@article{BakirciFrankGumbeletal.2021,
  author    = {Bakirci, Ezgi and Frank, Andreas and Gumbel, Simon and Otto, Paul F. and F{\"u}rsattel, Eva and Tessmer, Ingrid and Schmidt, Hans-Werner and Dalton, Paul D.},
  title     = {Melt Electrowriting of Amphiphilic Physically Crosslinked Segmented Copolymers},
  series = {Macromolecular Chemistry and Physics},
  volume    = {222},
  journal   = {Macromolecular Chemistry and Physics},
  number    = {22},
  doi       = {10.1002/macp.202100259},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257572},
  year      = {2021},
  abstract  = {Various (AB)\(_{n}\) and (ABAC)\(_{n}\) segmented copolymers with hydrophilic and hydrophobic segments are processed via melt electrowriting (MEW). Two different (AB)\(_{n}\) segmented copolymers composed of bisurea segments and hydrophobic poly(dimethyl siloxane) (PDMS) or hydrophilic poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEG-PPO) segments, while the amphiphilic (ABAC)\(_{n}\) segmented copolymers consist of bisurea segments in the combination of hydrophobic PDMS segments and hydrophilic PPO-PEG-PPO segments with different ratios, are explored. All copolymer compositions are processed using the same conditions, including nozzle temperature, applied voltage, and collector distance, while changes in applied pressure and collector speed altered the fiber diameter in the range of 7 and 60 µm. All copolymers showed excellent processability with MEW, well-controlled fiber stacking, and inter-layer bonding. Notably, the surfaces of all four copolymer fibers are very smooth when visualized using scanning electron microscopy. However, the fibers show different roughness demonstrated with atomic force microscopy. The non-cytotoxic copolymers increased L929 fibroblast attachment with increasing PDMS content while the different copolymer compositions result in a spectrum of physical properties.},
  language  = {en}
}
@article{CanuPuglisiBerchiallaetal.2021,
  author    = {Canu, Letizia and Puglisi, Soraya and Berchialla, Paola and De Filpo, Giuseppina and Brignardello, Francesca and Schiavi, Francesca and Ferrara, Alfonso Massimiliano and Zovato, Stefania and Luconi, Michaela and Pia, Anna and Appetecchia, Marialuisa and Arvat, Emanuela and Letizia, Claudio and Maccario, Mauro and Parasiliti-Caprino, Mirko and Altieri, Barbara and Faggiano, Antongiulio and Modica, Roberta and Morelli, Valentina and Arosio, Maura and Verga, Uberta and Pellegrino, Micaela and Petramala, Luigi and Concistr{\`e}, Antonio and Razzore, Paola and Ercolino, Tonino and Rapizzi, Elena and Maggi, Mario and Stigliano, Antonio and Burrello, Jacopo and Terzolo, Massimo and Opocher, Giuseppe and Mannelli, Massimo and Reimondo, Giuseppe},
  title     = {A multicenter epidemiological study on second malignancy in non-syndromic pheochromocytoma/paraganglioma patients in Italy},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {22},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13225831},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250148},
  year      = {2021},
  abstract  = {No studies have carried out an extensive analysis of the possible association between non-syndromic pheochromocytomas and paragangliomas (PPGLs) and other malignancies. To assess >the risk of additional malignancy in PPGL, we retrospectively evaluated 741 patients with PPGLs followed-up in twelve referral centers in Italy. Incidence of second malignant tumors was compared between this cohort and Italian patients with two subsequent malignancies. Among our patients, 95 (12.8\%) developed a second malignant tumor, which were mainly prostate, colorectal and lung/bronchial cancers in males, breast cancer, differentiated thyroid cancer and melanoma in females. The standardized incidence ratio was 9.59 (95\% CI 5.46-15.71) in males and 13.21 (95\% CI 7.52-21.63) in females. At multivariable analysis, the risk of developing a second malignant tumor increased with age at diagnosis (HR 2.50, 95\% CI 1.15-5.44, p = 0.021 for 50-59 vs. <50-year category; HR 3.46, 95\% CI 1.67-7.15, p < 0.001 for >60- vs. <50-year). In patients with available genetic evaluation, a positive genetic test was inversely associated with the risk of developing a second tumor (HR 0.25, 95\% CI 0.10-0.63, p = 0.003). In conclusion, PPGLs patients have higher incidence of additional malignant tumors compared to the general population who had a first malignancy, which could have an impact on the surveillance strategy.},
  language  = {en}
}
@article{PerniaAndradeWengerEspositoetal.2021,
  author    = {Pern{\´i}a-Andrade, Alejandro J. and Wenger, Nikolaus and Esposito, Maria S. and Tovote, Philip},
  title     = {Circuits for State-Dependent Modulation of Locomotion},
  series = {Frontiers in Human Neuroscience},
  volume    = {15},
  journal   = {Frontiers in Human Neuroscience},
  issn      = {1662-5161},
  doi       = {10.3389/fnhum.2021.745689},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249995},
  year      = {2021},
