@article{FaustFreitagBarrientosetal.2021, author = {Faust, Kirstin and Freitag, Nancy and Barrientos, Gabriela and Hartel, Christoph and Blois, Sandra M.}, title = {Galectin-Levels Are Elevated in Infants Born Preterm Due to Amniotic Infection and Rapidly Decline in the Neonatal Period}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.599104}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230701}, year = {2021}, abstract = {Galectin (gal)-1, -3, and -9 are members of a family of glycan binding proteins that mediate complex interactions between decidual, inflammatory and trophoblast cells modulating several processes during gestation, control of the maternal immune system, and parturition. Their immunomodulatory role in preterm birth and postnatal expression in preterm infants is unknown. We performed a single center prospective study of 170 preterm infants with a gestational age below 35 weeks. Peripheral venous blood samples were collected during the neonatal period and galectin-1, -3, and -9 were determined by ELISA. We noted a strong decline of circulating gal-1 and -3 levels but not gal-9 from birth to day 7 of life. There was an inverse correlation of gal-1 and -3 levels at birth with gestational age. Gal-1 levels were remarkably increased in infants born to amniotic infection syndrome (AIS), which was also observed for gal-9 levels. Infants who developed early-onset sepsis had higher levels of gal-3 at day 1 as compared to unaffected infants. Our observational data imply that galectin-1, -3, and -9 levels are elevated in preterm infants born in an inflammatory milieu such as AIS or EOS. Future studies need to address whether galectins mediate inflammation-induced preterm birth and could therefore be a target for clinical trials.}, language = {en} } @article{RasouliKianiPouyaShabalaetal.2021, author = {Rasouli, Fatemeh and Kiani-Pouya, Ali and Shabala, Lana and Li, Leiting and Tahir, Ayesha and Yu, Min and Hedrich, Rainer and Chen, Zhonghua and Wilson, Richard and Zhang, Heng and Shabala, Sergey}, title = {Salinity effects on guard cell proteome in Chenopodium quinoa}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {1}, issn = {1422-0067}, doi = {10.3390/ijms22010428}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285625}, year = {2021}, abstract = {Epidermal fragments enriched in guard cells (GCs) were isolated from the halophyte quinoa (Chenopodium quinoa Wild.) species, and the response at the proteome level was studied after salinity treatment of 300 mM NaCl for 3 weeks. In total, 2147 proteins were identified, of which 36\% were differentially expressed in response to salinity stress in GCs. Up and downregulated proteins included signaling molecules, enzyme modulators, transcription factors and oxidoreductases. The most abundant proteins induced by salt treatment were desiccation-responsive protein 29B (50-fold), osmotin-like protein OSML13 (13-fold), polycystin-1, lipoxygenase, alpha-toxin, and triacylglycerol lipase (PLAT) domain-containing protein 3-like (eight-fold), and dehydrin early responsive to dehydration (ERD14) (eight-fold). Ten proteins related to the gene ontology term "response to ABA" were upregulated in quinoa GC; this included aspartic protease, phospholipase D and plastid-lipid-associated protein. Additionally, seven proteins in the sucrose-starch pathway were upregulated in the GC in response to salinity stress, and accumulation of tryptophan synthase and L-methionine synthase (enzymes involved in the amino acid biosynthesis) was observed. Exogenous application of sucrose and tryptophan, L-methionine resulted in reduction in stomatal aperture and conductance, which could be advantageous for plants under salt stress. Eight aspartic proteinase proteins were highly upregulated in GCs of quinoa, and exogenous application of pepstatin A (an inhibitor of aspartic proteinase) was accompanied by higher oxidative stress and extremely low stomatal aperture and conductance, suggesting a possible role of aspartic proteinase in mitigating oxidative stress induced by saline conditions.}, language = {en} } @article{HuangDingRoelfsemaetal.2021, author = {Huang, Shouguang and Ding, Meiqi and Roelfsema, M. Rob G. and Dreyer, Ingo and Scherzer, S{\"o}nke and Al-Rasheid, Khaled A. S and Gao, Shiqiang and Nagel, Georg and Hedrich, Rainer and Konrad, Kai R.}, title = {Optogenetic control of the guard cell membrane potential and stomatal movement by the light-gated anion channel GtACR1}, series = {Science Advances}, volume = {7}, journal = {Science Advances}, number = {28}, doi = {10.1126/sciadv.abg4619}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260925}, year = {2021}, abstract = {Guard cells control the aperture of plant stomata, which are crucial for global fluxes of CO\(_2\) and water. In turn, guard cell anion channels are seen as key players for stomatal closure, but is activation of these channels sufficient to limit plant water loss? To answer this open question, we used an optogenetic approach based on the light-gated anion channelrhodopsin 1 (GtACR1). In tobacco guard cells that express GtACR1, blue- and green-light pulses elicit Cl\(^-\) and NO\(_3\)\(^-\) currents of -1 to -2 nA. The anion currents depolarize the plasma membrane by 60 to 80 mV, which causes opening of voltage-gated K+ channels and the extrusion of K+. As a result, continuous stimulation with green light leads to loss of guard cell turgor and closure of stomata at conditions that provoke stomatal opening in wild type. GtACR1 optogenetics thus provides unequivocal evidence that opening of anion channels is sufficient to close stomata.}, language = {en} } @article{SchieferleTappeKorteetal.2021, author = {Schieferle, Sebastian and Tappe, Beeke and Korte, Pamela and Mueller, Martin J. and Berger, Susanne}, title = {Pathogens and Elicitors Induce Local and Systemic Changes in Triacylglycerol Metabolism in Roots and in Leaves of Arabidopsis thaliana}, series = {Biology}, volume = {10}, journal = {Biology}, number = {9}, issn = {2079-7737}, doi = {10.3390/biology10090920}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246198}, year = {2021}, abstract = {Simple Summary Abiotic and biotic stress conditions result in profound changes in plant lipid metabolism. Vegetable oil consists of triacylglycerols, which are important energy and carbon storage compounds in seeds of various plant species. These compounds are also present in vegetative tissue, and levels have been reported to increase with different abiotic stresses in leaves. This work shows that triacylglycerols accumulate in roots and in distal, non-treated leaves upon treatment with a fungal pathogen or lipopolysaccharide (a common bacterial-derived elicitor in animals and plants). Treatment of leaves with a bacterial pathogen or a bacterial effector molecule results in triacylglycerol accumulation in leaves, but not systemically in roots. These results suggest that elicitor molecules are sufficient to induce an increase in triacylglycerol levels, and that unidirectional long-distance signaling from roots to leaves is involved in pathogen and elicitor-induced triacylglycerol accumulation. Abstract Interaction of plants with the environment affects lipid metabolism. Changes in the pattern of phospholipids have been reported in response to abiotic stress, particularly accumulation of triacylglycerols, but less is known about the alteration of lipid metabolism in response to biotic stress and leaves have been more intensively studied than roots. This work investigates the levels of lipids in roots as well as leaves of Arabidopsis thaliana in response to pathogens and elicitor molecules by UPLC-TOF-MS. Triacylglycerol levels increased in roots and systemically in leaves upon treatment of roots with the fungus Verticillium longisporum. Upon spray infection of leaves with the bacterial pathogen Pseudomonas syringae, triacylglycerols accumulated locally in leaves but not in roots. Treatment of roots with a bacterial lipopolysaccharide elicitor induced a strong triacylglycerol accumulation in roots and leaves. Induction of the expression of the bacterial effector AVRRPM1 resulted in a dramatic increase of triacylglycerol levels in leaves, indicating that elicitor molecules are sufficient to induce accumulation of triacylglycerols. These results give insight into local and systemic changes to lipid metabolism in roots and leaves in response to biotic stresses.}, language = {en} } @article{JobBittlingmaierMayeretal.2021, author = {Job, Hubert and Bittlingmaier, Sarah and Mayer, Marius and von Ruschkowski, Eick and Woltering, Manuel}, title = {Park-People Relationships: The Socioeconomic Monitoring of National Parks in Bavaria, Germany}, series = {Sustainability}, volume = {13}, journal = {Sustainability}, number = {16}, issn = {2071-1050}, doi = {10.3390/su13168984}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245061}, year = {2021}, abstract = {Questions about park-people relationships and the understanding and handling of the conflicts that may result from the creation and management of national parks in the surrounding area are prerequisites for both successful park management and sustainable rural tourism development. This paper analyzes the roles that research may play in relation to park-people relationships in the context of the two oldest German national parks located in Bavaria. The different fields of action of national parks are used to identify the potential for conflict, using detailed case studies from the Bavarian Forest and Berchtesgaden National Parks using quantitative population surveys carried out in 2018. The overall attitude towards both national parks is overwhelmingly positive, with trust towards park administrations and the perceived economic benefits from rural tourism being the attitudes most strongly correlated to the overall level of park-people relationships. Nevertheless, some points of contention still exist, like the ecological integrity approach towards strict nature conservation and related landscape changes (e.g., deadwood cover). A comparison over time shows in both cases that the spatial proximity to the protected area negatively influences people's attitudes towards the parks, but less so than in the past. Recommendations for national park management include communicating proactively and with greater transparency with locals and decision-makers, to identify conflicts earlier and, where possible, to eliminate them. Furthermore, developing a standardized method to monitor park-people relationships in Germany is a must and would benefit integrated approaches in research and management based on conservation social science.}, language = {en} } @article{BuddeHassounTangosetal.2021, author = {Budde, Heidi and Hassoun, Roua and Tangos, Melina and Zhazykbayeva, Saltanat and Herwig, Melissa and Varatnitskaya, Marharyta and Sieme, Marcel and Delalat, Simin and Sultana, Innas and Kolijn, Detmar and G{\"o}m{\"o}ri, Kamilla and Jarkas, Muhammad and L{\´o}di, M{\´a}ria and Jaquet, Kornelia and Kov{\´a}cs, {\´A}rp{\´a}d and Mannherz, Hans Georg and Sequeira, Vasco and M{\"u}gge, Andreas and Leichert, Lars I. and Sossalla, Samuel and Hamdani, Nazha}, title = {The interplay between S-glutathionylation and phosphorylation of cardiac troponin I and myosin binding protein C in end-stage human failing hearts}, series = {Antioxidants}, volume = {10}, journal = {Antioxidants}, number = {7}, issn = {2076-3921}, doi = {10.3390/antiox10071134}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242701}, year = {2021}, abstract = {Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell damage occurs, due to protein, DNA and lipid oxidation. Here, we investigated the oxidative modifications of myofilament proteins, and their role in modulating cardiomyocyte function in end-stage human failing hearts. We found altered maximum Ca\(^{2+}\)-activated tension and Ca\(^{2+}\) sensitivity of force production of skinned single cardiomyocytes in end-stage human failing hearts compared to non-failing hearts, which was corrected upon treatment with reduced glutathione enzyme. This was accompanied by the increased oxidation of troponin I and myosin binding protein C, and decreased levels of protein kinases A (PKA)- and C (PKC)-mediated phosphorylation of both proteins. The Ca\(^{2+}\) sensitivity and maximal tension correlated strongly with the myofilament oxidation levels, hypo-phosphorylation, and oxidative stress parameters that were measured in all the samples. Furthermore, we detected elevated titin-based myocardial stiffness in HF myocytes, which was reversed by PKA and reduced glutathione enzyme treatment. Finally, many oxidative stress and inflammation parameters were significantly elevated in failing hearts compared to non-failing hearts, and corrected upon treatment with the anti-oxidant GSH enzyme. Here, we provide evidence that the altered mechanical properties of failing human cardiomyocytes are partially due to phosphorylation, S-glutathionylation, and the interplay between the two post-translational modifications, which contribute to the development of heart failure.