@article{TamihardjaLutyjKraftetal.2021,
  author    = {Tamihardja, J{\"o}rg and Lutyj, Paul and Kraft, Johannes and Lisowski, Dominik and Weick, Stefan and Flentje, Michael and Polat, B{\"u}lent},
  title     = {Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis},
  series = {Frontiers in Oncology},
  volume    = {11},
  journal   = {Frontiers in Oncology},
  issn      = {2234-943X},
  doi       = {10.3389/fonc.2021.764536},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250992},
  year      = {2021},
  abstract  = {Purpose Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer. Methods 338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90\%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1\%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition. Results Median follow-up was 101.8 months. 15 (4.4\%)/115 (34.0\%)/208 (61.5\%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7\% and 75.9\% for all patients. The estimated 5-year bRFS was 93.3\%, 93.4\% and 79.5\% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5\% and 70.0\%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3\% and 5.0\% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6\%/0.3\%. Conclusions Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.},
  language  = {en}
}
@article{StrilciucVecseiBoeringetal.2021,
  author    = {Strilciuc, Stefan and V{\´e}csei, L{\´a}szl{\´o} and Boering, Dana and Pražnikar, Aleš and Kaut, Oliver and Riederer, Peter and Battistin, Leontino},
  title     = {Safety of Cerebrolysin for neurorecovery after acute ischemic stroke: a systematic review and meta-analysis of twelve randomized-controlled trials},
  series = {Pharmaceuticals},
  volume    = {14},
  journal   = {Pharmaceuticals},
  number    = {12},
  issn      = {1424-8247},
  doi       = {10.3390/ph14121297},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252403},
  year      = {2021},
  abstract  = {We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed, and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis were conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95\% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p > 0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.},
  language  = {en}
}
@article{NguemeniHiewKoegleretal.2021,
  author    = {Nguemeni, Carine and Hiew, Shawn and K{\"o}gler, Stefanie and Homola, Gy{\"o}rgy A. and Volkmann, Jens and Zeller, Daniel},
  title     = {Split-belt training but not cerebellar anodal tDCS improves stability control and reduces risk of fall in patients with multiple sclerosis},
  series = {Brain Sciences},
  volume    = {12},
  journal   = {Brain Sciences},
  number    = {1},
  issn      = {2076-3425},
  doi       = {10.3390/brainsci12010063},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252179},
  year      = {2021},
  abstract  = {The objective of this study was to examine the therapeutic potential of multiple sessions of training on a split-belt treadmill (SBT) combined with cerebellar anodal transcranial direct current stimulation (tDCS) on gait and balance in People with Multiple Sclerosis (PwMS). Twenty-two PwMS received six sessions of anodal (PwMS\(_{real}\), n = 12) or sham (PwMS\(_{sham}\), n = 10) tDCS to the cerebellum prior to performing the locomotor adaptation task on the SBT. To evaluate the effect of the intervention, functional gait assessment (FGA) scores and distance walked in 2 min (2MWT) were measured at the baseline (T0), day 6 (T5), and at the 4-week follow up (T6). Locomotor performance and changes of motor outcomes were similar in PwMS\(_{real}\) and PwMS\(_{sham}\) independently from tDCS mode applied to the cerebellum (anodal vs. sham, on FGA, p = 0.23; and 2MWT, p = 0.49). When the data were pooled across the groups to investigate the effects of multiple sessions of SBT training alone, significant improvement of gait and balance was found on T5 and T6, respectively, relative to baseline (FGA, p < 0.001 for both time points). The FGA change at T6 was significantly higher than at T5 (p = 0.01) underlining a long-lasting improvement. An improvement of the distance walked during the 2MWT was also observed on T5 and T6 relative to T0 (p = 0.002). Multiple sessions of SBT training resulted in a lasting improvement of gait stability and endurance, thus potentially reducing the risk of fall as measured by FGA and 2MWT. Application of cerebellar tDCS during SBT walking had no additional effect on locomotor outcomes.},
  language  = {en}
}
@article{KhareDeslauriersMorinetal.2021,
  author    = {Khare, Siddhartha and Deslauriers, Annie and Morin, Hubert and Latifi, Hooman and Rossi, Sergio},
  title     = {Comparing time-lapse PhenoCams with satellite observations across the boreal forest of Quebec, Canada},
  series = {Remote Sensing},
  volume    = {14},
  journal   = {Remote Sensing},
  number    = {1},
  issn      = {2072-4292},
  doi       = {10.3390/rs14010100},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252213},
  year      = {2021},
  abstract  = {Intercomparison of satellite-derived vegetation phenology is scarce in remote locations because of the limited coverage area and low temporal resolution of field observations. By their reliable near-ground observations and high-frequency data collection, PhenoCams can be a robust tool for intercomparison of land surface phenology derived from satellites. This study aims to investigate the transition dates of black spruce (Picea mariana (Mill.) B.S.P.) phenology by comparing fortnightly the MODIS normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI) extracted using the Google Earth Engine (GEE) platform with the daily PhenoCam-based green chromatic coordinate (GCC) index. Data were collected from 2016 to 2019 by PhenoCams installed in six mature stands along a latitudinal gradient of the boreal forests of Quebec, Canada. All time series were fitted by double-logistic functions, and the estimated parameters were compared between NDVI, EVI, and GCC. The onset of GCC occurred in the second week of May, whereas the ending of GCC occurred in the last week of September. We demonstrated that GCC was more correlated with EVI (R\(^2\) from 0.66 to 0.85) than NDVI (R\(^2\) from 0.52 to 0.68). In addition, the onset and ending of phenology were shown to differ by 3.5 and 5.4 days between EVI and GCC, respectively. Larger differences were detected between NDVI and GCC, 17.05 and 26.89 days for the onset and ending, respectively. EVI showed better estimations of the phenological dates than NDVI. This better performance is explained by the higher spectral sensitivity of EVI for multiple canopy leaf layers due to the presence of an additional blue band and an optimized soil factor value. Our study demonstrates that the phenological observations derived from PhenoCam are comparable with the EVI index. We conclude that EVI is more suitable than NDVI to assess phenology in evergreen species of the northern boreal region, where PhenoCam data are not available. The EVI index could be used as a reliable proxy of GCC for monitoring evergreen species phenology in areas with reduced access, or where repeated data collection from remote areas are logistically difficult due to the extreme weather.},
  language  = {en}
}
@article{Dosoo2021,
  author    = {Dosoo, Korshi},
  title     = {Healing traditions in Coptic magical texts},
  series = {Trends in Classics},
  volume    = {13},
  journal   = {Trends in Classics},
  number    = {1},
  issn      = {1866-7473},
  doi       = {10.1515/tc-2021-0003},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251219},
  pages     = {44 -- 94},
  year      = {2021},
  abstract  = {Within the 'market of healing' of Christian Egypt (here broadly considered as the fourth through twelfth centuries CE), 'magical' practitioners represent an elusive yet recurrent category. This article explores the evidence for magical healing from three perspectives - first, literary texts which situate 'magicians' in competition with medical and ecclesiastical healing; second, the papyrological evidence of Coptic-language magical texts, which provide evidence for concepts of disease, wellness, and their mediation; and finally confronting the question of how these healing traditions might be understood within the methodologically materialistic framework of academic history, using the concepts of placebo and healing as a performance.},
  language  = {en}
}
@article{SchmidtJakubietzGilbertetal.2021,
  author    = {Schmidt, Karsten and Jakubietz, Michael Georg and Gilbert, Fabian and Fenwick, Annabel and Meffert, Reiner Heribert and Jakubietz, Rafael Gregor},
  title     = {Muscle cuff in distal pedicled adipofascial sural artery flaps: a retrospective case control study},
  series = {PRS Global Open},
  volume    = {9},
  journal   = {PRS Global Open},
  number    = {3},
  doi       = {10.1097/GOX.0000000000003464},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259875},
  year      = {2021},
  abstract  = {Background: Amputation after open tibial fracture occurs in 3\% of cases. The rate increases when flap reconstruction is required. The standard care involves microsurgical tissue transfer although the pedicled reverse sural artery adipofascial flap (PRSAF) is a local alternative in patients endangered by a prolonged operative time. Incorporation of a gastrocnemius muscle cuff in this flap can be used to fill dead space and increase healing potential. Literature shows superior survival rates for both PRSAF and inclusion of a muscle cuff in comparison with the cutaneous version. The aim of the study was to compare the outcome of the PRSAF and the musculoadipofascial version (PRSMAF). We hypothesize that the PRSMAF provides similar lap viability and flap-related complication rates as does the adipofascial version. The muscle component may reduce the long-term osteomyelitis rate. Methods: Patients were evaluated retrospectively after reconstruction with either PRSAF or PRSMAF. Preoperative osteomyelitis, flap survival, complications and osteomyelitis clearance were analyzed. Results: The study shows preliminary results supporting the potential use of the PRSMAF. We compare either 23 PRSMAF or 20 PRSAF flaps. We found no statistically significant differences in flap survival or in complication rate. Conclusions: Although the anatomical situation may sometimes dictate the use of a free flap, a technically less-complicated option may in some cases offer a viable alternative. This study shows that the PRSMAF can serve as an alternative for complex bone defects in the limb, though it does not provide statistical improvement to the PRSAF.},
  language  = {en}
}
@article{HojsgaardSchartl2021,
  author    = {Hojsgaard, Diego and Schartl, Manfred},
  title     = {Skipping sex: A nonrecombinant genomic assemblage of complementary reproductive modules},
  series = {BioEssays},
  volume    = {43},
  journal   = {BioEssays},
  number    = {1},
  doi       = {10.1002/bies.202000111},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225818},
  year      = {2021},
  abstract  = {The unusual occurrence and developmental diversity of asexual eukaryotes remain a puzzle. De novo formation of a functioning asexual genome requires a unique assembly of sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and to affect discrete components of sexuality and produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, that is, a nonrecombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.},
  language  = {en}
}
@article{BousquetAntoBachertetal.2021,
  author    = {Bousquet, Jean and Anto, Josep M. and Bachert, Claus and Haahtela, Tari and Zuberbier, Torsten and Czarlewski, Wienczyslawa and Bedbrook, Anna and Bosnic-Anticevich, Sinthia and Walter Canonica, G. and Cardona, Victoria and Costa, Elisio and Cruz, Alvaro A. and Erhola, Marina and Fokkens, Wytske J. and Fonseca, Joao A. and Illario, Maddalena and Ivancevich, Juan-Carlos and Jutel, Marek and Klimek, Ludger and Kuna, Piotr and Kvedariene, Violeta and Le, LTT and Larenas-Linnemann, D{\´e}sir{\´e}e E. and Laune, Daniel and Louren{\c{c}}o, Olga M. and Mel{\´e}n, Erik and Mullol, Joaquim and Niedoszytko, Marek and Odemyr, Mika{\"e}la and Okamoto, Yoshitaka and Papadopoulos, Nikos G. and Patella, Vincenzo and Pfaar, Oliver and Pham-Thi, Nh{\^a}n and Rolland, Christine and Samolinski, Boleslaw and Sheikh, Aziz and Sofiev, Mikhail and Suppli Ulrik, Charlotte and Todo-Bom, Ana and Tomazic, Peter-Valentin and Toppila-Salmi, Sanna and Tsiligianni, Ioanna and Valiulis, Arunas and Valovirta, Erkka and Ventura, Maria-Teresa and Walker, Samantha and Williams, Sian and Yorgancioglu, Arzu and Agache, Ioana and Akdis, Cezmi A. and Almeida, Rute and Ansotegui, Ignacio J. and Annesi-Maesano, Isabella and Arnavielhe, Sylvie and Basaga{\~n}a, Xavier and D. Bateman, Eric and B{\´e}dard, Annabelle and Bedolla-Barajas, Martin and Becker, Sven and Bennoor, Kazi S. and Benveniste, Samuel and Bergmann, Karl C. and Bewick, Michael and Bialek, Slawomir and E. Billo, Nils and Bindslev-Jensen, Carsten and Bjermer, Leif and Blain, Hubert and Bonini, Matteo and Bonniaud, Philippe and Bosse, Isabelle and Bouchard, Jacques and Boulet, Louis-Philippe and Bourret, Rodolphe and Boussery, Koen and Braido, Fluvio and Briedis, Vitalis and Briggs, Andrew and Brightling, Christopher E. and Brozek, Jan and Brusselle, Guy and Brussino, Luisa and Buhl, Roland and Buonaiuto, Roland and Calderon, Moises A. and Camargos, Paulo and Camuzat, Thierry and Caraballo, Luis and Carriazo, Ana-Maria and Carr, Warner and Cartier, Christine and Casale, Thomas and Cecchi, Lorenzo and Cepeda Sarabia, Alfonso M. and H. Chavannes, Niels and Chkhartishvili, Ekaterine and Chu, Derek K. and Cingi, Cemal and Correia de Sousa, Jaime and Costa, David J. and Courbis, Anne-Lise and Custovic, Adnan and Cvetkosvki, Biljana and D'Amato, Gennaro and da Silva, Jane and Dantas, Carina and Dokic, Dejan and Dauvilliers, Yves and De Feo, Giulia and De Vries, Govert and Devillier, Philippe and Di Capua, Stefania and Dray, Gerard and Dubakiene, Ruta and Durham, Stephen R. and Dykewicz, Mark and Ebisawa, Motohiro and Gaga, Mina and El-Gamal, Yehia and Heffler, Enrico and Emuzyte, Regina and Farrell, John and Fauquert, Jean-Luc and Fiocchi, Alessandro and Fink-Wagner, Antje and Fontaine, Jean-Fran{\c{c}}ois and Fuentes Perez, Jos{\´e} M. and Gemicioğlu, Bilun and Gamkrelidze, Amiran and Garcia-Aymerich, Judith and Gevaert, Philippe and Gomez, Ren{\´e} Maximiliano and Gonz{\´a}lez Diaz, Sandra and Gotua, Maia and Guldemond, Nick A. and Guzm{\´a}n, Maria-Antonieta and Hajjam, Jawad and Huerta Villalobos, Yunuen R. and Humbert, Marc and Iaccarino, Guido and Ierodiakonou, Despo and Iinuma, Tomohisa and Jassem, Ewa and Joos, Guy and Jung, Ki-Suck and Kaidashev, Igor and Kalayci, Omer and Kardas, Przemyslaw and Keil, Thomas and Khaitov, Musa and Khaltaev, Nikolai and Kleine-Tebbe, Jorg and Kouznetsov, Rostislav and Kowalski, Marek L. and Kritikos, Vicky and Kull, Inger and La Grutta, Stefania and Leonardini, Lisa and Ljungberg, Henrik and Lieberman, Philip and Lipworth, Brian and Lodrup Carlsen, Karin C. and Lopes-Pereira, Catarina and Loureiro, Claudia C. and Louis, Renaud and Mair, Alpana and Mahboub, Bassam and Makris, Micha{\"e}l and Malva, Joao and Manning, Patrick and Marshall, Gailen D. and Masjedi, Mohamed R. and Maspero, Jorge F. and Carreiro-Martins, Pedro and Makela, Mika and Mathieu-Dupas, Eve and Maurer, Marcus and De Manuel Keenoy, Esteban and Melo-Gomes, Elisabete and Meltzer, Eli O. and Menditto, Enrica and Mercier, Jacques and Micheli, Yann and Miculinic, Neven and Mihaltan, Florin and Milenkovic, Branislava and Mitsias, Dimitirios I. and Moda, Giuliana and Mogica-Martinez, Maria-Dolores and Mohammad, Yousser and Montefort, Steve and Monti, Ricardo and Morais-Almeida, Mario and M{\"o}sges, Ralph and M{\"u}nter, Lars and Muraro, Antonella and Murray, Ruth and Naclerio, Robert and Napoli, Luigi and Namazova-Baranova, Leyla and Neffen, Hugo and Nekam, Kristoff and Neou, Angelo and Nordlund, Bj{\"o}rn and Novellino, Ettore and Nyembue, Dieudonn{\´e} and O'Hehir, Robyn and Ohta, Ken and Okubo, Kimi and Onorato, Gabrielle L. and Orlando, Valentina and Ouedraogo, Solange and Palamarchuk, Julia and Pali-Sch{\"o}ll, Isabella and Panzner, Peter and Park, Hae-Sim and Passalacqua, Gianni and P{\´e}pin, Jean-Louis and Paulino, Ema and Pawankar, Ruby and Phillips, Jim and Picard, Robert and Pinnock, Hilary and Plavec, Davor and Popov, Todor A. and Portejoie, Fabienne and Price, David and Prokopakis, Emmanuel P. and Psarros, Fotis and Pugin, Benoit and Puggioni, Francesca and Quinones-Delgado, Pablo and Raciborski, Filip and Rajabian-S{\"o}derlund, Rojin and Regateiro, Frederico S. and Reitsma, Sietze and Rivero-Yeverino, Daniela and Roberts, Graham and Roche, Nicolas and Rodriguez-Zagal, Erendira and Rolland, Christine and Roller-Wirnsberger, Regina E. and Rosario, Nelson and Romano, Antonino and Rottem, Menachem and Ryan, Dermot and Salim{\"a}ki, Johanna and Sanchez-Borges, Mario M. and Sastre, Joaquin and Scadding, Glenis K. and Scheire, Sophie and Schmid-Grendelmeier, Peter and Sch{\"u}nemann, Holger J. and Sarquis Serpa, Faradiba and Shamji, Mohamed and Sisul, Juan-Carlos and Sofiev, Mikhail and Sol{\´e}, Dirceu and Somekh, David and Sooronbaev, Talant and Sova, Milan and Spertini, Fran{\c{c}}ois and Spranger, Otto and Stellato, Cristiana and Stelmach, Rafael and Thibaudon, Michel and To, Teresa and Toumi, Mondher and Usmani, Omar and Valero, Antonio A. and Valenta, Rudolph and Valentin-Rostan, Marylin and Pereira, Marilyn Urrutia and van der Kleij, Rianne and Van Eerd, Michiel and Vandenplas, Olivier and Vasankari, Tuula and Vaz Carneiro, Antonio and Vezzani, Giorgio and Viart, Fr{\´e}d{\´e}ric and Viegi, Giovanni and Wallace, Dana and Wagenmann, Martin and Wang, De Yun and Waserman, Susan and Wickman, Magnus and Williams, Dennis M. and Wong, Gary and Wroczynski, Piotr and Yiallouros, Panayiotis K. and Yusuf, Osman M. and Zar, Heather J. and Zeng, St{\´e}phane and Zernotti, Mario E. and Zhang, Luo and Shan Zhong, Nan and Zidarn, Mihaela},
  title     = {ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice},
  series = {Allergy},
  volume    = {76},
  journal   = {Allergy},
  number    = {1},
  doi       = {10.1111/all.14422},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228339},
  pages     = {168 -- 190},
  year      = {2021},
  abstract  = {Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.},
  language  = {en}
}
@article{DohrnIhneHegenbartetal.2021,
  author    = {Dohrn, Maike F. and Ihne, Sandra and Hegenbart, Ute and Medina, Jessica and Z{\"u}chner, Stephan L. and Coelho, Teresa and Hahn, Katrin},
  title     = {Targeting transthyretin - Mechanism-based treatment approaches and future perspectives in hereditary amyloidosis},
  series = {Journal of Neurochemistry},
  volume    = {156},
  journal   = {Journal of Neurochemistry},
  number    = {6},
  doi       = {10.1111/jnc.15233},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224481},
  pages     = {802 -- 818},
  year      = {2021},
  abstract  = {The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate-limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence-specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac-conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood-brain barrier, but its half-life is short and liver failure a potential side effect. Amyloid-directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR-amyloidosis has become a model disease for pathophysiology-based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood-brain barrier permeability.},
  language  = {en}
}
@article{FlentjeRichter2021,
  author    = {Flentje, Michael and Richter, J{\"u}rgen},
  title     = {Professor Dr. Werner Bohndorf gestorben},
  series = {Strahlentherapie und Onkologie},
  volume    = {197},
  journal   = {Strahlentherapie und Onkologie},
  number    = {7},
  issn      = {1439-099X},
  doi       = {10.1007/s00066-021-01792-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264838},
  pages     = {664-665},
  year      = {2021},
  abstract  = {Kein Abstract verf{\"u}gbar.},
  language  = {de}
}
@article{LinsenmannCattaneoMaerzetal.2021,
  author    = {Linsenmann, Thomas and Cattaneo, Andrea and M{\"a}rz, Alexander and Weiland, Judith and Stetter, Christian and Nickl, Robert and Westermaier, Thomas},
  title     = {Combined frameless stereotactical biopsy and intraoperative cerebral angiography by 3D-rotational fluoroscopy with intravenous contrast administration: a feasibility study},
  series = {BMC Medical Imaging},
  volume    = {21},
  journal   = {BMC Medical Imaging},
  doi       = {10.1186/s12880-021-00622-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270370},
  year      = {2021},
  abstract  = {Background Mobile 3-dimensional fluoroscopes are an integral part of modern neurosurgical operating theatres and can also be used in combination with free available image post processing to depict cerebral vessels. In preparation of stereotactic surgery, preoperative Computed Tomography (CT) may be required for image fusion. Contrast CT may be of further advantage for image fusion as it regards the vessel anatomy in trajectory planning. Time-consuming in-hospital transports are necessary for this purpose. Mobile 3D-fluoroscopes may be used to generate a CT equal preoperative data set without an in-hospital transport. This study was performed to determine the feasibility and image quality of intraoperative 3-dimensional fluoroscopy with intravenous contrast administration in combination with stereotactical procedures. Methods 6 patients were included in this feasibility study. After fixation in a radiolucent Mayfield clamp a rotational fluoroscopy scan was performed with 50 mL iodine contrast agent. The image data sets were merged with the existing MRI images at a planning station and visually evaluated by two observer. The operation times were compared between the frame-based and frameless systems ("skin-to-skin" and "OR entry to exit"). Results The procedure proves to be safe. The entire procedure from fluoroscope positioning to the transfer to the planning station took 5-6 min with an image acquisition time of 24 s. In 5 of 6 cases, the fused imaging was able to reproduce the vascular anatomy accurately and in good quality. Both time end-points were significantly shorter compared to frame-based interventions. Conclusion The images could easily be transferred to the planning and navigation system and were successfully merged with the MRI data set. The procedure can be completely integrated into the surgical workflow. Preoperative CT imaging or transport under anaesthesia may even be replaced by this technique in the future. Furthermore, hemorrhages can be successfully visualized intraoperatively and might prevent time delays in emergencies.},
  language  = {en}
}
@article{KannBlessmannWinkelmannetal.2021,
  author    = {Kann, Simone and Blessmann, Joerg and Winkelmann, Yvonne and Hansen, Jessica and Maya Amaya, Leonardo J. and Rivera Salcedo, Gadith E. and Halas, Hussein El and Schmidt-Chanasit, Jonas and Keoviengkhone, Latdamone and Sopraseuth, Vatsana and Deschermeier, Christina and Mika, Angela},
  title     = {Dengue virus detection in Lao PDR and Colombia: Comparative evaluation of PCR tests},
  series = {Tropical Medicine \& International Health},
  volume    = {26},
  journal   = {Tropical Medicine \& International Health},
  number    = {10},
  doi       = {10.1111/tmi.13670},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262703},
  pages     = {1296 -- 1302},
  year      = {2021},