  abstract  = {Brain-wide neural circuits enable bi- and quadrupeds to express adaptive locomotor behaviors in a context- and state-dependent manner, e.g., in response to threats or rewards. These behaviors include dynamic transitions between initiation, maintenance and termination of locomotion. Advances within the last decade have revealed an intricate coordination of these individual locomotion phases by complex interaction of multiple brain circuits. This review provides an overview of the neural basis of state-dependent modulation of locomotion initiation, maintenance and termination, with a focus on insights from circuit-centered studies in rodents. The reviewed evidence indicates that a brain-wide network involving excitatory circuit elements connecting cortex, midbrain and medullary areas appears to be the common substrate for the initiation of locomotion across different higher-order states. Specific network elements within motor cortex and the mesencephalic locomotor region drive the initial postural adjustment and the initiation of locomotion. Microcircuits of the basal ganglia, by implementing action-selection computations, trigger goal-directed locomotion. The initiation of locomotion is regulated by neuromodulatory circuits residing in the basal forebrain, the hypothalamus, and medullary regions such as locus coeruleus. The maintenance of locomotion requires the interaction of an even larger neuronal network involving motor, sensory and associative cortical elements, as well as defined circuits within the superior colliculus, the cerebellum, the periaqueductal gray, the mesencephalic locomotor region and the medullary reticular formation. Finally, locomotor arrest as an important component of defensive emotional states, such as acute anxiety, is mediated via a network of survival circuits involving hypothalamus, amygdala, periaqueductal gray and medullary premotor centers. By moving beyond the organizational principle of functional brain regions, this review promotes a circuit-centered perspective of locomotor regulation by higher-order states, and emphasizes the importance of individual network elements such as cell types and projection pathways. The realization that dysfunction within smaller, identifiable circuit elements can affect the larger network function supports more mechanistic and targeted therapeutic intervention in the treatment of motor network disorders.},
  language  = {en}
}
@article{SerflingZhiSchirbeletal.2021,
  author    = {Serfling, S. and Zhi, Y. and Schirbel, A. and Lindner, T. and Meyer, T. and Gerhard-Hartmann, E. and Lappa, C. and Hagen, R. and Hackenberg, S. and Buck, A. K. and Scherzad, A.},
  title     = {Improved cancer detection in Waldeyer's tonsillar ring by \(^{68}\)Ga-FAPI PET/CT imaging},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {48},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  issn      = {1619-7070},
  doi       = {10.1007/s00259-020-05055-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235271},
  pages     = {1178-1187},
  year      = {2021},
  abstract  = {Purpose In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [\(^{18}\)F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [\(^{18}\)F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer's tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer's tonsillar ring, the novel PET tracer [\(^{68}\)Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging. Methods Eight patients with suspicion of a malignant tumor in Waldeyer's tonsillar ring or a CUP syndrome were examined. PET/CT scans with [\(^{18}\)F]-FDG and [\(^{68}\)Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings. Results Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [\(^{18}\)F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [\(^{68}\)Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUVmax for the primary tumors was 21.29 ± 7.97 for \(^{18}\)F-FDG and 16.06 ± 6.29 for \(^{68}\)Ga-FAPI, respectively (p = 0.2). The mean SUVmax for the healthy contralateral tonsils was 8.38 ± 2.45 for [\(^{18}\)F]FDG and 3.55 ± 0.47 for [\(^{68}\)Ga]FAPI (p < 0.001). The SUVmax ratio of [68Ga]FAPI was significantly different from [\(^{18}\)F] FDG (p = 0.03). Mean TBRmax for the [\(^{68}\)Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [\(^{18}\)F]FDG (10.90 vs. 4.11). Conclusion Non-invasive imaging of FAP expression by [\(^{68}\)Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [\(^{18}\)F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [\(^{68}\)Ga]FAPI PET/CT imaging.},
  language  = {en}
}
@article{FaustFreitagBarrientosetal.2021,
  author    = {Faust, Kirstin and Freitag, Nancy and Barrientos, Gabriela and Hartel, Christoph and Blois, Sandra M.},
  title     = {Galectin-Levels Are Elevated in Infants Born Preterm Due to Amniotic Infection and Rapidly Decline in the Neonatal Period},
  series = {Frontiers in Immunology},
  volume    = {11},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2020.599104},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230701},
  year      = {2021},