}, language = {en} } @article{SahitiMorbachCejkaetal.2021, author = {Sahiti, Floran and Morbach, Caroline and Cejka, Vladimir and Albert, Judith and Eichner, Felizitas A. and Gelbrich, G{\"o}tz and Heuschmann, Peter U. and St{\"o}rk, Stefan}, title = {Left Ventricular Remodeling and Myocardial Work: Results From the Population-Based STAAB Cohort Study}, series = {Frontiers in Cardiovascular Medicine}, volume = {8}, journal = {Frontiers in Cardiovascular Medicine}, issn = {2297-055X}, doi = {10.3389/fcvm.2021.669335}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240480}, year = {2021}, abstract = {Introduction: Left ventricular (LV) dilatation and LV hypertrophy are acknowledged precursors of myocardial dysfunction and ultimately of heart failure, but the implications of abnormal LV geometry on myocardial function are not well-understood. Non-invasive LV myocardial work (MyW) assessment based on echocardiography-derived pressure-strain loops offers the opportunity to study detailed myocardial function in larger cohorts. We aimed to assess the relationship of LV geometry with MyW indices in general population free from heart failure. Methods and Results: We report cross-sectional baseline data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of the general population of W{\"u}rzburg, Germany, aged 30-79 years. MyW analysis was performed in 1,926 individuals who were in sinus rhythm and free from valvular disease (49.3\% female, 54 ± 12 years). In multivariable regression, higher LV volume was associated with higher global wasted work (GWW) (+0.5 mmHg\% per mL/m\(^2\), p < 0.001) and lower global work efficiency (GWE) (-0.02\% per mL/m\(^2\), p < 0.01), while higher LV mass was associated with higher GWW (+0.45 mmHg\% per g/m\(^2\), p < 0.001) and global constructive work (GCW) (+2.05 mmHg\% per g/m\(^2\), p < 0.01) and lower GWE (-0.015\% per g/m\(^2\), p < 0.001). This was dominated by the blood pressure level and also observed in participants with normal LV geometry and concomitant hypertension. Conclusion: Abnormal LV geometric profiles were associated with a higher amount of wasted work, which translated into reduced work efficiency. The pattern of a disproportionate increase in GWW with higher LV mass might be an early sign of hypertensive heart disease.}, language = {en} } @article{WohlfartHolzgrabe2021, author = {Wohlfart, Jonas and Holzgrabe, Ulrike}, title = {Analysis of histamine and sisomicin in gentamicin: search for the causative agents of adverse effects}, series = {Archiv der Pharmazie}, volume = {354}, journal = {Archiv der Pharmazie}, number = {12}, doi = {10.1002/ardp.202100260}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256596}, year = {2021}, abstract = {In 1998, the aminoglycoside antibiotic gentamicin sulfate caused several cases of deaths in the United States, after the switch from twice- to once-daily application. Endotoxins were discussed as the cause for the adverse effects and sisomicin was identified as the lead impurity; batches containing sisomicin were contaminated with more impurities and were responsible for the fatalities. In 2016, anaphylactic reactions in horses, and later in humans with one fatality, were observed after application of gentamicin sulfate contaminated with histamine. To determine whether histamine was responsible for the 1990s death cases as well, histamine was quantified by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 30 samples of gentamicin sulfate analyzed in previous studies. Furthermore, a relative quantification of sisomicin was performed to check for a correlation between histamine and the lead impurity. A maximum amount of 11.52 ppm histamine was detected, which is below the limit for anaphylactic reactions of 16 ppm, and no correlation of the two impurities was observed. However, the European Medicines Agency recommends a stricter limit with regard to the maximum single dose of gentamicin sulfate to reach a greater gap between the maximum histamine exposition of 4.3 µg and the quantity known to cause hypotension of 7 µg. The low amounts of histamine and the fact that there is no connection with the contamination with sisomicin showed that histamine was not the cause for the death cases in the United States in 1998, and endotoxins remain the most probable explanation.}, language = {en} } @article{PhilippDietzBucheltetal.2021, author = {Philipp, Marius and Dietz, Andreas and Buchelt, Sebastian and Kuenzer, Claudia}, title = {Trends in satellite earth observation for permafrost related analyses — A review}, series = {Remote Sensing}, volume = {13}, journal = {Remote Sensing}, number = {6}, doi = {10.3390/rs13061217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234198}, year = {2021}, abstract = {Climate change and associated Arctic amplification cause a degradation of permafrost which in turn has major implications for the environment. The potential turnover of frozen ground from a carbon sink to a carbon source, eroding coastlines, landslides, amplified surface deformation and endangerment of human infrastructure are some of the consequences connected with thawing permafrost. Satellite remote sensing is hereby a powerful tool to identify and monitor these features and processes on a spatially explicit, cheap, operational, long-term basis and up to circum-Arctic scale. By filtering after a selection of relevant keywords, a total of 325 articles from 30 international journals published during the last two decades were analyzed based on study location, spatio- temporal resolution of applied remote sensing data, platform, sensor combination and studied environmental focus for a comprehensive overview of past achievements, current efforts, together with future challenges and opportunities. The temporal development of publication frequency, utilized platforms/sensors and the addressed environmental topic is thereby highlighted. The total number of publications more than doubled since 2015. Distinct geographical study hot spots were revealed, while at the same time large portions of the continuous permafrost zone are still only sparsely covered by satellite remote sensing investigations. Moreover, studies related to Arctic greenhouse gas emissions in the context of permafrost degradation appear heavily underrepresented. New tools (e.g., Google Earth Engine (GEE)), methodologies (e.g., deep learning or data fusion etc.)and satellite data (e.g., the Methane Remote Sensing LiDAR Mission (Merlin) and the Sentinel-fleet)will thereby enable future studies to further investigate the distribution of permafrost, its thermal state and its implications on the environment such as thermokarst features and greenhouse gas emission rates on increasingly larger spatial and temporal scales.}, language = {en} } @article{SchumannScherthanPfestroffetal.2021, author = {Schumann, S. and Scherthan, H. and Pfestroff, K. and Schoof, S. and Pfestroff, A. and Hartrampf, P. and Hasenauer, N. and Buck, A. K. and Luster, M. and Port, M. and Lassmann, M. and Eberlein, U.}, title = {DNA damage and repair in peripheral blood mononuclear cells after internal ex vivo irradiation of patient blood with \(^{131}\)I}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, doi = {10.1007/s00259-021-05605-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258863}, year = {2021}, abstract = {Aim The aim of this study was to provide a systematic approach to characterize DNA damage induction and repair in isolated peripheral blood mononuclear cells (PBMCs) after internal ex vivo irradiation with [\(^{131}\)I]NaI. In this approach, we tried to mimic ex vivo the irradiation of patient blood in the first hours after radioiodine therapy. Material and methods Blood of 33 patients of two centres was collected immediately before radioiodine therapy of differentiated thyroid cancer (DTC) and split into two samples. One sample served as non-irradiated control. The second sample was exposed to ionizing radiation by adding 1 ml of [\(^{131}\)I]NaI solution to 7 ml of blood, followed by incubation at 37 °C for 1 h. PBMCs of both samples were isolated, split in three parts each and (i) fixed in 70\% ethanol and stored at - 20 °C directly (0 h) after irradiation, (ii) after 4 h and (iii) 24 h after irradiation and culture in RPMI medium. After immunofluorescence staining microscopically visible co-localizing γ-H2AX + 53BP1 foci were scored in 100 cells per sample as biomarkers for radiation-induced double-strand breaks (DSBs). Results Thirty-two of 33 blood samples could be analysed. The mean absorbed dose to the blood in all irradiated samples was 50.1 ± 2.3 mGy. For all time points (0 h, 4 h, 24 h), the average number of γ-H2AX + 53BP1 foci per cell was significantly different when compared to baseline and the other time points. The average number of radiation-induced foci (RIF) per cell after irradiation was 0.72 ± 0.16 at t = 0 h, 0.26 ± 0.09 at t = 4 h and 0.04 ± 0.09 at t = 24 h. A monoexponential fit of the mean values of the three time points provided a decay rate of 0.25 ± 0.05 h\(^{-1}\), which is in good agreement with data obtained from external irradiation with γ- or X-rays. Conclusion This study provides novel data about the ex vivo DSB repair in internally irradiated PBMCs of patients before radionuclide therapy. Our findings show, in a large patient sample, that efficient repair occurs after internal irradiation with 50 mGy absorbed dose, and that the induction and repair rate after \(^{131}\)I exposure is comparable to that of external irradiation with γ- or X-rays.}, language = {en} } @article{UrlaubKaiserScherf‐Claveletal.2021, author = {Urlaub, Jonas and Kaiser, Reinhard P. and Scherf-Clavel, Oliver and Bolm, Carsten and Holzgrabe, Ulrike}, title = {Investigation of isomerization of dexibuprofen in a ball mill using chiral capillary electrophoresis}, series = {Electrophoresis}, volume = {42}, journal = {Electrophoresis}, number = {17-18}, doi = {10.1002/elps.202000307}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225852}, pages = {1790 -- 1799}, year = {2021}, abstract = {Besides the racemate, the S-enantiomer of ibuprofen (Ibu) is used for the treatment of inflammation and pain. Since the configurational stability of S-Ibu in solid state is of interest, it was studied by means of ball milling experiments. For the evaluation of the enantiomeric composition, a chiral CE method was developed and validated according to the ICH guideline Q2(R1). The addition of Mg\(^{2+}\), Ca\(^{2+}\), or Zn\(^{2+}\) ions to the background electrolyte (BGE) was found to improve Ibu enantioresolution. Chiral separation of Ibu enantiomers was achieved on a 60.2 cm (50.0 cm effective length) x 75 μm fused-silica capillary using a background electrolyte (BGE) composed of 50 mM sodium acetate, 10 mM magnesium acetate tetrahydrate, and 35 mM heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) as chiral selector. The quantification of R-Ibu in the mixture was performed using the normalization procedure. Linearity was evaluated in the range of 0.68-5.49\% R-Ibu (R\(^{2}\) = 0.999), recovery was found to range between 97 and 103\%, the RSD of intra- and interday precision below 2.5\%, and the limit of quantification for R- in S-Ibu was calculated to be 0.21\% (extrapolated) and 0.15\% (dilution of racemic ibuprofen), respectively. Isomerization of S-Ibu was observed under basic conditions by applying long milling times and high milling frequencies.