@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{ApelblatConsiglioMainardi2021, author = {Apelblat, Alexander and Consiglio, Armando and Mainardi, Francesco}, title = {The Bateman functions revisited after 90 years — a survey of old and new results}, series = {Mathematics}, volume = {9}, journal = {Mathematics}, number = {11}, issn = {2227-7390}, doi = {10.3390/math9111273}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240970}, year = {2021}, abstract = {The Bateman functions and the allied Havelock functions were introduced as solutions of some problems in hydrodynamics about ninety years ago, but after a period of one or two decades they were practically neglected. In handbooks, the Bateman function is only mentioned as a particular case of the confluent hypergeometric function. In order to revive our knowledge on these functions, their basic properties (recurrence functional and differential relations, series, integrals and the Laplace transforms) are presented. Some new results are also included. Special attention is directed to the Bateman and Havelock functions with integer orders, to generalizations of these functions and to the Bateman-integral function known in the literature.}, 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{HolzmannLittigBraunischKrankeetal.2021, author = {Holzmann-Littig, Christopher and Braunisch, Matthias Christoph and Kranke, Peter and Popp, Maria and Seeber, Christian and Fichtner, Falk and Littig, Bianca and Carbajo-Lozoya, Javier and Allwang, Christine and Frank, Tamara and Meerpohl, Joerg Johannes and Haller, Bernhard and Schmaderer, Christoph}, title = {COVID-19 vaccination acceptance and hesitancy among healthcare workers in germany}, series = {Vaccines}, volume = {9}, journal = {Vaccines}, number = {7}, issn = {2076-393X}, doi = {10.3390/vaccines9070777}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242627}, year = {2021}, abstract = {Vaccination hesitancy is a threat to herd immunity. Healthcare workers (HCWs) play a key role in promoting Coronavirus disease 2019 (COVID-19) vaccination in the general population. We therefore aimed to provide data on COVID-19 vaccination acceptance/hesitancy among German HCWs. For this exploratory, cross-sectional study, an online survey was conducted in February 2021. The survey included 54 items on demographics; previous vaccination behavior; trust in vaccines, physicians, the pharmaceutical industry and health politics; fear of adverse effects; assumptions regarding the consequences of COVID-19; knowledge about vaccines; and information seeking behavior. Odds ratios with 95\% confidence intervals were calculated and chi-square tests were performed. Four thousand five hundred surveys were analyzed. The overall vaccination acceptance was 91.7\%. The age group ≤20 years showed the lowest vaccination acceptance. Factors associated with vaccination hesitancy were lack of trust in authorities and pharmaceutical companies. Attitudes among acquaintances were associated with vaccination hesitancy too. Participants with vaccination hesitancy more often obtained information about COVID-19 vaccines via messenger services or online video platforms and underperformed in the knowledge test. We found high acceptance amongst German HCWs. Several factors associated with vaccination hesitancy were identified which could be targeted in HCW vaccination campaigns.}, language = {en} } @article{FortmannDammannHumbergetal.2021, author = {Fortmann, Ingmar and Dammann, Marie-Theres and Humberg, Alexander and Siller, Bastian and Stichtenoth, Guido and Engels, Geraldine and Marißen, Janina and Faust, Kirstin and Hanke, Kathrin and Goedicke-Fritz, Sybelle and Derouet, Christoph and Meyer, Sascha and Stutz, Regine and Kaiser, Elisabeth and Herting, Egbert and G{\"o}pel, Wolfgang and H{\"a}rtel, Christoph and Zemlin, Michael}, title = {Five year follow up of extremely low gestational age infants after timely or delayed administration of routine vaccinations}, series = {Vaccines}, volume = {9}, journal = {Vaccines}, number = {5}, issn = {2076-393X}, doi = {10.3390/vaccines9050493}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239592}, year = {2021}, abstract = {This study is aimed at detecting the rate of untimely immunization in a large cohort of extremely low gestational age neonates (ELGANs) of the German Neonatal Network (GNN) and at addressing