  abstract  = {Galectin (gal)-1, -3, and -9 are members of a family of glycan binding proteins that mediate complex interactions between decidual, inflammatory and trophoblast cells modulating several processes during gestation, control of the maternal immune system, and parturition. Their immunomodulatory role in preterm birth and postnatal expression in preterm infants is unknown. We performed a single center prospective study of 170 preterm infants with a gestational age below 35 weeks. Peripheral venous blood samples were collected during the neonatal period and galectin-1, -3, and -9 were determined by ELISA. We noted a strong decline of circulating gal-1 and -3 levels but not gal-9 from birth to day 7 of life. There was an inverse correlation of gal-1 and -3 levels at birth with gestational age. Gal-1 levels were remarkably increased in infants born to amniotic infection syndrome (AIS), which was also observed for gal-9 levels. Infants who developed early-onset sepsis had higher levels of gal-3 at day 1 as compared to unaffected infants. Our observational data imply that galectin-1, -3, and -9 levels are elevated in preterm infants born in an inflammatory milieu such as AIS or EOS. Future studies need to address whether galectins mediate inflammation-induced preterm birth and could therefore be a target for clinical trials.},
  language  = {en}
}
@article{BuddeHassounTangosetal.2021,
  author    = {Budde, Heidi and Hassoun, Roua and Tangos, Melina and Zhazykbayeva, Saltanat and Herwig, Melissa and Varatnitskaya, Marharyta and Sieme, Marcel and Delalat, Simin and Sultana, Innas and Kolijn, Detmar and G{\"o}m{\"o}ri, Kamilla and Jarkas, Muhammad and L{\´o}di, M{\´a}ria and Jaquet, Kornelia and Kov{\´a}cs, {\´A}rp{\´a}d and Mannherz, Hans Georg and Sequeira, Vasco and M{\"u}gge, Andreas and Leichert, Lars I. and Sossalla, Samuel and Hamdani, Nazha},
  title     = {The interplay between S-glutathionylation and phosphorylation of cardiac troponin I and myosin binding protein C in end-stage human failing hearts},
  series = {Antioxidants},
  volume    = {10},
  journal   = {Antioxidants},
  number    = {7},
  issn      = {2076-3921},
  doi       = {10.3390/antiox10071134},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242701},
  year      = {2021},
  abstract  = {Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell damage occurs, due to protein, DNA and lipid oxidation. Here, we investigated the oxidative modifications of myofilament proteins, and their role in modulating cardiomyocyte function in end-stage human failing hearts. We found altered maximum Ca\(^{2+}\)-activated tension and Ca\(^{2+}\) sensitivity of force production of skinned single cardiomyocytes in end-stage human failing hearts compared to non-failing hearts, which was corrected upon treatment with reduced glutathione enzyme. This was accompanied by the increased oxidation of troponin I and myosin binding protein C, and decreased levels of protein kinases A (PKA)- and C (PKC)-mediated phosphorylation of both proteins. The Ca\(^{2+}\) sensitivity and maximal tension correlated strongly with the myofilament oxidation levels, hypo-phosphorylation, and oxidative stress parameters that were measured in all the samples. Furthermore, we detected elevated titin-based myocardial stiffness in HF myocytes, which was reversed by PKA and reduced glutathione enzyme treatment. Finally, many oxidative stress and inflammation parameters were significantly elevated in failing hearts compared to non-failing hearts, and corrected upon treatment with the anti-oxidant GSH enzyme. Here, we provide evidence that the altered mechanical properties of failing human cardiomyocytes are partially due to phosphorylation, S-glutathionylation, and the interplay between the two post-translational modifications, which contribute to the development of heart failure.},
  language  = {en}
}
@article{SahitiMorbachCejkaetal.2021,
  author    = {Sahiti, Floran and Morbach, Caroline and Cejka, Vladimir and Albert, Judith and Eichner, Felizitas A. and Gelbrich, G{\"o}tz and Heuschmann, Peter U. and St{\"o}rk, Stefan},
  title     = {Left Ventricular Remodeling and Myocardial Work: Results From the Population-Based STAAB Cohort Study},
  series = {Frontiers in Cardiovascular Medicine},
  volume    = {8},
  journal   = {Frontiers in Cardiovascular Medicine},
  issn      = {2297-055X},
  doi       = {10.3389/fcvm.2021.669335},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240480},
  year      = {2021},