}, language = {en} } @article{ZahoranovaLuxenhofer2021, author = {Zahoranov{\´a}, Anna and Luxenhofer, Robert}, title = {Poly(2-oxazoline)- and Poly(2-oxazine)-Based Self-Assemblies, Polyplexes, and Drug Nanoformulations—An Update}, series = {Advanced Healthcare Materials}, volume = {10}, journal = {Advanced Healthcare Materials}, number = {6}, doi = {10.1002/adhm.202001382}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225833}, year = {2021}, abstract = {For many decades, poly(2-oxazoline)s and poly(2-oxazine)s, two closely related families of polymers, have led the life of a rather obscure research topic with only a few research groups world-wide working with them. This has changed in the last five to ten years, presumably triggered significantly by very promising clinical trials of the first poly(2-oxazoline)-based drug conjugate. The huge chemical and structural toolbox poly(2-oxazoline)s and poly(2-oxazine)s has been extended very significantly in the last few years, but their potential still remains largely untapped. Here, specifically, the developments in macromolecular self-assemblies and non-covalent drug delivery systems such as polyplexes and drug nanoformulations based on poly(2-oxazoline)s and poly(2-oxazine)s are reviewed. This highly dynamic field benefits particularly from the extensive synthetic toolbox poly(2-oxazoline)s and poly(2-oxazine)s offer and also may have the largest potential for a further development. It is expected that the research dynamics will remain high in the next few years, particularly as more about the safety and therapeutic potential of poly(2-oxazoline)s and poly(2-oxazine)s is learned.}, language = {en} } @article{AvotaBodemChithelenetal.2021, author = {Avota, Elita and Bodem, Jochen and Chithelen, Janice and Mandasari, Putri and Beyersdorf, Niklas and Schneider-Schaulies, J{\"u}rgen}, title = {The Manifold Roles of Sphingolipids in Viral Infections}, series = {Frontiers in Physiology}, volume = {12}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2021.715527}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246975}, year = {2021}, abstract = {Sphingolipids are essential components of eukaryotic cells. In this review, we want to exemplarily illustrate what is known about the interactions of sphingolipids with various viruses at different steps of their replication cycles. This includes structural interactions during entry at the plasma membrane or endosomal membranes, early interactions leading to sphingolipid-mediated signal transduction, interactions with internal membranes and lipids during replication, and interactions during virus assembly and budding. Targeted interventions in sphingolipid metabolism - as far as they can be tolerated by cells and organisms - may open novel possibilities to support antiviral therapies. Human immunodeficiency virus type 1 (HIV-1) infections have intensively been studied, but for other viral infections, such as influenza A virus (IAV), measles virus (MV), hepatitis C virus (HCV), dengue virus, Ebola virus, and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), investigations are still in their beginnings. As many inhibitors of sphingolipid metabolism are already in clinical use against other diseases, repurposing studies for applications in some viral infections appear to be a promising approach.}, language = {en} } @article{ZwirnerBohnertFrankeetal.2021, author = {Zwirner, Johann and Bohnert, Simone and Franke, Heike and Garland, Jack and Hammer, Niels and M{\"o}bius, Dustin and Tse, Rexson and Ondruschka, Benjamin}, title = {Assessing protein biomarkers to detect lethal acute traumatic brain injuries in cerebrospinal fluid}, series = {Biomolecules}, volume = {11}, journal = {Biomolecules}, number = {11}, issn = {2218-273X}, doi = {10.3390/biom11111577}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248587}, year = {2021}, abstract = {Diagnosing traumatic brain injury (TBI) from body fluids in cases where there are no obvious external signs of impact would be useful for emergency physicians and forensic pathologists alike. None of the previous attempts has so far succeeded in establishing a single biomarker to reliably detect TBI with regards to the sensitivity: specificity ratio in a post mortem setting. This study investigated a combination of body fluid biomarkers (obtained post mortem), which may be a step towards increasing the accuracy of biochemical TBI detection. In this study, serum and cerebrospinal fluid (CSF) samples from 30 acute lethal TBI cases and 70 controls without a TBI-related cause of death were evaluated for the following eight TBI-related biomarkers: brain-derived neurotrophic factor (BDNF), ferritin, glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), lactate dehydrogenase, neutrophil gelatinase-associated lipocalin (NGAL), neuron-specific enolase and S100 calcium-binding protein B. Correlations among the individual TBI biomarkers were assessed, and a specificity-accentuated threshold value analysis was conducted for all biomarkers. Based on these values, a decision tree modelling approach was performed to assess the most accurate biomarker combination to detect acute lethal TBIs. The results showed that 92.45\% of acute lethal TBIs were able to be diagnosed using a combination of IL-6 and GFAP in CSF. The probability of detecting an acute lethal TBI was moderately increased by GFAP alone and considerably increased by the remaining biomarkers. BDNF and NGAL were almost perfectly correlated (p = 0.002; R\(^2\) = 0.944). This study provides evidence that acute lethal TBIs can be detected to a high degree of statistical accuracy using forensic biochemistry. The high inter-individual correlations of biomarkers may help to estimate the CSF concentration of an unknown biomarker, using extrapolation techniques.}, language = {en} } @article{GrobHeinigGruebeletal.2021, author = {Grob, Robin and Heinig, Niklas and Gr{\"u}bel, Kornelia and R{\"o}ssler, Wolfgang and Fleischmann, Pauline N.}, title = {Sex-specific and caste-specific brain adaptations related to spatial orientation in Cataglyphis ants}, series = {Journal of Comparative Neurology}, volume = {529}, journal = {Journal of Comparative Neurology}, number = {18}, doi = {10.1002/cne.25221}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257299}, pages = {3882-3892}, year = {2021}, abstract = {Cataglyphis desert ants are charismatic central place foragers. After long-ranging foraging trips, individual workers navigate back to their nest relying mostly on visual cues. The reproductive caste faces other orientation challenges, i.e. mate finding and colony foundation. Here we compare brain structures involved in spatial orientation of Cataglyphis nodus males, gynes, and foragers by quantifying relative neuropil volumes associated with two visual pathways, and numbers and volumes of antennal lobe (AL) olfactory glomeruli. Furthermore, we determined absolute numbers of synaptic complexes in visual and olfactory regions of the mushroom bodies (MB) and a major relay station of the sky-compass pathway to the central complex (CX). Both female castes possess enlarged brain centers for sensory integration, learning, and memory, reflected in voluminous MBs containing about twice the numbers of synaptic complexes compared with males. Overall, male brains are smaller compared with both female castes, but the relative volumes of the optic lobes and CX are enlarged indicating the importance of visual guidance during innate behaviors. Male ALs contain greatly enlarged glomeruli, presumably involved in sex-pheromone detection. Adaptations at both the neuropil and synaptic levels clearly reflect differences in sex-specific and caste-specific demands for sensory processing and behavioral plasticity underlying spatial orientation.}, language = {en} } @article{KadeOttoLuxenhoferetal.2021, author = {Kade, Juliane C. and Otto, Paul F. and Luxenhofer, Robert and Dalton, Paul D.}, title = {Melt electrowriting of poly(vinylidene difluoride) using a heated collector}, series = {Polymers for Advanced Technologies}, volume = {32}, journal = {Polymers for Advanced Technologies}, number = {12}, issn = {1042-7147}, doi = {10.1002/pat.5463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318493}, pages = {4951 -- 4955}, year = {2021}, abstract = {Previous research on the melt electrowriting (MEW) of poly(vinylidene difluoride) (PVDF) resulted in electroactive fibers, however, printing more than five layers is challenging. Here, we investigate the influence of a heated collector to adjust the solidification rate of the PVDF jet so that it adheres sufficiently to each layer. A collector temperature of 110°C is required to improve fiber processing, resulting in a total of 20 fiber layers. For higher temperatures and higher layers, an interesting phenomenon occurred, where the intersection points of the fibers coalesced into periodic spheres of diameter 206 ± 52 μm (26G, 150°C collector temperature, 2000 mm/min, 10 layers in x- and y-direction).The heated collector is an important component of a MEW printer that allows polymers with a high melting point to be processable with increased layers.}, language = {en} } @article{ZimniakKirschnerHilpertetal.2021, author = {Zimniak, Melissa and Kirschner, Luisa and Hilpert, Helen and Geiger, Nina and Danov, Olga and Oberwinkler, Heike and Steinke, Maria and Sewald, Katherina and Seibel, J{\"u}rgen and Bodem, Jochen}, title = {The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, doi = {10.1038/s41598-021-85049-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259820}, pages = {5890}, year = {2021}, abstract = {To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications "off-label" against SARS-CoV-2. Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8 mu g/ml significantly in these screenings, and the EC50 was determined with 387 ng/ml. Furthermore, Fluoxetine reduced viral infectivity in precision-cut human lung slices showing its activity in relevant human tissue targeted in severe infections. Fluoxetine treatment resulted in a decrease in viral protein expression. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus, indicating that the R-form might specifically be used for SARS-CoV-2 treatment. Fluoxetine inhibited neither Rabies virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex virus type 1 gene expression, indicating that it acts virus-specific. Moreover, since it is known that Fluoxetine inhibits cytokine release, we see the role of Fluoxetine in the treatment of SARS-CoV-2 infected patients of risk groups.}, language = {en} } @article{DoryabTaskinStahlhutetal.2021, author = {Doryab, Ali and Taskin, Mehmet Berat and Stahlhut, Philipp and Schr{\"o}ppel, Andreas and Orak, Sezer and Voss, Carola and Ahluwalia, Arti and Rehberg, Markus and Hilgendorff, Anne and St{\"o}ger, Tobias and Groll, J{\"u}rgen and Schmid, Otmar}, title = {A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {9}, journal = {Frontiers in Bioengineering and Biotechnology}, issn = {2296-4185}, doi = {10.3389/fbioe.2021.616830}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223830}, year = {2021}, abstract = {Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m\(^{2}\)) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) "breathing" lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o\(^{-}\)) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35\% PCL and 6.34\% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10\% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung.}, language = {en} } @article{ZioutiRummlerSteynetal.2021, author = {Ziouti, Fani and Rummler, Maximilian and Steyn, Beatrice and Thiele, Tobias and Seliger, Anne and Duda, Georg N. and Bogen, Bjarne and Willie, Bettina M. and Jundt, Franziska}, title = {Prevention of bone destruction by mechanical loading is not enhanced by the Bruton's tyrosine kinase inhibitor CC-292 in myeloma bone disease}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {8}, issn = {1422-0067}, doi = {10.3390/ijms22083840}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284943}, year = {2021}, abstract = {Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton's tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD.}, language = {en} } @article{BenKraiemSauerNorwigetal.2021, author = {Ben-Kraiem, Adel and Sauer, Reine-Solange and Norwig, Carla and Popp, Maria and Bettenhausen, Anna-Lena and Atalla, Mariam Sobhy and Brack, Alexander and Blum, Robert and Doppler, Kathrin and Rittner, Heike Lydia}, title = {Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy}, series = {Journal of Molecular Medicine}, volume = {99}, journal = {Journal of Molecular Medicine}, number = {9}, doi = {10.1007/s00109-021-02091-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265237}, pages = {1237-1250}, year = {2021}, abstract = {Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26\% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN. In this study, we analyzed the spatiotemporal tight junction protein profile, barrier permeability, and vessel-associated macrophages in Wistar rats with streptozotocin-induced DPN. In these rats, mechanical hypersensitivity developed after 2 weeks and loss of motor function after 8 weeks, while the BNB and the blood-DRG barrier were leakier for small, but not for large molecules after 8 weeks only. The blood-spinal cord barrier remained sealed throughout the observation period. No gross changes in tight junction protein or cytokine expression were observed in all barriers to blood. However, expression of Cldn1 mRNA in perineurium was specifically downregulated in conjunction with weaker vessel-associated macrophage shielding of the BNB. Our results underline the role of specific tight junction proteins and BNB breakdown in DPN maintenance and differentiate DPN from traumatic nerve injury. Targeting claudins and sealing the BNB could stabilize pain and prevent further nerve damage.}, language = {en} } @article{BrumbergKuzkinaLapaetal.2021, author = {Brumberg, Joachim and Kuzkina, Anastasia and Lapa, Constantin and Mammadova, Sona and Buck, Andreas and Volkmann, Jens and Sommer, Claudia and Isaias, Ioannis U. and Doppler, Kathrin}, title = {Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy}, series = {Neurobiology of Disease}, volume = {153}, journal = {Neurobiology of Disease}, doi = {10.1016/j.nbd.2021.105332}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260061}, pages = {105332}, year = {2021}, abstract = {Pathological aggregates of alpha-synuclein in peripheral dermal nerve fibers can be detected in patients with idiopathic Parkinson's disease and multiple system atrophy. This study combines skin biopsy staining for p-alpha-synuclein depositions and radionuclide imaging of the heart with [\(^{123}\)I]-metaiodobenzylguanidine to explore peripheral denervation in both diseases. To this purpose, 42 patients with a clinical diagnosis of Parkinson's disease or multiple system atrophy were enrolled. All patients underwent a standardized clinical workup including neurological evaluation, neurography, and blood samples. Skin biopsies were obtained from the distal and proximal leg, back, and neck for immunofluorescence double labeling with anti-p-alpha-synuclein and anti-PGP9.5. All patients underwent myocardial [\(^{123}\)I]-metaiodobenzylguanidine scintigraphy. Dermal p-alpha-synuclein was observed in 47.6\% of Parkinson's disease patients and was mainly found in autonomic structures. 81.0\% of multiple system atrophy patients had deposits with most of cases in somatosensory fibers. The [\(^{123}\)I]-metaiodobenzylguanidine heart-to-mediastinum ratio was lower in Parkinson's disease than in multiple system atrophy patients (1.94 +/- 0.63 vs. 2.91 +/- 0.96; p < 0.0001). Irrespective of the diagnosis, uptake was lower in patients with than without p-alpha-synuclein in autonomic structures (1.42 +/- 0.51 vs. 2.74 +/- 0.83; p < 0.0001). Rare cases of Parkinson's disease with p-alpha-synuclein in somatosensory fibers and multiple system atrophy patients with deposits in autonomic structures or both fiber types presented with clinically overlapping features. In conclusion, this study suggests that alpha-synuclein contributes to peripheral neurodegeneration and mediates the impairment of cardiac sympathetic neurons in patients with synucleinopathies. Furthermore, it indicates that Parkinson's disease and multiple system atrophy share pathophysiologic mechanisms of peripheral nervous system dysfunction with a clinical overlap.}, language = {en} } @article{SeifertGrollWeichholdetal.2021, author = {Seifert, Annika and Groll, J{\"u}rgen and Weichhold, Jan and Boehm, Anne V. and M{\"u}ller, Frank A. and Gbureck, Uwe}, title = {Phase Conversion of Ice-Templated α-Tricalcium Phosphate Scaffolds into Low-Temperature Calcium Phosphates with Anisotropic Open Porosity}, series = {Advanced Engineering Materials}, volume = {23}, journal = {Advanced Engineering Materials}, number = {5}, doi = {10.1002/adem.202001417}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256311}, year = {2021}, abstract = {The current study aims to extend the material platform for anisotropically structured calcium phosphates to low-temperature phases such as calcium-deficient hydroxyapatite (CDHA) or the secondary phosphates monetite and brushite. This is achieved by the phase conversion of highly porous α-tricalcium phosphate (α-TCP) scaffolds fabricated by ice-templating into the aforementioned phases by hydrothermal treatment or incubation in phosphoric acid. Prior to these steps, α-TCP scaffolds are either sintered for 8 h at 1400 °C or remain in their original state. Both nonsintered and sintered α-TCP specimens are converted into CDHA by hydrothermal treatment, while a transformation into monetite and brushite is achieved by incubation in phosphoric acid. Hydrothermal treatment for 72 h at 175 °C increases the porosity in nonsintered samples from 85\% to 88\% and from 75\% to 88\% in the sintered ones. An increase in the specific surface area from (1.102 ± 0.005) to (9.17 ± 0.01) m2 g-1 and from (0.190 ± 0.004) to (2.809 ± 0.002) m2 g-1 due to the phase conversion is visible for both the nonsintered and sintered samples. Compressive strength of the nonsintered samples increases significantly from (0.76 ± 0.11) to (5.29 ± 0.94) MPa due to incubation in phosphoric acid.}, language = {en} } @article{GaertnerMarekArrowsmithetal.2021, author = {G{\"a}rtner, Annalena and Marek, Matth{\"a}us and Arrowsmith, Merle and Auerhammer, Dominic and Radacki, Krzysztof and Prieschl, Dominic and Dewhurst, Rian D. and Braunschweig, Holger}, title = {Boron- versus Nitrogen-Centered Nucleophilic Reactivity of (Cyano)hydroboryl Anions: Synthesis of Cyano(hydro)organoboranes and 2-Aza-1,4-diborabutatrienes}, series = {Chemistry—A European Journal}, volume = {27}, journal = {Chemistry—A European Journal}, number = {37}, doi = {10.1002/chem.202101025}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256853}, pages = {9694-9699}, year = {2021}, abstract = {Cyclic alkyl(amino)carbene-stabilized (cyano)hydroboryl anions were synthesized by deprotonation of (cyano)dihydroborane precursors. While they display boron-centered nucleophilic reactivity towards organohalides, generating fully unsymmetrically substituted cyano(hydro)organoboranes, they show cyano-nitrogen-centered nucleophilic reactivity towards haloboranes, resulting in the formation of hitherto unknown linear 2-aza-1,4-diborabutatrienes.}, language = {en} } @article{MachataSreekantapuramHuennigeretal.2021, author = {Machata, Silke and Sreekantapuram, Sravya and H{\"u}nniger, Kerstin and Kurzai, Oliver and Dunker, Christine and Schubert, Katja and Kr{\"u}ger, Wibke and Schulze-Richter, Bianca and Speth, Cornelia and Rambach, G{\"u}nter and Jacobsen, Ilse D.}, title = {Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.565869}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222575}, year = {2021}, abstract = {Murine infection models are widely used to study systemic candidiasis caused by C. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for several Candida species in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation of C. albicans was observed. This coincided with less fungal association with leukocytes, especially neutrophils. The lower neutrophil number in murine blood only partially explains insufficient infection and filamentation control, as spiking with murine neutrophils had only limited effects on fungal killing. Furthermore, increased fungal survival is not mediated by enhanced filamentation, as a filament-deficient mutant was likewise not eliminated. We also observed host-dependent differences for interaction of platelets with C. albicans, showing enhanced platelet aggregation, adhesion and activation in murine blood. For human blood, opsonization was shown to decrease platelet interaction suggesting that complement factors interfere with fungus-to-platelet binding. Our results reveal substantial differences between murine and human whole-blood models infected with C. albicans and thereby demonstrate limitations in the translatability of this ex vivo model between hosts.}, language = {en} } @article{ShemerMekiesBenJehudaetal.2021, author = {Shemer, Yuval and Mekies, Lucy N. and Ben Jehuda, Ronen and Baskin, Polina and Shulman, Rita and Eisen, Binyamin and Regev, Danielle and Arbustini, Eloisa and Gerull, Brenda and Gherghiceanu, Mihaela and Gottlieb, Eyal and Arad, Michael and Binah, Ofer}, title = {Investigating LMNA-related dilated cardiomyopathy using human induced Pluripotent Stem Cell-derived cardiomyocytes}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {15}, issn = {1422-0067}, doi = {10.3390/ijms22157874}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285673}, year = {2021}, abstract = {LMNA-related dilated cardiomyopathy is an inherited heart disease caused by mutations in the LMNA gene encoding for lamin A/C. The disease is characterized by left ventricular enlargement and impaired systolic function associated with conduction defects and ventricular arrhythmias. We hypothesized that LMNA-mutated patients' induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) display electrophysiological abnormalities, thus constituting a suitable tool for deciphering the arrhythmogenic mechanisms of the disease, and possibly for developing novel therapeutic modalities. iPSC-CMs were generated from two related patients (father and son) carrying the same E342K mutation in the LMNA gene. Compared to control iPSC-CMs, LMNA-mutated iPSC-CMs exhibited the following electrophysiological abnormalities: (1) decreased spontaneous action potential beat rate and decreased pacemaker current (I\(_f\)) density; (2) prolonged action potential duration and increased L-type Ca\(^{2+}\) current (I\(_{Ca,L}\)) density; (3) delayed afterdepolarizations (DADs), arrhythmias and increased beat rate variability; (4) DADs, arrhythmias and cessation of spontaneous firing in response to β-adrenergic stimulation and rapid pacing. Additionally, compared to healthy control, LMNA-mutated iPSC-CMs displayed nuclear morphological irregularities and gene expression alterations. Notably, KB-R7943, a selective inhibitor of the reverse-mode of the Na\(^+\)/Ca\(^{2+}\) exchanger, blocked the DADs in LMNA-mutated iPSC-CMs. Our findings demonstrate cellular electrophysiological mechanisms underlying the arrhythmias in LMNA-related dilated cardiomyopathy.