder among geriatric patients that decreases the quality of life and increases morbidity and mortality. Vitamin D as a neuro-steroid hormone might play a role in the onset and treatment of depression. In the present study, the association between depressive symptoms and vitamin D concentration in serum was evaluated. 140 patients of a psychogeriatric day-care unit were included. The geriatric depression scale (GDS) and the Hamilton depression rating scale (HDRS) were assessed at the beginning and end of treatment, GDS scores additionally 6 weeks after discharge from the day-care unit. Vitamin D levels were measured at the beginning of the treatment, routinely. Patients with levels below 30 µg/L were treated with 1000 IU vitamin D per day. There was no association between the severity of depressive symptoms and the concentration of vitamin D at the beginning of the treatment. Patients with higher vitamin D levels showed a stronger decline of depressive symptoms measured by the GDS during their stay in the day-care unit. We provide evidence that vitamin D serum levels might influence antidepressant therapy response in a geriatric population. Prospective studies are necessary to determine which patients may profit from add-on vitamin D therapy.}, language = {en} } @article{GerhardHartmannWiegeringBenoitetal.2021, author = {Gerhard-Hartmann, Elena and Wiegering, Verena and Benoit, Clemens and Meyer, Thomas and Rosenwald, Andreas and Maurus, Katja and Ernestus, Karen}, title = {A large retroperitoneal lipoblastoma as an incidental finding: a case report}, series = {BMC Pediatrics}, volume = {21}, journal = {BMC Pediatrics}, doi = {10.1186/s12887-021-02628-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260173}, year = {2021}, abstract = {Background Lipoblastoma is a rare benign mesenchymal neoplasm of infancy that most commonly occurs on the extremities and trunk but can arise at variable sites of the body. Retroperitoneal lipoblastomas are particularly rare but can grow to enormous size, and preoperative diagnosis is difficult with diverse, mostly malignant differential diagnoses that would lead to aggressive therapy. Since lipoblastoma is a benign tumor that has an excellent prognosis after resection, correct diagnosis is crucial. Case presentation A case of a large retroperitoneal tumor of a 24-month old infant that was clinically suspicious of a malignant tumor is presented. Due to proximity to the right kidney, clinically most probably a nephroblastoma or clear cell sarcoma of the kidney was suspected. Radiological findings were ambiguous. Therefore, the mass was biopsied, and histology revealed an adipocytic lesion. Although mostly composed of mature adipocytes, in view of the age of the patient, the differential diagnosis of a (maturing) lipoblastoma was raised, which was supported by molecular analysis demonstrating a HAS2-PLAG1 fusion. The tumor was completely resected, and further histopathological workup led to the final diagnosis of a 13 cm large retroperitoneal maturing lipoblastoma. The child recovered promptly from surgery and showed no evidence of recurrence so far. Conclusion Although rare, lipoblastoma should be included in the differential diagnoses of retroperitoneal tumors in infants and children, and molecular diagnostic approaches could be a helpful diagnostic adjunct in challenging cases.}, language = {en} } @article{SchilcherHilsmannRauscheretal.2021, author = {Schilcher, Felix and Hilsmann, Lioba and Rauscher, Lisa and Değirmenci, Laura and Krischke, Markus and Krischke, Beate and Ankenbrand, Markus and Rutschmann, Benjamin and Mueller, Martin J. and Steffan-Dewenter, Ingolf and Scheiner, Ricarda}, title = {In vitro rearing changes social task performance and physiology in honeybees}, series = {Insects}, volume = {13}, journal = {Insects}, number = {1}, issn = {2075-4450}, doi = {10.3390/insects13010004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252305}, year = {2021}, abstract = {In vitro rearing of honeybee larvae is an established method that enables exact control and monitoring of developmental factors and allows controlled application of pesticides or pathogens. However, only a few studies have investigated how the rearing method itself affects the behavior of the resulting adult honeybees. We raised honeybees in vitro according to a standardized protocol: marking the emerging honeybees individually and inserting them into established colonies. Subsequently, we investigated the behavioral performance of nurse bees and foragers and quantified the physiological factors underlying the social organization. Adult honeybees raised in vitro differed from naturally reared honeybees in their probability of performing social tasks. Further, in vitro-reared bees foraged for a shorter duration in their life and performed fewer foraging trips. Nursing behavior appeared to be unaffected by rearing condition. Weight was also unaffected by rearing condition. Interestingly, juvenile hormone titers, which normally increase strongly around the time when a honeybee becomes a forager, were significantly lower in three- and four-week-old in vitro bees. The effects of the rearing environment on individual sucrose responsiveness and lipid levels were rather minor. These data suggest that larval rearing conditions can affect the task performance and physiology of adult bees despite equal weight, pointing to an important role of the colony environment for these factors. Our observations of behavior and metabolic pathways offer important novel insight into how the rearing environment affects adult honeybees.