  abstract  = {Objectives Dengue virus (DENV) detection by polymerase chain reaction (PCR) facilitates diagnosis of dengue fever, which is the most frequent arboviral disease globally. Two studies were performed in countries with high dengue incidence, to assess the diagnostic performance of different PCR techniques. Methods/Results Two hundred and seventy-nine acute phase blood samples from febrile patients were analyzed for DENV by the RealStar Dengue RT-PCR kit (Altona Diagnostics) as gold standard in comparison with the Tropical Fever Core multiplex PCR (Fast Track Diagnostics). In total, 102 samples collected in Savannakhet Province (Lao PDR, Southeast Asia) in 2013 and 35 samples from Valledupar (Colombia, South America) tested positive for DENV by RealStar RT-PCR. In comparison, the Tropical Fever Core multiplex PCR detected 65.0\% (65/102) and 68.6\% (24/35) of these samples as positive for DENV in Savannakhet and Valledupar, respectively. Diagnostic sensitivity of the multiplex PCR strongly correlated with viral load. A subset of DENV PCR-confirmed samples was additionally tested by BNITM in house Dengue Type RT-PCR in comparison with two commercial test kits (RealStar Dengue Type RT-PCR [Altona Diagnostics], Dengue differentiation PCR [Fast Track Diagnostics]). The leading dengue serotype in Savannakhet was DENV-3 (58\% [29/50]), while DENV-1 (53.8\% [14/26]) was the predominant serotype found in samples collected in Valledupar by BNITM-type PCR. However, three DENV serotypes were circulating in Valledupar and in Savannakhet. In 2015, additional studies found predominantly DENV-4 (71\% [12/17]) in Savannakhet. Conclusions Both studies emphasized that routine diagnostics in both regions will benefit from an expanded use of highly sensitive pan-dengue PCRs.},
  language  = {en}
}
@article{Freitag‐WolfMunzJungeetal.2021,
  author    = {Freitag-Wolf, Sandra and Munz, Matthias and Junge, Olaf and Graetz, Christian and Jockel-Schneider, Yvonne and Staufenbiel, Ingmar and Bruckmann, Corinna and Lieb, Wolfgang and Franke, Andre and Loos, Bruno G. and Jepsen, S{\o}ren and Dommisch, Henrik and Schaefer, Arne S.},
  title     = {Sex-specific genetic factors affect the risk of early-onset periodontitis in Europeans},
  series = {Journal of Clinical Periodontology},
  volume    = {48},
  journal   = {Journal of Clinical Periodontology},
  number    = {11},
  doi       = {10.1111/jcpe.13538},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262445},
  pages     = {1404 -- 1413},
  year      = {2021},
  abstract  = {Aims Various studies have reported that young European women are more likely to develop early-onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the increased prevalence and severity. Materials and methods Using the case-only design, we tested for differences in genetic effects between men and women in 896 North-West European early-onset cases, using imputed genotypes from the OmniExpress genotyping array. Population-representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population. Results In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13). Conclusions Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter-sex phenotypic variation in early-onset periodontitis.},
  language  = {en}
}
@article{KarimiFreundWageretal.2021,
  author    = {Karimi, Sohail M. and Freund, Matthias and Wager, Brittney M. and Knoblauch, Michael and Fromm, J{\"o}rg and M. Mueller, Heike and Ache, Peter and Krischke, Markus and Mueller, Martin J. and M{\"u}ller, Tobias and Dittrich, Marcus and Geilfus, Christoph-Martin and Alfaran, Ahmed H. and Hedrich, Rainer and Deeken, Rosalia},
  title     = {Under salt stress guard cells rewire ion transport and abscisic acid signaling},
  series = {New Phytologist},
  volume    = {231},
  journal   = {New Phytologist},
  number    = {3},
  doi       = {10.1111/nph.17376},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259635},
  pages     = {1040-1055},
  year      = {2021},
  abstract  = {Soil salinity is an increasingly global problem which hampers plant growth and crop yield. Plant productivity depends on optimal water-use efficiency and photosynthetic capacity balanced by stomatal conductance. Whether and how stomatal behavior contributes to salt sensitivity or tolerance is currently unknown. This work identifies guard cell-specific signaling networks exerted by a salt-sensitive and salt-tolerant plant under ionic and osmotic stress conditions accompanied by increasing NaCl loads. We challenged soil-grown Arabidopsis thaliana and Thellungiella salsuginea plants with short- and long-term salinity stress and monitored genome-wide gene expression and signals of guard cells that determine their function. Arabidopsis plants suffered from both salt regimes and showed reduced stomatal conductance while Thellungiella displayed no obvious stress symptoms. The salt-dependent gene expression changes of guard cells supported the ability of the halophyte to maintain high potassium to sodium ratios and to attenuate the abscisic acid (ABA) signaling pathway which the glycophyte kept activated despite fading ABA concentrations. Our study shows that salinity stress and even the different tolerances are manifested on a single cell level. Halophytic guard cells are less sensitive than glycophytic guard cells, providing opportunities to manipulate stomatal behavior and improve plant productivity.},
  language  = {en}
}
@article{Lemm2021,
  author    = {Lemm, Lukas},
  title     = {Is there a decline of democracy in the EU between 2004 and 2016? The relevance of data selection: a replication study of Smolka (2021) and comparison of democracy measures},
  series = {Zeitschrift f{\"u}r Vergleichende Politikwissenschaft},
  volume    = {15},
  journal   = {Zeitschrift f{\"u}r Vergleichende Politikwissenschaft},
  number    = {3},
  issn      = {1865-2654},
  doi       = {10.1007/s12286-021-00502-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270107},
  pages     = {375-400},
  year      = {2021},
  abstract  = {Is there a Decline of Democracy? Democracy measurement provides the basis for answering this question. However, there are different measurement tools based on different meanings of democracy that have been shown to vary in their concept validity. Therefore, it is relevant to examine whether the results of the different measurement tools converge or diverge with respect to a potential decline of democracy. Smolka (2021) finds a decline of democracy for new and old EU states based on standardized data from the Democracy Barometer. A re-analysis using the original data of the Democracy Barometer and the Democracy Matrix can hardly replicate these results. A comparison of further measurements shows that the instruments diverge rather than converge. I therefore conclude with some thoughts on overcoming the selection problem that arises in light of these contrasts.},
  language  = {en}
}
@article{SchmittEguWalteretal.2021,
  author    = {Schmitt, T. and Egu, D.T. and Walter, E. and Sigmund, A.M. and Eichkorn, R. and Yazdi, A. and Schmidt, E. and S{\´a}rdy, M. and Eming, R. and Goebeler, M. and Waschke, J.},
  title     = {Ca\(^{2+}\) signalling is critical for autoantibody-induced blistering of human epidermis in pemphigus},
  series = {British Journal of Dermatology},
  volume    = {185},
  journal   = {British Journal of Dermatology},
  number    = {3},
  doi       = {10.1111/bjd.20091},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262810},
  pages     = {595 -- 604},
  year      = {2021},
  abstract  = {Background Pemphigus is a severe bullous autoimmune skin disease. Pemphigus foliaceus (PF) is characterized by antidesmoglein (Dsg) 1 IgG causing epidermal blistering; mucosal pemphigus vulgaris (mPV) by anti-Dsg3 IgG inducing erosions in the mucosa; and mucocutaneous pemphigus vulgaris (PV) by affecting both, with autoantibodies targeting Dsg1 and Dsg3. Objectives To characterize the Ca\(^{2+}\) flux pathway and delineate its importance in pemphigus pathogenesis and clinical phenotypes caused by different antibody profiles. Methods Immunoprecipitation, Ca\(^{2+}\) flux analysis, Western blotting, immunofluorescence staining, dissociation assays and a human skin ex vivo model were used. Results PV IgG and PF IgG, but neither Dsg3-specific monoclonal antibody (AK23) nor mPV IgG, caused Ca\(^{2+}\) influx in primary human keratinocytes. Phosphatidylinositol 4-kinase α interacts with Dsg1 but not with Dsg3. Its downstream target - phospholipase-C-γ1 (PLC) - was activated by PV IgG and PF IgG but not AK23 or mPV IgG. PLC releases inositol 1,4,5-trisphosphate (IP3) causing IP3 receptor (IP3R) activation and Ca2+ flux from the endoplasmic reticulum into the cytosol, which stimulates Ca2+ release-activated channels (CRAC)-mediated Ca\(^{2+}\) influx. Inhibitors against PLC, IP3R and CRAC effectively blocked PV IgG and PF IgG-induced Ca\(^{2+}\) influx; ameliorated alterations of Dsg1 and Dsg3 localization, and reorganization of keratin and actin filaments; and inhibited loss of cell adhesion in vitro. Finally, inhibiting PLC or IP3R was protective against PV IgG-induced blister formation and redistribution of Dsg1 and Dsg3 in human skin ex vivo. Conclusions Ca2+-mediated signalling is important for epidermal blistering and dependent on the autoantibody profile, which indicates different roles for signalling complexes organized by Dsg1 and Dsg3. Interfering with PLC and Ca\(^{2+}\) signalling may be a promising approach to treat epidermal manifestations of pemphigus.},
  language  = {en}
}
@article{Dittmann2021,
  author    = {Dittmann, Lara A.},
  title     = {Sprach- und Kommunikationsnuancen in literarischen Interspeziesbegegnungen - Juan Ram{\´o}n Jim{\´e}nezʼ Platero y yo (1914/1917) und Thomas Manns Herr und Hund (1919)},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {7},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2364-6705},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305658},
  pages     = {55-71},
  year      = {2021},
  abstract  = {The encounter with non-human animals has always been a major preoccupation in the (philosophical) quest of understanding the human (condition). Of course, they are not only present in literary texts, but also in other media such as music and art. We consider ourselves aware of their selves, natures and skills as well as their sensory perceptions. Indeed, the ways we interact with non-human animals in everyday life and in the fictional world, how we perceive, think and talk about them as well as how we communicate with them are often related to our own self-perceptions in the social collective and in social-historical discourse. If we take a closer look at literary interspecies relations, we can detect clear shades in language and communication. Based on the approaches of Human-Animal Studies, this article deals with those nuances regarding animal-human encounters in Juan Ram{\´o}n Jim{\´e}nez' Platero y yo (1914/1917) and Thomas Mann's Herr und Hund (1919) in a comparative perspective. In addition to this, a special focus is placed on the effect these elements can have on (inter)acting literary subjects as well as on extra-textual recipients.},
  language  = {de}
}
@article{Henk2021,
  author    = {Henk, Lars Thorben},
  title     = {«We're on the road to nowhere» - Felwine Sarrs narrativer Weg in die Afrotopie},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {7},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2364-6705},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305662},
  pages     = {73-90},
  year      = {2021},
  abstract  = {According to the Senegalesian scholar Felwine Sarr who conceives an African utopia in his programmatic essay Afrotopia (2016), this Afrotopos has already germinated in contemporary African literature. However, it still needs to be enquired to what extent the narrated topos of the street in Sarr's own anthology 105 Rue Carnot (2011) has already realized the Afrotopos. In order to respond to this question, we would like to mobilise Michel Foucault's concept of heterotopia, which elaborates on the interactions between truth production/knowledge, power and space, and permits us to conceive of «les lieux utopiques» (Foucault 2005: 40) as actually locatable on the map and real other places outside of all places (cf. Foucault 1994: 755). Thus, in the street, a different relationship between global North and South is founded, which becomes legible as an African «utopie localis{\´e}e» (Foucault 2005: 41) that Sarr calls for in Afrotopia (2016).},
  language  = {de}
}
@article{Kneifel2021,
  author    = {Kneifel, Malte},
  title     = {Futur-Formen und ihre Funktionen im Portugu{\^e}s Arcaico},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {7},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2364-6705},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305673},
  pages     = {91-109},
  year      = {2021},
  abstract  = {This article aims to trace the development of different verb forms that express future tense of Old Portuguese from the 13th to the 15th century by analyzing a historical text corpus. During this period, Portuguese future tense could be expressed through one synthetical as well as two analytical morphological verb constructions. Adapting an analytic model formerly employed by the Mexican researcher Concepci{\´o}n Company Company for an investigation of similar future tense forms in Old Spanish, this article seeks to point out that the use of the different verb forms in Portuguese followed distinct functions regarding aspects of both information structure as well as modality.},
  language  = {de}
}
@article{Klamp2021,
  author    = {Klamp, Yannic},
  title     = {Alma und {\´a}nima in spanisch-zapotekischen Evangelisierungswerken: die Translation des Konzepts Seele im kolonialen Missionskontext (Neu-Spanien, 16.-18. Jh.)},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {7},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2364-6705},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305681},
  pages     = {111-130},
  year      = {2021},
  abstract  = {The arrival of the Spanish in present-day Oaxaca, Mexico, led to manifold communicative challenges and was the origin of the first written documents in the local indigenous languages. This paper focuses on Spanish-Zapotec translations produced by Christian missionaries during the colonial period. In this context, it aims to investigate the expression of the concept of soul in their catechisms and confesionarios by analyzing chronologically how different authors apply the Spanish synonyms alma and {\´a}nima. On the one hand, we can observe some similar tendencies in central Mexican documents for the early colonial period so that we can assume that the corpus was influenced by Nahuatl translations. On the other hand, there is an independent development in Spanish-Zapotec translations not only regarding the target text but also the source text.},
  language  = {de}
}
@article{Scholz2021,
  author    = {Scholz, Janek},
  title     = {S{\´e}rgio Zimbas Covid-19-Karikaturen im Kontext {\"o}ffentlicher Gesundheitsf{\"u}rsorge in Mosambik},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {7},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2364-6705},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305692},
  pages     = {133-155},
  year      = {2021},
  abstract  = {The article deals with the educational comics of the Mozambican artist S{\´e}rgio Zimba, especially in the context of the current pandemic situation caused by Covid-19. First, comics from and comic research on Africa will be presented, especially in their repercussion within the German-language comics landscape. This will be followed by a discussion of the special situation in lusophone Africa, exemplified and illustrated by the works of the Mozambican cartoonist S{\´e}rgio Zimba. The article closes with a brief comparison of Zimba's work with the cartoons of S{\´e}rgio Pi{\c{c}}arra from Angola, to better classify the artist's work.},
  language  = {de}
}
@article{Christmann2021,
  author    = {Christmann, Tim},
  title     = {Grenzerfahrung, Grenz{\"u}berschreitung, Grenz{\"u}berwindung: Das Falkland/Malvinas Malvinas-Trauma in Lola Arias' Film Teatro de Guerra (2018)},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {7},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2364-6705},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305577},
  pages     = {17-33},
  year      = {2021},
  abstract  = {This article will examine the cinematic approach to the trauma of the Falklands/Malvinas War in Lola Ariasʼ film Teatro de Guerra (AR/ES, 2018). The armed conflict between Ar-gentina and Great Britain in 1982 can be understood as a traumatic liminal experience, whose artistic reception pushes conventional aesthetics to their limits and calls for innova-tive representational strategies. Based on a cultural studies approach to the Falklands/Mal-vinas War as a collective trauma, this contribution will highlight selected moments of aes-thetic border crossing in Teatro de Guerra, by which the film succeeds in transcending boundaries between former enemies of the war.},
  language  = {de}
}
@article{deCringis2021,
  author    = {de Cringis, Patricia},
  title     = {100 Jahre Vokalschw{\"a}chung in den tierras altas: historische Perspektiven eines (zu) wenig beachteten Aussprachemerkmal},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {7},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2364-6705},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305638},
  pages     = {35-52},
  year      = {2021},
  abstract  = {This paper deals with the origin of the hundred-year old theory of tierras bajas and tierras altas, focusing on the description of vowel weakening within that theory developed in 1921 by Henr{\´i}quez Ure{\~n}a. I argue that the early conception of vowel weakening and its dialectal distribution has strongly influenced the kind of research we have been conducting about this phonetic feature to this day. The aim of this study therefore, is to sharpen our understanding of the former zeitgeist of research and to stimulate further big data-based studies on vowel weakening overcoming the traditional dialectal division of tierras bajas and tierras altas.},
  language  = {de}
}
@article{SbieraKircherAltierietal.2021,
  author    = {Sbiera, Iuliu and Kircher, Stefan and Altieri, Barbara and Fassnacht, Martin and Kroiss, Matthias and Sbiera, Silviu},
  title     = {Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {7},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13071736},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236486},
  year      = {2021},
  abstract  = {A clinically relevant proportion of adrenocortical carcinoma (ACC) cases shows a tendency to metastatic spread. The objective was to determine whether the epithelial to mesenchymal transition (EMT), a mechanism associated with metastasizing in several epithelial cancers, might play a crucial role in ACC. 138 ACC, 29 adrenocortical adenomas (ACA), three normal adrenal glands (NAG), and control tissue samples were assessed for the expression of epithelial (E-cadherin and EpCAM) and mesenchymal (N-cadherin, SLUG and SNAIL) markers by immunohistochemistry. Using real-time RT-PCR we quantified the alternative isoform splicing of FGFR 2 and 3, another known indicator of EMT. We also assessed the impact of these markers on clinical outcome. Results show that both normal and neoplastic adrenocortical tissues lacked expression of epithelial markers but strongly expressed mesenchymal markers N-cadherin and SLUG. FGFR isoform splicing confirmed higher similarity of adrenocortical tissues to mesenchymal compared to epithelial tissues. In ACC, higher SLUG expression was associated with clinical markers indicating aggressiveness, while N-cadherin expression inversely associated with these markers. In conclusion, we could not find any indication of EMT as all adrenocortical tissues lacked expression of epithelial markers and exhibited closer similarity to mesenchymal tissues. However, while N-cadherin might play a positive role in tissue structure upkeep, SLUG seems to be associated with a more aggressive phenotype.},
  language  = {en}
}
@article{RajendranBoettigerDentzienetal.2021,
  author    = {Rajendran, Ranjithkumar and B{\"o}ttiger, Gregor and Dentzien, Niklas and Rajendran, Vinothkumar and Sharifi, Bischand and Erg{\"u}n, S{\"u}leyman and Stadelmann, Christine and Karnati, Srikanth and Berghoff, Martin},
  title     = {Effects of FGFR tyrosine kinase inhibition in OLN-93 oligodendrocytes},
  series = {Cells},
  volume    = {10},
  journal   = {Cells},
  number    = {6},
  issn      = {2073-4409},
  doi       = {10.3390/cells10061318},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239600},
  year      = {2021},
  abstract  = {Fibroblast growth factor (FGF) signaling is involved in the pathogenesis of multiple sclerosis (MS). Data from neuropathology studies suggest that FGF signaling contributes to the failure of remyelination in MS. In MOG\(_{35-55}\)-induced EAE, oligodendrocyte-specific deletion of FGFR1 and FGFR2 resulted in a less severe disease course, reduced inflammation, myelin and axon degeneration and changed FGF/FGFR and BDNF/TrkB signaling. Since signaling cascades in oligodendrocytes could not be investigated in the EAE studies, we here aimed to characterize FGFR-dependent oligodendrocyte-specific signaling in vitro. FGFR inhibition was achieved by application of the multi-kinase-inhibitor dovitinib and the FGFR1/2/3-inhibitor AZD4547. Both substances are potent inhibitors of FGF signaling; they are effective in experimental tumor models and patients with malignancies. Effects of FGFR inhibition in oligodendrocytes were studied by immunofluorescence microscopy, protein and gene analyses. Application of the tyrosine kinase inhibitors reduced FGFR1, phosphorylated ERK and Akt expression, and it enhanced BDNF and TrkB expression. Furthermore, the myelin proteins CNPase and PLP were upregulated by FGFR inhibition. In summary, inhibition of FGFR signaling in oligodendrocytes can be achieved by application of tyrosine kinase inhibitors. Decreased phosphorylation of ERK and Akt is associated with an upregulation of BDNF/TrkB signaling, which may be responsible for the increased production of myelin proteins. Furthermore, these data suggest that application of FGFR inhibitors may have the potential to promote remyelination in the CNS.},
  language  = {en}
}
@article{LeistnerHolzgrabe2021,
  author    = {Leistner, Adrian and Holzgrabe, Ulrike},
  title     = {Impurity Profiling of Baclofen Using Gradient HPLC-UV Method},
  series = {Chromatographia},
  volume    = {84},
  journal   = {Chromatographia},
  number    = {10},
  issn      = {1612-1112},
  doi       = {10.1007/s10337-021-04079-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268921},
  pages     = {927-935},
  year      = {2021},
  abstract  = {The GABA\(_{B}\) receptor agonist baclofen is a medication commonly used for the treatment of muscle spasticity. It is an amino acid and related to the neurotransmitter GABA. In this study, we developed a new, gradient high-performance liquid chromatography (HPLC) method for the impurity assessment of baclofen, which is appropriate for pharmacopoeial purposes. Since the impurities related to the synthesis pathway are acids, zwitterionic, or neutral, the method development is challenging. However, the separation of all components was achieved on a C18 stationary phase using a water-acetonitrile-trifluoroacetic acid gradient. A limit of detection (LOD) of at least 0.02\% was registered for all specified impurities. Additionally, CAD detection was performed to detect potential impurities lacking off a chromophore. The baclofen batches analyzed are far more pure than expected. All impurities were found below the specification limit, and thus, they can be regarded as unspecified. Moreover, the required runtime could be significantly reduced compared to the current USP or Ph. Eur. method.},
  language  = {en}
}
@article{ElMoualiGerovacMineikaitėetal.2021,
  author    = {El Mouali, Youssef and Gerovac, Milan and Mineikaitė, Raminta and Vogel, J{\"o}rg},
  title     = {In vivo targets of Salmonella FinO include a FinP-like small RNA controlling copy number of a cohabitating plasmid},
  series = {Nucleic Acids Research},
  volume    = {49},
  journal   = {Nucleic Acids Research},
  number    = {9},
  doi       = {10.1093/nar/gkab281},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261072},
  pages     = {5319-5335},
  year      = {2021},