}, language = {en} } @article{GottschollDiezSoltamovetal.2021, author = {Gottscholl, Andreas and Diez, Matthias and Soltamov, Victor and Kasper, Christian and Krauße, Dominik and Sperlich, Andreas and Kianinia, Mehran and Bradac, Carlo and Aharonovich, Igor and Dyakonov, Vladimir}, title = {Spin defects in hBN as promising temperature, pressure and magnetic field quantum sensors}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, number = {1}, doi = {10.1038/s41467-021-24725-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261581}, year = {2021}, abstract = {Spin defects in solid-state materials are strong candidate systems for quantum information technology and sensing applications. Here we explore in details the recently discovered negatively charged boron vacancies (V\(_B\)\(^-\)) in hexagonal boron nitride (hBN) and demonstrate their use as atomic scale sensors for temperature, magnetic fields and externally applied pressure. These applications are possible due to the high-spin triplet ground state and bright spin-dependent photoluminescence of the V\(_B\)\(^-\). Specifically, we find that the frequency shift in optically detected magnetic resonance measurements is not only sensitive to static magnetic fields, but also to temperature and pressure changes which we relate to crystal lattice parameters. We show that spin-rich hBN films are potentially applicable as intrinsic sensors in heterostructures made of functionalized 2D materials.}, language = {en} } @article{MegasSimonsKimetal.2021, author = {Megas, Ioannis-Fivos and Simons, David and Kim, Bong-Sung and Stoppe, Christian and Piatkowski, Andrzej and Fikatas, Panagiotis and Fuchs, Paul Christian and Bastiaanse, Jacqueline and Pallua, Norbert and Bernhagen, J{\"u}rgen and Grieb, Gerrit}, title = {Macrophage migration inhibitory factor — an innovative indicator for free flap ischemia after microsurgical reconstruction}, series = {Healthcare}, volume = {9}, journal = {Healthcare}, number = {6}, issn = {2227-9032}, doi = {10.3390/healthcare9060616}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239632}, year = {2021}, abstract = {(1) Background: Nowadays, the use of microsurgical free flaps is a standard operative procedure in reconstructive surgery. Still, thrombosis of the microanastomosis is one of the most fatal postoperative complications. Clinical evaluation, different technical devices and laboratory markers are used to monitor critical flap perfusion. Macrophage migration inhibitory factor (MIF), a structurally unique cytokine with chemokine-like characteristics, could play a role in predicting vascular problems and the failure of flap perfusion. (2) Methods: In this prospective observational study, 26 subjects that underwent microsurgical reconstruction were observed. Besides clinical data, the number of blood leukocytes, CRP and MIF were monitored. (3) Results: Blood levels of MIF, C-reactive protein (CRP) and leukocytes increased directly after surgery. Subjects that needed surgical revision due to thrombosis of the microanastomosis showed significantly higher blood levels of MIF than subjects without revision. (4) Conclusion: We conclude that MIF is a potential and innovative indicator for thrombosis of the microanastomosis after free flap surgery. Since it is easy to obtain diagnostically, MIF could be an additional tool to monitor flap perfusion besides clinical and technical assessments.}, language = {en} } @article{HabensteinThammRoessler2021, author = {Habenstein, Jens and Thamm, Markus and R{\"o}ssler, Wolfgang}, title = {Neuropeptides as potential modulators of behavioral transitions in the ant Cataglyphis nodus}, series = {Journal of Comparative Neurology}, volume = {529}, journal = {Journal of Comparative Neurology}, number = {12}, doi = {10.1002/cne.25166}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244751}, pages = {3155 -- 3170}, year = {2021}, abstract = {Age-related behavioral plasticity is a major prerequisite for the ecological success of insect societies. Although ecological aspects of behavioral flexibility have been targeted in many studies, the underlying intrinsic mechanisms controlling the diverse changes in behavior along the individual life history of social insects are not completely understood. Recently, the neuropeptides allatostatin-A, corazonin, and tachykinin have been associated with the regulation of behavioral transitions in social insects. Here, we investigated changes in brain localization and expression of these neuropeptides following major behavioral transitions in Cataglyphis nodus ants. Our immunohistochemical analyses in the brain revealed that the overall branching pattern of neurons immunoreactive (ir) for the three neuropeptides is largely independent of the behavioral stages. Numerous allatostatin-A- and tachykinin-ir neurons innervate primary sensory neuropils and high-order integration centers of the brain. In contrast, the number of corazonergic neurons is restricted to only four neurons per brain hemisphere with cell bodies located in the pars lateralis and axons extending to the medial protocerebrum and the retrocerebral complex. Most interestingly, the cell-body volumes of these neurons are significantly increased in foragers compared to freshly eclosed ants and interior workers. Quantification of mRNA expression levels revealed a stage-related change in the expression of allatostatin-A and corazonin mRNA in the brain. Given the presence of the neuropeptides in major control centers of the brain and the neurohemal organs, these mRNA-changes strongly suggest an important modulatory role of both neuropeptides in the behavioral maturation of Cataglyphis ants.}, language = {en} } @article{SchembriKimLiessetal.2021, author = {Schembri, Tim and Kim, Jin Hong and Liess, Andreas and Stepanenko, Vladimir and Stolte, Matthias and W{\"u}rthner, Frank}, title = {Semitransparent Layers of Social Self-Sorting Merocyanine Dyes for Ultranarrow Bandwidth Organic Photodiodes}, series = {Advanced Optical Materials}, volume = {9}, journal = {Advanced Optical Materials}, number = {15}, doi = {10.1002/adom.202100213}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244762}, year = {2021}, abstract = {Two dipolar merocyanines consisting of the same π-conjugated chromophore but different alkyl substituents adopt very different packing arrangements in their respective solid state with either H- or J-type exciton coupling, leading to ultranarrow absorption bands at 477 and 750 nm, respectively, due to exchange narrowing. The social self-sorting behavior of these push-pull chromophores in their mixed thin films is evaluated and the impact on morphology as well as opto-electronical properties is determined. The implementation of this well-tuned two-component material with tailored optical features allows to optimize planar heterojunction organic photodiodes with fullerene ​(C\(_{60}\)) with either dual or single wavelength selectivity in the blue and NIR spectral range with ultranarrow bandwidths of only 11 nm (200 cm\(^{-1}\)) and an external quantum efficiency of up to 18\% at 754 nm under 0 V bias. The application of these photodiodes as low-power consuming heart rate monitors is demonstrated by a reflectance-mode photoplethysmography (PPG) sensor.}, language = {en} } @article{HolfelderMulanskySchleeetal.2021, author = {Holfelder, Marc and Mulansky, Lena and Schlee, Winfried and Baumeister, Harald and Schobel, Johannes and Greger, Helmut and Hoff, Andreas and Pryss, R{\"u}diger}, title = {Medical device regulation efforts for mHealth apps during the COVID-19 pandemic — an experience report of Corona Check and Corona Health}, series = {J — Multidisciplinary Scientific Journal}, volume = {4}, journal = {J — Multidisciplinary Scientific Journal}, number = {2}, issn = {2571-8800}, doi = {10.3390/j4020017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285434}, pages = {206 -- 222}, year = {2021}, abstract = {Within the healthcare environment, mobile health (mHealth) applications (apps) are becoming more and more important. The number of new mHealth apps has risen steadily in the last years. Especially the COVID-19 pandemic has led to an enormous amount of app releases. In most countries, mHealth applications have to be compliant with several regulatory aspects to be declared a "medical app". However, the latest applicable medical device regulation (MDR) does not provide more details on the requirements for mHealth applications. When developing a medical app, it is essential that all contributors in an interdisciplinary team — especially software engineers — are aware of the specific regulatory requirements beforehand. The development process, however, should not be stalled due to integration of the MDR. Therefore, a developing framework that includes these aspects is required to facilitate a reliable and quick development process. The paper at hand introduces the creation of such a framework on the basis of the Corona Health and Corona Check apps. The relevant regulatory guidelines are listed and summarized as a guidance for medical app developments during the pandemic and beyond. In particular, the important stages and challenges faced that emerged during the entire development process are highlighted.}, language = {en} } @article{AertsEberleinHolmetal.2021, author = {Aerts, An and Eberlein, Uta and Holm, S{\"o}ren and Hustinx, Roland and Konijnenberg, Mark and Strigari, Lidia and van Leeuwen, Fijs W. B. and Glatting, Gerhard and Lassmann, Michael}, title = {EANM position paper on the role of radiobiology in nuclear medicine}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {48}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {11}, doi = {10.1007/s00259-021-05345-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265595}, pages = {3365-3377}, year = {2021}, abstract = {With an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.}, language = {en} } @article{Briegel2021, author = {Briegel, Wolfgang}, title = {Psychiatric comorbidities in 1p36 deletion syndrome and their treatment — a case report}, series = {International Journal of Environmental Research and Public Health}, volume = {18}, journal = {International Journal of Environmental Research and Public Health}, number = {22}, issn = {1660-4601}, doi = {10.3390/ijerph182212064}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250189}, year = {2021}, abstract = {1p36 deletion syndrome represents the most common terminal deletion observed in humans. Major clinical findings comprise developmental delay/intellectual disability, poor or absent expressive language, congenital central muscular hypotonia, brain anomalies, brachydactyly/camptodactyly, short feet, and characteristic facial features like straight eyebrows, deep-set eyes, and midface hypoplasia. So far, there is very limited knowledge about comorbid psychiatric disorders and their effective treatment in this special population. To fill this gap, this case report presents an initially four-year-old girl with 1p36.33-1p36.32 deletion, moderate intellectual disability, insomnia, oppositional-defiant disorder and attention deficit/hyperactivity disorder covering a period of time of about 1.5 years comprising initial psychological/psychiatric assessment, subsequent day clinic/outpatient treatment (amongst others including off-label use of melatonin and methylphenidate as well as parent-child interaction therapy) and follow-up assessment. Follow-up results indicated good efficacy of melatonin and methylphenidate medication without any adverse effects. Multidisciplinarity in diagnosis and treatment are mandatory to meet needs of patients with complex genetic disorders like 1p36 deletion syndrome. Off-label use of melatonin (for insomnia) and methylphenidate (for attention deficit/hyperactivity disorder) should be considered in young children with 1p36 deletion syndrome if behavioral interventions are not sufficient.