  abstract  = {Introduction: Left ventricular (LV) dilatation and LV hypertrophy are acknowledged precursors of myocardial dysfunction and ultimately of heart failure, but the implications of abnormal LV geometry on myocardial function are not well-understood. Non-invasive LV myocardial work (MyW) assessment based on echocardiography-derived pressure-strain loops offers the opportunity to study detailed myocardial function in larger cohorts. We aimed to assess the relationship of LV geometry with MyW indices in general population free from heart failure. Methods and Results: We report cross-sectional baseline data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of the general population of W{\"u}rzburg, Germany, aged 30-79 years. MyW analysis was performed in 1,926 individuals who were in sinus rhythm and free from valvular disease (49.3\% female, 54 ± 12 years). In multivariable regression, higher LV volume was associated with higher global wasted work (GWW) (+0.5 mmHg\% per mL/m\(^2\), p < 0.001) and lower global work efficiency (GWE) (-0.02\% per mL/m\(^2\), p < 0.01), while higher LV mass was associated with higher GWW (+0.45 mmHg\% per g/m\(^2\), p < 0.001) and global constructive work (GCW) (+2.05 mmHg\% per g/m\(^2\), p < 0.01) and lower GWE (-0.015\% per g/m\(^2\), p < 0.001). This was dominated by the blood pressure level and also observed in participants with normal LV geometry and concomitant hypertension. Conclusion: Abnormal LV geometric profiles were associated with a higher amount of wasted work, which translated into reduced work efficiency. The pattern of a disproportionate increase in GWW with higher LV mass might be an early sign of hypertensive heart disease.},
  language  = {en}
}
@article{FuchsEdenGilbertetal.2021,
  author    = {Fuchs, Konrad F. and Eden, Lars and Gilbert, Fabian and Bernuth, Silvia and Wurmb, Thomas and Meffert, Rainer H. and Jordan, Martin C.},
  title     = {F{\"u}hrt eine COVID-19 bedingte Ausgangsbeschr{\"a}nkung zu einer Reduktion schwerverletzter Patienten an einem {\"u}berregionalen Traumazentrum?},
  series = {Der Unfallchirurg},
  volume    = {124},
  journal   = {Der Unfallchirurg},
  issn      = {0177-5537},
  doi       = {10.1007/s00113-020-00924-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232547},
  pages     = {352-357},
  year      = {2021},
  abstract  = {Hintergrund Intensiv- und Beatmungskapazit{\"a}ten sind f{\"u}r die Behandlung COVID-19-erkrankter Patienten essenziell. Unabh{\"a}ngig davon beanspruchen auch schwer verletzte Patienten h{\"a}ufig Intensiv- und Beatmungskapazit{\"a}ten. Daraus ergibt sich folgende Fragestellung: F{\"u}hrt eine Ausgangsbeschr{\"a}nkung zu einer Reduktion schwer verletzter Patienten, und kann hierdurch mit frei werdenden Intensivkapazit{\"a}ten gerechnet werden? Material und Methoden Es erfolgte eine retrospektive Auswertung schwer verletzter Patienten mit einem Injury Severity Score (ISS) ≥16 zwischen dem 17.03.2020 und 30.04.2020 (landesweiter Shutdown) an einem {\"u}berregionalen Traumazentrum. Erfasst wurden der Unfallmechanismus, ISS, Versicherungstr{\"a}ger (BG vs. GKV/PKV), ob es sich um einen dokumentierten Suizidversuch handelte, und ob eine operative Intervention innerhalb der ersten 24 h erforderlich war. Als Kontrollgruppe wurden die Daten des gleichen Zeitraums der Jahre 2018 und 2019 ausgewertet. Ergebnisse Es konnte keine wesentliche Ver{\"a}nderung bez{\"u}glich der Anzahl an schwer verletzten Patienten festgestellt werden (2018 n = 30, 2019 n = 23, 2020 n = 27). Es zeigten sich insgesamt keine deutlichen Ver{\"a}nderungen der absoluten Zahlen bez{\"u}glich der Intensivpflichtigkeit in den ersten 24 h und der Beatmungspflichtigkeit beim Verlassen des Schockraums. Die Anzahl an Patienten, die eine Operation innerhalb der ersten 24 h nach Eintreffen im Schockraum ben{\"o}tigten, war 2020 sogar leicht erh{\"o}ht, jedoch nicht statistisch signifikant. Der durchschnittliche ISS blieb konstant. Bez{\"u}glich der Unfallursache zeigte sich 2020 kein Motorradfahrer, der einen nicht berufsgenossenschaftlich versicherten Unfall erlitt (2018 n = 5, 2019 n = 4, 2020 n = 0). Es wurde 2020 ein erh{\"o}hter Anteil an Arbeitsunf{\"a}llen mit einem ISS ≥16 festgestellt (2018: 10 \%, 2019: 26,1 \%, 2020: 44,4 \%). Diskussion Eine Ausgangsbeschr{\"a}nkung f{\"u}hrte zu keiner Reduktion verletzter- und intensivpflichtiger Patienten am untersuchten Zentrum. Auch unter einer landesweiten Ausgangsbeschr{\"a}nkung muss f{\"u}r dieses Patientenkollektiv eine ausreichende Menge an Intensiv- und OP-Kapazit{\"a}ten vorgehalten werden. Die Best{\"a}tigung dieser Ergebnisse durch Auswertung nationaler Register steht noch aus.},
  language  = {de}
}
@article{AvotaBodemChithelenetal.2021,
  author    = {Avota, Elita and Bodem, Jochen and Chithelen, Janice and Mandasari, Putri and Beyersdorf, Niklas and Schneider-Schaulies, J{\"u}rgen},
  title     = {The Manifold Roles of Sphingolipids in Viral Infections},
  series = {Frontiers in Physiology},
  volume    = {12},
  journal   = {Frontiers in Physiology},
  issn      = {1664-042X},
  doi       = {10.3389/fphys.2021.715527},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246975},
  year      = {2021},