  abstract  = {FinO-domain proteins represent an emerging family of RNA-binding proteins (RBPs) with diverse roles in bacterial post-transcriptional control and physiology. They exhibit an intriguing targeting spectrum, ranging from an assumed single RNA pair (FinP/traJ) for the plasmid-encoded FinO protein, to transcriptome-wide activity as documented for chromosomally encoded ProQ proteins. Thus, the shared FinO domain might bear an unusual plasticity enabling it to act either selectively or promiscuously on the same cellular RNA pool. One caveat to this model is that the full suite of in vivo targets of the assumedly highly selective FinO protein is unknown. Here, we have extensively profiled cellular transcripts associated with the virulence plasmid-encoded FinO in Salmonella enterica. While our analysis confirms the FinP sRNA of plasmid pSLT as the primary FinO target, we identify a second major ligand: the RepX sRNA of the unrelated antibiotic resistance plasmid pRSF1010. FinP and RepX are strikingly similar in length and structure, but not in primary sequence, and so may provide clues to understanding the high selectivity of FinO-RNA interactions. Moreover, we observe that the FinO RBP encoded on the Salmonella virulence plasmid controls the replication of a cohabitating antibiotic resistance plasmid, suggesting cross-regulation of plasmids on the RNA level.},
  language  = {en}
}
@article{GrunzPennigFieberetal.2021,
  author    = {Grunz, Jan-Peter and Pennig, Lenhard and Fieber, Tabea and Gietzen, Carsten Herbert and Heidenreich, Julius Frederik and Huflage, Henner and Gruschwitz, Philipp and Kuhl, Philipp Josef and Petritsch, Bernhard and Kosmala, Aleksander and Bley, Thorsten Alexander and Gassenmaier, Tobias},
  title     = {Twin robotic x-ray system in small bone and joint trauma: Impact of cone-beam computed tomography on treatment decisions},
  series = {European Radiology},
  volume    = {31},
  journal   = {European Radiology},
  issn      = {0938-7994},
  doi       = {10.1007/s00330-020-07563-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235233},
  pages     = {3600-3609},
  year      = {2021},
  abstract  = {Objectives Trauma evaluation of extremities can be challenging in conventional radiography. A multi-use x-ray system with cone-beam CT (CBCT) option facilitates ancillary 3-D imaging without repositioning. We assessed the clinical value of CBCT scans by analyzing the influence of additional findings on therapy. Methods Ninety-two patients underwent radiography and subsequent CBCT imaging with the twin robotic scanner (76 wrist/hand/finger and 16 ankle/foot/toe trauma scans). Reports by on-call radiologists before and after CBCT were compared regarding fracture detection, joint affliction, comminuted injuries, and diagnostic confidence. An orthopedic surgeon recommended therapy based on reported findings. Surgical reports (N = 52) and clinical follow-up (N = 85) were used as reference standard. Results CBCT detected more fractures (83/64 of 85), joint involvements (69/53 of 71), and multi-fragment situations (68/50 of 70) than radiography (all p < 0.001). Six fractures suspected in radiographs were ruled out by CBCT. Treatment changes based on additional information from CBCT were recommended in 29 patients (31.5\%). While agreement between advised therapy before CBCT and actual treatment was moderate (κ = 0.41 [95\% confidence interval 0.35-0.47]; p < 0.001), agreement after CBCT was almost perfect (κ = 0.88 [0.83-0.93]; p < 0.001). Diagnostic confidence increased considerably for CBCT studies (p < 0.001). Median effective dose for CBCT was 4.3 μSv [3.3-5.3 μSv] compared to 0.2 μSv [0.1-0.2 μSv] for radiography. Conclusions CBCT provides advantages for the evaluation of acute small bone and joint trauma by detecting and excluding extremity fractures and fracture-related findings more reliably than radiographs. Additional findings induced therapy change in one third of patients, suggesting substantial clinical impact.},
  language  = {en}
}
@article{EssigBabilonVollmuthetal.2021,
  author    = {Essig, Fabian and Babilon, Lilith and Vollmuth, Christoph and Kollikowski, Alexander M. and Pham, Mirko and Solymosi, L{\´a}szl{\´o} and Haeusler, Karl Georg and Kraft, Peter and Stoll, Guido and Schuhmann, Michael K.},
  title     = {High mobility group box 1 protein in cerebral thromboemboli},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {20},
  issn      = {1422-0067},
  doi       = {10.3390/ijms222011276},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265568},
  year      = {2021},
  abstract  = {High-mobility group box 1 protein (HMGB1) is a damage-associated molecular pattern (DAMP) involved in neutrophil extracellular trap (NET) formation and thrombosis. NETs are regularly found in cerebral thromboemboli. We here analyzed associated HMGB1 expression in human thromboemboli retrieved via mechanical thrombectomy from 37 stroke patients with large vessel occlusion. HMGB1 was detected in all thromboemboli, accounting for 1.7\% (IQR 0.6-6.2\%) of the total thromboemboli area and was found to be colocalized with neutrophils and NETs and in spatial proximity to platelets. Correlation analysis revealed that the detection of HMGB1 was strongly related to the number of neutrophils (r = 0.58, p = 0.0002) and platelets (r = 0.51, p = 0.001). Our results demonstrate that HMGB1 is a substantial constituent of thromboemboli causing large vessel occlusion stroke.},
  language  = {en}
}
@article{GrassingerFlorenMuelleretal.2021,
  author    = {Grassinger, Julia Maria and Floren, Andreas and M{\"u}ller, Tobias and Cerezo-Echevarria, Argi{\~n}e and Beitzinger, Christoph and Conrad, David and T{\"o}rner, Katrin and Staudacher, Marlies and Aupperle-Lellbach, Heike},
  title     = {Digital lesions in dogs: a statistical breed analysis of 2912 cases},
  series = {Veterinary Sciences},
  volume    = {8},
  journal   = {Veterinary Sciences},
  number    = {7},
  issn      = {2306-7381},
  doi       = {10.3390/vetsci8070136},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242690},
  year      = {2021},
  abstract  = {Breed predispositions to canine digital neoplasms are well known. However, there is currently no statistical analysis identifying the least affected breeds. To this end, 2912 canine amputated digits submitted from 2014-2019 to the Laboklin GmbH \& Co. KG for routine diagnostics were statistically analyzed. The study population consisted of 155 different breeds (most common: 634 Mongrels, 411 Schnauzers, 197 Labrador Retrievers, 93 Golden Retrievers). Non-neoplastic processes were present in 1246 (43\%), tumor-like lesions in 138 (5\%), and neoplasms in 1528 cases (52\%). Benign tumors (n = 335) were characterized by 217 subungual keratoacanthomas, 36 histiocytomas, 35 plasmacytomas, 16 papillomas, 12 melanocytomas, 9 sebaceous gland tumors, 6 lipomas, and 4 bone tumors. Malignant neoplasms (n = 1193) included 758 squamous cell carcinomas (SCC), 196 malignant melanomas (MM), 76 soft tissue sarcomas, 52 mast cell tumors, 37 non-specified sarcomas, 29 anaplastic neoplasms, 24 carcinomas, 20 bone tumors, and 1 histiocytic sarcoma. Predisposed breeds for SCC included the Schnauzer (log OR = 2.61), Briard (log OR = 1.78), Rottweiler (log OR = 1.54), Poodle (log OR = 1.40), and Dachshund (log OR = 1.30). Jack Russell Terriers (log OR = -2.95) were significantly less affected by SCC than Mongrels. Acral MM were significantly more frequent in Rottweilers (log OR = 1.88) and Labrador Retrievers (log OR = 1.09). In contrast, Dachshunds (log OR = -2.17), Jack Russell Terriers (log OR = -1.88), and Rhodesian Ridgebacks (log OR = -1.88) were rarely affected. This contrasted with the well-known predisposition of Dachshunds and Rhodesian Ridgebacks to oral and cutaneous melanocytic neoplasms. Further studies are needed to explain the underlying reasons for breed predisposition or "resistance" to the development of specific acral tumors and/or other sites.},
  language  = {en}
}
@article{RappVanDijckLaugwitzetal.2021,
  author    = {Rapp, Christina K. and Van Dijck, Ine and Laugwitz, Lucia and Boon, Mieke and Briassoulis, George and Ilia, Stavroula and Kammer, Birgit and Reu, Simone and Hornung, Stefanie and Buchert, Rebecca and Sofan, Linda and Froukh, Tawfiq and Witters, Peter and Rymen, Daisy and Haack, Tobias B. and Proesmans, Marijke and Griese, Matthias},
  title     = {Expanding the phenotypic spectrum of FINCA (fibrosis, neurodegeneration, and cerebral angiomatosis) syndrome beyond infancy},
  series = {Clinical Genetics},
  volume    = {100},
  journal   = {Clinical Genetics},
  number    = {4},
  doi       = {10.1111/cge.14016},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262732},
  pages     = {453 -- 461},
  year      = {2021},
  abstract  = {Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA, MIM\#618278) is a rare clinical condition caused by bi-allelic variants in NHL repeat containing protein 2 (NHLRC2, MIM*618277). Pulmonary disease may be the presenting sign and the few patients reported so far, all deceased in early infancy. Exome sequencing was performed on patients with childhood interstitial lung disease (chILD) and additional neurological features. The chILD-EU register database and an in-house database were searched for patients with NHLRC2 variants and clinical features overlapping FINCA syndrome. Six patients from three families were identified with bi-allelic variants in NHLRC2. Two of these children died before the age of two while four others survived until childhood. Interstitial lung disease was pronounced in almost all patients during infancy and stabilized over the course of the disease with neurodevelopmental delay (NDD) evolving as the key clinical finding. We expand the phenotype of FINCA syndrome to a multisystem disorder with variable severity. FINCA syndrome should also be considered in patients beyond infancy with NDD and a history of distinct interstitial lung disease. Managing patients in registers for rare diseases helps identifying new diagnostic entities and advancing care for these patients.},
  language  = {en}
}
@article{MonteagudoMartinezLeandroGarciaetal.2021,
  author    = {Monteagudo, Mar{\´i}a and Mart{\´i}nez, Paula and Leandro-Garc{\´i}a, Luis J. and Mart{\´i}nez-Montes, {\´A}ngel M. and Calsina, Bruna and Pulgar{\´i}n-Alfaro, Marta and D{\´i}az-Talavera, Alberto and Mellid, Sara and Let{\´o}n, Roc{\´i}o and Gil, Eduardo and P{\´e}rez-Mart{\´i}nez, Manuel and Meg{\´i}as, Diego and Torres-Ruiz, Ra{\´u}l and Rodriguez-Perales, Sandra and Gonz{\´a}lez, Patricia and Caleiras, Eduardo and Jim{\´e}nez-Villa, Scherezade and Roncador, Giovanna and {\´A}lvarez-Escol{\´a}, Cristina and Regojo, Rita M. and Calatayud, Mar{\´i}a and Guadalix, Sonsoles and Curr{\´a}s-Freixes, Maria and Rapizzi, Elena and Canu, Letizia and N{\"o}lting, Svenja and Remde, Hanna and Fassnacht, Martin and Bechmann, Nicole and Eisenhofer, Graeme and Mannelli, Massimo and Beuschlein, Felix and Quinkler, Marcus and Rodr{\´i}guez-Antona, Cristina and Casc{\´o}n, Alberto and Blasco, Mar{\´i}a A. and Montero-Conde, Cristina and Robledo, Mercedes},
  title     = {Analysis of telomere maintenance related genes reveals NOP10 as a new metastatic-risk marker in pheochromocytoma/paraganglioma},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {19},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13194758},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246321},
  year      = {2021},
  abstract  = {One of the main problems we face with PPGL is the lack of molecular markers capable of predicting the development of metastases in patients. Telomere-related genes, such as TERT and ATRX, have been recently described in PPGL, supporting the association between the activation of immortalization mechanisms and disease progression. However, the contribution of other genes involving telomere preservation machinery has not been previously investigated. In this work, we aimed to analyze the prognostic value of a comprehensive set of genes involved in telomere maintenance. For this study, we collected 165 PPGL samples (97 non-metastatic/63 metastatic), genetically characterized, in which the expression of 29 genes of interest was studied by NGS. Three of the 29 genes studied, TERT, ATRX and NOP10, showed differential expression between metastatic and non-metastatic cases, and alterations in these genes were associated with a shorter time to progression, independent of SDHB-status. We studied telomere length by Q-FISH in patient samples and in an in vitro model. NOP10 overexpressing tumors displayed an intermediate-length telomere phenotype without ALT, and in vitro results suggest that NOP10 has a role in telomerase-dependent telomere maintenance. We also propose the implementation of NOP10 IHC to better stratify PPGL patients.},
  language  = {en}
}
@article{SchuchForstnerRappetal.2021,
  author    = {Schuch, Luise A. and Forstner, Maria and Rapp, Christina K. and Li, Yang and Smith, Desiree E. C. and Mendes, Marisa I. and Delhommel, Florent and Sattler, Michael and Emiralioğlu, Nagehan and Taskiran, Ekim Z. and Orhan, Diclehan and Kiper, Nural and Rohlfs, Meino and Jeske, Tim and Hastreiter, Maximilian and Gerstlauer, Michael and Torrent-Vernetta, Alba and Moreno-Gald{\´o}, Antonio and Kammer, Birgit and Brasch, Frank and Reu-Hofer, Simone and Griese, Matthias},
  title     = {FARS1-related disorders caused by bi-allelic mutations in cytosolic phenylalanyl-tRNA synthetase genes: Look beyond the lungs!},
  series = {Clinical Genetics},
  volume    = {99},
  journal   = {Clinical Genetics},
  number    = {6},
  doi       = {10.1111/cge.13943},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238827},
  pages     = {789 -- 801},
  year      = {2021},
  abstract  = {Aminoacyl-tRNA synthetases (ARSs) catalyze the first step of protein biosynthesis (canonical function) and have additional (non-canonical) functions outside of translation. Bi-allelic pathogenic variants in genes encoding ARSs are associated with various recessive mitochondrial and multisystem disorders. We describe here a multisystem clinical phenotype based on bi-allelic mutations in the two genes (FARSA, FARSB) encoding distinct subunits for tetrameric cytosolic phenylalanyl-tRNA synthetase (FARS1). Interstitial lung disease with cholesterol pneumonitis on histology emerged as an early characteristic feature and significantly determined disease burden. Additional clinical characteristics of the patients included neurological findings, liver dysfunction, and connective tissue, muscular and vascular abnormalities. Structural modeling of newly identified missense mutations in the alpha subunit of FARS1, FARSA, showed exclusive mapping to the enzyme's conserved catalytic domain. Patient-derived mutant cells displayed compromised aminoacylation activity in two cases, while remaining unaffected in another. Collectively, these findings expand current knowledge about the human ARS disease spectrum and support a loss of canonical and non-canonical function in FARS1-associated recessive disease.},
  language  = {en}
}
@article{FicklThereseKroegerDietrichetal.2021,
  author    = {Fickl, Stefan and Therese Kr{\"o}ger, Annika and Dietrich, Thomas and Kebschull, Moritz},
  title     = {Influence of soft tissue augmentation procedures around dental implants on marginal bone level changes-A systematic review},
  series = {Clinical Oral Implants Research},
  volume    = {32},
  journal   = {Clinical Oral Implants Research},
  number    = {S21},
  doi       = {10.1111/clr.13829},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258394},
  pages     = {108-137},
  year      = {2021},
  abstract  = {Objectives This systematic review assessed the influence of soft tissue augmentation procedures on marginal bone level changes in partial or fully edentulous patients. Material and Methods We identified three relevant PICO questions related to soft tissue augmentation procedures and conducted a systematic search of four major electronic databases for clinical studies in systemically healthy patients receiving at least one dental implant and a minimum follow-up of one year after implant placement. The primary outcome was mean difference in marginal bone levels, and secondary outcomes were clinical and patient-related outcomes such as thickness of peri-implant mucosa, bleeding indices, and Pink Esthetic Score. Results We identified 20 publications reporting on 16 relevant comparisons. Studies varied considerably and thus only two meta-analyses could be performed. This systematic review showed that: Soft tissue augmentation either for augmentation of keratinized mucosa or soft tissue volume inconsistently had an effect on marginal bone level changes when compared to no soft tissue augmentation, but consistently improved secondary outcomes. The combination soft and hard tissue augmentation showed no statistically significant difference in terms of marginal bone level changes when compared to hard tissue augmentation alone, but resulted in less marginal soft tissue recession as shown by a meta-analysis. Soft or hard tissue augmentation performed as contour augmentations resulted in comparable marginal bone level changes. Conclusions Peri-implant soft and hard tissues seem to have a bidirectional relationship: "Bone stands hard, but soft tissue is the guard".},
  language  = {en}
}
@article{WelkerKerstenMuelleretal.2021,
  author    = {Welker, Armin and Kersten, Christian and M{\"u}ller, Christin and Madhugiri, Ramakanth and Zimmer, Collin and M{\"u}ller, Patrick and Zimmermann, Robert and Hammerschmidt, Stefan and Maus, Hannah and Ziebuhr, John and Sotriffer, Christoph and Schirmeister, Tanja},
  title     = {Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2},
  series = {ChemMedChem},
  volume    = {16},
  journal   = {ChemMedChem},
  number    = {2},
  doi       = {10.1002/cmdc.202000548},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225700},
  pages     = {340 -- 354},
  year      = {2021},
  abstract  = {Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL\(^{pro}\)) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL\(^{pro}\). Moreover, we report the discovery of isoindolines as a new class of potent PL\(^{pro}\) inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL\(^{pro}\) are valuable starting points for the development of new pan-coronaviral inhibitors.},
  language  = {en}
}
@article{LohPoigneeWamseretal.2021,
  author    = {Loh, Frank and Poign{\´e}e, Fabian and Wamser, Florian and Leidinger, Ferdinand and Hoßfeld, Tobias},
  title     = {Uplink vs. Downlink: Machine Learning-Based Quality Prediction for HTTP Adaptive Video Streaming},
  series = {Sensors},
  volume    = {21},
  journal   = {Sensors},
  number    = {12},
  issn      = {1424-8220},
  doi       = {10.3390/s21124172},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241121},
  year      = {2021},
  abstract  = {Streaming video is responsible for the bulk of Internet traffic these days. For this reason, Internet providers and network operators try to make predictions and assessments about the streaming quality for an end user. Current monitoring solutions are based on a variety of different machine learning approaches. The challenge for providers and operators nowadays is that existing approaches require large amounts of data. In this work, the most relevant quality of experience metrics, i.e., the initial playback delay, the video streaming quality, video quality changes, and video rebuffering events, are examined using a voluminous data set of more than 13,000 YouTube video streaming runs that were collected with the native YouTube mobile app. Three Machine Learning models are developed and compared to estimate playback behavior based on uplink request information. The main focus has been on developing a lightweight approach using as few features and as little data as possible, while maintaining state-of-the-art performance.},
  language  = {en}
}
@article{LiaqatSednevStilleretal.2021,
  author    = {Liaqat, Anam and Sednev, Maksim V. and Stiller, Carina and H{\"o}bartner, Claudia},
  title     = {RNA-cleaving deoxyribozymes differentiate methylated cytidine isomers in RNA},
  series = {Angewandte Chemie International Edition},
  volume    = {60},
  journal   = {Angewandte Chemie International Edition},
  doi       = {10.1002/anie.202106517},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256519},
  pages     = {19058-19062},
  year      = {2021},
  abstract  = {Deoxyribozymes are emerging as modification-specific endonucleases for the analysis of epigenetic RNA modifications. Here, we report RNA-cleaving deoxyribozymes that differentially respond to the presence of natural methylated cytidines, 3-methylcytidine (m\(^3\)C), N\(^4\)-methylcytidine (m\(^4\)C), and 5-methylcytidine (m\(^5\)C), respectively. Using in vitro selection, we found several DNA catalysts, which are selectively activated by only one of the three cytidine isomers, and display 10- to 30-fold accelerated cleavage of their target m\(^3\)C-, m\(^4\)C- or m\(^5\)C-modified RNA. An additional deoxyribozyme is strongly inhibited by any of the three methylcytidines, but effectively cleaves unmodified RNA. The mXC-detecting deoxyribozymes are programmable for the interrogation of natural RNAs of interest, as demonstrated for human mitochondrial tRNAs containing known m\(^3\)C and m\(^5\)C sites. The results underline the potential of synthetic functional DNA to shape highly selective active sites.},
  language  = {en}
}
@article{HalbigLatoschik2021,
  author    = {Halbig, Andreas and Latoschik, Marc Erich},
  title     = {A systematic review of physiological measurements, factors, methods, and applications in virtual reality},
  series = {Frontiers in Virtual Reality},
  volume    = {2},
  journal   = {Frontiers in Virtual Reality},
  doi       = {10.3389/frvir.2021.694567},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260503},
  year      = {2021},
  abstract  = {Measurements of physiological parameters provide an objective, often non-intrusive, and (at least semi-)automatic evaluation and utilization of user behavior. In addition, specific hardware devices of Virtual Reality (VR) often ship with built-in sensors, i.e. eye-tracking and movements sensors. Hence, the combination of physiological measurements and VR applications seems promising. Several approaches have investigated the applicability and benefits of this combination for various fields of applications. However, the range of possible application fields, coupled with potentially useful and beneficial physiological parameters, types of sensor, target variables and factors, and analysis approaches and techniques is manifold. This article provides a systematic overview and an extensive state-of-the-art review of the usage of physiological measurements in VR. We identified 1,119 works that make use of physiological measurements in VR. Within these, we identified 32 approaches that focus on the classification of characteristics of experience, common in VR applications. The first part of this review categorizes the 1,119 works by field of application, i.e. therapy, training, entertainment, and communication and interaction, as well as by the specific target factors and variables measured by the physiological parameters. An additional category summarizes general VR approaches applicable to all specific fields of application since they target typical VR qualities. In the second part of this review, we analyze the target factors and variables regarding the respective methods used for an automatic analysis and, potentially, classification. For example, we highlight which measurement setups have been proven to be sensitive enough to distinguish different levels of arousal, valence, anxiety, stress, or cognitive workload in the virtual realm. This work may prove useful for all researchers wanting to use physiological data in VR and who want to have a good overview of prior approaches taken, their benefits and potential drawbacks.},
  language  = {en}
}
@article{LenschowFussKircheretal.2021,
  author    = {Lenschow, Christina and Fuss, Carmina Teresa and Kircher, Stefan and Buck, Andreas and Kickuth, Ralph and Reibetanz, Joachim and Wiegering, Armin and Stenzinger, Albrecht and H{\"u}bschmann, Daniel and Germer, Christoph Thomas and Fassnacht, Martin and Fr{\"o}hling, Stefan and Schlegel, Nicolas and Kroiss, Matthias},
  title     = {Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management},
  series = {Frontiers in Endocrinology},
  volume    = {12},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2021.643328},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233362},