}, language = {en} } @article{RogersGilesDraperetal.2021, author = {Rogers, Bruce and Giles, David and Draper, Nick and Hoos, Olaf and Gronwald, Thomas}, title = {A New Detection Method Defining the Aerobic Threshold for Endurance Exercise and Training Prescription Based on Fractal Correlation Properties of Heart Rate Variability}, series = {Frontiers in Physiology}, volume = {11}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2020.596567}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222601}, year = {2021}, abstract = {The short-term scaling exponent alpha1 of detrended fluctuation analysis (DFA a1), a nonlinear index of heart rate variability (HRV) based on fractal correlation properties, has been shown to steadily change with increasing exercise intensity. To date, no study has specifically examined using the behavior of this index as a method for defining a low intensity exercise zone. The aim of this report is to compare both oxygen intake (VO\(_{2}\)) and heart rate (HR) reached at the first ventilatory threshold (VT1), a well-established delimiter of low intensity exercise, to those derived from a predefined DFA a1 transitional value. Gas exchange and HRV data were obtained from 15 participants during an incremental treadmill run. Comparison of both VO\(_{2}\) and HR reached at VT1 defined by gas exchange (VT1 GAS) was made to those parameters derived from analysis of DFA a1 reaching a value of 0.75 (HRVT). Based on Bland Altman analysis, linear regression, intraclass correlation (ICC) and t testing, there was strong agreement between VT1 GAS and HRVT as measured by both HR and VO\(_{2}\). Mean VT1 GAS was reached at 39.8 ml/kg/min with a HR of 152 bpm compared to mean HRVT which was reached at 40.1 ml/kg/min with a HR of 154 bpm. Strong linear relationships were seen between test modalities, with Pearson's r values of 0.99 (p < 0.001) and.97 (p < 0.001) for VO\(_{2}\) and HR comparisons, respectively. Intraclass correlation between VT1 GAS and HRVT was 0.99 for VO\(_{2}\) and 0.96 for HR. In addition, comparison of VT1 GAS and HRVT showed no differences by t testing, also supporting the method validity. In conclusion, it appears that reaching a DFA a1 value of 0.75 on an incremental treadmill test is closely associated with crossing the first ventilatory threshold. As training intensity below the first ventilatory threshold is felt to have great importance for endurance sport, utilization of DFA a1 activity may provide guidance for a valid low training zone.}, language = {en} } @article{PetritschPannbeckerWengetal.2021, author = {Petritsch, Bernhard and Pannbecker, Pauline and Weng, Andreas M. and Grunz, Jan-Peter and Veldhoen, Simon and Bley, Thorsten A. and Kosmala, Aleksander}, title = {Split-filter dual-energy CT pulmonary angiography for the diagnosis of acute pulmonary embolism: a study on image quality and radiation dose}, series = {Quantitative Imaging in Medicine and Surgery}, volume = {11}, journal = {Quantitative Imaging in Medicine and Surgery}, number = {5}, doi = {10.21037/qims-20-740}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231456}, pages = {1817-1827}, year = {2021}, abstract = {Background: Computed tomography (CT) pulmonary angiography is the diagnostic reference standard in suspected pulmonary embolism (PE). Favorable results for dual-energy CT (DECT) images have been reported for this condition. Nowadays, dual-energy data acquisition is feasible with different technical options, including a single-source split-filter approach. Therefore, the aim of this retrospective study was to investigate image quality and radiation dose of thoracic split-filter DECT in comparison to conventional single-energy CT in patients with suspected PE. Methods: A total of 110 CT pulmonary angiographies were accomplished either as standard single-energy CT with automatic tube voltage selection (ATVS) (n=58), or as split-filter DECT (n=52). Objective [pulmonary artery CT attenuation, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)] and subjective image quality [four-point Likert scale; three readers (R)] were compared among the two study groups. Size-specific dose estimates (SSDE), dose-length-product (DLP) and volume CT dose index (CTDIvol) were assessed for radiation dose analysis. Results: Split-filter DECT images yielded 67.7\% higher SNR (27.0 vs. 16.1; P<0.001) and 61.9\% higher CNR (22.5 vs. 13.9; P<0.001) over conventional single-energy images, whereas CT attenuation was significantly lower (344.5 vs. 428.2 HU; P=0.013). Subjective image quality was rated good or excellent in 93.0\%/98.3\%/77.6\% (R1/R2/R3) of the single-energy CT scans, and 84.6\%/82.7\%/80.8\% (R1/R2/R3) of the split-filter DECT scans. SSDE, DLP and CTDIvol were significantly lower for conventional single-energy CT compared to split-filter DECT (all P<0.05), which was associated with 26.7\% higher SSDE. Conclusions: In the diagnostic workup of acute PE, the split-filter allows for dual-energy data acquisition from single-source single-layer CT scanners. The existing opportunity to assess pulmonary "perfusion" based on analysis of iodine distribution maps is associated with higher radiation dose in terms of increased SSDE than conventional single-energy CT with ATVS. Moreover, a proportion of up to 3.8\% non-diagnostic examinations in the current reference standard test for PE is not negligible.}, language = {en} } @article{SchwabBussPulligetal.2021, author = {Schwab, Andrea and Buss, Alexa and Pullig, Oliver and Ehlicke, Franziska}, title = {Ex vivo osteochondral test system with control over cartilage defect depth - A pilot study to investigate the effect of oxygen tension and chondrocyte based treatments in chondral and full thickness defects in an organ model}, series = {Osteoarthritis and Cartilage Open}, volume = {3}, journal = {Osteoarthritis and Cartilage Open}, number = {2}, doi = {10.1016/j.ocarto.2021.100173}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260511}, year = {2021}, abstract = {Objective Cartilage defect treatment strategies are dependent on the lesion size and severity. Osteochondral explant models are a platform to test cartilage repair strategies ex vivo. Current models lack in mimicking the variety of clinically relevant defect scenarios. In this controlled laboratory study, an automated device (artificial tissue cutter, ARTcut®) was implemented to reproducibly create cartilage defects with controlled depth. In a pilot study, the effect of cartilage defect depth and oxygen tension on cartilage repair was investigated. Design Osteochondral explants were isolated from porcine condyles. 4 ​mm chondral and full thickness defects were treated with either porcine chondrocytes (CHON) or co-culture of 20\% CHON and 80\% MSCs (MIX) embedded in collagen hydrogel. Explants were cultured with tissue specific media (without TGF-β) under normoxia (20\% O\(_2\)) and physiological hypoxia (2\% O\(_2\)). After 28 days, immune-histological stainings (collagen II and X, aggrecan) were scored (modified Bern score, 3 independent scorer) to quantitatively compare treatment outcome. Results ARTcut® represents a software-controlled device for creation of uniform cartilage defects. Comparing the scoring results of the MIX and the CHON treatment, a positive relation between oxygen tension and defect depth was observed. Low oxygen tension stimulated cartilaginous matrix deposition in MIX group in chondral defects and CHON treatment in full thickness defects. Conclusion ARTcut® has proved a powerful tool to create cartilage defects and thus opens a wide range of novel applications of the osteochondral model, including the relation between oxygen tension and defect depth on cartilage repair.}, language = {en} } @article{HeydarianSchweinlinSchwarzetal.2021, author = {Heydarian, Motaharehsadat and Schweinlin, Matthias and Schwarz, Thomas and Rawal, Ravisha and Walles, Heike and Metzger, Marco and Rudel, Thomas and Kozjak-Pavlovic, Vera}, title = {Triple co-culture and perfusion bioreactor for studying the interaction between Neisseria gonorrhoeae and neutrophils: A novel 3D tissue model for bacterial infection and immunity}, series = {Journal of Tissue Engineering}, volume = {12}, journal = {Journal of Tissue Engineering}, doi = {10.1177/2041731420988802}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259032}, pages = {2041731420988802}, year = {2021}, abstract = {Gonorrhea, a sexually transmitted disease caused by the bacteria Neisseria gonorrhoeae, is characterized by a large number of neutrophils recruited to the site of infection. Therefore, proper modeling of the N. gonorrhoeae interaction with neutrophils is very important for investigating and understanding the mechanisms that gonococci use to evade the immune response. We have used a combination of a unique human 3D tissue model together with a dynamic culture system to study neutrophil transmigration to the site of N. gonorrhoeae infection. The triple co-culture model consisted of epithelial cells (T84 human colorectal carcinoma cells), human primary dermal fibroblasts, and human umbilical vein endothelial cells on a biological scaffold (SIS). After the infection of the tissue model with N. gonorrhoeae, we introduced primary human neutrophils to the endothelial side of the model using a perfusion-based bioreactor system. By this approach, we were able to demonstrate the activation and transmigration of neutrophils across the 3D tissue model and their recruitment to the site of infection. In summary, the triple co-culture model supplemented by neutrophils represents a promising tool for investigating N. gonorrhoeae and other bacterial infections and interactions with the innate immunity cells under conditions closely resembling the native tissue environment.}, language = {en} } @article{BannaschBergerSchwartkoppetal.2021, author = {Bannasch, Johannes H. and Berger, Benjamin and Schwartkopp, Claus-Peter and Berning, Marco and Goetze, Oliver and Panning, Marcus and Fritz-Weltin, Miriam and Trendelenburg, George and Gelderblom, Mathias and L{\"u}tgehetmann, Marc and Stute, Fridrike and Horvatits, Thomas and Dirks, Meike and Antoni, Christoph and Behrendt, Patrick and Pischke, Sven}, title = {HEV-associated neuralgic amyotrophy: a multicentric case series}, series = {Pathogens}, volume = {10}, journal = {Pathogens}, number = {6}, issn = {2076-0817}, doi = {10.3390/pathogens10060672}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239691}, year = {2021}, abstract = {Background: Neuralgic amyotrophy (NA) has been described as a possible extrahepatic manifestation of hepatitis E virus (HEV) infection. Usually, HEV-associated NA occurs bilaterally. The clinical characteristics determining the course of HEV-associated NA have still not been defined. Methods: In this retrospective multicentric case series, 16 patients with HEV-associated NA were studied and compared to 176 HEV patients without NA in terms of their age, sex, and ALT levels. Results: Neither gender distribution (75\% vs. 67\% male) nor age (47 vs. 48 years median) differed significantly between the NA patients and controls. Eight NA patients (50\%) presented with bilateral involvement — seven of these had right-side dominance and one had left-side dominance. Thirteen cases (81\%) were hospitalized. Eight of these patients stayed in hospital for five to seven days, and five patients stayed for up to two weeks. The time from the onset of NA to the HEV diagnosis, as well as the diagnostic and therapeutic proceedings, showed a large variability. In total, 13 (81\%) patients received treatment: 1/13 (8\%) received intravenous immunoglobulins, 8/13 (62\%) received glucocorticoids, 3/13 (23\%) received ribavirin, and 6/13 (46\%) received pregabalin/gabapentin. Patients with ages above the median (47 years) were more likely to be treated (p = 0.001). Conclusion: HEV-associated NA causes a relevant morbidity. In our case series neither the type of treatment nor the time of initiation of therapy had a significant effect on the duration of hospitalization or the course of the disease. The clinical presentation, the common diagnostic and therapeutic procedures, and the patients' characteristics showed large variability, demonstrating the necessity of standardized protocols for this rare but relevant disease.