  abstract  = {Sphingolipids are essential components of eukaryotic cells. In this review, we want to exemplarily illustrate what is known about the interactions of sphingolipids with various viruses at different steps of their replication cycles. This includes structural interactions during entry at the plasma membrane or endosomal membranes, early interactions leading to sphingolipid-mediated signal transduction, interactions with internal membranes and lipids during replication, and interactions during virus assembly and budding. Targeted interventions in sphingolipid metabolism - as far as they can be tolerated by cells and organisms - may open novel possibilities to support antiviral therapies. Human immunodeficiency virus type 1 (HIV-1) infections have intensively been studied, but for other viral infections, such as influenza A virus (IAV), measles virus (MV), hepatitis C virus (HCV), dengue virus, Ebola virus, and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), investigations are still in their beginnings. As many inhibitors of sphingolipid metabolism are already in clinical use against other diseases, repurposing studies for applications in some viral infections appear to be a promising approach.},
  language  = {en}
}
@article{ZwirnerBohnertFrankeetal.2021,
  author    = {Zwirner, Johann and Bohnert, Simone and Franke, Heike and Garland, Jack and Hammer, Niels and M{\"o}bius, Dustin and Tse, Rexson and Ondruschka, Benjamin},
  title     = {Assessing protein biomarkers to detect lethal acute traumatic brain injuries in cerebrospinal fluid},
  series = {Biomolecules},
  volume    = {11},
  journal   = {Biomolecules},
  number    = {11},
  issn      = {2218-273X},
  doi       = {10.3390/biom11111577},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248587},
  year      = {2021},
  abstract  = {Diagnosing traumatic brain injury (TBI) from body fluids in cases where there are no obvious external signs of impact would be useful for emergency physicians and forensic pathologists alike. None of the previous attempts has so far succeeded in establishing a single biomarker to reliably detect TBI with regards to the sensitivity: specificity ratio in a post mortem setting. This study investigated a combination of body fluid biomarkers (obtained post mortem), which may be a step towards increasing the accuracy of biochemical TBI detection. In this study, serum and cerebrospinal fluid (CSF) samples from 30 acute lethal TBI cases and 70 controls without a TBI-related cause of death were evaluated for the following eight TBI-related biomarkers: brain-derived neurotrophic factor (BDNF), ferritin, glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), lactate dehydrogenase, neutrophil gelatinase-associated lipocalin (NGAL), neuron-specific enolase and S100 calcium-binding protein B. Correlations among the individual TBI biomarkers were assessed, and a specificity-accentuated threshold value analysis was conducted for all biomarkers. Based on these values, a decision tree modelling approach was performed to assess the most accurate biomarker combination to detect acute lethal TBIs. The results showed that 92.45\% of acute lethal TBIs were able to be diagnosed using a combination of IL-6 and GFAP in CSF. The probability of detecting an acute lethal TBI was moderately increased by GFAP alone and considerably increased by the remaining biomarkers. BDNF and NGAL were almost perfectly correlated (p = 0.002; R\(^2\) = 0.944). This study provides evidence that acute lethal TBIs can be detected to a high degree of statistical accuracy using forensic biochemistry. The high inter-individual correlations of biomarkers may help to estimate the CSF concentration of an unknown biomarker, using extrapolation techniques.},
  language  = {en}
}
@article{KadeOttoLuxenhoferetal.2021,
  author    = {Kade, Juliane C. and Otto, Paul F. and Luxenhofer, Robert and Dalton, Paul D.},
  title     = {Melt electrowriting of poly(vinylidene difluoride) using a heated collector},
  series = {Polymers for Advanced Technologies},
  volume    = {32},
  journal   = {Polymers for Advanced Technologies},
  number    = {12},
  issn      = {1042-7147},
  doi       = {10.1002/pat.5463},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318493},
  pages     = {4951 -- 4955},
  year      = {2021},
  abstract  = {Previous research on the melt electrowriting (MEW) of poly(vinylidene difluoride) (PVDF) resulted in electroactive fibers, however, printing more than five layers is challenging. Here, we investigate the influence of a heated collector to adjust the solidification rate of the PVDF jet so that it adheres sufficiently to each layer. A collector temperature of 110°C is required to improve fiber processing, resulting in a total of 20 fiber layers. For higher temperatures and higher layers, an interesting phenomenon occurred, where the intersection points of the fibers coalesced into periodic spheres of diameter 206 ± 52 μm (26G, 150°C collector temperature, 2000 mm/min, 10 layers in x- and y-direction).The heated collector is an important component of a MEW printer that allows polymers with a high melting point to be processable with increased layers.},
  language  = {en}
}
@article{ZimniakKirschnerHilpertetal.2021,
  author    = {Zimniak, Melissa and Kirschner, Luisa and Hilpert, Helen and Geiger, Nina and Danov, Olga and Oberwinkler, Heike and Steinke, Maria and Sewald, Katherina and Seibel, J{\"u}rgen and Bodem, Jochen},
  title     = {The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-021-85049-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259820},
  pages     = {5890},