  year      = {2021},
  abstract  = {Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1\% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.},
  language  = {en}
}
@article{RadeloffWeissHagenetal.2021,
  author    = {Radeloff, Katrin and Weiss, Dorothee and Hagen, Rudolf and Kleinsasser, Norbert and Radeloff, Andreas},
  title     = {Differentiation behaviour of adipose-derived stromal cells (ASCs) seeded on polyurethane-fibrin scaffolds in vitro and in vivo},
  series = {Biomedicines},
  volume    = {9},
  journal   = {Biomedicines},
  number    = {8},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines9080982},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245030},
  year      = {2021},
  abstract  = {Adipose-derived stromal cells (ASCs) are a promising cell source for tissue engineering and regenerative medicine approaches for cartilage replacement. For chondrogenic differentiation, human (h)ASCs were seeded on three-dimensional polyurethane (PU) fibrin composites and induced with a chondrogenic differentiation medium containing TGF-ß3, BMP-6, and IGF-1 in various combinations. In addition, in vitro predifferentiated cell-seeded constructs were implanted into auricular cartilage defects of New Zealand White Rabbits for 4 and 12 weeks. Histological, immunohistochemical, and RT-PCR analyses were performed on the constructs maintained in vitro to determine extracellular matrix (ECM) deposition and expression of specific cartilage markers. Chondrogenic differentiated constructs showed a uniform distribution of cells and ECM proteins. RT-PCR showed increased gene expression of collagen II, collagen X, and aggrecan and nearly stable expression of SOX-9 and collagen I. Rabbit (r)ASC-seeded PU-fibrin composites implanted in ear cartilage defects of New Zealand White Rabbits showed deposition of ECM with structures resembling cartilage lacunae by Alcian blue staining. However, extracellular calcium deposition became detectable over the course of 12 weeks. RT-PCR showed evidence of endochondral ossification during the time course with the expression of specific marker genes (collagen X and RUNX-2). In conclusion, hASCs show chondrogenic differentiation capacity in vitro with the expression of specific marker genes and deposition of cartilage-specific ECM proteins. After implantation of predifferentiated rASC-seeded PU-fibrin scaffolds into a cartilage defect, the constructs undergo the route of endochondral ossification.},
  language  = {en}
}
@article{GernertKieselFroehlichetal.2021,
  author    = {Gernert, Michael and Kiesel, Matthias and Fr{\"o}hlich, Matthias and Renner, Regina and Strunz, Patrick-Pascal and Portegys, Jan and Tony, Hans-Peter and Schmalzing, Marc and Schwaneck, Eva Christina},
  title     = {High Prevalence of Genital Human Papillomavirus Infection in Patients With Primary Immunodeficiencies},
  series = {Frontiers in Immunology},
  volume    = {12},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2021.789345},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250273},
  year      = {2021},
  abstract  = {Background Genital human papillomavirus (HPV)-infections are common in the general population and are responsible for relevant numbers of epithelial malignancies. Much data on the HPV-prevalence is available for secondary immunodeficiencies, especially for patients with human immunodeficiency virus (HIV)-infection. Little is known about the genital HPV-prevalence in patients with primary immunodeficiencies (PIDs). Methods We performed a cross-sectional study of patients with PIDs and took genital swabs from male and female patients, which were analyzed with polymerase chain reaction for the presence of HPV-DNA. Clinical and laboratory data was collected to identify risk factors. Results 28 PID patients were included in this study. 10 of 28 (35.7\%) had HPV-DNA in their genital swabs. 6 patients had high-risk HPV-types (21.4\%). Most patients had asymptomatic HPV-infections, as genital warts were rare (2 of 28 patients) and HPV-associated malignancy was absent. Differences in the HPV-positivity regarding clinical PID-diagnosis, duration of PID, age, sex, immunosuppression, immunoglobulin replacement, or circumcision in males were not present. HPV-positive PID patients had higher numbers of T cells (CD3\(^+\)), of cytotoxic T cells (CD3\(^+\)/CD8\(^+\)), of transitional B cells (CD19\(^+\)/CD38\(^{++}\)/CD10\(^+\)/IgD\(^+\)), and of plasmablasts (CD19\(^+\)/CD38\(^+\)/CD27\(^{++}\)/IgD\(^-\)) compared to HPV-negative. Conclusion PID patients exhibit a high rate of genital HPV-infections with a high rate of high-risk HPV-types. Regular screening for symptomatic genital HPV-infection and HPV-associated malignancy in PID patients seems recommendable.},
  language  = {en}
}
@article{HendricksLenschowKroissetal.2021,
  author    = {Hendricks, Anne and Lenschow, Christina and Kroiss, Matthias and Buck, Andreas and Kickuth, Ralph and Germer, Christoph-Thomas and Schlegel, Nicolas},
  title     = {Evaluation of diagnostic efficacy for localization of parathyroid adenoma in patients with primary hyperparathyroidism undergoing repeat surgery},
  series = {Langenbeck's Archives of Surgery},
  volume    = {406},
  journal   = {Langenbeck's Archives of Surgery},
  number    = {5},
  issn      = {1435-2451},
  doi       = {10.1007/s00423-021-02191-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267520},
  pages     = {1615-1624},
  year      = {2021},
  abstract  = {Purpose Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse. Methods A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated. Results Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24-48h after surgery and was achieved in 26/28 patients (92.9\%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100\%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80\%. Conclusion These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT.},
  language  = {en}
}
@article{GhanawiHennleinZareetal.2021,
  author    = {Ghanawi, Hanaa and Hennlein, Luisa and Zare, Abdolhossein and Bader, Jakob and Salehi, Saeede and Hornburg, Daniel and Ji, Changhe and Sivadasan, Rajeeve and Drepper, Carsten and Meissner, Felix and Mann, Matthias and Jablonka, Sibylle and Briese, Michael and Sendtner, Michael},
  title     = {Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin},
  series = {Nucleic Acids Research},
  volume    = {49},
  journal   = {Nucleic Acids Research},
  number    = {21},
  doi       = {10.1093/nar/gkab1120},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265687},
  pages     = {12284-12305},
  year      = {2021},
  abstract  = {Neurons critically rely on the functions of RNA-binding proteins to maintain their polarity and resistance to neurotoxic stress. HnRNP R has a diverse range of post-transcriptional regulatory functions and is important for neuronal development by regulating axon growth. Hnrnpr pre-mRNA undergoes alternative splicing giving rise to a full-length protein and a shorter isoform lacking its N-terminal acidic domain. To investigate functions selectively associated with the full-length hnRNP R isoform, we generated a Hnrnpr knockout mouse (Hnrnpr\(^{tm1a/tm1a}\)) in which expression of full-length hnRNP R was abolished while production of the truncated hnRNP R isoform was retained. Motoneurons cultured from Hnrnpr\(^{tm1a/tm1a}\) mice did not show any axonal growth defects but exhibited enhanced accumulation of double-strand breaks and an impaired DNA damage response upon exposure to genotoxic agents. Proteomic analysis of the hnRNP R interactome revealed the multifunctional protein Yb1 as a top interactor. Yb1-depleted motoneurons were defective in DNA damage repair. We show that Yb1 is recruited to chromatin upon DNA damage where it interacts with gamma-H2AX, a mechanism that is dependent on full-length hnRNP R. Our findings thus suggest a novel role of hnRNP R in maintaining genomic integrity and highlight the function of its N-terminal acidic domain in this context.},
  language  = {en}
}
@article{GuptaSrivastavaMinochaetal.2021,
  author    = {Gupta, Shishir K. and Srivastava, Mugdha and Minocha, Rashmi and Akash, Aman and Dangwal, Seema and Dandekar, Thomas},
  title     = {Alveolar regeneration in COVID-19 patients: a network perspective},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {20},
  issn      = {1422-0067},
  doi       = {10.3390/ijms222011279},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284307},
  year      = {2021},
  abstract  = {A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.},
  language  = {en}
}
@article{SuratVogelWiegeringetal.2021,
  author    = {Surat, G{\"u}zin and Vogel, Ulrich and Wiegering, Armin and Germer, Christoph-Thomas and Lock, Johan Friso},
  title     = {Defining the scope of antimicrobial stewardship interventions on the prescription quality of antibiotics for surgical intra-abdominal infections},
  series = {Antibiotics},
  volume    = {10},
  journal   = {Antibiotics},
  number    = {1},
  issn      = {2079-6382},
  doi       = {10.3390/antibiotics10010073},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223034},
  year      = {2021},
  abstract  = {Background: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications. Methods: A single-center quality improvement study with retrospective evaluation of the impact of antimicrobial stewardship measures on optimizing antibacterial use in intra-abdominal infections requiring emergency surgery was performed. The study was conducted in a tertiary hospital in Germany from January 1, 2016, to January 30, 2020, three years after putting a set of antimicrobial stewardship standards into effect. Results: 767 patients were analyzed (n = 495 in 2016 and 2017, the baseline period; n = 272 in 2018, the antimicrobial stewardship period). The total days of therapy per 100 patient days declined from 47.0 to 42.2 days (p = 0.035). The rate of patients receiving postoperative therapy decreased from 56.8\% to 45.2\% (p = 0.002), comparing both periods. There was a significant decline in the rate of inappropriate indications (17.4\% to 8.1 \%, p = 0.015) as well as a significant change from broad-spectrum to narrow-spectrum antibiotic use (28.8\% to 6.5\%, p ≤ 0.001) for postoperative therapy. The significant decline in antibiotic use did not affect either clinical outcomes or the rate of postoperative wound complications. Conclusions: Postoperative antibiotic use for intra-abdominal infections could be significantly reduced by antimicrobial stewardship interventions. The identification of inappropriate indications remains a key target for antimicrobial stewardship programs.},
  language  = {en}
}
@article{GloegglerHellmannVonMansteinetal.2021,
  author    = {Gl{\"o}ggler, Julia C. and Hellmann, Daniel and Von Manstein, Maja and J{\"a}ger, Rudolph and Repky, Stefan and Beyersmann, Jan and Lapatki, Bernd G.},
  title     = {Motor learning might contribute to a therapeutic anterior shift of the habitual mandibular position—An exploratory study},
  series = {Journal of Oral Rehabilitation},
  volume    = {48},
  journal   = {Journal of Oral Rehabilitation},
  number    = {8},
  doi       = {10.1111/joor.13183},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262644},
  pages     = {891 -- 900},
  year      = {2021},
  abstract  = {Background Passive mandibular advancement with functional appliances is commonly used to treat juvenile patients with mandibular retrognathism. Objective The aim of this study was to investigate whether active repetitive training of the mandible into an anterior position would result in a shift of the habitual mandibular position (HMP). Methods Twenty adult healthy subjects were randomly assigned to one of two groups: a training group receiving six supervised functional training sessions of 10 min each and a control group without training. Bonded lateral biteplates disengaged occlusion among both groups throughout the 15-day experiment. Customised registration-training appliances consisted of a maxillary component with an anterior plane and a mandibular component with an attached metal sphere. Training sessions consisted of repeated mouth-opening/closing cycles (frequency: 30/min) to hit an anteriorly positioned hemispherical target notch with this metal sphere. The HMP was registered at defined times during the experiment. Results The HMP in the training group showed a statistically significant anterior shift of 1.6 mm (interquartile range [IQR]: 1.2 mm), compared with a significant posterior shift of -0.8 mm (IQR: 2.8 mm) in the control group (p < .05). Although the anterior shift among the training group showed a partial relapse 4 days after the first training block, it then advanced slightly in the 4-day interval after the second training block, which might indicate neuroplasticity of the masticatory motor system. Conclusions Motor learning by repetitive training of the mandible into an anterior position might help to improve the results of functional appliance therapy among patients with mandibular retrognathism.},
  language  = {en}
}
@article{DietzKudsiGarciaUrenaetal.2021,
  author    = {Dietz, Ulrich A. and Kudsi, O. Yusef and Garcia-Ure{\~n}a, Miguel and Baur, Johannes and Ramser, Michaela and Maksimovic, Sladjana and Keller, Nicola and D{\"o}rfer, J{\"o}rg and Eisner, Lukas and Wiegering, Armin},
  title     = {Robotische Hernienchirurgie III: Robotische Inzisionalhernienversorgung mit „transversus abdominis release" (r-TAR). Videobeitrag und Ergebnisse einer Kohortenstudie},
  series = {Der Chirurg},
  volume    = {92},
  journal   = {Der Chirurg},
  number    = {10},
  doi       = {10.1007/s00104-021-01480-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265172},
  pages     = {936-947},
  year      = {2021},
  abstract  = {Das Prinzip der gezielten Trennung bzw. Schw{\"a}chung einzelner Komponenten der Bauchdecke zur Spannungsentlastung der Medianlinie bei großen abdominellen Rekonstruktionen ist seit {\"u}ber 30 Jahren als anteriore Komponentenseparation (aKS) bekannt und ein etabliertes Verfahren. Auf der Suche nach Alternativen mit geringerer Komplikationsrate wurde die posteriore Komponentenseparation (pKS) entwickelt; der „transversus abdominis release" (TAR) ist eine nervenschonende Modifikation der pKS. Mit den ergonomischen Ressourcen der Robotik (z. B. abgewinkelte Instrumente) kann der TAR minimal-invasiv durchgef{\"u}hrt werden (r-TAR): Bruchl{\"u}cken von bis zu 14 cm lassen sich verschließen und ein großes extraperitoneales Netz implantieren. In diesem Videobeitrag wird die Versorgung großer Inzisionalhernien in der r‑TAR-Technik pr{\"a}sentiert. Exemplarisch werden die Ergebnisse einer Kohortenstudie an 13 konsekutiven Patienten vorgestellt. Der Eingriff ist anspruchsvoll, die eigenen Ergebnisse sind - wie auch die Berichte aus der Literatur - ermutigend. Der r‑TAR entwickelt sich zur K{\"o}nigsdisziplin der Bauchdeckenrekonstruktion.},
  language  = {de}
}
@article{ZwirnerAndersBohnertetal.2021,
  author    = {Zwirner, Johann and Anders, Sven and Bohnert, Simone and Burkhardt, Ralph and Da Broi, Ugo and Hammer, Niels and Pohlers, Dirk and Tse, Rexson and Ondruschka, Benjamin},
  title     = {Screening for fatal traumatic brain injuries in cerebrospinal fluid using blood-validated CK and CK-MB immunoassays},
  series = {Biomolecules},
  volume    = {11},
  journal   = {Biomolecules},
  number    = {7},
  issn      = {2218-273X},
  doi       = {10.3390/biom11071061},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242769},
  year      = {2021},
  abstract  = {A single, specific, sensitive biochemical biomarker that can reliably diagnose a traumatic brain injury (TBI) has not yet been found, but combining different biomarkers would be the most promising approach in clinical and postmortem settings. In addition, identifying new biomarkers and developing laboratory tests can be time-consuming and economically challenging. As such, it would be efficient to use established clinical diagnostic assays for postmortem biochemistry. In this study, postmortem cerebrospinal fluid samples from 45 lethal TBI cases and 47 controls were analyzed using commercially available blood-validated assays for creatine kinase (CK) activity and its heart-type isoenzyme (CK-MB). TBI cases with a survival time of up to two hours showed an increase in both CK and CK-MB with moderate (CK-MB: AUC = 0.788, p < 0.001) to high (CK: AUC = 0.811, p < 0.001) diagnostic accuracy. This reflected the excessive increase of the brain-type CK isoenzyme (CK-BB) following a TBI. The results provide evidence that CK immunoassays can be used as an adjunct quantitative test aid in diagnosing acute TBI-related fatalities.},
  language  = {en}
}
@article{LauruschkatPageWhiteetal.2021,
  author    = {Lauruschkat, Chris D. and Page, Lukas and White, P. Lewis and Etter, Sonja and Davies, Helen E. and Duckers, Jamie and Ebel, Frank and Schnack, Elisabeth and Backx, Matthijs and Dragan, Mariola and Schlegel, Nicolas and Kniemeyer, Olaf and Brakhage, Axel A. and Einsele, Hermann and Loeffler, Juergen and Wurster, Sebastian},
  title     = {Development of a simple and robust whole blood assay with dual co-stimulation to quantify the release of T-cellular signature cytokines in response to Aspergillus fumigatus antigens},
  series = {Journal of Fungi},
  volume    = {7},
  journal   = {Journal of Fungi},
  number    = {6},
  issn      = {2309-608X},
  doi       = {10.3390/jof7060462},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241025},
  year      = {2021},
  abstract  = {Deeper understanding of mold-induced cytokine signatures could promote advances in the diagnosis and treatment of invasive mycoses and mold-associated hypersensitivity syndromes. Currently, most T-cellular immunoassays in medical mycology require the isolation of mononuclear cells and have limited robustness and practicability, hampering their broader applicability in clinical practice. Therefore, we developed a simple, cost-efficient whole blood (WB) assay with dual α-CD28 and α-CD49d co-stimulation to quantify cytokine secretion in response to Aspergillus fumigatus antigens. Dual co-stimulation strongly enhanced A. fumigatus-induced release of T-cellular signature cytokines detectable by enzyme-linked immunosorbent assay (ELISA) or a multiplex cytokine assay. Furthermore, T-cell-dependent activation and cytokine response of innate immune cells was captured by the assay. The protocol consistently showed little technical variation and high robustness to pre-analytic delays of up to 8 h. Stimulation with an A. fumigatus lysate elicited at least 7-fold greater median concentrations of key T-helper cell signature cytokines, including IL-17 and the type 2 T-helper cell cytokines IL-4 and IL-5 in WB samples from patients with Aspergillus-associated lung pathologies versus patients with non-mold-related lung diseases, suggesting high discriminatory power of the assay. These results position WB-ELISA with dual co-stimulation as a simple, accurate, and robust immunoassay for translational applications, encouraging further evaluation as a platform to monitor host immunity to opportunistic pathogens.},
  language  = {en}
}
@article{KuckaWajant2021,
  author    = {Kucka, Kirstin and Wajant, Harald},
  title     = {Receptor Oligomerization and Its Relevance for Signaling by Receptors of the Tumor Necrosis Factor Receptor Superfamily},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {8},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2020.615141},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227180},
  year      = {2021},
  abstract  = {With the exception of a few signaling incompetent decoy receptors, the receptors of the tumor necrosis factor receptor superfamily (TNFRSF) are signaling competent and engage in signaling pathways resulting in inflammation, proliferation, differentiation, and cell migration and also in cell death induction. TNFRSF receptors (TNFRs) become activated by ligands of the TNF superfamily (TNFSF). TNFSF ligands (TNFLs) occur as trimeric type II transmembrane proteins but often also as soluble ligand trimers released from the membrane-bound form by proteolysis. The signaling competent TNFRs are efficiently activated by the membrane-bound TNFLs. The latter recruit three TNFR molecules, but there is growing evidence that this is not sufficient to trigger all aspects of TNFR signaling; rather, the formed trimeric TNFL-TNFR complexes have to cluster secondarily in the cell-to-cell contact zone for full TNFR activation. With respect to their response to soluble ligand trimers, the signaling competent TNFRs can be subdivided into two groups. TNFRs of one group, designated as category I TNFRs, are robustly activated by soluble ligand trimers. The receptors of a second group (category II TNFRs), however, failed to become properly activated by soluble ligand trimers despite high affinity binding. The limited responsiveness of category II TNFRs to soluble TNFLs can be overcome by physical linkage of two or more soluble ligand trimers or, alternatively, by anchoring the soluble ligand molecules to the cell surface or extracellular matrix. This suggests that category II TNFRs have a limited ability to promote clustering of trimeric TNFL-TNFR complexes outside the context of cell-cell contacts. In this review, we will focus on three aspects on the relevance of receptor oligomerization for TNFR signaling: (i) the structural factors which promote clustering of free and liganded TNFRs, (ii) the signaling pathway specificity of the receptor oligomerization requirement, and (iii) the consequences for the design and development of TNFR agonists.},
  language  = {en}
}
@article{CarolusWienrichToerkeetal.2021,
  author    = {Carolus, Astrid and Wienrich, Carolin and T{\"o}rke, Anna and Friedel, Tobias and Schwietering, Christian and Sperzel, Mareike},
  title     = {'Alexa, I feel for you!' Observers' empathetic reactions towards a conversational agent},
  series = {Frontiers in Computer Science},
  volume    = {3},
  journal   = {Frontiers in Computer Science},
  doi       = {10.3389/fcomp.2021.682982},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258807},
  year      = {2021},
  abstract  = {Conversational agents and smart speakers have grown in popularity offering a variety of options for use, which are available through intuitive speech operation. In contrast to the standard dyad of a single user and a device, voice-controlled operations can be observed by further attendees resulting in new, more social usage scenarios. Referring to the concept of 'media equation' and to research on the idea of 'computers as social actors,' which describes the potential of technology to trigger emotional reactions in users, this paper asks for the capacity of smart speakers to elicit empathy in observers of interactions. In a 2 × 2 online experiment, 140 participants watched a video of a man talking to an Amazon Echo either rudely or neutrally (factor 1), addressing it as 'Alexa' or 'Computer' (factor 2). Controlling for participants' trait empathy, the rude treatment results in participants' significantly higher ratings of empathy with the device, compared to the neutral treatment. The form of address had no significant effect. Results were independent of the participants' gender and usage experience indicating a rather universal effect, which confirms the basic idea of the media equation. Implications for users, developers and researchers were discussed in the light of (future) omnipresent voice-based technology interaction scenarios.},
  language  = {en}
}
@article{KumarKhamzinaKnoefeletal.2021,
  author    = {Kumar, Navneet and Khamzina, Asia and Kn{\"o}fel, Patrick and Lamers, John P. A. and Tischbein, Bernhard},
  title     = {Afforestation of degraded croplands as a water-saving option in irrigated region of the Aral Sea Basin},
  series = {Water},
  volume    = {13},
  journal   = {Water},
  number    = {10},
  issn      = {2073-4441},
  doi       = {10.3390/w13101433},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239626},
  year      = {2021},