}, language = {en} } @article{MeirMaurusKuperetal.2021, author = {Meir, Michael and Maurus, Katja and Kuper, Jochen and Hankir, Mohammed and Wardelmann, Eva and Rosenwald, Andreas and Germer, Christoph-Thomas and Wiegering, Armin}, title = {The novel KIT exon 11 germline mutation K558N is associated with gastrointestinal stromal tumor, mastocytosis, and seminoma development}, series = {Genes, Chromosomes \& Cancer}, volume = {60}, journal = {Genes, Chromosomes \& Cancer}, number = {12}, doi = {10.1002/gcc.22988}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257476}, pages = {827-832}, year = {2021}, abstract = {Familial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are frequently found in mastocytosis and GISTs, germline mutations of KIT have only been described in 39 families until now. We detected a novel germline mutation of KIT in exon 11 (p.Lys-558-Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic KIT mutations. Structural analysis suggests that the primary germline mutation alone is not sufficient to release the autoinhibitory region of KIT located in the transmembrane domain. Instead, the KIT kinase module becomes constitutively activated when K558N combines with different secondary somatic mutations. The identical germline mutation in combination with an additional somatic KIT mutation was detected in a second patient of the kindred with seminoma while a third patient within the family had a cutaneous mastocytosis. These findings suggest that the K558N mutation interferes with the juxtamembranous part of KIT, since seminoma and mastocystosis are usually not associated with exon 11 mutations.}, language = {en} } @article{MuellerMuellerRiederer2021, author = {M{\"u}ller, Thomas and Mueller, Bernhard Klaus and Riederer, Peter}, title = {Perspective: Treatment for disease modification in chronic neurodegeneration}, series = {Cells}, volume = {10}, journal = {Cells}, number = {4}, issn = {2073-4409}, doi = {10.3390/cells10040873}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236644}, year = {2021}, abstract = {Symptomatic treatments are available for Parkinson's disease and Alzheimer's disease. An unmet need is cure or disease modification. This review discusses possible reasons for negative clinical study outcomes on disease modification following promising positive findings from experimental research. It scrutinizes current research paradigms for disease modification with antibodies against pathological protein enrichment, such as α-synuclein, amyloid or tau, based on post mortem findings. Instead a more uniform regenerative and reparative therapeutic approach for chronic neurodegenerative disease entities is proposed with stimulation of an endogenously existing repair system, which acts independent of specific disease mechanisms. The repulsive guidance molecule A pathway is involved in the regulation of peripheral and central neuronal restoration. Therapeutic antagonism of repulsive guidance molecule A reverses neurodegeneration according to experimental outcomes in numerous disease models in rodents and monkeys. Antibodies against repulsive guidance molecule A exist. First clinical studies in neurological conditions with an acute onset are under way. Future clinical trials with these antibodies should initially focus on well characterized uniform cohorts of patients. The efficiency of repulsive guidance molecule A antagonism and associated stimulation of neurogenesis should be demonstrated with objective assessment tools to counteract dilution of therapeutic effects by subjectivity and heterogeneity of chronic disease entities. Such a research concept will hopefully enhance clinical test strategies and improve the future therapeutic armamentarium for chronic neurodegeneration.}, language = {en} } @article{HaggeMuellerBirkemoeetal.2021, author = {Hagge, Jonas and M{\"u}ller, J{\"o}rg and Birkemoe, Tone and Buse, J{\"o}rn and Christensen, Rune Haubo Bojesen and Gossner, Martin M. and Gruppe, Axel and Heibl, Christoph and Jarzabek-M{\"u}ller, Andrea and Seibold, Sebastian and Siitonen, Juha and Soutinho, Jo{\~a}o Gon{\c{c}}alo and Sverdrup-Thygeson, Anne and Thorn, Simon and Drag, Lukas}, title = {What does a threatened saproxylic beetle look like? Modelling extinction risk using a new morphological trait database}, series = {Journal of Animal Ecology}, volume = {90}, journal = {Journal of Animal Ecology}, number = {8}, doi = {10.1111/1365-2656.13512}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244717}, pages = {1934 -- 1947}, year = {2021}, abstract = {The extinction of species is a non-random process, and understanding why some species are more likely to go extinct than others is critical for conservation efforts. Functional trait-based approaches offer a promising tool to achieve this goal. In forests, deadwood-dependent (saproxylic) beetles comprise a major part of threatened species, but analyses of their extinction risk have been hindered by the availability of suitable morphological traits. To better understand the mechanisms underlying extinction in insects, we investigated the relationships between morphological features and the extinction risk of saproxylic beetles. Specifically, we hypothesised that species darker in colour, with a larger and rounder body, a lower mobility, lower sensory perception and more robust mandibles are at higher risk. We first developed a protocol for morphological trait measurements and present a database of 37 traits for 1,157 European saproxylic beetle species. Based on 13 selected, independent traits characterising aspects of colour, body shape, locomotion, sensory perception and foraging, we used a proportional-odds multiple linear mixed-effects model to model the German Red List categories of 744 species as an ordinal index of extinction risk. Six out of 13 traits correlated significantly with extinction risk. Larger species as well as species with a broad and round body had a higher extinction risk than small, slim and flattened species. Species with short wings had a higher extinction risk than those with long wings. On the contrary, extinction risk increased with decreasing wing load and with higher mandibular aspect ratio (shorter and more robust mandibles). Our study provides new insights into how morphological traits, beyond the widely used body size, determine the extinction risk of saproxylic beetles. Moreover, our approach shows that the morphological characteristics of beetles can be comprehensively represented by a selection of 13 traits. We recommend them as a starting point for functional analyses in the rapidly growing field of ecological and conservation studies of deadwood.}, language = {en} } @article{GieselKratochwilSchlittenhardtetal.2021, author = {Giesel, Frederik L. and Kratochwil, Clemens and Schlittenhardt, Joel and Dendl, Katharina and Eiber, Matthias and Staudinger, Fabian and Kessler, Lukas and Fendler, Wolfgang P. and Lindner, Thomas and Koerber, Stefan A. and Cardinale, Jens and Sennung, David and Roehrich, Manuel and Debus, Juergen and Sathekge, Mike and Haberkorn, Uwe and Calais, Jeremie and Serfling, Sebastian and Buck, Andreas L.}, title = {Head-to-head intra-individual comparison of biodistribution and tumor uptake of \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG PET/CT in cancer patients}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {48}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {13}, issn = {1619-7070}, doi = {10.1007/s00259-021-05307-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307252}, pages = {4377-4385}, year = {2021}, abstract = {Purpose FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of \(^{68}\)Ga-FAPI versus standard-of-care \(^{18}\)F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. Material and Methods This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). Results A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. \(^{68}\)Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for \(^{68}\)Ga-FAPI than \(^{18}\)F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, \(^{68}\)Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases. Conclusion Quantitative tumor uptake is comparable between \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for \(^{68}\)Ga-FAPI. Thus, \(^{68}\)Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological \(^{18}\)F-FDG uptake.}, language = {en} } @article{FeketeEgbertsPreissleretal.2021, author = {Fekete, Stefanie and Egberts, K. and Preissler, T. and Wewetzer, C. and Mehler-Wex, C. and Romanos, M. and Gerlach, M.}, title = {Estimation of a preliminary therapeutic reference range for children and adolescents with tic disorders treated with tiapride}, series = {European Journal of Clinical Pharmacology}, volume = {77}, journal = {European Journal of Clinical Pharmacology}, number = {2}, doi = {10.1007/s00228-020-03000-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279893}, pages = {163-170}, year = {2021}, abstract = {Purpose Tiapride is commonly used in Europe for the treatment of tics. The aim of this study was to examine the relationship between dose and serum concentrations of tiapride and potential influential pharmacokinetic factors in children and adolescents. In addition, a preliminary therapeutic reference range for children and adolescents with tics treated with tiapride was calculated. Methods Children and adolescents treated with tiapride at three university hospitals and two departments of child and adolescents psychiatry in Germany and Austria were included in the study. Patient characteristics, doses, serum concentrations, and therapeutic outcome were assessed during clinical routine care using standardised measures. Results In the 49 paediatric patients (83.7\% male, mean age = 12.5 years), a positive correlation was found between tiapride dose (median 6.9 mg/kg, range 0.97-19.35) and serum concentration with marked inter-individual variability. The variation in dose explained 57\% of the inter-patient variability in tiapride serum concentrations; age, gender, and concomitant medication did not contribute to the variability. The symptoms improved in 83.3\% of the patients. 27.1\% of the patients had mild or moderate ADRs. No patient suffered from severe ADRs. Conclusions This study shows that tiapride treatment was effective and safe in most patients with tics. Compared with the therapeutic concentration range established for adults with Chorea Huntington, our data hinted at a lower lower limit (560 ng/ml) and similar upper limit (2000 ng/ml).}, language = {en} } @article{GuthHueserRothetal.2021, author = {Guth, Sabine and H{\"u}ser, Stephanie and Roth, Angelika and Degen, Gisela and Diel, Patrick and Edlund, Karolina and Eisenbrand, Gerhard and Engel, Karl-Heinz and Epe, Bernd and Grune, Tilman and Heinz, Volker and Henle, Thomas and Humpf, Hans-Ulrich and J{\"a}ger, Henry and Joost, Hans-Georg and Kulling, Sabine E. and Lampen, Alfonso and Mally, Angela and Marchan, Rosemarie and Marko, Doris and M{\"u}hle, Eva and Nitsche, Michael A. and R{\"o}hrdanz, Elke and Stadler, Richard and van Thriel, Christoph and Vieths, Stefan and Vogel, Rudi F. and Wascher, Edmund and Watzl, Carsten and N{\"o}thlings, Ute and Hengstler, Jan G.}, title = {Contribution to the ongoing discussion on fluoride toxicity}, series = {Archives of Toxicology}, volume = {95}, journal = {Archives of Toxicology}, number = {7}, issn = {0340-5761}, doi = {10.1007/s00204-021-03072-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307161}, pages = {2571-2587}, year = {2021}, abstract = {Since the addition of fluoride to drinking water in the 1940s, there have been frequent and sometimes heated discussions regarding its benefits and risks. In a recently published review, we addressed the question if current exposure levels in Europe represent a risk to human health. This review was discussed in an editorial asking why we did not calculate benchmark doses (BMD) of fluoride neurotoxicity for humans. Here, we address the question, why it is problematic to calculate BMDs based on the currently available data. Briefly, the conclusions of the available studies are not homogeneous, reporting negative as well as positive results; moreover, the positive studies lack control of confounding factors such as the influence of well-known neurotoxicants. We also discuss the limitations of several further epidemiological studies that did not meet the inclusion criteria of our review. Finally, it is important to not only focus on epidemiological studies. Rather, risk analysis should consider all available data, including epidemiological, animal, as well as in vitro studies. Despite remaining uncertainties, the totality of evidence does not support the notion that fluoride should be considered a human developmental neurotoxicant at current exposure levels in European countries.