  year      = {2021},
  abstract  = {To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications "off-label" against SARS-CoV-2. Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8 mu g/ml significantly in these screenings, and the EC50 was determined with 387 ng/ml. Furthermore, Fluoxetine reduced viral infectivity in precision-cut human lung slices showing its activity in relevant human tissue targeted in severe infections. Fluoxetine treatment resulted in a decrease in viral protein expression. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus, indicating that the R-form might specifically be used for SARS-CoV-2 treatment. Fluoxetine inhibited neither Rabies virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex virus type 1 gene expression, indicating that it acts virus-specific. Moreover, since it is known that Fluoxetine inhibits cytokine release, we see the role of Fluoxetine in the treatment of SARS-CoV-2 infected patients of risk groups.},
  language  = {en}
}
@article{DoryabTaskinStahlhutetal.2021,
  author    = {Doryab, Ali and Taskin, Mehmet Berat and Stahlhut, Philipp and Schr{\"o}ppel, Andreas and Orak, Sezer and Voss, Carola and Ahluwalia, Arti and Rehberg, Markus and Hilgendorff, Anne and St{\"o}ger, Tobias and Groll, J{\"u}rgen and Schmid, Otmar},
  title     = {A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions},
  series = {Frontiers in Bioengineering and Biotechnology},
  volume    = {9},
  journal   = {Frontiers in Bioengineering and Biotechnology},
  issn      = {2296-4185},
  doi       = {10.3389/fbioe.2021.616830},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223830},
  year      = {2021},
  abstract  = {Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m\(^{2}\)) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) "breathing" lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o\(^{-}\)) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35\% PCL and 6.34\% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10\% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung.},
  language  = {en}
}
@article{ZioutiRummlerSteynetal.2021,
  author    = {Ziouti, Fani and Rummler, Maximilian and Steyn, Beatrice and Thiele, Tobias and Seliger, Anne and Duda, Georg N. and Bogen, Bjarne and Willie, Bettina M. and Jundt, Franziska},
  title     = {Prevention of bone destruction by mechanical loading is not enhanced by the Bruton's tyrosine kinase inhibitor CC-292 in myeloma bone disease},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {8},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22083840},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284943},
  year      = {2021},
  abstract  = {Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton's tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD.},
  language  = {en}
}
@article{BenKraiemSauerNorwigetal.2021,
  author    = {Ben-Kraiem, Adel and Sauer, Reine-Solange and Norwig, Carla and Popp, Maria and Bettenhausen, Anna-Lena and Atalla, Mariam Sobhy and Brack, Alexander and Blum, Robert and Doppler, Kathrin and Rittner, Heike Lydia},
  title     = {Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy},
  series = {Journal of Molecular Medicine},
  volume    = {99},
  journal   = {Journal of Molecular Medicine},
  number    = {9},
  doi       = {10.1007/s00109-021-02091-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265237},
  pages     = {1237-1250},
  year      = {2021},
  abstract  = {Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26\% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN. In this study, we analyzed the spatiotemporal tight junction protein profile, barrier permeability, and vessel-associated macrophages in Wistar rats with streptozotocin-induced DPN. In these rats, mechanical hypersensitivity developed after 2 weeks and loss of motor function after 8 weeks, while the BNB and the blood-DRG barrier were leakier for small, but not for large molecules after 8 weeks only. The blood-spinal cord barrier remained sealed throughout the observation period. No gross changes in tight junction protein or cytokine expression were observed in all barriers to blood. However, expression of Cldn1 mRNA in perineurium was specifically downregulated in conjunction with weaker vessel-associated macrophage shielding of the BNB. Our results underline the role of specific tight junction proteins and BNB breakdown in DPN maintenance and differentiate DPN from traumatic nerve injury. Targeting claudins and sealing the BNB could stabilize pain and prevent further nerve damage.},
  language  = {en}
}
@article{BrumbergKuzkinaLapaetal.2021,
  author    = {Brumberg, Joachim and Kuzkina, Anastasia and Lapa, Constantin and Mammadova, Sona and Buck, Andreas and Volkmann, Jens and Sommer, Claudia and Isaias, Ioannis U. and Doppler, Kathrin},
  title     = {Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy},
  series = {Neurobiology of Disease},
  volume    = {153},
  journal   = {Neurobiology of Disease},
  doi       = {10.1016/j.nbd.2021.105332},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260061},