}, language = {en} } @article{MeyerGerhardHartmannLodesetal.2021, author = {Meyer, Till Jasper and Gerhard-Hartmann, Elena and Lodes, Nina and Scherzad, Agmal and Hagen, Rudolf and Steinke, Maria and Hackenberg, Stephan}, title = {Pilot study on the value of Raman spectroscopy in the entity assignment of salivary gland tumors}, series = {PLoS One}, volume = {16}, journal = {PLoS One}, number = {9}, doi = {10.1371/journal.pone.0257470}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264736}, year = {2021}, abstract = {Background The entity assignment of salivary gland tumors (SGT) based on histomorphology can be challenging. Raman spectroscopy has been applied to analyze differences in the molecular composition of tissues. The aim of this study was to evaluate the suitability of RS for entity assignment in SGT. Methods Raman data were collected in deparaffinized sections of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Multivariate data and chemometric analysis were completed using the Unscrambler software. Results The Raman spectra detected in ACC samples were mostly assigned to nucleic acids, lipids, and amides. In a principal component-based linear discriminant analysis (LDA) 18 of 20 tumor samples were classified correctly. Conclusion In this proof of concept study, we show that a reliable SGT diagnosis based on LDA algorithm appears possible, despite variations in the entity-specific mean spectra. However, a standardized workflow for tissue sample preparation, measurement setup, and chemometric algorithms is essential to get reliable results.}, language = {en} } @article{FriedmannFicklFischeretal.2021, author = {Friedmann, Anton and Fickl, Stefan and Fischer, Kai R. and Dalloul, Milad and Goetz, Werner and Kauffmann, Frederic}, title = {Horizontal augmentation of chronic mandibular defects by the Guided Bone Regeneration approach: a randomized study in dogs}, series = {Materials}, volume = {15}, journal = {Materials}, number = {1}, issn = {1996-1944}, doi = {10.3390/ma15010238}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252351}, year = {2021}, abstract = {Various biomaterial combinations have been studied focusing on their ability to stabilize blood clots and maintain space under soft tissue to support new bone formation. A popular combination is Deproteinized Bovine Bone Mineral (DBBM) placed with a native collagen membrane (NCM) tacked to native bone. In this study, we compared the outcome of this treatment option to those achieved with three different graft/membrane combinations with respect to total newly occupied area and the mineralized compound inside. After bi-lateral extraction of two mandibular premolars in five adult beagles L-shaped alveolar defects were created. A total of 20 defects healed for 6 weeks resulting in chronic type bone defects. At baseline, four options were randomly allocated to five defects each: a. DBBM + NCM with a four-pin fixation across the ridge; b. DBBM + RCLC (ribose cross-linked collagen membrane); c. DBBM + NPPM (native porcine pericardium membrane); and d. Ca-sulfate (CS) + RCLC membrane. Membranes in b/c/d were not fixed; complete tensionless wound closure was achieved by CAF. Termination after 3 months and sampling followed, and non-decalcified processing and toluidine blue staining were applied. Microscopic images obtained at standardized magnification were histomorphometrically assessed by ImageJ software (NIH). An ANOVA post hoc test was applied; histomorphometric data are presented in this paper as medians and interquartile ranges (IRs). All sites healed uneventfully, all sites were sampled and block separation followed before Technovit embedding. Two central sections per block for each group were included. Two of five specimen were lost due to processing error and were excluded from group b. New bone area was significantly greater for option b. compared to a. (p = 0.001), c. (p = 0.002), and d. (p = 0.046). Residual non-bone graft area was significantly less for option d. compared to a. (p = 0.026) or c. (p = 0.021). We conclude that collagen membranes with a prolonged resorption/barrier profile combined with bone substitutes featuring different degradation profiles sufficiently support new bone formation. Tacking strategy/membrane fixation appears redundant when using these biomaterials.