  abstract  = {Climate change is likely to decrease surface water availability in Central Asia, thereby necessitating land use adaptations in irrigated regions. The introduction of trees to marginally productive croplands with shallow groundwater was suggested for irrigation water-saving and improving the land's productivity. Considering the possible trade-offs with water availability in large-scale afforestation, our study predicted the impacts on water balance components in the lower reaches of the Amudarya River to facilitate afforestation planning using the Soil and Water Assessment Tool (SWAT). The land-use scenarios used for modeling analysis considered the afforestation of 62\% and 100\% of marginally productive croplands under average and low irrigation water supply identified from historical land-use maps. The results indicate a dramatic decrease in the examined water balance components in all afforestation scenarios based largely on the reduced irrigation demand of trees compared to the main crops. Specifically, replacing current crops (mostly cotton) with trees on all marginal land (approximately 663 km\(^2\)) in the study region with an average water availability would save 1037 mln m\(^3\) of gross irrigation input within the study region and lower the annual drainage discharge by 504 mln m\(^3\). These effects have a considerable potential to support irrigation water management and enhance drainage functions in adapting to future water supply limitations.},
  language  = {en}
}
@article{ZechScherfClavelDanielsetal.2021,
  author    = {Zech, Linda D. and Scherf-Clavel, Maike and Daniels, Christine and Schwab, Michael and Deckert, J{\"u}rgen and Unterecker, Stefan and Herr, Alexandra S.},
  title     = {Patients with higher vitamin D levels show stronger improvement of self-reported depressive symptoms in psychogeriatric day-care setting},
  series = {Journal of Neural Transmission},
  volume    = {128},
  journal   = {Journal of Neural Transmission},
  number    = {8},
  issn      = {1435-1463},
  doi       = {10.1007/s00702-021-02385-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268525},
  pages     = {1233-1238},
  year      = {2021},
  abstract  = {Depression is a common psychiatric disorder among geriatric patients that decreases the quality of life and increases morbidity and mortality. Vitamin D as a neuro-steroid hormone might play a role in the onset and treatment of depression. In the present study, the association between depressive symptoms and vitamin D concentration in serum was evaluated. 140 patients of a psychogeriatric day-care unit were included. The geriatric depression scale (GDS) and the Hamilton depression rating scale (HDRS) were assessed at the beginning and end of treatment, GDS scores additionally 6 weeks after discharge from the day-care unit. Vitamin D levels were measured at the beginning of the treatment, routinely. Patients with levels below 30 µg/L were treated with 1000 IU vitamin D per day. There was no association between the severity of depressive symptoms and the concentration of vitamin D at the beginning of the treatment. Patients with higher vitamin D levels showed a stronger decline of depressive symptoms measured by the GDS during their stay in the day-care unit. We provide evidence that vitamin D serum levels might influence antidepressant therapy response in a geriatric population. Prospective studies are necessary to determine which patients may profit from add-on vitamin D therapy.},
  language  = {en}
}
@article{GerhardHartmannWiegeringBenoitetal.2021,
  author    = {Gerhard-Hartmann, Elena and Wiegering, Verena and Benoit, Clemens and Meyer, Thomas and Rosenwald, Andreas and Maurus, Katja and Ernestus, Karen},
  title     = {A large retroperitoneal lipoblastoma as an incidental finding: a case report},
  series = {BMC Pediatrics},
  volume    = {21},
  journal   = {BMC Pediatrics},
  doi       = {10.1186/s12887-021-02628-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260173},
  year      = {2021},
  abstract  = {Background Lipoblastoma is a rare benign mesenchymal neoplasm of infancy that most commonly occurs on the extremities and trunk but can arise at variable sites of the body. Retroperitoneal lipoblastomas are particularly rare but can grow to enormous size, and preoperative diagnosis is difficult with diverse, mostly malignant differential diagnoses that would lead to aggressive therapy. Since lipoblastoma is a benign tumor that has an excellent prognosis after resection, correct diagnosis is crucial. Case presentation A case of a large retroperitoneal tumor of a 24-month old infant that was clinically suspicious of a malignant tumor is presented. Due to proximity to the right kidney, clinically most probably a nephroblastoma or clear cell sarcoma of the kidney was suspected. Radiological findings were ambiguous. Therefore, the mass was biopsied, and histology revealed an adipocytic lesion. Although mostly composed of mature adipocytes, in view of the age of the patient, the differential diagnosis of a (maturing) lipoblastoma was raised, which was supported by molecular analysis demonstrating a HAS2-PLAG1 fusion. The tumor was completely resected, and further histopathological workup led to the final diagnosis of a 13 cm large retroperitoneal maturing lipoblastoma. The child recovered promptly from surgery and showed no evidence of recurrence so far. Conclusion Although rare, lipoblastoma should be included in the differential diagnoses of retroperitoneal tumors in infants and children, and molecular diagnostic approaches could be a helpful diagnostic adjunct in challenging cases.},
  language  = {en}
}
@article{SchilcherHilsmannRauscheretal.2021,
  author    = {Schilcher, Felix and Hilsmann, Lioba and Rauscher, Lisa and Değirmenci, Laura and Krischke, Markus and Krischke, Beate and Ankenbrand, Markus and Rutschmann, Benjamin and Mueller, Martin J. and Steffan-Dewenter, Ingolf and Scheiner, Ricarda},
  title     = {In vitro rearing changes social task performance and physiology in honeybees},
  series = {Insects},
  volume    = {13},
  journal   = {Insects},
  number    = {1},
  issn      = {2075-4450},
  doi       = {10.3390/insects13010004},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252305},
  year      = {2021},
  abstract  = {In vitro rearing of honeybee larvae is an established method that enables exact control and monitoring of developmental factors and allows controlled application of pesticides or pathogens. However, only a few studies have investigated how the rearing method itself affects the behavior of the resulting adult honeybees. We raised honeybees in vitro according to a standardized protocol: marking the emerging honeybees individually and inserting them into established colonies. Subsequently, we investigated the behavioral performance of nurse bees and foragers and quantified the physiological factors underlying the social organization. Adult honeybees raised in vitro differed from naturally reared honeybees in their probability of performing social tasks. Further, in vitro-reared bees foraged for a shorter duration in their life and performed fewer foraging trips. Nursing behavior appeared to be unaffected by rearing condition. Weight was also unaffected by rearing condition. Interestingly, juvenile hormone titers, which normally increase strongly around the time when a honeybee becomes a forager, were significantly lower in three- and four-week-old in vitro bees. The effects of the rearing environment on individual sucrose responsiveness and lipid levels were rather minor. These data suggest that larval rearing conditions can affect the task performance and physiology of adult bees despite equal weight, pointing to an important role of the colony environment for these factors. Our observations of behavior and metabolic pathways offer important novel insight into how the rearing environment affects adult honeybees.},
  language  = {en}
}
@article{MeyerGerhardHartmannLodesetal.2021,
  author    = {Meyer, Till Jasper and Gerhard-Hartmann, Elena and Lodes, Nina and Scherzad, Agmal and Hagen, Rudolf and Steinke, Maria and Hackenberg, Stephan},
  title     = {Pilot study on the value of Raman spectroscopy in the entity assignment of salivary gland tumors},
  series = {PLoS One},
  volume    = {16},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0257470},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264736},
  year      = {2021},
  abstract  = {Background The entity assignment of salivary gland tumors (SGT) based on histomorphology can be challenging. Raman spectroscopy has been applied to analyze differences in the molecular composition of tissues. The aim of this study was to evaluate the suitability of RS for entity assignment in SGT. Methods Raman data were collected in deparaffinized sections of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Multivariate data and chemometric analysis were completed using the Unscrambler software. Results The Raman spectra detected in ACC samples were mostly assigned to nucleic acids, lipids, and amides. In a principal component-based linear discriminant analysis (LDA) 18 of 20 tumor samples were classified correctly. Conclusion In this proof of concept study, we show that a reliable SGT diagnosis based on LDA algorithm appears possible, despite variations in the entity-specific mean spectra. However, a standardized workflow for tissue sample preparation, measurement setup, and chemometric algorithms is essential to get reliable results.},
  language  = {en}
}
@article{FriedmannFicklFischeretal.2021,
  author    = {Friedmann, Anton and Fickl, Stefan and Fischer, Kai R. and Dalloul, Milad and Goetz, Werner and Kauffmann, Frederic},
  title     = {Horizontal augmentation of chronic mandibular defects by the Guided Bone Regeneration approach: a randomized study in dogs},
  series = {Materials},
  volume    = {15},
  journal   = {Materials},
  number    = {1},
  issn      = {1996-1944},
  doi       = {10.3390/ma15010238},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252351},
  year      = {2021},
  abstract  = {Various biomaterial combinations have been studied focusing on their ability to stabilize blood clots and maintain space under soft tissue to support new bone formation. A popular combination is Deproteinized Bovine Bone Mineral (DBBM) placed with a native collagen membrane (NCM) tacked to native bone. In this study, we compared the outcome of this treatment option to those achieved with three different graft/membrane combinations with respect to total newly occupied area and the mineralized compound inside. After bi-lateral extraction of two mandibular premolars in five adult beagles L-shaped alveolar defects were created. A total of 20 defects healed for 6 weeks resulting in chronic type bone defects. At baseline, four options were randomly allocated to five defects each: a. DBBM + NCM with a four-pin fixation across the ridge; b. DBBM + RCLC (ribose cross-linked collagen membrane); c. DBBM + NPPM (native porcine pericardium membrane); and d. Ca-sulfate (CS) + RCLC membrane. Membranes in b/c/d were not fixed; complete tensionless wound closure was achieved by CAF. Termination after 3 months and sampling followed, and non-decalcified processing and toluidine blue staining were applied. Microscopic images obtained at standardized magnification were histomorphometrically assessed by ImageJ software (NIH). An ANOVA post hoc test was applied; histomorphometric data are presented in this paper as medians and interquartile ranges (IRs). All sites healed uneventfully, all sites were sampled and block separation followed before Technovit embedding. Two central sections per block for each group were included. Two of five specimen were lost due to processing error and were excluded from group b. New bone area was significantly greater for option b. compared to a. (p = 0.001), c. (p = 0.002), and d. (p = 0.046). Residual non-bone graft area was significantly less for option d. compared to a. (p = 0.026) or c. (p = 0.021). We conclude that collagen membranes with a prolonged resorption/barrier profile combined with bone substitutes featuring different degradation profiles sufficiently support new bone formation. Tacking strategy/membrane fixation appears redundant when using these biomaterials.},
  language  = {en}
}
@article{MaucherSrourDanhofetal.2021,
  author    = {Maucher, Marius and Srour, Micha and Danhof, Sophia and Einsele, Hermann and Hudecek, Michael and Yakoub-Agha, Ibrahim},
  title     = {Current limitations and perspectives of chimeric antigen receptor-T-cells in acute myeloid leukemia},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {24},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13246157},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252180},
  year      = {2021},
  abstract  = {Adoptive transfer of gene-engineered chimeric antigen receptor (CAR)-T-cells has emerged as a powerful immunotherapy for combating hematologic cancers. Several target antigens that are prevalently expressed on AML cells have undergone evaluation in preclinical CAR-T-cell testing. Attributes of an 'ideal' target antigen for CAR-T-cell therapy in AML include high-level expression on leukemic blasts and leukemic stem cells (LSCs), and absence on healthy tissues, normal hematopoietic stem and progenitor cells (HSPCs). In contrast to other blood cancer types, where CAR-T therapies are being similarly studied, only a rather small number of AML patients has received CAR-T-cell treatment in clinical trials, resulting in limited clinical experience for this therapeutic approach in AML. For curative AML treatment, abrogation of bulk blasts and LSCs is mandatory with the need for hematopoietic recovery after CAR-T administration. Herein, we provide a critical review of the current pipeline of candidate target antigens and corresponding CAR-T-cell products in AML, assess challenges for clinical translation and implementation in routine clinical practice, as well as perspectives for overcoming them.},
  language  = {en}
}
@article{AidoZaitsevaWajantetal.2021,
  author    = {Aido, Ahmed and Zaitseva, Olena and Wajant, Harald and Buzgo, Matej and Simaite, Aiva},
  title     = {Anti-Fn14 antibody-conjugated nanoparticles display membrane TWEAK-like agonism},
  series = {Pharmaceutics},
  volume    = {13},
  journal   = {Pharmaceutics},
  number    = {7},
  issn      = {1999-4923},
  doi       = {10.3390/pharmaceutics13071072},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242710},
  year      = {2021},
  abstract  = {Conventional bivalent IgG antibodies targeting a subgroup of receptors of the TNF superfamily (TNFSF) including fibroblast growth factor-inducible 14 (anti-Fn14) typically display no or only very limited agonistic activity on their own and can only trigger receptor signaling by crosslinking or when bound to Fcγ receptors (FcγR). Both result in proximity of multiple antibody-bound TNFRSF receptor (TNFR) molecules, which enables engagement of TNFR-associated signaling pathways. Here, we have linked anti-Fn14 antibodies to gold nanoparticles to mimic the "activating" effect of plasma membrane-presented FcγR-anchored anti-Fn14 antibodies. We functionalized gold nanoparticles with poly-ethylene glycol (PEG) linkers and then coupled antibodies to the PEG surface of the nanoparticles. We found that Fn14 binding of the anti-Fn14 antibodies PDL192 and 5B6 is preserved upon attachment to the nanoparticles. More importantly, the gold nanoparticle-presented anti-Fn14 antibody molecules displayed strong agonistic activity. Our results suggest that conjugation of monoclonal anti-TNFR antibodies to gold nanoparticles can be exploited to uncover their latent agonism, e.g., for immunotherapeutic applications.},
  language  = {en}
}
@article{LoddeForschnerHasseletal.2021,
  author    = {Lodde, Georg and Forschner, Andrea and Hassel, Jessica and Wulfken, Lena M. and Meier, Friedegund and Mohr, Peter and K{\"a}hler, Katharina and Schilling, Bastian and Loquai, Carmen and Berking, Carola and H{\"u}ning, Svea and Schatton, Kerstin and Gebhardt, Christoffer and Eckardt, Julia and Gutzmer, Ralf and Reinhardt, Lydia and Glutsch, Valerie and Nikfarjam, Ulrike and Erdmann, Michael and Stang, Andreas and Kowall, Bernd and Roesch, Alexander and Ugurel, Selma and Zimmer, Lisa and Schadendorf, Dirk and Livingstone, Elisabeth},
  title     = {Factors influencing the adjuvant therapy decision: results of a real-world multicenter data analysis of 904 melanoma patients},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {10},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13102319},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239583},
  year      = {2021},
  abstract  = {Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) and targeted therapy (TT) significantly improved recurrence-free survival. This study investigates the real-world situation of 904 patients from 13 German skin cancer centers with an indication for adjuvant treatment since the approval of adjuvant ICI and TT. From adjusted log-binomial regression models, we estimated relative risks for associations between various influence factors and treatment decisions (adjuvant therapy yes/no, TT vs. ICI in BRAF mutant patients). Of these patients, 76.9\% (95\% CI 74-80) opted for a systemic adjuvant treatment. The probability of starting an adjuvant treatment was 26\% lower in patients >65 years (RR 0.74, 95\% CI 68-80). The most common reasons against adjuvant treatment given by patients were age (29.4\%, 95\% CI 24-38), and fear of adverse events (21.1\%, 95\% CI 16-28) and impaired quality of life (11.9\%, 95\% CI 7-16). Of all BRAF-mutated patients who opted for adjuvant treatment, 52.9\% (95\% CI 47-59) decided for ICI. Treatment decision for TT or ICI was barely associated with age, gender and tumor stage, but with comorbidities and affiliated center. Shortly after their approval, adjuvant treatments have been well accepted by physicians and patients. Age plays a decisive role in the decision for adjuvant treatment, while pre-existing autoimmune disease and regional differences influence the choice between TT or ICI.},
  language  = {en}
}
@article{SchadtIsraelSamnick2021,
  author    = {Schadt, Fabian and Israel, Ina and Samnick, Samuel},
  title     = {Development and Validation of a Semi-Automated, Preclinical, MRI-Template Based PET Image Data Analysis Tool for Rodents},
  series = {Frontiers in Neuroinformatics},
  volume    = {15},
  journal   = {Frontiers in Neuroinformatics},
  issn      = {1662-5196},
  doi       = {10.3389/fninf.2021.639643},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240289},
  year      = {2021},
  abstract  = {AimIn PET imaging, the different types of radiotracers and accumulations, as well as the diversity of disease patterns, make the analysis of molecular imaging data acquired in vivo challenging. Here, we evaluate and validate a semi-automated MRI template-based data analysis tool that allows preclinical PET images to be aligned to a self-created PET template. Based on the user-defined volume-of-interest (VOI), image data can then be evaluated using three different semi-quantitative parameters: normalized activity, standardized uptake value, and uptake ratio. Materials and MethodsThe nuclear medicine Data Processing Analysis tool (NU_DPA) was implemented in Matlab. Testing and validation of the tool was performed using two types of radiotracers in different kinds of stroke-related brain diseases in rat models. The radiotracers used are 2-[\(^{18}\)F]fluoro-2-deoxyglucose ([\(^{18}\)F]FDG), a metabol\(^{68}\)Ga]Ga-Fucoidan, a target-selective radioligand specifically binding to p-selectin. After manual image import, the NU_DPA tool automatically creates an averaged PET template out of the acquired PET images, to which all PET images are then aligned onto. The added MRI template-based information, resized to the lower PET resolution, defines the VOI and also allows a precise subdivision of the VOI into individual sub-regions. The aligned PET images can then be evaluated semi-quantitatively for all regions defined in the MRI atlas. In addition, a statistical analysis and evaluation of the semi-quantitative parameters can then be performed in the NU_DPA tool. ResultsUsing ischemic stroke data in Wistar rats as an example, the statistical analysis of the tool should be demonstrated. In this [\(^{18}\)F]FDG-PET experiment, three different experimental states were compared: healthy control state, ischemic stroke without electrical stimulation, ischemic stroke with electrical stimulation. Thereby, statistical data evaluation using the NU_DPA tool showed that the glucose metabolism in a photothrombotic lesion can be influenced by electrical stimulation. ConclusionOur NU_DPA tool allows a very flexible data evaluation of small animal PET data in vivo including statistical data evaluation. Using the radiotracers [\(^{18}\)F]FDG and [\(^{68}\)Ga]Ga-Fucoidan, it was shown that the semi-automatic MRI-template based data analysis of the NU_DPA tool is potentially suitable for both metabolic radiotracers as well as target-selective radiotracers.},
  language  = {en}
}
@article{BrandtLauerFehrenzetal.2021,
  author    = {Brandt, Silvia and Lauer, Hans-Christoph and Fehrenz, Michael and G{\"u}th, Jan-Frederik and Romanos, Georgios and Winter, Anna},
  title     = {Ball versus Locator\(^®\) attachments: a retrospective study on prosthetic maintenance and effect on oral-health-related quality of life},
  series = {Materials},
  volume    = {14},
  journal   = {Materials},
  number    = {4},
  issn      = {1996-1944},
  doi       = {10.3390/ma14041051},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228909},
  year      = {2021},
  abstract  = {Locator\(^®\) and ball attachments are well-established systems to attach overdentures to two inter-foraminal implants. This study aimed to evaluate differences between the two systems regarding prosthetic maintenance and patients' oral-health-related quality of life (OHRQoL). Dental records of patients with a mandibular implant-retained overdenture were retrospectively analyzed. Prosthetic maintenance measures involving the denture suprastructure and attachment matrix and patrix were analyzed. Furthermore, the Oral Health Impact Profile-G14 (OHIP-G14) was used to evaluate OHRQoL. Results were analyzed by means of Kaplan-Meier analysis and Student's t- and log-rank tests. The records of 122 patients were evaluated. Kaplan-Meier survival analysis revealed a significant difference between ball attachments (Group B; n patients = 47) and Locator\(^®\) attachments (Group L; n patients = 75) regarding the occurrence of denture fractures (p < 0.001) and events affecting the matrix (p = 0.028) and patrix (p = 0.030). Group L had a significantly lower total OHIP-G14 score than Group B (p = 0.002). The most common maintenance events were matrix-related and denture relining for both attachment systems. Group B required more maintenance measures than Group L. Moreover, patients in Group L had better OHRQoL than patients in Group B.},
  language  = {en}
}
@article{MeisterLangeAthinodorouUllmann2021,
  author    = {Meister, Julia and Lange-Athinodorou, Eva and Ullmann, Tobias},
  title     = {Preface: Special Issue "Geoarchaeology of the Nile Delta"},
  series = {E\&G Quarternary Science Journal},
  volume    = {70},
  journal   = {E\&G Quarternary Science Journal},
  doi       = {10.5194/egqsj-70-187-2021},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261195},
  pages     = {187-190},
  year      = {2021},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{ObremskiLugrinSchaperetal.2021,
  author    = {Obremski, David and Lugrin, Jean-Luc and Schaper, Philipp and Lugrin, Birgit},
  title     = {Non-native speaker perception of Intelligent Virtual Agents in two languages: the impact of amount and type of grammatical mistakes},
  series = {Journal on Multimodal User Interfaces},
  volume    = {15},
  journal   = {Journal on Multimodal User Interfaces},
  number    = {2},
  issn      = {1783-8738},
  doi       = {10.1007/s12193-021-00369-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269984},
  pages     = {229-238},
  year      = {2021},