  pages     = {105332},
  year      = {2021},
  abstract  = {Pathological aggregates of alpha-synuclein in peripheral dermal nerve fibers can be detected in patients with idiopathic Parkinson's disease and multiple system atrophy. This study combines skin biopsy staining for p-alpha-synuclein depositions and radionuclide imaging of the heart with [\(^{123}\)I]-metaiodobenzylguanidine to explore peripheral denervation in both diseases. To this purpose, 42 patients with a clinical diagnosis of Parkinson's disease or multiple system atrophy were enrolled. All patients underwent a standardized clinical workup including neurological evaluation, neurography, and blood samples. Skin biopsies were obtained from the distal and proximal leg, back, and neck for immunofluorescence double labeling with anti-p-alpha-synuclein and anti-PGP9.5. All patients underwent myocardial [\(^{123}\)I]-metaiodobenzylguanidine scintigraphy. Dermal p-alpha-synuclein was observed in 47.6\% of Parkinson's disease patients and was mainly found in autonomic structures. 81.0\% of multiple system atrophy patients had deposits with most of cases in somatosensory fibers. The [\(^{123}\)I]-metaiodobenzylguanidine heart-to-mediastinum ratio was lower in Parkinson's disease than in multiple system atrophy patients (1.94 +/- 0.63 vs. 2.91 +/- 0.96; p < 0.0001). Irrespective of the diagnosis, uptake was lower in patients with than without p-alpha-synuclein in autonomic structures (1.42 +/- 0.51 vs. 2.74 +/- 0.83; p < 0.0001). Rare cases of Parkinson's disease with p-alpha-synuclein in somatosensory fibers and multiple system atrophy patients with deposits in autonomic structures or both fiber types presented with clinically overlapping features. In conclusion, this study suggests that alpha-synuclein contributes to peripheral neurodegeneration and mediates the impairment of cardiac sympathetic neurons in patients with synucleinopathies. Furthermore, it indicates that Parkinson's disease and multiple system atrophy share pathophysiologic mechanisms of peripheral nervous system dysfunction with a clinical overlap.},
  language  = {en}
}
@article{SeifertGrollWeichholdetal.2021,
  author    = {Seifert, Annika and Groll, J{\"u}rgen and Weichhold, Jan and Boehm, Anne V. and M{\"u}ller, Frank A. and Gbureck, Uwe},
  title     = {Phase Conversion of Ice-Templated α-Tricalcium Phosphate Scaffolds into Low-Temperature Calcium Phosphates with Anisotropic Open Porosity},
  series = {Advanced Engineering Materials},
  volume    = {23},
  journal   = {Advanced Engineering Materials},
  number    = {5},
  doi       = {10.1002/adem.202001417},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256311},
  year      = {2021},
  abstract  = {The current study aims to extend the material platform for anisotropically structured calcium phosphates to low-temperature phases such as calcium-deficient hydroxyapatite (CDHA) or the secondary phosphates monetite and brushite. This is achieved by the phase conversion of highly porous α-tricalcium phosphate (α-TCP) scaffolds fabricated by ice-templating into the aforementioned phases by hydrothermal treatment or incubation in phosphoric acid. Prior to these steps, α-TCP scaffolds are either sintered for 8 h at 1400 °C or remain in their original state. Both nonsintered and sintered α-TCP specimens are converted into CDHA by hydrothermal treatment, while a transformation into monetite and brushite is achieved by incubation in phosphoric acid. Hydrothermal treatment for 72 h at 175 °C increases the porosity in nonsintered samples from 85\% to 88\% and from 75\% to 88\% in the sintered ones. An increase in the specific surface area from (1.102 ± 0.005) to (9.17 ± 0.01) m2 g-1 and from (0.190 ± 0.004) to (2.809 ± 0.002) m2 g-1 due to the phase conversion is visible for both the nonsintered and sintered samples. Compressive strength of the nonsintered samples increases significantly from (0.76 ± 0.11) to (5.29 ± 0.94) MPa due to incubation in phosphoric acid.},
  language  = {en}
}
@article{MachataSreekantapuramHuennigeretal.2021,
  author    = {Machata, Silke and Sreekantapuram, Sravya and H{\"u}nniger, Kerstin and Kurzai, Oliver and Dunker, Christine and Schubert, Katja and Kr{\"u}ger, Wibke and Schulze-Richter, Bianca and Speth, Cornelia and Rambach, G{\"u}nter and Jacobsen, Ilse D.},
  title     = {Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood},
  series = {Frontiers in Immunology},
  volume    = {11},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2020.565869},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222575},
  year      = {2021},