}, language = {en} } @article{MaucherSrourDanhofetal.2021, author = {Maucher, Marius and Srour, Micha and Danhof, Sophia and Einsele, Hermann and Hudecek, Michael and Yakoub-Agha, Ibrahim}, title = {Current limitations and perspectives of chimeric antigen receptor-T-cells in acute myeloid leukemia}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {24}, issn = {2072-6694}, doi = {10.3390/cancers13246157}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252180}, year = {2021}, abstract = {Adoptive transfer of gene-engineered chimeric antigen receptor (CAR)-T-cells has emerged as a powerful immunotherapy for combating hematologic cancers. Several target antigens that are prevalently expressed on AML cells have undergone evaluation in preclinical CAR-T-cell testing. Attributes of an 'ideal' target antigen for CAR-T-cell therapy in AML include high-level expression on leukemic blasts and leukemic stem cells (LSCs), and absence on healthy tissues, normal hematopoietic stem and progenitor cells (HSPCs). In contrast to other blood cancer types, where CAR-T therapies are being similarly studied, only a rather small number of AML patients has received CAR-T-cell treatment in clinical trials, resulting in limited clinical experience for this therapeutic approach in AML. For curative AML treatment, abrogation of bulk blasts and LSCs is mandatory with the need for hematopoietic recovery after CAR-T administration. Herein, we provide a critical review of the current pipeline of candidate target antigens and corresponding CAR-T-cell products in AML, assess challenges for clinical translation and implementation in routine clinical practice, as well as perspectives for overcoming them.}, language = {en} } @article{AidoZaitsevaWajantetal.2021, author = {Aido, Ahmed and Zaitseva, Olena and Wajant, Harald and Buzgo, Matej and Simaite, Aiva}, title = {Anti-Fn14 antibody-conjugated nanoparticles display membrane TWEAK-like agonism}, series = {Pharmaceutics}, volume = {13}, journal = {Pharmaceutics}, number = {7}, issn = {1999-4923}, doi = {10.3390/pharmaceutics13071072}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242710}, year = {2021}, abstract = {Conventional bivalent IgG antibodies targeting a subgroup of receptors of the TNF superfamily (TNFSF) including fibroblast growth factor-inducible 14 (anti-Fn14) typically display no or only very limited agonistic activity on their own and can only trigger receptor signaling by crosslinking or when bound to Fcγ receptors (FcγR). Both result in proximity of multiple antibody-bound TNFRSF receptor (TNFR) molecules, which enables engagement of TNFR-associated signaling pathways. Here, we have linked anti-Fn14 antibodies to gold nanoparticles to mimic the "activating" effect of plasma membrane-presented FcγR-anchored anti-Fn14 antibodies. We functionalized gold nanoparticles with poly-ethylene glycol (PEG) linkers and then coupled antibodies to the PEG surface of the nanoparticles. We found that Fn14 binding of the anti-Fn14 antibodies PDL192 and 5B6 is preserved upon attachment to the nanoparticles. More importantly, the gold nanoparticle-presented anti-Fn14 antibody molecules displayed strong agonistic activity. Our results suggest that conjugation of monoclonal anti-TNFR antibodies to gold nanoparticles can be exploited to uncover their latent agonism, e.g., for immunotherapeutic applications.}, language = {en} } @article{LoddeForschnerHasseletal.2021, author = {Lodde, Georg and Forschner, Andrea and Hassel, Jessica and Wulfken, Lena M. and Meier, Friedegund and Mohr, Peter and K{\"a}hler, Katharina and Schilling, Bastian and Loquai, Carmen and Berking, Carola and H{\"u}ning, Svea and Schatton, Kerstin and Gebhardt, Christoffer and Eckardt, Julia and Gutzmer, Ralf and Reinhardt, Lydia and Glutsch, Valerie and Nikfarjam, Ulrike and Erdmann, Michael and Stang, Andreas and Kowall, Bernd and Roesch, Alexander and Ugurel, Selma and Zimmer, Lisa and Schadendorf, Dirk and Livingstone, Elisabeth}, title = {Factors influencing the adjuvant therapy decision: results of a real-world multicenter data analysis of 904 melanoma patients}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {10}, issn = {2072-6694}, doi = {10.3390/cancers13102319}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239583}, year = {2021}, abstract = {Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) and targeted therapy (TT) significantly improved recurrence-free survival. This study investigates the real-world situation of 904 patients from 13 German skin cancer centers with an indication for adjuvant treatment since the approval of adjuvant ICI and TT. From adjusted log-binomial regression models, we estimated relative risks for associations between various influence factors and treatment decisions (adjuvant therapy yes/no, TT vs. ICI in BRAF mutant patients). Of these patients, 76.9\% (95\% CI 74-80) opted for a systemic adjuvant treatment. The probability of starting an adjuvant treatment was 26\% lower in patients >65 years (RR 0.74, 95\% CI 68-80). The most common reasons against adjuvant treatment given by patients were age (29.4\%, 95\% CI 24-38), and fear of adverse events (21.1\%, 95\% CI 16-28) and impaired quality of life (11.9\%, 95\% CI 7-16). Of all BRAF-mutated patients who opted for adjuvant treatment, 52.9\% (95\% CI 47-59) decided for ICI. Treatment decision for TT or ICI was barely associated with age, gender and tumor stage, but with comorbidities and affiliated center. Shortly after their approval, adjuvant treatments have been well accepted by physicians and patients. Age plays a decisive role in the decision for adjuvant treatment, while pre-existing autoimmune disease and regional differences influence the choice between TT or ICI.}, language = {en} }