  abstract  = {Having a mixed-cultural membership becomes increasingly common in our modern society. It is thus beneficial in several ways to create Intelligent Virtual Agents (IVAs) that reflect a mixed-cultural background as well, e.g., for educational settings. For research with such IVAs, it is essential that they are classified as non-native by members of a target culture. In this paper, we focus on variations of IVAs' speech to create the impression of non-native speakers that are identified as such by speakers of two different mother tongues. In particular, we investigate grammatical mistakes and identify thresholds beyond which the agents is clearly categorised as a non-native speaker. Therefore, we conducted two experiments: one for native speakers of German, and one for native speakers of English. Results of the German study indicate that beyond 10\% of word order mistakes and 25\% of infinitive mistakes German-speaking IVAs are perceived as non-native speakers. Results of the English study indicate that beyond 50\% of omission mistakes and 50\% of infinitive mistakes English-speaking IVAs are perceived as non-native speakers. We believe these thresholds constitute helpful guidelines for computational approaches of non-native speaker generation, simplifying research with IVAs in mixed-cultural settings.},
  language  = {en}
}
@article{EisslerWernerAriasLozaetal.2021,
  author    = {Eissler, Cristoph and Werner, Rudolf A. and Arias-Loza, Paula and Nose, Naoko and Chen, Xinyu and Pomper, Martin G. and Rowe, Steven P. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro},
  title     = {The number of frames on ECG-gated \(^{18}\)F-FDG small animal PET has a significant impact on LV systolic and diastolic functional parameters},
  series = {Molecular Imaging},
  volume    = {2021},
  journal   = {Molecular Imaging},
  doi       = {10.1155/2021/4629459},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265778},
  year      = {2021},
  abstract  = {Objectives. This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. Methods. \(^{18}\)F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed. Results. Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 \& PLUSMN; 57.7 mu l*, 380.8 \& PLUSMN; 57.2 mu l*, 398.0 \& PLUSMN; 63.1 mu l*, and 444.8 \& PLUSMN; 75.3 mu l at 4, 8, 12, and 16 frames, respectively; *P < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed (P < 0.005), but not for 4, 8, and 12 frames. Conclusions. Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.},
  language  = {en}
}
@article{HauserDornbergerMalzahnetal.2021,
  author    = {Hauser, T. and Dornberger, V. and Malzahn, U. and Grebe, S. J. and Liu, D. and St{\"o}rk, S. and Nauck, M. and Friedrich, N. and D{\"o}rr, M. and Wanner, C. and Krane, V. and Hammer, F.},
  title     = {The effect of spironolactone on diastolic function in haemodialysis patients},
  series = {The International Journal of Cardiovascular Imaging},
  volume    = {37},
  journal   = {The International Journal of Cardiovascular Imaging},
  number    = {6},
  issn      = {1573-0743},
  doi       = {10.1007/s10554-021-02176-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269033},
  pages     = {1927-1936},
  year      = {2021},
  abstract  = {Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in patients on maintenance haemodialysis (HD) and lacks effective treatment. We investigated the effect of spironolactone on cardiac structure and function with a specific focus on diastolic function parameters. The MiREnDa trial examined the effect of 50 mg spironolactone once daily versus placebo on left ventricular mass index (LVMi) among 97 HD patients during 40 weeks of treatment. In this echocardiographic substudy, diastolic function was assessed using predefined structural and functional parameters including E/e'. Changes in the frequency of HFpEF were analysed using the comprehensive 'HFA-PEFF score'. Complete echocardiographic assessment was available in 65 individuals (59.5 ± 13.0 years, 21.5\% female) with preserved left ventricular ejection fraction (LVEF > 50\%). At baseline, mean E/e' was 15.2 ± 7.8 and 37 (56.9\%) patients fulfilled the criteria of HFpEF according to the HFA-PEFF score. There was no significant difference in mean change of E/e' between the spironolactone group and the placebo group (+ 0.93 ± 5.39 vs. + 1.52 ± 5.94, p = 0.68) or in mean change of left atrial volume index (LAVi) (1.9 ± 12.3 ml/m\(^{2}\) vs. 1.7 ± 14.1 ml/m\(^{2}\), p = 0.89). Furthermore, spironolactone had no significant effect on mean change in LVMi (+ 0.8 ± 14.2 g/m\(^{2}\) vs. + 2.7 ± 15.9 g/m\(^{2}\); p = 0.72) or NT-proBNP (p = 0.96). Treatment with spironolactone did not alter HFA-PEFF score class compared with placebo (p = 0.63). Treatment with 50 mg of spironolactone for 40 weeks had no significant effect on diastolic function parameters in HD patients.},
  language  = {en}
}
@article{RiyasSyedKumaretal.2021,
  author    = {Riyas, Moidu Jameela and Syed, Tajdarul Hassan and Kumar, Hrishikesh and Kuenzer, Claudia},
  title     = {Detecting and analyzing the evolution of subsidence due to coal fires in Jharia coalfield, India using Sentinel-1 SAR data},
  series = {Remote Sensing},
  volume    = {13},
  journal   = {Remote Sensing},
  number    = {8},
  issn      = {2072-4292},
  doi       = {10.3390/rs13081521},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236703},
  year      = {2021},
  abstract  = {Public safety and socio-economic development of the Jharia coalfield (JCF) in India is critically dependent on precise monitoring and comprehensive understanding of coal fires, which have been burning underneath for more than a century. This study utilizes New-Small BAseline Subset (N-SBAS) technique to compute surface deformation time series for 2017-2020 to characterize the spatiotemporal dynamics of coal fires in JCF. The line-of-sight (LOS) surface deformation estimated from ascending and descending Sentinel-1 SAR data are subsequently decomposed to derive precise vertical subsidence estimates. The most prominent subsidence (~22 cm) is observed in Kusunda colliery. The subsidence regions also correspond well with the Landsat-8 based thermal anomaly map and field evidence. Subsequently, the vertical surface deformation time-series is analyzed to characterize temporal variations within the 9.5 km\(^2\) area of coal fires. Results reveal that nearly 10\% of the coal fire area is newly formed, while 73\% persisted throughout the study period. Vulnerability analyses performed in terms of the susceptibility of the population to land surface collapse demonstrate that Tisra, Chhatatanr, and Sijua are the most vulnerable towns. Our results provide critical information for developing early warning systems and remediation strategies.},
  language  = {en}
}
@article{KanzowRaharjaSchwartz2021,
  author    = {Kanzow, Christian and Raharja, Andreas B. and Schwartz, Alexandra},
  title     = {An Augmented Lagrangian Method for Cardinality-Constrained Optimization Problems},
  series = {Journal of Optimization Theory and Applications},
  volume    = {189},
  journal   = {Journal of Optimization Theory and Applications},
  number    = {3},
  issn      = {1573-2878},
  doi       = {10.1007/s10957-021-01854-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269166},
  pages     = {793-813},
  year      = {2021},
  abstract  = {A reformulation of cardinality-constrained optimization problems into continuous nonlinear optimization problems with an orthogonality-type constraint has gained some popularity during the last few years. Due to the special structure of the constraints, the reformulation violates many standard assumptions and therefore is often solved using specialized algorithms. In contrast to this, we investigate the viability of using a standard safeguarded multiplier penalty method without any problem-tailored modifications to solve the reformulated problem. We prove global convergence towards an (essentially strongly) stationary point under a suitable problem-tailored quasinormality constraint qualification. Numerical experiments illustrating the performance of the method in comparison to regularization-based approaches are provided.},
  language  = {en}
}
@article{BasilePuglisiAltierietal.2021,
  author    = {Basile, Vittoria and Puglisi, Soraya and Altieri, Barbara and Canu, Letizia and Lib{\`e}, Rossella and Ceccato, Filippo and Beuschlein, Felix and Quinkler, Marcus and Calabrese, Anna and Perotti, Paola and Berchialla, Paola and Dischinger, Ulrich and Megerle, Felix and Baudin, Eric and Bourdeau, Isabelle and Lacroix, Andr{\´e} and Loli, Paola and Berruti, Alfredo and Kastelan, Darko and Haak, Harm R. and Fassnacht, Martin and Terzolo, Massimo},
  title     = {What is the optimal duration of adjuvant mitotane therapy in adrenocortical carcinoma? An unanswered question},
  series = {Journal of Personalized Medicine},
  volume    = {11},
  journal   = {Journal of Personalized Medicine},
  number    = {4},
  issn      = {2075-4426},
  doi       = {10.3390/jpm11040269},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236507},
  year      = {2021},
  abstract  = {A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3\%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence.},
  language  = {en}
}
@article{GerlachMonningerSchleieretal.2021,
  author    = {Gerlach, Marius and Monninger, Sophie and Schleier, Domenik and Hemberger, Patrick and Goettel, James T. and Braunschweig, Holger and Fischer, Ingo},
  title     = {Photoelectron Photoion Coincidence Spectroscopy of NCl\(_{3}\) and NCl\(_{2}\)},
  series = {ChemPhysChem},
  volume    = {22},
  journal   = {ChemPhysChem},
  number    = {21},
  doi       = {10.1002/cphc.202100537},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257322},
  pages     = {2164-2167},
  year      = {2021},
  abstract  = {We investigate NCl\(_{3}\) and the NCl\(_{2}\) radical by photoelectron-photoion coincidence spectroscopy using synchrotron radiation. The mass selected threshold photoelectron spectrum (ms-TPES) of NCl\(_{3}\) is broad and unstructured due to the large geometry change. An ionization energy of 9.7±0.1 eV is estimated from the spectrum and supported by computations. NCl2 is generated by photolysis at 213 nm from NCl\(_{3}\) and its ms-TPES shows an extended vibrational progression with a 90 meV spacing that is assigned to the symmetric N-Cl stretching mode in the cation. An adiabatic ionization energy of 9.94 ± 0.02 eV is determined.},
  language  = {en}
}
@article{KayisogluSchlegelBartfeld2021,
  author    = {Kayisoglu, {\"O}zge and Schlegel, Nicolas and Bartfeld, Sina},
  title     = {Gastrointestinal epithelial innate immunity-regionalization and organoids as new model},
  series = {Journal of Molecular Medicine},
  volume    = {99},
  journal   = {Journal of Molecular Medicine},
  number    = {4},
  doi       = {10.1007/s00109-021-02043-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265220},
  pages     = {517-530},
  year      = {2021},
  abstract  = {The human gastrointestinal tract is in constant contact with microbial stimuli. Its barriers have to ensure co-existence with the commensal bacteria, while enabling surveillance of intruding pathogens. At the centre of the interaction lies the epithelial layer, which marks the boundaries of the body. It is equipped with a multitude of different innate immune sensors, such as Toll-like receptors, to mount inflammatory responses to microbes. Dysfunction of this intricate system results in inflammation-associated pathologies, such as inflammatory bowel disease. However, the complexity of the cellular interactions, their molecular basis and their development remains poorly understood. In recent years, stem cell-derived organoids have gained increasing attention as promising models for both development and a broad range of pathologies, including infectious diseases. In addition, organoids enable the study of epithelial innate immunity in vitro. In this review, we focus on the gastrointestinal epithelial barrier and its regional organization to discuss innate immune sensing and development.},
  language  = {en}
}
@article{BreilKanskePittigetal.2021,
  author    = {Breil, Christina and Kanske, Philipp and Pittig, Roxana and B{\"o}ckler, Anne},
  title     = {A revised instrument for the assessment of empathy and Theory of Mind in adolescents: Introducing the EmpaToM-Y},
  series = {Behavior Research Methods},
  volume    = {53},
  journal   = {Behavior Research Methods},
  doi       = {10.3758/s13428-021-01589-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-302877},
  pages     = {2487-2501},
  year      = {2021},
  abstract  = {Empathy and Theory of Mind (ToM) are two core components of social understanding. The EmpaToM is a validated social video task that allows for independent manipulation and assessment of the two capacities. First applications revealed that empathy and ToM are dissociable constructs on a neuronal as well as on a behavioral level. As the EmpaToM has been designed for the assessment of social understanding in adults, it has a high degree of complexity and comprises topics that are inadequate for minors. For this reason, we designed a new version of the EmpaToM that is especially suited to measure empathy and ToM in youths. In experiment 1, we successfully validated the EmpaToM-Y on the original EmpaToM in an adult sample (N = 61), revealing a similar pattern of results across tasks and strong correlations of all constructs. As intended, the performance measure for ToM and the control condition of the EmpaToM-Y showed reduced difficulty. In experiment 2, we tested the feasibility of the EmpaToM-Y in a group of teenagers (N = 36). Results indicate a reliable empathy induction and higher demands of ToM questions for adolescents. We provide a promising task for future research targeting inter-individual variability of socio-cognitive and socio-affective capacities as well as their precursors and outcomes in healthy minors and clinical populations.},
  language  = {en}
}
@article{MamontovaTrifaultBotenetal.2021,
  author    = {Mamontova, Victoria and Trifault, Barbara and Boten, Lea and Burger, Kaspar},
  title     = {Commuting to work: Nucleolar long non-coding RNA control ribosome biogenesis from near and far},
  series = {Non-Coding RNA},
  volume    = {7},
  journal   = {Non-Coding RNA},
  number    = {3},
  issn      = {2311-553X},
  doi       = {10.3390/ncrna7030042},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242756},
  year      = {2021},
  abstract  = {Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.},
  language  = {en}
}
@article{LombardiMayerSemleretal.2021,
  author    = {Lombardi, Jolina and Mayer, Benjamin and Semler, Elisa and Anderl-Straub, Sarah and Uttner, Ingo and Kassubek, Jan and Diehl-Schmid, Janine and Danek, Adrian and Levin, Johannes and Fassbender, Klaus and Fliessbach, Klaus and Schneider, Anja and Huppertz, Hans-J{\"u}rgen and Jahn, Holger and Volk, Alexander and Kornhuber, Johannes and Landwehrmeyer, Bernhard and Lauer, Martin and Prudlo, Johannes and Wiltfang, Jens and Schroeter, Matthias L. and Ludolph, Albert and Otto, Markus},
  title     = {Quantifying progression in primary progressive aphasia with structural neuroimaging},
  series = {Alzheimer's \& Dementia},
  volume    = {17},
  journal   = {Alzheimer's \& Dementia},
  number    = {10},
  doi       = {10.1002/alz.12323},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262605},
  pages     = {1595 -- 1609},
  year      = {2021},
  abstract  = {Introduction The term primary progressive aphasia (PPA) sums up the non-fluent (nfv), the semantic (sv), and the logopenic (lv) variant. Up to now, there is only limited data available concerning magnetic resonance imaging volumetry to monitor disease progression. Methods Structural brain imaging and an extensive assessment were applied at baseline and up to 4-year(s) follow-up in 269 participants. With automated atlas-based volumetry 56 brain regions were assessed. Atrophy progression served to calculate sample sizes for therapeutic trials. Results At baseline highest atrophy appeared in parts of the left frontal lobe for nfvPPA (-17\%) and of the left temporal lobe for svPPA (-34\%) and lvPPA (-24\%). Severest progression within 1-year follow-up occurred in the basal ganglia in nfvPPA (-7\%), in the hippocampus/amygdala in svPPA (-9\%), and in (medial) temporal regions in lvPPA (-6\%). Conclusion PPA presents as a left-dominant, mostly gray matter sensitive disease with considerable atrophy at baseline that proceeds variant-specific.},
  language  = {en}
}
@article{SchuhmannPappStolletal.2021,
  author    = {Schuhmann, Michael K. and Papp, Lena and Stoll, Guido and Blum, Robert and Volkmann, Jens and Fluri, Felix},
  title     = {Mesencephalic electrical stimulation reduces neuroinflammation after photothrombotic stroke in rats by targeting the cholinergic anti-inflammatory pathway},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {3},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22031254},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259099},
  year      = {2021},
  abstract  = {Inflammation is crucial in the pathophysiology of stroke and thus a promising therapeutic target. High-frequency stimulation (HFS) of the mesencephalic locomotor region (MLR) reduces perilesional inflammation after photothrombotic stroke (PTS). However, the underlying mechanism is not completely understood. Since distinct neural and immune cells respond to electrical stimulation by releasing acetylcholine, we hypothesize that HFS might trigger the cholinergic anti-inflammatory pathway via activation of the α7 nicotinic acetylcholine receptor (α7nAchR). To test this hypothesis, rats underwent PTS and implantation of a microelectrode into the MLR. Three hours after intervention, either HFS or sham-stimulation of the MLR was applied for 24 h. IFN-γ, TNF-α, and IL-1α were quantified by cytometric bead array. Choline acetyltransferase (ChAT)\(^+\) CD4\(^+\)-cells and α7nAchR\(^+\)-cells were quantified visually using immunohistochemistry. Phosphorylation of NFĸB, ERK1/2, Akt, and Stat3 was determined by Western blot analyses. IFN-γ, TNF-α, and IL-1α were decreased in the perilesional area of stimulated rats compared to controls. The number of ChAT\(^+\) CD4\(^+\)-cells increased after MLR-HFS, whereas the amount of α7nAchR\(^+\)-cells was similar in both groups. Phospho-ERK1/2 was reduced significantly in stimulated rats. The present study suggests that MLR-HFS may trigger anti-inflammatory processes within the perilesional area by modulating the cholinergic system, probably via activation of the α7nAchR.},
  language  = {en}
}
@article{WermkeRobbSchulter2021,
  author    = {Wermke, Kathleen and Robb, Michael P. and Schulter, Philip J.},
  title     = {Melody complexity of infants' cry and non-cry vocalisations increases across the first six months},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  issn      = {2045-2322},
  doi       = {10.1038/s41598-021-83564-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258669},
  year      = {2021},
  abstract  = {In early infancy, melody provides the most salient prosodic element for language acquisition and there is huge evidence for infants' precocious aptitudes for musical and speech melody perception. Yet, a lack of knowledge remains with respect to melody patterns of infants' vocalisations. In a search for developmental regularities of cry and non-cry vocalisations and for building blocks of prosody (intonation) over the first 6 months of life, more than 67,500 melodies (fundamental frequency contours) of 277 healthy infants from monolingual German families were quantitatively analysed. Based on objective criteria, vocalisations with well-identifiable melodies were grouped into those exhibiting a simple (single-arc) or complex (multiple-arc) melody pattern. Longitudinal analysis using fractional polynomial multi-level mixed effects logistic regression models were applied to these patterns. A significant age (but not sex) dependent developmental pattern towards more complexity was demonstrated in both vocalisation types over the observation period. The theoretical concept of melody development (MD-Model) contends that melody complexification is an important building block on the path towards language. Recognition of this developmental process will considerably improve not only our understanding of early preparatory processes for language acquisition, but most importantly also allow for the creation of clinically robust risk markers for developmental language disorders.},
  language  = {en}
}
@article{FoellThiesse2021,
  author    = {F{\"o}ll, Patrick and Thiesse, Fr{\´e}d{\´e}ric},
  title     = {Exploring Information Systems Curricula},
  series = {Business \& Information Systems Engineering},
  volume    = {63},
  journal   = {Business \& Information Systems Engineering},
  number    = {6},
  issn      = {1867-0202},
  doi       = {10.1007/s12599-021-00702-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270178},
  pages     = {711-732},
  year      = {2021},
  abstract  = {The study considers the application of text mining techniques to the analysis of curricula for study programs offered by institutions of higher education. It presents a novel procedure for efficient and scalable quantitative content analysis of module handbooks using topic modeling. The proposed approach allows for collecting, analyzing, evaluating, and comparing curricula from arbitrary academic disciplines as a partially automated, scalable alternative to qualitative content analysis, which is traditionally conducted manually. The procedure is illustrated by the example of IS study programs in Germany, based on a data set of more than 90 programs and 3700 distinct modules. The contributions made by the study address the needs of several different stakeholders and provide insights into the differences and similarities among the study programs examined. For example, the results may aid academic management in updating the IS curricula and can be incorporated into the curricular design process. With regard to employers, the results provide insights into the fulfillment of their employee skill expectations by various universities and degrees. Prospective students can incorporate the results into their decision concerning where and what to study, while university sponsors can utilize the results in their grant processes.},
  language  = {en}
}
@article{SzymskiAchenbachSiebentrittetal.2021,
  author    = {Szymski, Dominik and Achenbach, Leonard and Siebentritt, Martin and Simoni, Karola and Kuner, Norbert and Pfeifer, Christian and Krutsch, Werner and Alt, Volker and Meffert, Rainer and Fehske, Kai},
  title     = {Injury epidemiology of 626 athletes in surfing, wind surfing and kite surfing},
  series = {Open Access Journal of Sports Medicine},
  volume    = {12},
  journal   = {Open Access Journal of Sports Medicine},
  doi       = {10.2147/OAJSM.S316642},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261545},
  pages     = {99-107},
  year      = {2021},
  abstract  = {Introduction/Background Surfing, wind surfing and kite surfing enjoy a growing popularity with a large number of athletes worldwide. The aim of this study was to identify and compare the injury profiles and compare the injury profiles of these three extreme water sports. Materials and Methods These data for this retrospective cohort study were collected through an online standardised questionnaire during the 2017-18 season. The questionnaire included questions about anthropometry, skill level, injury diagnosis, injury mechanism, environmental conditions and training regimes. Results The 626 athletes included reported 2584 injuries. On average, each athlete sustained 4.12 injuries during the season. The most frequent injury location was in the lower extremity, in particular the foot, with 49 (16.4\%) injuries in surfing, 344 (18.3\%) in wind surfing and 79 (19.7\%) in kite surfing. Surfing demonstrated a particularly high rate of head injuries (n = 37; 12.4\%). Other frequent injury types were skin lesions (up to 42.1\%) and contusions (up to 40.5\%). The most common injury across all surfing sports was skin lesions of the foot (wind surfing: 11.7\%; kite surfing: 13.2\%; surfing: 12.7\%). In surfing, skin lesions of the head were frequently observed (n = 24; 8.0\%). In surfing, a 'too large wave' (n = 18; 24.7\%) was main cause of the injury, while in wind surfing (n = 189; 34.5\%) and kite surfing (n = 65; 36.7\%) 'own incompetence' led to the most injuries. Conclusion This unique study compares injury epidemiology and mechanism in the three most popular surfing sports: wind surfing, kite surfing and surfing. Overall, injuries were sustained mainly in the lower extremity, while surfing also demonstrated a high rate of head injuries.},