risk factors for delayed vaccination and associated long-term consequences. We performed an observational study of the GNN between 1st January 2010 and 31st December 2019. The immunization status for the hexavalent and pneumococcal immunization was evaluated in n = 8401 preterm infants <29 weeks of gestation. Univariate analysis and logistic/linear regression models were used to identify risk factors for vaccination delay and outcomes at a 5-year follow-up. In our cohort n = 824 (9.8\%) ELGANs did not receive a timely first immunization with the hexavalent and pneumococcal vaccine. Risk factors for delayed vaccination were SGA status (18.1\% vs. 13.5\%; OR 1.3; 95\% CI: 1.1-1.7), impaired growth and surrogates for complicated clinical courses (i.e., need for inotropes, necrotizing enterocolitis). At 5 years of age, timely immunized children had a lower risk of bronchitis (episodes within last year: 27.3\% vs. 37.7\%; OR 0.60, 95\% CI: 0.42-0.86) but spirometry measures were unaffected. In conclusion, a significant proportion of ELGANs are untimely immunized, specifically those with increased vulnerability, even though they might particularly benefit from the immune-promoting effects of a timely vaccination.}, language = {en} } @article{HomburgWeissFrahmetal.2021, author = {Homburg, Annika and Weiß, Christian H. and Frahm, Gabriel and Alwan, Layth C. and G{\"o}b, Rainer}, title = {Analysis and forecasting of risk in count processes}, series = {Journal of Risk and Financial Management}, volume = {14}, journal = {Journal of Risk and Financial Management}, number = {4}, issn = {1911-8074}, doi = {10.3390/jrfm14040182}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236692}, year = {2021}, abstract = {Risk measures are commonly used to prepare for a prospective occurrence of an adverse event. If we are concerned with discrete risk phenomena such as counts of natural disasters, counts of infections by a serious disease, or counts of certain economic events, then the required risk forecasts are to be computed for an underlying count process. In practice, however, the discrete nature of count data is sometimes ignored and risk forecasts are calculated based on Gaussian time series models. But even if methods from count time series analysis are used in an adequate manner, the performance of risk forecasting is affected by estimation uncertainty as well as certain discreteness phenomena. To get a thorough overview of the aforementioned issues in risk forecasting of count processes, a comprehensive simulation study was done considering a broad variety of risk measures and count time series models. It becomes clear that Gaussian approximate risk forecasts substantially distort risk assessment and, thus, should be avoided. In order to account for the apparent estimation uncertainty in risk forecasting, we use bootstrap approaches for count time series. The relevance and the application of the proposed approaches are illustrated by real data examples about counts of storm surges and counts of financial transactions.}, language = {en} } @article{GoettschBeerenwinkelDengetal.2021, author = {Goettsch, Winfried and Beerenwinkel, Niko and Deng, Li and D{\"o}lken, Lars and Dutilh, Bas E. and Erhard, Florian and Kaderali, Lars and Kleist, Max von and Marquet, Roland and Matthijnssens, Jelle and McCallin, Shawna and McMahon, Dino and Rattei, Thomas and Van Rij, Ronald P. and Robertson, David L. and Schwemmle, Martin and Stern-Ginossar, Noam and Marz, Manja}, title = {ITN—VIROINF: Understanding (harmful) virus-host interactions by linking virology and bioinformatics}, series = {Viruses}, volume = {13}, journal = {Viruses}, number = {5}, issn = {1999-4915}, doi = {10.3390/v13050766}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236687}, year = {2021}, abstract = {Many recent studies highlight the fundamental importance of viruses. Besides their important role as human and animal pathogens, their beneficial, commensal or harmful functions are poorly understood. By developing and applying tailored bioinformatical tools in important virological models, the Marie Skłodowska-Curie Initiative International Training Network VIROINF will provide a better understanding of viruses and the interaction with their hosts. This will open the door to validate methods of improving viral growth, morphogenesis and development, as well as to control strategies against unwanted microorganisms. The key feature of VIROINF is its interdisciplinary nature, which brings together virologists and bioinformaticians to achieve common goals.