  abstract  = {Murine infection models are widely used to study systemic candidiasis caused by C. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for several Candida species in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation of C. albicans was observed. This coincided with less fungal association with leukocytes, especially neutrophils. The lower neutrophil number in murine blood only partially explains insufficient infection and filamentation control, as spiking with murine neutrophils had only limited effects on fungal killing. Furthermore, increased fungal survival is not mediated by enhanced filamentation, as a filament-deficient mutant was likewise not eliminated. We also observed host-dependent differences for interaction of platelets with C. albicans, showing enhanced platelet aggregation, adhesion and activation in murine blood. For human blood, opsonization was shown to decrease platelet interaction suggesting that complement factors interfere with fungus-to-platelet binding. Our results reveal substantial differences between murine and human whole-blood models infected with C. albicans and thereby demonstrate limitations in the translatability of this ex vivo model between hosts.},
  language  = {en}
}
@article{ShemerMekiesBenJehudaetal.2021,
  author    = {Shemer, Yuval and Mekies, Lucy N. and Ben Jehuda, Ronen and Baskin, Polina and Shulman, Rita and Eisen, Binyamin and Regev, Danielle and Arbustini, Eloisa and Gerull, Brenda and Gherghiceanu, Mihaela and Gottlieb, Eyal and Arad, Michael and Binah, Ofer},
  title     = {Investigating LMNA-related dilated cardiomyopathy using human induced Pluripotent Stem Cell-derived cardiomyocytes},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {15},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22157874},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285673},
  year      = {2021},
  abstract  = {LMNA-related dilated cardiomyopathy is an inherited heart disease caused by mutations in the LMNA gene encoding for lamin A/C. The disease is characterized by left ventricular enlargement and impaired systolic function associated with conduction defects and ventricular arrhythmias. We hypothesized that LMNA-mutated patients' induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) display electrophysiological abnormalities, thus constituting a suitable tool for deciphering the arrhythmogenic mechanisms of the disease, and possibly for developing novel therapeutic modalities. iPSC-CMs were generated from two related patients (father and son) carrying the same E342K mutation in the LMNA gene. Compared to control iPSC-CMs, LMNA-mutated iPSC-CMs exhibited the following electrophysiological abnormalities: (1) decreased spontaneous action potential beat rate and decreased pacemaker current (I\(_f\)) density; (2) prolonged action potential duration and increased L-type Ca\(^{2+}\) current (I\(_{Ca,L}\)) density; (3) delayed afterdepolarizations (DADs), arrhythmias and increased beat rate variability; (4) DADs, arrhythmias and cessation of spontaneous firing in response to β-adrenergic stimulation and rapid pacing. Additionally, compared to healthy control, LMNA-mutated iPSC-CMs displayed nuclear morphological irregularities and gene expression alterations. Notably, KB-R7943, a selective inhibitor of the reverse-mode of the Na\(^+\)/Ca\(^{2+}\) exchanger, blocked the DADs in LMNA-mutated iPSC-CMs. Our findings demonstrate cellular electrophysiological mechanisms underlying the arrhythmias in LMNA-related dilated cardiomyopathy.},
  language  = {en}
}
@article{MegasSimonsKimetal.2021,
  author    = {Megas, Ioannis-Fivos and Simons, David and Kim, Bong-Sung and Stoppe, Christian and Piatkowski, Andrzej and Fikatas, Panagiotis and Fuchs, Paul Christian and Bastiaanse, Jacqueline and Pallua, Norbert and Bernhagen, J{\"u}rgen and Grieb, Gerrit},
  title     = {Macrophage migration inhibitory factor — an innovative indicator for free flap ischemia after microsurgical reconstruction},
  series = {Healthcare},
  volume    = {9},
  journal   = {Healthcare},
  number    = {6},
  issn      = {2227-9032},
  doi       = {10.3390/healthcare9060616},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239632},
  year      = {2021},
  abstract  = {(1) Background: Nowadays, the use of microsurgical free flaps is a standard operative procedure in reconstructive surgery. Still, thrombosis of the microanastomosis is one of the most fatal postoperative complications. Clinical evaluation, different technical devices and laboratory markers are used to monitor critical flap perfusion. Macrophage migration inhibitory factor (MIF), a structurally unique cytokine with chemokine-like characteristics, could play a role in predicting vascular problems and the failure of flap perfusion. (2) Methods: In this prospective observational study, 26 subjects that underwent microsurgical reconstruction were observed. Besides clinical data, the number of blood leukocytes, CRP and MIF were monitored. (3) Results: Blood levels of MIF, C-reactive protein (CRP) and leukocytes increased directly after surgery. Subjects that needed surgical revision due to thrombosis of the microanastomosis showed significantly higher blood levels of MIF than subjects without revision. (4) Conclusion: We conclude that MIF is a potential and innovative indicator for thrombosis of the microanastomosis after free flap surgery. Since it is easy to obtain diagnostically, MIF could be an additional tool to monitor flap perfusion besides clinical and technical assessments.},
  language  = {en}
}