  language  = {en}
}
@article{DanhofRascheMottoketal.2021,
  author    = {Danhof, Sophia and Rasche, Leo and Mottok, Anja and Steinm{\"u}ller, Tabea and Zhou, Xiang and Schreder, Martin and Kilian, Teresa and Strifler, Susanne and Rosenwald, Andreas and Hudecek, Michael and Einsele, Hermann and Gerhard-Hartmann, Elena},
  title     = {Elotuzumab for the treatment of extramedullary myeloma: a retrospective analysis of clinical efficacy and SLAMF7 expression patterns},
  series = {Annals of Hematology},
  volume    = {100},
  journal   = {Annals of Hematology},
  number    = {6},
  issn      = {1432-0584},
  doi       = {10.1007/s00277-021-04447-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266468},
  pages     = {1537-1546},
  year      = {2021},
  abstract  = {Extramedullary disease (EMD) represents a high-risk state of multiple myeloma (MM) associated with poor prognosis. While most anti-myeloma therapeutics demonstrate limited efficacy in this setting, some studies exploring the utility of chimeric antigen receptor (CAR)-modified T cells reported promising results. We have recently designed SLAMF7-directed CAR T cells for the treatment of MM. SLAMF7 is a transmembrane receptor expressed on myeloma cells that plays a role in myeloma cell homing to the bone marrow. Currently, the only approved anti-SLAMF7 therapeutic is the monoclonal antibody elotuzumab, but its efficacy in EMD has not been investigated thoroughly. Thus, we retrospectively analyzed the efficacy of elotuzumab-based combination therapy in a cohort of 15 patients with EMD. Moreover, since the presence of the target antigen is an indispensable prerequisite for effective targeted therapy, we investigated the SLAMF7 expression on extramedullary located tumor cells before and after treatment. We observed limited efficacy of elotuzumab-based combination therapies, with an overall response rate of 40\% and a progression-free and overall survival of 3.8 and 12.9 months, respectively. Before treatment initiation, all available EMD tissue specimens (n = 3) demonstrated a strong and consistent SLAMF7 surface expression by immunohistochemistry. Furthermore, to investigate a potential antigen reduction under therapeutic selection pressure, we analyzed samples of de novo EMD (n = 3) outgrown during elotuzumab treatment. Again, immunohistochemistry documented strong and consistent SLAMF7 expression in all samples. In aggregate, our data point towards a retained expression of SLAMF7 in EMD and encourage the development of more potent SLAMF7-directed immunotherapies, such as CAR T cells.},
  language  = {en}
}
@article{GlatzelPatzkoMatlachetal.2021,
  author    = {Glatzel, Caroline Maria and Patzk{\´o}, {\´A}gnes and Matlach, Juliane and Grehn, Franz},
  title     = {Ergebnisse der filtrierenden Trabekulotomie (FTO) im Vergleich zur konventionellen Trabekulektomie (TE) - eine gematchte Fall-Kontroll-Studie},
  series = {Der Ophthalmologe},
  volume    = {118},
  journal   = {Der Ophthalmologe},
  number    = {5},
  doi       = {10.1007/s00347-021-01365-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266542},
  pages     = {461-469},
  year      = {2021},
  abstract  = {Ziel Ziel dieser Studie war es, die 2‑Jahres-Ergebnisse der filtrierenden Trabekulotomie (FTO) im Vergleich zur konventionellen Trabekulektomie (TE) bei prim{\"a}rem Offenwinkelglaukom, Pseudoexfoliationsglaukom und Pigmentglaukom zu untersuchen. Patienten und Methoden Es wurden 30 konsekutive Patienten nach FTO und 87 Patienten nach TE nach intraokularem Druck (IOD) und Alter im Verh{\"a}ltnis 1:3 gematcht. Prim{\"a}rer Endpunkt war das Erreichen des Zieldrucks nach 2 Jahren. Als vollst{\"a}ndiger Erfolg wurde ein IOD ohne Medikamente von ≤ 18 mm Hg bei gleichzeitiger IOD-Reduktion um ≥ 30 \% definiert, als qualifizierter Erfolg, wenn hierf{\"u}r zus{\"a}tzlich Medikamente erforderlich waren. Sekund{\"a}re Endpunkte waren mittlere Drucksenkung, resultierende Sehsch{\"a}rfe, Komplikationen und nachfolgende Operationen. Die Operationstechnik der filtrierenden Trabekulotomie ist als Video zu diesem Beitrag abrufbar. Ergebnisse Zwei-Jahres-Daten konnten von 27 Patienten aus der FTO-Gruppe und 68 Patienten aus der TE-Gruppe erhoben werden. Die Patienten beider Gruppen wurden vor Beginn der Studie bez{\"u}glich Alter und IOD gematcht, waren aber auch bez{\"u}glich Sehsch{\"a}rfe, Geschlecht und Medikation nicht unterschiedlich. Der Median des pr{\"a}operativen IOD unter Therapie betrug in beiden Gruppen 23,0 mm Hg. Nach den oben genannten Kriterien wurde ein qualifizierter 2‑Jahres-Erfolg bei 70,4 \% der FTO-Gruppe und bei 77,6 \% der TE-Gruppe erzielt (p = 0,60), ein vollst{\"a}ndiger 2‑Jahres-Erfolg bei 33,3 \% der FTO-Gruppe und bei 56,7 \% der TE-Gruppe (p = 0,07). Beide Operationsmethoden senkten den Augeninnendruck nach 24 Monaten signifikant (p < 0,001), und zwar auf 12,8 mm Hg in der FTO-Gruppe und 11,0 mm Hg in der TE-Gruppe. Die Sehsch{\"a}rfe war postoperativ bei beiden Gruppen etwas verringert, unterschied sich jedoch nicht signifikant zwischen beiden Gruppen. Komplikations- und Reoperationsrate waren gering und unterschieden sich nicht zwischen den Gruppen. Schlussfolgerung FTO und TE sind nach 2 Jahren weitgehend gleichwertig bez{\"u}glich Zieldruck, IOD-Senkung, Sehsch{\"a}rfe und Komplikationen.},
  language  = {de}
}
@article{BartmannFischerHuebneretal.2021,
  author    = {Bartmann, Catharina and Fischer, Leah-Maria and H{\"u}bner, Theresa and M{\"u}ller-Reiter, Max and W{\"o}ckel, Achim and McNeill, Rhiannon V. and Schlaiss, Tanja and Kittel-Schneider, Sarah and K{\"a}mmerer, Ulrike and Diessner, Joachim},
  title     = {The effects of the COVID-19 pandemic on psychological stress in breast cancer patients},
  series = {BMC Cancer},
  volume    = {21},
  journal   = {BMC Cancer},
  doi       = {10.1186/s12885-021-09012-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265802},
  year      = {2021},
  abstract  = {Background: The majority of breast cancer patients are severely psychologically affected by breast cancer diagnosis and subsequent therapeutic procedures. The COVID-19 pandemic and associated restrictions on public life have additionally caused significant psychological distress for much of the population. It is therefore plausible that breast cancer patients might be particularly susceptible to the additional psychological stress caused by the pandemic, increasing suffering. In this study we therefore aimed to assess the level of psychological distress currently experienced by a defined group of breast cancer patients in our breast cancer centre, compared to distress levels preCOVID-19 pandemic. Methods: Female breast cancer patients of all ages receiving either adjuvant, neoadjuvant, or palliative therapies were recruited for the study. All patients were screened for current or previous COVID-19 infection. The participants completed a self-designed COVID-19 pandemic questionnaire, the Stress and Coping Inventory (SCI), the National Comprehensive Cancer Network (R) (NCCN (R)) Distress Thermometer (DT), the European Organization for Research and Treatment of Cancer (EORTC) QLQ C30, and the BR23. Results: Eighty-two breast cancer patients were included. Therapy status and social demographic factors did not have a significant effect on the distress caused by the COVID-19 pandemic. The results of the DT pre and during COVID-19 pandemic did not differ significantly. Using the self-designed COVID-19 pandemic questionnaire, we detected three distinct subgroups demonstrating different levels of concerns in relation to SARS-CoV-2. The subgroup with the highest levels of concern reported significantly decreased life quality, related parameters and symptoms. Conclusions: This monocentric study demonstrated that the COVID-19 pandemic significantly affected psychological health in a subpopulation of breast cancer patients. The application of a self-created "COVID-19 pandemic questionnaire"could potentially be used to help identify breast cancer patients who are susceptible to increased psychological distress due to the COVID-19 pandemic, and therefore may need additional intensive psychological support.},
  language  = {en}
}
@article{MartinSchlosserFurtwaengleretal.2021,
  author    = {Mart{\´i}n, Ovidio Jim{\´e}nez and Schlosser, Andreas and Furtw{\"a}ngler, Rhoikos and Wegert, Jenny and Gessler, Manfred},
  title     = {MYCN and MAX alterations in Wilms tumor and identification of novel N-MYC interaction partners as biomarker candidates},
  series = {Cancer Cell International},
  volume    = {21},
  journal   = {Cancer Cell International},
  doi       = {10.1186/s12935-021-02259-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265542},
  year      = {2021},
  abstract  = {Background Wilms tumor (WT) is the most common renal tumor in childhood. Among others, MYCN copy number gain and MYCN P44L and MAX R60Q mutations have been identified in WT. MYCN encodes a transcription factor that requires dimerization with MAX to activate transcription of numerous target genes. MYCN gain has been associated with adverse prognosis in different childhood tumors including WT. The MYCN P44L and MAX R60Q mutations, located in either the transactivating or basic helix-loop-helix domain, respectively, are predicted to be damaging by different pathogenicity prediction tools, but the functional consequences remain to be characterized. Methods We screened a large cohort of unselected WTs for MYCN and MAX alterations. Wild-type and mutant protein function were characterized biochemically, and we analyzed the N-MYC protein interactome by mass spectrometric analysis of N-MYC containing protein complexes. Results Mutation screening revealed mutation frequencies of 3\% for MYCN P44L and 0.9\% for MAX R60Q that are associated with a higher risk of relapse. Biochemical characterization identified a reduced transcriptional activation potential for MAX R60Q, while the MYCN P44L mutation did not change activation potential or protein stability. The protein interactome of N-MYC-P44L was likewise not altered as shown by mass spectrometric analyses of purified N-MYC complexes. Nevertheless, we could identify a number of novel N-MYC partner proteins, e.g. PEG10, YEATS2, FOXK1, CBLL1 and MCRS1, whose expression is correlated with MYCN in WT samples and several of these are known for their own oncogenic potential. Conclusions The strongly elevated risk of relapse associated with mutant MYCN and MAX or elevated MYCN expression corroborates their role in WT oncogenesis. Together with the newly identified co-expressed interactors they expand the range of potential biomarkers for WT stratification and targeting, especially for high-risk WT.},
  language  = {en}
}
@article{BieberFoersterHaefelietal.2021,
  author    = {Bieber, Michael and Foerster, Kathrin I. and Haefeli, Walter E. and Pham, Mirko and Schuhmann, Michael K. and Kraft, Peter},
  title     = {Treatment with edoxaban attenuates acute stroke severity in mice by reducing blood-brain barrier damage and inflammation},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {18},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22189893},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284481},
  year      = {2021},
  abstract  = {Patients with atrial fibrillation and previous ischemic stroke (IS) are at increased risk of cerebrovascular events despite anticoagulation. In these patients, treatment with non-vitamin K oral anticoagulants (NOAC) such as edoxaban reduced the probability and severity of further IS without increasing the risk of major bleeding. However, the detailed protective mechanism of edoxaban has not yet been investigated in a model of ischemia/reperfusion injury. Therefore, in the current study we aimed to assess in a clinically relevant setting whether treatment with edoxaban attenuates stroke severity, and whether edoxaban has an impact on the local cerebral inflammatory response and blood-brain barrier (BBB) function after experimental IS in mice. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in male mice receiving edoxaban, phenprocoumon or vehicle. Infarct volumes, functional outcome and the occurrence of intracerebral hemorrhage were assessed. BBB damage and the extent of local inflammatory response were determined. Treatment with edoxaban significantly reduced infarct volumes and improved neurological outcome and BBB function on day 1 and attenuated brain tissue inflammation. In summary, our study provides evidence that edoxaban might exert its protective effect in human IS by modulating different key steps of IS pathophysiology, but further studies are warranted.},
  language  = {en}
}
@article{WamserSeufertHalletal.2021,
  author    = {Wamser, Florian and Seufert, Anika and Hall, Andrew and Wunderer, Stefan and Hoßfeld, Tobias},
  title     = {Valid statements by the crowd: statistical measures for precision in crowdsourced mobile measurements},
  series = {Network},
  volume    = {1},
  journal   = {Network},
  number    = {2},
  issn      = {2673-8732},
  doi       = {10.3390/network1020013},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284154},
  pages     = {215 -- 232},
  year      = {2021},
  abstract  = {Crowdsourced network measurements (CNMs) are becoming increasingly popular as they assess the performance of a mobile network from the end user's perspective on a large scale. Here, network measurements are performed directly on the end-users' devices, thus taking advantage of the real-world conditions end-users encounter. However, this type of uncontrolled measurement raises questions about its validity and reliability. The problem lies in the nature of this type of data collection. In CNMs, mobile network subscribers are involved to a large extent in the measurement process, and collect data themselves for the operator. The collection of data on user devices in arbitrary locations and at uncontrolled times requires means to ensure validity and reliability. To address this issue, our paper defines concepts and guidelines for analyzing the precision of CNMs; specifically, the number of measurements required to make valid statements. In addition to the formal definition of the aspect, we illustrate the problem and use an extensive sample data set to show possible assessment approaches. This data set consists of more than 20.4 million crowdsourced mobile measurements from across France, measured by a commercial data provider.},
  language  = {en}
}
@article{BaumgaertnerKernLevenetal.2021,
  author    = {Baumg{\"a}rtner, Ingrid and Kern, Manfred and Leven, Karl-Heinz and Toepfer, Regina},
  title     = {Mittelalter erschließen},
  series = {Das Mittelalter},
  volume    = {26},
  journal   = {Das Mittelalter},
  number    = {1},
  issn      = {0949-0345},
  doi       = {0.17885/heiup.1mial.2021.1.24310},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299110},
  pages     = {68-86},
  year      = {2021},
  abstract  = {Research communication has been gaining public attention in recent years. Therefore, medievalists also need to focus on the transfer of their research topics to the public both within and outside the university. Based on current political demands calling for a change in communication culture, the article first of all deals theoretically with two different concepts of research communication, by distinguishing between forms of translation and those of popularization. Numerous public events, exhibitions, and cooperative projects with cities, schools, adult education centres, museums, and other educational institutions show that knowledge about the Middle Ages has been trans-mitted to interested laypersons for a long time. The authors see a particular challenge in the alterity of medieval culture, which at the same time provides an excellent opportunity for transferring research findings into society. The fascination with medieval materiality facilitates the transfer of knowledge by those disciplines that work with concrete objects, addressing issues of visuality and aesthetic experience. The article pinpoints conditions, strategies, and perspectives of successful research communication in medieval studies, and when focussing on cur-rent topics, the authors refer to concrete occasions and regional examples, showing why medieval research is still relevant today.},
  subject      = {Wissenschaftskommunikation},
  language  = {de}
}
@article{PittigHeinigGoerigketal.2021,
  author    = {Pittig, Andre and Heinig, Ingmar and Goerigk, Stephan and Thiel, Freya and Hummel, Katrin and Scholl, Lucie and Deckert, J{\"u}rgen and Pauli, Paul and Domschke, Katharina and Lueken, Ulrike and Fydrich, Thomas and Fehm, Lydia and Plag, Jens and Str{\"o}hle, Andreas and Kircher, Tilo and Straube, Benjamin and Rief, Winfried and Koelkebeck, Katja and Arolt, Volker and Dannlowski, Udo and Margraf, J{\"u}rgen and Totzeck, Christina and Schneider, Silvia and Neudeck, Peter and Craske, Michelle G. and Hollandt, Maike and Richter, Jan and Hamm, Alfons and Wittchen, Hans-Ulrich},
  title     = {Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial},
  series = {Depression and Anxiety},
  volume    = {38},
  journal   = {Depression and Anxiety},
  number    = {11},
  doi       = {10.1002/da.23204},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257331},
  pages     = {1169-1181},
  year      = {2021},
  abstract  = {Background The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. Methods This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. Results Both treatments resulted in substantial improvements at post (PeEx-I: d\(_{within}\) = 1.50, PeEx-S: d\(_{within}\) = 1.78) and follow-up (PeEx-I: d\(_{within}\) = 2.34; PeEx-S: d\(_{within}\) = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32\% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR\(_{PeEx-I}\)-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse. Conclusions Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.},
  language  = {en}
}
@article{GaryLenhardLenhard2021,
  author    = {Gary, Sebastian and Lenhard, Wolfgang and Lenhard, Alexandra},
  title     = {Modelling norm scores with the cNORM package in R},
  series = {Psych},
  volume    = {3},
  journal   = {Psych},
  number    = {3},
  issn      = {2624-8611},
  doi       = {10.3390/psych3030033},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284143},
  pages     = {501 -- 521},
  year      = {2021},
  abstract  = {In this article, we explain and demonstrate how to model norm scores with the cNORM package in R. This package is designed specifically to determine norm scores when the latent ability to be measured covaries with age or other explanatory variables such as grade level. The mathematical method used in this package draws on polynomial regression to model a three-dimensional hyperplane that smoothly and continuously captures the relation between raw scores, norm scores and the explanatory variable. By doing so, it overcomes the typical problems of classical norming methods, such as overly large age intervals, missing norm scores, large amounts of sampling error in the subsamples or huge requirements with regard to the sample size. After a brief introduction to the mathematics of the model, we describe the individual methods of the package. We close the article with a practical example using data from a real reading comprehension test.},
  language  = {en}
}
@article{LiaqatSednevStilleretal.2021,
  author    = {Liaqat, Anam and Sednev, Maksim V. and Stiller, Carina and H{\"o}bartner, Claudia},
  title     = {RNA-Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA},
  series = {Angewandte Chemie International Edition},
  volume    = {60},
  journal   = {Angewandte Chemie International Edition},
  number    = {35},
  doi       = {10.1002/anie.202106517},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254544},
  pages     = {19058-19062},
  year      = {2021},
  abstract  = {Deoxyribozymes are emerging as modification-specific endonucleases for the analysis of epigenetic RNA modifications. Here, we report RNA-cleaving deoxyribozymes that differentially respond to the presence of natural methylated cytidines, 3-methylcytidine (m\(^3\)C), N\(^4\)-methylcytidine (m\(^4\)C), and 5-methylcytidine (m\(^5\)C), respectively. Using in vitro selection, we found several DNA catalysts, which are selectively activated by only one of the three cytidine isomers, and display 10- to 30-fold accelerated cleavage of their target m\(^3\)C-, m\(^4\)C- or m\(^5\)C-modified RNA. An additional deoxyribozyme is strongly inhibited by any of the three methylcytidines, but effectively cleaves unmodified RNA. The m\(^X\)C-detecting deoxyribozymes are programmable for the interrogation of natural RNAs of interest, as demonstrated for human mitochondrial tRNAs containing known m\(^3\)C and m\(^5\)C sites. The results underline the potential of synthetic functional DNA to shape highly selective active sites.},
  language  = {en}
}
@article{StaabLotterMuehleetal.2021,
  author    = {Staab, Torsten E. M. and Lotter, Frank and M{\"u}hle, Uwe and Elsayed, Mohamed and Petschke, Danny and Schubert, Thomas and Ibrahim, Alaa M. and Krause-Rehberg, Reinhard and Kieback, Bernd},
  title     = {The decomposition process in high-purity Al-1.7 at.\% Cu alloys with trace elements: preservation of quenched-in vacancies by In, Sn and Pb influencing the ​θ′formation},
  series = {Journal of Materials Science},
  volume    = {56},
  journal   = {Journal of Materials Science},
  number    = {14},
  issn      = {1573-4803},
  doi       = {10.1007/s10853-020-05742-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269103},
  pages     = {8717-8731},
  year      = {2021},
  abstract  = {Aluminium-copper alloys of the 2xxx type receive their excellent mechanical properties by the formation of copper-rich precipitates during hardening. Size, distribution and crystal structure of the formed precipitates determine the final strength of those alloys. Adding traces of certain elements, which bind to vacancies, significantly influences the decomposition behaviour, i.e. the diffusion of the copper atoms. For high-purity ternary alloys (Al-1.7 at.\% Cu-X), we investigate the interaction of copper and trace element atoms (X=In, Sn, and Pb) with quenched-in vacancies by Positron Annihilation Lifetime Spectroscopy (PALS). By employing Vickers microhardness, Differential Scanning Calorimetry (DSC) and Small Angle X-Ray Scattering (SAXS) we obtain a comprehensive picture of the decomposition process: opposite to predicted binding energies to vacancies by ab-initio calculations we find during ageing at room and elevated temperature a more retarded clustering of copper in the presence of In rather than for Sn additions, while Pb, having the highest predicted binding to vacancies, shows nearly no retarding effect compared to pure Al-Cu. If the latter would be due to a limited solubility of lead, it had to be below 2 ppm. Transmission Electron Microscopy (TEM) as imaging method complements our findings. Annealing the quenched Al-1.7 at.\% Cu-X-alloys containing 100 ppm In or Sn at 150∘C leads to finely distributed θ′-precipitates on the nanoscale, since due to the trace additions the formation temperature of θ′ is lowered by more than 100∘C. According to TEM small agglomerates of trace elements (In, Sn) may support the early nucleation for the θ′-precipitates.},
  language  = {en}
}
@article{SanchezNayaStepanenkoMandeletal.2021,
  author    = {Sanchez-Naya, Roberto and Stepanenko, Vladimir and Mandel, Karl and Beuerle, Florian},
  title     = {Modulation of Crystallinity and Optical Properties in Composite Materials Combining Iron Oxide Nanoparticles and Dye-Containing Covalent Organic Frameworks},
  series = {Organic Materials},
  volume    = {3},
  journal   = {Organic Materials},
  doi       = {10.1055/s-0040-1722655},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231480},
  pages     = {17-24},
  year      = {2021},