}, language = {en} } @article{MoratinIckrathScherzadetal.2021, author = {Moratin, Helena and Ickrath, Pascal and Scherzad, Agmal and Meyer, Till Jasper and Naczenski, Sebastian and Hagen, Rudolf and Hackenberg, Stephan}, title = {Investigation of the immune modulatory potential of zinc oxide nanoparticles in human lymphocytes}, series = {Nanomaterials}, volume = {11}, journal = {Nanomaterials}, number = {3}, issn = {2079-4991}, doi = {10.3390/nano11030629}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234016}, year = {2021}, abstract = {Zinc oxide nanoparticles (ZnO-NP) are commonly used for a variety of applications in everyday life. In addition, due to its versatility, nanotechnology supports promising approaches in the medical sector. NP can act as drug-carriers in the context of targeted chemo- or immunotherapy, and might also exhibit autonomous immune-modulatory characteristics. Knowledge of potential immunosuppressive or stimulating effects of NP is indispensable for the safety of consumers as well as patients. In this study, primary human peripheral blood lymphocytes of 9 donors were treated with different sub-cytotoxic concentrations of ZnO-NP for the duration of 1, 2, or 3 days. Flow cytometry was performed to investigate changes in the activation profile and the proportion of T cell subpopulations. ZnO-NP applied in this study did not induce any significant alterations in the examined markers, indicating their lack of impairment in terms of immune modulation. However, physicochemical characteristics exert a major influence on NP-associated bioactivity. To allow a precise simulation of the complex molecular processes of immune modulation, a physiological model including the different components of an immune response is needed.}, 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{NedopilDelmanHowelletal.2021, author = {Nedopil, Alexander J. and Delman, Connor and Howell, Stephen M. and Hull, Maury L.}, title = {Restoring the patient's pre-arthritic posterior slope is the correct target for maximizing internal tibial rotation when implanting a PCL retaining TKA with calipered kinematic alignment}, series = {Journal of Personalized Medicine}, volume = {11}, journal = {Journal of Personalized Medicine}, number = {6}, issn = {2075-4426}, doi = {10.3390/jpm11060516}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240996}, year = {2021}, abstract = {Introduction: The calipered kinematically-aligned (KA) total knee arthroplasty (TKA) strives to restore the patient's individual pre-arthritic (i.e., native) posterior tibial slope when retaining the posterior cruciate ligament (PCL). Deviations from the patient's individual pre-arthritic posterior slope tighten and slacken the PCL in flexion that drives tibial rotation, and such a change might compromise passive internal tibial rotation and coupled patellofemoral kinematics. Methods: Twenty-one patients were treated with a calipered KA TKA and a PCL retaining implant with a medial ball-in-socket and a lateral flat articular insert conformity that mimics the native (i.e., healthy) knee. The slope of the tibial resection was set parallel to the medial joint line by adjusting the plane of an angel wing inserted in the tibial guide. Three trial inserts that matched and deviated 2°> and 2°< from the patient's pre-arthritic slope were 3D printed with goniometric markings. The goniometer measured the orientation of the tibia (i.e., trial insert) relative to the femoral component. Results: There was no difference between the radiographic preoperative and postoperative tibial slope (0.7 ± 3.2°, NS). From extension to 90° flexion, the mean passive internal tibial rotation with the pre-arthritic slope insert of 19° was greater than the 15° for the 2°> slope (p < 0.000), and 15° for the 2°< slope (p < 0.000). Discussion: When performing a calipered KA TKA with PCL retention, the correct target for setting the tibial component is the patient's individual pre-arthritic slope within a tolerance of ±2°, as this target resulted in a 15-19° range of internal tibial rotation that is comparable to the 15-18° range reported for the native knee from extension to 90° flexion.}, language = {en} }