}, language = {en} } @article{MorisChristmannWirtgenetal.2021, author = {Moris, Victoria C. and Christmann, Katharina and Wirtgen, Aline and Belokobylskij, Sergey A. and Berg, Alexander and Liebig, Wolf-Harald and Soon, Villu and Baur, Hannes and Schmitt, Thomas and Niehuis, Oliver}, title = {Cuticular hydrocarbons on old museum specimens of the spiny mason wasp, Odynerus spinipes (Hymenoptera: Vespidae: Eumeninae), shed light on the distribution and on regional frequencies of distinct chemotypes}, series = {Chemoecology}, volume = {31}, journal = {Chemoecology}, number = {5}, issn = {0937-7409}, doi = {10.1007/s00049-021-00350-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-306999}, pages = {311-322}, year = {2021}, abstract = {The mason wasp Odynerus spinipes shows an exceptional case of intrasexual cuticular hydrocarbon (CHC) profile dimorphism. Females of this species display one of two CHC profiles (chemotypes) that differ qualitatively and quantitatively from each other. The ratio of the two chemotypes was previously shown to be close to 1:1 at three sites in Southern Germany, which might not be representative given the Palearctic distribution of the species. To infer the frequency of the two chemotypes across the entire distributional range of the species, we analyzed with GC-MS the CHC profile of 1042 dry-mounted specimens stored in private and museum collections. We complemented our sampling by including 324 samples collected and preserved specifically for studying their CHCs. We were capable of reliably identifying the chemotypes in 91\% of dry-mounted samples, some of which collected almost 200 years ago. We found both chemotypes to occur in the Far East, the presumed glacial refuge of the species, and their frequency to differ considerably between sites and geographic regions. The geographic structure in the chemotype frequencies could be the result of differential selection regimes and/or different dispersal routes during the colonization of the Western Palearctic. The presented data pave the route for disentangling these factors by providing information where to geographically sample O. spinipes for population genetic analyses. They also form the much-needed basis for future studies aiming to understand the evolutionary and geographic origin as well as the genetics of the astounding CHC profile dimorphism that O. spinipes females exhibit.}, language = {en} } @article{PinkawaAebersoldBoehmeretal.2021, author = {Pinkawa, Michael and Aebersold, Daniel M. and B{\"o}hmer, Dirk and Flentje, Michael and Ghadjar, Pirus and Schmidt-Hegemann, Nina-Sophie and H{\"o}cht, Stefan and H{\"o}lscher, Tobias and M{\"u}ller, Arndt-Christian and Niehoff, Peter and Sedlmayer, Felix and Wolf, Frank and Zamboglou, Constantinos and Zips, Daniel and Wiegel, Thomas}, title = {Radiotherapy in nodal oligorecurrent prostate cancer}, series = {Strahlentherapie und Onkologie}, volume = {197}, journal = {Strahlentherapie und Onkologie}, number = {7}, issn = {0179-7158}, doi = {10.1007/s00066-021-01778-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307763}, pages = {575-580}, year = {2021}, abstract = {Objective The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results Metastasis-directed radiotherapy results in high local control (often > 90\% within a follow-up of 1-2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.}, language = {en} } @article{BarileBerryBlaauboeretal.2021, author = {Barile, Frank A. and Berry, Colin and Blaauboer, Bas and Boobis, Alan and Bolt, Herrmann M. and Borgert, Christopher and Dekant, Wolfgang and Dietrich, Daniel and Domingo, Jose L. and Galli, Corrado L. and Gori, Gio Batta and Greim, Helmut and Hengstler, Jan G. and Heslop-Harrison, Pat and Kacew, Sam and Marquardt, Hans and Mally, Angela and Pelkonen, Olavi and Savolainen, Kai and Testai, Emanuela and Tsatsakis, Aristides and Vermeulen, Nico P.}, title = {The EU chemicals strategy for sustainability: in support of the BfR position}, series = {Archives of Toxicology}, volume = {95}, journal = {Archives of Toxicology}, number = {9}, issn = {0340-5761}, doi = {10.1007/s00204-021-03125-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307154}, pages = {3133-3136}, year = {2021}, abstract = {The EU chemicals strategy for sustainability (CSS) asserts that both human health and the environment are presently threatened and that further regulation is necessary. In a recent Guest Editorial, members of the German competent authority for risk assessment, the BfR, raised concerns about the scientific justification for this strategy. The complexity and interdependence of the networks of regulation of chemical substances have ensured that public health and wellbeing in the EU have continuously improved. A continuous process of improvement in consumer protection is clearly desirable but any initiative directed towards this objective must be based on scientific knowledge. It must not confound risk with other factors in determining policy. This conclusion is fully supported in the present Commentary including the request to improve both, data collection and the time-consuming and bureaucratic procedures that delay the publication of regulations.}, language = {en} } @article{DornHerzberg2021, author = {Dorn, Franziska and Herzberg, Moriz}, title = {Response to Letter to the Editor "Keeping Late Thrombectomy Imaging Protocols Simple to Avoid Analysis Paralysis"}, series = {Clinical Neuroradiology}, volume = {31}, journal = {Clinical Neuroradiology}, number = {3}, issn = {1869-1439}, doi = {10.1007/s00062-021-01091-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307023}, pages = {813-814}, year = {2021}, language = {en} } @article{PennigHoyerKrauskopfetal.2021, author = {Pennig, Lenhard and Hoyer, Ulrike Cornelia Isabel and Krauskopf, Alexandra and Shahzad, Rahil and J{\"u}nger, Stephanie T. and Thiele, Frank and Laukamp, Kai Roman and Grunz, Jan-Peter and Perkuhn, Michael and Schlamann, Marc and Kabbasch, Christoph and Borggrefe, Jan and Goertz, Lukas}, title = {Deep learning assistance increases the detection sensitivity of radiologists for secondary intracranial aneurysms in subarachnoid hemorrhage}, series = {Neuroradiology}, volume = {63}, journal = {Neuroradiology}, number = {12}, issn = {0028-3940}, doi = {10.1007/s00234-021-02697-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308117}, pages = {1985-1994}, year = {2021}, abstract = {Purpose To evaluate whether a deep learning model (DLM) could increase the detection sensitivity of radiologists for intracranial aneurysms on CT angiography (CTA) in aneurysmal subarachnoid hemorrhage (aSAH). Methods Three different DLMs were trained on CTA datasets of 68 aSAH patients with 79 aneurysms with their outputs being combined applying ensemble learning (DLM-Ens). The DLM-Ens was evaluated on an independent test set of 104 aSAH patients with 126 aneuryms (mean volume 129.2 ± 185.4 mm3, 13.0\% at the posterior circulation), which were determined by two radiologists and one neurosurgeon in consensus using CTA and digital subtraction angiography scans. CTA scans of the test set were then presented to three blinded radiologists (reader 1: 13, reader 2: 4, and reader 3: 3 years of experience in diagnostic neuroradiology), who assessed them individually for aneurysms. Detection sensitivities for aneurysms of the readers with and without the assistance of the DLM were compared. Results In the test set, the detection sensitivity of the DLM-Ens (85.7\%) was comparable to the radiologists (reader 1: 91.2\%, reader 2: 86.5\%, and reader 3: 86.5\%; Fleiss κ of 0.502). DLM-assistance significantly increased the detection sensitivity (reader 1: 97.6\%, reader 2: 97.6\%,and reader 3: 96.0\%; overall P=.024; Fleiss κ of 0.878), especially for secondary aneurysms (88.2\% of the additional aneurysms provided by the DLM). Conclusion Deep learning significantly improved the detection sensitivity of radiologists for aneurysms in aSAH, especially for secondary aneurysms. It therefore represents a valuable adjunct for physicians to establish an accurate diagnosis in order to optimize patient treatment.}, language = {en} } @article{PilgramEberweinWilleetal.2021, author = {Pilgram, Lisa and Eberwein, Lukas and Wille, Kai and Koehler, Felix C. and Stecher, Melanie and Rieg, Siegbert and Kielstein, Jan T. and Jakob, Carolin E. M. and R{\"u}thrich, Maria and Burst, Volker and Prasser, Fabian and Borgmann, Stefan and M{\"u}ller, Roman-Ulrich and Lanznaster, Julia and Isberner, Nora and Tometten, Lukas and Dolff, Sebastian}, title = {Clinical course and predictive risk factors for fatal outcome of SARS-CoV-2 infection in patients with chronic kidney disease}, series = {Infection}, volume = {49}, journal = {Infection}, number = {4}, organization = {LEOSS Study group}, issn = {0300-8126}, doi = {10.1007/s15010-021-01597-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308957}, pages = {725-737}, year = {2021}, abstract = {Purpose The ongoing pandemic caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) has stressed health systems worldwide. Patients with chronic kidney disease (CKD) seem to be more prone to a severe course of coronavirus disease (COVID-19) due to comorbidities and an altered immune system. The study's aim was to identify factors predicting mortality among SARS-CoV-2-infected patients with CKD. Methods We analyzed 2817 SARS-CoV-2-infected patients enrolled in the Lean European Open Survey on SARS-CoV-2-infected patients and identified 426 patients with pre-existing CKD. Group comparisons were performed via Chi-squared test. Using univariate and multivariable logistic regression, predictive factors for mortality were identified. Results Comparative analyses to patients without CKD revealed a higher mortality (140/426, 32.9\% versus 354/2391, 14.8\%). Higher age could be confirmed as a demographic predictor for mortality in CKD patients (> 85 years compared to 15-65 years, adjusted odds ratio (aOR) 6.49, 95\% CI 1.27-33.20, p = 0.025). We further identified markedly elevated lactate dehydrogenase (> 2 × upper limit of normal, aOR 23.21, 95\% CI 3.66-147.11, p < 0.001), thrombocytopenia (< 120,000/µl, aOR 11.66, 95\% CI 2.49-54.70, p = 0.002), anemia (Hb < 10 g/dl, aOR 3.21, 95\% CI 1.17-8.82, p = 0.024), and C-reactive protein (≥ 30 mg/l, aOR 3.44, 95\% CI 1.13-10.45, p = 0.029) as predictors, while renal replacement therapy was not related to mortality (aOR 1.15, 95\% CI 0.68-1.93, p = 0.611). Conclusion The identified predictors include routinely measured and universally available parameters. Their assessment might facilitate risk stratification in this highly vulnerable cohort as early as at initial medical evaluation for SARS-CoV-2.}, language = {en} } @article{HornKristLiebetal.2021, author = {Horn, A. and Krist, L. and Lieb, W. and Montellano, F. A. and Kohls, M. and Haas, K. and Gelbrich, G. and Bolay-Gehrig, S. J. and Morbach, C. and Reese, J. P. and St{\"o}rk, S. and Fricke, J. and Zoller, T. and Schmidt, S. and Triller, P. and Kretzler, L. and R{\"o}nnefarth, M. and Von Kalle, C. and Willich, S. N. and Kurth, F. and Steinbeis, F. and Witzenrath, M. and Bahmer, T. and Hermes, A. and Krawczak, M. and Reinke, L. and Maetzler, C. and Franzenburg, J. and Enderle, J. and Flinspach, A. and Vehreschild, J. and Schons, M. and Illig, T. and Anton, G. and Ungeth{\"u}m, K. and Finkenberg, B. C. and Gehrig, M. T. and Savaskan, N. and Heuschmann, P. U. and Keil, T. and Schreiber, S.}, title = {Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP)}, series = {Infection}, volume = {49}, journal = {Infection}, number = {6}, issn = {0300-8126}, doi = {10.1007/s15010-021-01707-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308960}, pages = {1277-1287}, year = {2021}, abstract = {Purpose Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. Methods The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, W{\"u}rzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. Results As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36\% wished to participate and 1295 have already been examined at least once. Conclusion NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. Trial registration Registered at the German registry for clinical studies (DRKS00023742).}, language = {en} }