  abstract  = {Two series of organic-inorganic composite materials were synthesized through solvothermal imine condensation between diketopyrrolopyrrole dialdehyde DPP-1 and 5,10,15,20-tetrakis(4-aminophenyl)porphyrin (TAPP) in the presence of varying amounts of either amino- or carboxy-functionalized superparamagnetic iron oxide nanoparticles (FeO). Whereas high FeO loading induced cross-linking of the inorganic nanoparticles by amorphous imine polymers, a lower FeO content resulted in the formation of crystalline covalent organic framework domains. All hybrid materials were analyzed by magnetization measurements, powder X-ray diffraction, electron microscopy, IR, and UV/Vis absorption spectroscopy. Crystallinity, chromophore stacking, and visible absorption features are directly correlated to the mass fraction of the components, thus allowing for a fine-tuning of materials properties.},
  language  = {en}
}
@article{LewerentzHoffmannSarmentoCabral2021,
  author    = {Lewerentz, Anne and Hoffmann, Markus and Sarmento Cabral, Juliano},
  title     = {Depth diversity gradients of macrophytes: Shape, drivers, and recent shifts},
  series = {Ecology and Evolution},
  volume    = {11},
  journal   = {Ecology and Evolution},
  number    = {20},
  doi       = {10.1002/ece3.8089},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260280},
  pages     = {13830-13845},
  year      = {2021},
  abstract  = {Investigating diversity gradients helps to understand biodiversity drivers and threats. However, one diversity gradient is rarely assessed, namely how plant species distribute along the depth gradient of lakes. Here, we provide the first comprehensive characterization of depth diversity gradient (DDG) of alpha, beta, and gamma species richness of submerged macrophytes across multiple lakes. We characterize the DDG for additive richness components (alpha, beta, gamma), assess environmental drivers, and address temporal change over recent years. We take advantage of yet the largest dataset of macrophyte occurrence along lake depth (274 depth transects across 28 deep lakes) as well as of physiochemical measurements (12 deep lakes from 2006 to 2017 across Bavaria), provided publicly online by the Bavarian State Office for the Environment. We found a high variability in DDG shapes across the study lakes. The DDGs for alpha and gamma richness are predominantly hump-shaped, while beta richness shows a decreasing DDG. Generalized additive mixed-effect models indicate that the depth of the maximum richness (Dmax) is influenced by light quality, light quantity, and layering depth, whereas the respective maximum alpha richness within the depth gradient (Rmax) is significantly influenced by lake area only. Most observed DDGs seem generally stable over recent years. However, for single lakes we found significant linear trends for Rmax and Dmax going into different directions. The observed hump-shaped DDGs agree with three competing hypotheses: the mid-domain effect, the mean-disturbance hypothesis, and the mean-productivity hypothesis. The DDG amplitude seems driven by lake area (thus following known species-area relationships), whereas skewness depends on physiochemical factors, mainly water transparency and layering depth. Our results provide insights for conservation strategies and for mechanistic frameworks to disentangle competing explanatory hypotheses for the DDG.},
  language  = {en}
}
@article{HorderGuazaLasherasGrummeletal.2021,
  author    = {Horder, Hannes and Guaza Lasheras, Mar and Grummel, Nadine and Nadernezhad, Ali and Herbig, Johannes and Erg{\"u}n, S{\"u}leyman and Teßmar, J{\"o}rg and Groll, J{\"u}rgen and Fabry, Ben and Bauer-Kreisel, Petra and Blunk, Torsten},
  title     = {Bioprinting and differentiation of adipose-derived stromal cell spheroids for a 3D breast cancer-adipose tissue model},
  series = {Cells},
  volume    = {10},
  journal   = {Cells},
  number    = {4},
  doi       = {10.3390/cells10040803},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236496},
  year      = {2021},
  abstract  = {Biofabrication, including printing technologies, has emerged as a powerful approach to the design of disease models, such as in cancer research. In breast cancer, adipose tissue has been acknowledged as an important part of the tumor microenvironment favoring tumor progression. Therefore, in this study, a 3D-printed breast cancer model for facilitating investigations into cancer cell-adipocyte interaction was developed. First, we focused on the printability of human adipose-derived stromal cell (ASC) spheroids in an extrusion-based bioprinting setup and the adipogenic differentiation within printed spheroids into adipose microtissues. The printing process was optimized in terms of spheroid viability and homogeneous spheroid distribution in a hyaluronic acid-based bioink. Adipogenic differentiation after printing was demonstrated by lipid accumulation, expression of adipogenic marker genes, and an adipogenic ECM profile. Subsequently, a breast cancer cell (MDA-MB-231) compartment was printed onto the adipose tissue constructs. After nine days of co-culture, we observed a cancer cell-induced reduction of the lipid content and a remodeling of the ECM within the adipose tissues, with increased fibronectin, collagen I and collagen VI expression. Together, our data demonstrate that 3D-printed breast cancer-adipose tissue models can recapitulate important aspects of the complex cell-cell and cell-matrix interplay within the tumor-stroma microenvironment},
  language  = {en}
}
@article{StetterWeidnerLillaetal.2021,
  author    = {Stetter, Christian and Weidner, Franziska and Lilla, Nadine and Weiland, Judith and Kunze, Ekkehard and Ernestus, Ralf-Ingo and Muellenbach, Ralf Michael and Westermaier, Thomas},
  title     = {Therapeutic hypercapnia for prevention of secondary ischemia after severe subarachnoid hemorrhage: physiological responses to continuous hypercapnia},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-91007-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260779},
  pages     = {11715},
  year      = {2021},
  abstract  = {Temporary hypercapnia has been shown to increase cerebral blood flow (CBF) and might be used as a therapeutical tool in patients with severe subarachnoid hemorrhage (SAH). It was the aim of this study was to investigate the optimum duration of hypercapnia. This point is assumed to be the time at which buffer systems become active, cause an adaptation to changes of the arterial partial pressure of carbon dioxide (PaCO2) and annihilate a possible therapeutic effect. In this prospective interventional study in a neurosurgical ICU the arterial partial pressure of carbon dioxide (PaCO\(_2\)) was increased to a target range of 55 mmHg for 120 min by modification of the respiratory minute volume (RMV) one time a day between day 4 and 14 in 12 mechanically ventilated poor-grade SAH-patients. Arterial blood gases were measured every 15 min. CBF and brain tissue oxygen saturation (StiO\(_2\)) were the primary and secondary end points. Intracranial pressure (ICP) was controlled by an external ventricular drainage. Under continuous hypercapnia (PaCO\(_2\) of 53.17 ± 5.07), CBF was significantly elevated between 15 and 120 min after the start of hypercapnia. During the course of the trial intervention, cardiac output also increased significantly. To assess the direct effect of hypercapnia on brain perfusion, the increase of CBF was corrected by the parallel increase of cardiac output. The maximum direct CBF enhancing effect of hypercapnia of 32\% was noted at 45 min after the start of hypercapnia. Thereafter, the CBF enhancing slowly declined. No relevant adverse effects were observed. CBF and StiO\(_2\) reproducibly increased by controlled hypercapnia in all patients. After 45 min, the curve of CBF enhancement showed an inflection point when corrected by cardiac output. It is concluded that 45 min might be the optimum duration for a therapeutic use and may provide an optimal balance between the benefits of hypercapnia and risks of a negative rebound effect after return to normal ventilation parameters.},
  language  = {en}
}
@article{StarkPickelOsterbergKaufmannetal.2021,
  author    = {Stark, Toralf and Pickel, Susanne and Osterberg-Kaufmann, Norma and Mohamad-Klotzbach, Christoph},
  title     = {„Dysfunktionale Demokratie(n): Merkmale, Ursachen und Folgen". Digitale Jahrestagung des AK Demokratieforschung der DVPW am 11. M{\"a}rz 2021},
  series = {Zeitschrift f{\"u}r Vergleichende Politikwissenschaft},
  volume    = {15},
  journal   = {Zeitschrift f{\"u}r Vergleichende Politikwissenschaft},
  number    = {1},
  issn      = {1865-2654},
  doi       = {10.1007/s12286-021-00482-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270084},
  pages     = {137-141},
  year      = {2021},
  abstract  = {Kein Abstract vorhanden.},
  language  = {de}
}
@article{MarincolaLiongSchoenetal.2021,
  author    = {Marincola, Gabriella and Liong, Olivia and Schoen, Christoph and Abouelfetouh, Alaa and Hamdy, Aisha and Wencker, Freya D. R. and Marciniak, Tessa and Becker, Karsten and K{\"o}ck, Robin and Ziebuhr, Wilma},
  title     = {Antimicrobial Resistance Profiles of Coagulase-Negative Staphylococci in Community-Based Healthy Individuals in Germany},
  series = {Frontiers in Public Health},
  volume    = {9},
  journal   = {Frontiers in Public Health},
  issn      = {2296-2565},
  doi       = {10.3389/fpubh.2021.684456},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240881},
  year      = {2021},
  abstract  = {Coagulase-negative staphylococci (CoNS) are common opportunistic pathogens, but also ubiquitous human and animal commensals. Infection-associated CoNS from healthcare environments are typically characterized by pronounced antimicrobial resistance (AMR) including both methicillin- and multidrug-resistant isolates. Less is known about AMR patterns of CoNS colonizing the general population. Here we report on AMR in commensal CoNS recovered from 117 non-hospitalized volunteers in a region of Germany with a high livestock density. Among the 69 individuals colonized with CoNS, 29 had reported contacts to either companion or farm animals. CoNS were selectively cultivated from nasal swabs, followed by species definition by 16S rDNA sequencing and routine antibiotic susceptibility testing. Isolates displaying phenotypic AMR were further tested by PCR for presence of selected AMR genes. A total of 127 CoNS were isolated and Staphylococcus epidermidis (75\%) was the most common CoNS species identified. Nine isolates (7\%) were methicillin-resistant (MR) and carried the mecA gene, with seven individuals (10\%) being colonized with at least one MR-CoNS isolate. While resistance against gentamicin, phenicols and spectinomycin was rare, high resistance rates were found against tetracycline (39\%), erythromycin (33\%) and fusidic acid (24\%). In the majority of isolates, phenotypic resistance could be associated with corresponding AMR gene detection. Multidrug-resistance (MDR) was observed in 23\% (29/127) of the isolates, with 33\% (23/69) of the individuals being colonized with MDR-CoNS. The combined data suggest that MR- and MDR-CoNS are present in the community, with previous animal contact not significantly influencing the risk of becoming colonized with such isolates.},
  language  = {en}
}
@article{RauchSalzwedelBjarnasonWehrensetal.2021,
  author    = {Rauch, Bernhard and Salzwedel, Annett and Bjarnason-Wehrens, Birna and Albus, Christian and Meng, Karin and Schmid, Jean-Paul and Benzer, Werner and Hackbusch, Matthes and Jensen, Katrin and Schwaab, Bernhard and Altenberger, Johann and Benjamin, Nicola and Bestehorn, Kurt and Bongarth, Christa and D{\"o}rr, Gesine and Eichler, Sarah and Einwang, Hans-Peter and Falk, Johannes and Glatz, Johannes and Gielen, Stephan and Grilli, Maurizio and Gr{\"u}nig, Ekkehard and Guha, Manju and Hermann, Matthias and Hoberg, Eike and H{\"o}fer, Stefan and Kaemmerer, Harald and Ladwig, Karl-Heinz and Mayer-Berger, Wolfgang and Metzendorf, Maria-Inti and Nebel, Roland and Neidenbach, Rhoia Clara and Niebauer, Josef and Nixdorff, Uwe and Oberhoffer, Renate and Reibis, Rona and Reiss, Nils and Saure, Daniel and Schlitt, Axel and V{\"o}ller, Heinz and K{\"a}nel, Roland von and Weinbrenner, Susanne and Westphal, Ronja},
  title     = {Cardiac rehabilitation in German speaking countries of Europe — evidence-based guidelines from Germany, Austria and Switzerland LLKardReha-DACH — Part 1},
  series = {Journal of Clinical Medicine},
  volume    = {10},
  journal   = {Journal of Clinical Medicine},
  number    = {10},
  issn      = {2077-0383},
  doi       = {10.3390/jcm10102192},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239709},
  year      = {2021},
  abstract  = {Background: Although cardiovascular rehabilitation (CR) is well accepted in general, CR-attendance and delivery still considerably vary between the European countries. Moreover, clinical and prognostic effects of CR are not well established for a variety of cardiovascular diseases. Methods: The guidelines address all aspects of CR including indications, contents and delivery. By processing the guidelines, every step was externally supervised and moderated by independent members of the "Association of the Scientific Medical Societies in Germany" (AWMF). Four meta-analyses were performed to evaluate the prognostic effect of CR after acute coronary syndrome (ACS), after coronary bypass grafting (CABG), in patients with severe chronic systolic heart failure (HFrEF), and to define the effect of psychological interventions during CR. All other indications for CR-delivery were based on a predefined semi-structured literature search and recommendations were established by a formal consenting process including all medical societies involved in guideline generation. Results: Multidisciplinary CR is associated with a significant reduction in all-cause mortality in patients after ACS and after CABG, whereas HFrEF-patients (left ventricular ejection fraction <40\%) especially benefit in terms of exercise capacity and health-related quality of life. Patients with other cardiovascular diseases also benefit from CR-participation, but the scientific evidence is less clear. There is increasing evidence that the beneficial effect of CR strongly depends on "treatment intensity" including medical supervision, treatment of cardiovascular risk factors, information and education, and a minimum of individually adapted exercise volume. Additional psychologic interventions should be performed on the basis of individual needs. Conclusions: These guidelines reinforce the substantial benefit of CR in specific clinical indications, but also describe remaining deficits in CR-delivery in clinical practice as well as in CR-science with respect to methodology and presentation.},
  language  = {en}
}
@article{FriedmannAngeliMeierjohann2021,
  author    = {Friedmann Angeli, Jos{\´e} Pedro and Meierjohann, Svenja},
  title     = {NRF2-dependent stress defense in tumor antioxidant control and immune evasion},
  series = {Pigment Cell \& Melanoma Research},
  volume    = {34},
  journal   = {Pigment Cell \& Melanoma Research},
  number    = {2},
  doi       = {10.1111/pcmr.12946},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224536},
  pages     = {268 -- 279},
  year      = {2021},
  abstract  = {The transcription factor NRF2 is known as the master regulator of the oxidative stress response. Tumor entities presenting oncogenic activation of NRF2, such as lung adenocarcinoma, are associated with drug resistance, and accumulating evidence demonstrates its involvement in immune evasion. In other cancer types, the KEAP1/NRF2 pathway is not commonly mutated, but NRF2 is activated by other means such as radiation, oncogenic activity, cytokines, or other pro-oxidant triggers characteristic of the tumor niche. The obvious effect of stress-activated NRF2 is the protection from oxidative or electrophilic damage and the adaptation of the tumor metabolism to changing conditions. However, data from melanoma also reveal a role of NRF2 in modulating differentiation and suppressing anti-tumor immunity. This review summarizes the function of NRF2 in this tumor entity and discusses the implications for current tumor therapies.},
  language  = {en}
}
@article{CullmannJahnSpindleretal.2021,
  author    = {Cullmann, Katharina and Jahn, Magdalena and Spindler, Markus and Schenk, Franziska and Manukjan, Georgi and Mucci, Adele and Steinemann, Doris and Boller, Klaus and Schulze, Harald and Bender, Markus and Moritz, Thomas and Modlich, Ute},
  title     = {Forming megakaryocytes from murine-induced pluripotent stem cells by the inducible overexpression of supporting factors},
  series = {Research and Practice in Thrombosis and Haemostasis},
  volume    = {5},
  journal   = {Research and Practice in Thrombosis and Haemostasis},
  number    = {1},
  doi       = {10.1002/rth2.12453},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224565},
  pages     = {111 -- 124},
  year      = {2021},
  abstract  = {Background Platelets are small anucleate cells that circulate in the blood in a resting state but can be activated by external cues. In case of need, platelets from blood donors can be transfused. As an alternative source, platelets can be produced from induced pluripotent stem cells (iPSCs); however, recovered numbers are low. Objectives To optimize megakaryocyte (MK) and platelet output from murine iPSCs, we investigated overexpression of the transcription factors GATA-binding factor 1 (GATA1); nuclear factor, erythroid 2; and pre-B-cell leukemia transcription factor 1 (Pbx1) and a hyperactive variant of the small guanosine triphosphatase RhoA (RhoAhc). Methods To avoid off-target effects, we generated iPSCs carrying the reverse tetracycline-responsive transactivator M2 (rtTA-M2) in the Rosa26 locus and expressed the factors from Tet-inducible gammaretroviral vectors. Differentiation of iPSCs was initiated by embryoid body (EB) formation. After EB dissociation, early hematopoietic progenitors were enriched and cocultivated on OP9 feeder cells with thrombopoietin and stem cell factor to induce megakaryocyte (MK) differentiation. Results Overexpression of GATA1 and Pbx1 increased MK output 2- to 2.5-fold and allowed prolonged collection of MK. Cytologic and ultrastructural analyses identified typical MK with enlarged cells, multilobulated nuclei, granule structures, and an internal membrane system. However, GATA1 and Pbx1 expression did not improve MK maturation or platelet release, although in vitro-generated platelets were functional in spreading on fibrinogen or collagen-related peptide. Conclusion We demonstrate that the use of rtTA-M2 transgenic iPSCs transduced with Tet-inducible retroviral vectors allowed for gene expression at later time points during differentiation. With this strategy we could identify factors that increased in vitro MK production.},
  language  = {en}
}
@article{GenestLindstroemSchereretal.2021,
  author    = {Genest, Franca and Lindstr{\"o}m, Sarah and Scherer, Sophia and Schneider, Michael and Seefried, Lothar},
  title     = {Feasibility of simple exercise interventions for men with osteoporosis - A prospective randomized controlled pilot study},
  series = {Bone Reports},
  volume    = {15},
  journal   = {Bone Reports},
  doi       = {10.1016/j.bonr.2021.101099},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261434},
  year      = {2021},
  abstract  = {Background Aging is associated with progressive loss of musculoskeletal performance. Exercise interventions can improve physical function in the elderly but there is a paucity of comparative assessments in order to understand what specific goals can be achieved particularly with less demanding exercise interventions readily accessible for untrained men. Methods Prospective randomized, controlled, single center exploratory trial to compare four distinct exercise interventions, i.e. Resistance Training (RT), Whole Body Vibration Exercise (WBV), Qi Gong (QG) and wearing a Spinal orthosis (SO) for 6 months in men at risk for osteoporosis aged 65-90 years. Primary endpoint was change in isometric one repetition maximum force trunk strength for extension (TSE) and flexion (TSF) compared to baseline, secondary endpoints covered key parameters of geriatric functional assessment, including Handgrip Strength (HS), Chair-Rise-Test (CRT), Usual Gait Speed (UGS) and Timed-Up-and-Go (TUG). Results Altogether 47 men (mean age 77 ±6.1 years) were randomized to RT, (n = 11) WBV (n = 13), QG (n = 10) and SO(n = 13). RT, defined as reference exercise intervention, lead to significant improvements for TSE (p = 0.009) and TSF (p = 0.013) and was significantly superior in the between-group analysis for TSE (p = 0.038). Vibration exercise caused sign. Improvements in TSE (p = 0.014) and CRT (p = 0.005), the Spinal orthosis improved CRT (p = 0.003) and Gait Speed (p = 0.027), while the QG intervention did not attain any sig. Developments. Subgroup analyses revealed most pronounced musculoskeletal progress in vulnerable patients (age ≥ 80 years, pre-sarcopenia, multimorbidity ≥3chronic diseases). Irrespective of the type of exercise, participants ≥80 years experienced significant gains in TSE (p = 0.029) and CRT (p = 0.017). Presarcopenic subjects (Skeletal muscle Index (SMI) ≤10.75 kg/m2) improved in TSE (p = 0.003), CRT (p = 0.001) and UGS (p = 0.016). Multimorbid participants achieved sig. Gains in TSE (p < 0.001), TSF (p = 0.002), UGS (p = 0.036) and HS (p = 0.046). Conclusions In this exploratory trial we found that simple exercise interventions are feasible in elderly men eliciting specific benefits, i.e. improvements are attained in those tasks addressed with the respective exercise modality. While targeted resistance training is superior in increasing TSE, alternative simple exercise interventions also appear to elicit beneficial effects, even in vulnerable patients, i.e. those with low muscle mass, above 80 years of age or multimorbidity.},
  language  = {en}
}
@article{KuzkinaBargarSchmittetal.2021,
  author    = {Kuzkina, Anastasia and Bargar, Connor and Schmitt, Daniela and R{\"o}ßle, Jonas and Wang, Wen and Schubert, Anna-Lena and Tatsuoka, Curtis and Gunzler, Steven A. and Zou, Wen-Quan and Volkmann, Jens and Sommer, Claudia and Doppler, Kathrin and Chen, Shu G.},
  title     = {Diagnostic value of skin RT-QuIC in Parkinson's disease: a two-laboratory study},
  series = {NPJ Parkinson's Disease},
  volume    = {7},
  journal   = {NPJ Parkinson's Disease},
  number    = {1},
  doi       = {10.1038/s41531-021-00242-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260451},
  year      = {2021},
  abstract  = {Skin alpha-synuclein deposition is considered a potential biomarker for Parkinson's disease (PD). Real-time quaking-induced conversion (RT-QuIC) is a novel, ultrasensitive, and efficient seeding assay that enables the detection of minute amounts of alpha-synuclein aggregates. We aimed to determine the diagnostic accuracy, reliability, and reproducibility of alpha-synuclein RT-QuIC assay of skin biopsy for diagnosing PD and to explore its correlation with clinical markers of PD in a two-center inter-laboratory comparison study. Patients with clinically diagnosed PD (n = 34), as well as control subjects (n = 30), underwent skin punch biopsy at multiple sites (neck, lower back, thigh, and lower leg). The skin biopsy samples (198 in total) were divided in half to be analyzed by RT-QuIC assay in two independent laboratories. The a-synuclein RT-QuIC assay of multiple skin biopsies supported the clinical diagnosis of PD with a diagnostic accuracy of 88.9\% and showed a high degree of inter-rater agreement between the two laboratories (92.2\%). Higher alpha-synuclein seeding activity in RT-QuIC was shown in patients with longer disease duration and more advanced disease stage and correlated with the presence of REM sleep behavior disorder, cognitive impairment, and constipation. The alpha-synuclein RT-QuIC assay of minimally invasive skin punch biopsy is a reliable and reproducible biomarker for Parkinson's disease. Moreover, alpha-synuclein RT-QuIC seeding activity in the skin may serve as a potential indicator of progression as it correlates with the disease stage and certain non-motor symptoms.},
  language  = {en}
}