@article{WallaschekReuterSilkenatetal.2021,
  author    = {Wallaschek, Nina and Reuter, Saskia and Silkenat, Sabrina and Wolf, Katharina and Niklas, Carolin and {\"O}zge, Kayisoglu and Aguilar, Carmen and Wiegering, Armin and Germer, Christoph-Thomas and Kircher, Stefan and Rosenwald, Andreas and Shannon-Lowe, Claire and Bartfeld, Sina},
  title     = {Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids},
  series = {PLoS Pathogens},
  volume    = {17},
  journal   = {PLoS Pathogens},
  number    = {2},
  doi       = {10.1371/journal.ppat.1009210},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259206},
  pages     = {e1009210},
  year      = {2021},
  abstract  = {Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8\% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection.},
  language  = {en}
}
@article{DrozdSaenkoBranovanetal.2021,
  author    = {Drozd, Valentina and Saenko, Vladimir and Branovan, Daniel I. and Brown, Kate and Yamashita, Shunichi and Reiners, Christoph},
  title     = {A search for causes of rising incidence of differentiated thyroid cancer in children and adolescents after Chernobyl and Fukushima: comparison of the clinical features and their relevance for treatment and prognosis},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {18},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {7},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph18073444},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234247},
  year      = {2021},
  abstract  = {The incidence of differentiated thyroid cancer (DTC) is steadily increasing globally. Epidemiologists usually explain this global upsurge as the result of new diagnostic modalities, screening and overdiagnosis as well as results of lifestyle changes including obesity and comorbidity. However, there is evidence that there is a real increase of DTC incidence worldwide in all age groups. Here, we review studies on pediatric DTC after nuclear accidents in Belarus after Chernobyl and Japan after Fukushima as compared to cohorts without radiation exposure of those two countries. According to the Chernobyl data, radiation-induced DTC may be characterized by a lag time of 4-5 years until detection, a higher incidence in boys, in children of youngest age, extrathyroidal extension and distant metastases. Radiation doses to the thyroid were considerably lower by appr. two orders of magnitude in children and adolescents exposed to Fukushima as compared to Chernobyl. In DTC patients detected after Fukushima by population-based screening, most of those characteristics were not reported, which can be taken as proof against the hypothesis, that radiation is the (main) cause of those tumors. However, roughly 80\% of the Fukushima cases presented with tumor stages higher than microcarcinomas pT1a and 80\% with lymph node metastases pN1. Mortality rates in pediatric DTC patients are generally very low, even at higher tumor stages. However, those cases considered to be clinically relevant should be followed-up carefully after treatment because of the risk of recurrencies which is expected to be not negligible. Considering that thyroid doses from the Fukushima accident were quite small, it makes sense to assess the role of other environmental and lifestyle-related factors in thyroid carcinogenesis. Well-designed studies with assessment of radiation doses from medical procedures and exposure to confounders/modifiers from the environment as e.g., nitrate are required to quantify their combined effect on thyroid cancer risk.},
  language  = {en}
}
@article{KleinertHillermannJablonkaetal.2021,
  author    = {Kleinert, Evelyn and Hillermann, Nele and Jablonka, Alexandra and Happle, Christine and M{\"u}ller, Frank and Simmenroth, Anne},
  title     = {Prescription of antibiotics in the medical care of newly arrived refugees and migrants},
  series = {Pharmacoepidemiology and Drug Safety},
  volume    = {30},
  journal   = {Pharmacoepidemiology and Drug Safety},
  number    = {8},
  doi       = {10.1002/pds.5254},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244771},
  pages     = {1074 -- 1083},
  year      = {2021},
  abstract  = {Purpose Unnecessary and inappropriate use of antibiotics is a widespread problem in primary care. However, current data on the care of refugees and migrants in initial reception centers is pending. This article provides data on prescription frequencies of various antibiotics and associated diagnoses. Methods In this retrospective observational study, patient data of 3255 patients with 6376 medical contacts in two initial reception centers in Germany were analyzed. Patient data, collected by chart review, included sociodemographic characteristics, diagnoses, and prescriptions. Antibiotic prescription behavior and corresponding physician-coded diagnoses were analyzed. Results Nineteen percent of all patients in our study received systemic antibiotics during the observation period, with children below the age of 10 years receiving antibiotics most frequently (24\%). The most commonly prescribed antibiotics were penicillins (65\%), macrolides (12\%), and cephalosporins (7\%). The most frequent diagnoses associated with antibiotic prescription were acute tonsillitis (26\%), bronchitis (21\%), infections of the upper respiratory tract (14\%), and urinary tract infections (10\%). In case of acute bronchitis 74\% of the antibiotic prescriptions were probably not indicated. In addition, we found a significant number of inappropriate prescriptions such as amoxicillin for tonsillitis (67\%), and ciprofloxacin and cotrimoxazol for urinary tract infections (49\%). Conclusion Regarding inappropriate prescription of antibiotics in refugee healthcare, this study shows a rate ranging from 8\% for upper respiratory tract infections to 75\% for acute bronchitis. Unnecessary use of antibiotics is a global problem contributing to gratuitous costs, side effects, and antimicrobial resistance. This research contributes to the development of stringent antibiotic stewardship regiments in the particularly vulnerable population of migrants and refugees.},
  language  = {en}
}
@article{BohnertWirthSchmitzetal.2021,
  author    = {Bohnert, Simone and Wirth, Christoph and Schmitz, Werner and Trella, Stefanie and Monoranu, Camelia-Maria and Ondruschka, Benjamin and Bohnert, Michael},
  title     = {Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury},
  series = {International Journal of Legal Medicine},
  volume    = {135},
  journal   = {International Journal of Legal Medicine},
  number    = {4},
  issn      = {1437-1596},
  doi       = {10.1007/s00414-021-02606-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266929},
  pages     = {1525-1535},
  year      = {2021},
  abstract  = {The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.},
  language  = {en}
}
@article{HoffmannEbertHankiretal.2021,
  author    = {Hoffmann, Annett and Ebert, Thomas and Hankir, Mohammed K. and Flehmig, Gesine and Kl{\"o}ting, Nora and Jessnitzer, Beate and L{\"o}ssner, Ulrike and Stumvoll, Michael and Bl{\"u}her, Matthias and Fasshauer, Mathias and T{\"o}njes, Anke and Miehle, Konstanze and Kralisch, Susan},
  title     = {Leptin improves parameters of brown adipose tissue thermogenesis in lipodystrophic mice},
  series = {Nutrients},
  volume    = {13},
  journal   = {Nutrients},
  number    = {8},
  issn      = {2072-6643},
  doi       = {10.3390/nu13082499},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242787},
  year      = {2021},
  abstract  = {Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the dysregulation of several key adipokines, including leptin. Treatment with leptin or its analogues is therefore sufficient to reverse some of the metabolic symptoms of LD in patients and in mouse models through distinct mechanisms. Brown adipose tissue (BAT) thermogenesis has emerged as an important regulator of systemic metabolism in rodents and in humans, but it is poorly understood how leptin impacts BAT in LD. Here, we show in transgenic C57Bl/6 mice overexpressing sterol regulatory element-binding protein 1c in adipose tissue (Tg (aP2-nSREBP1c)), an established model of congenital LD, that daily subcutaneous administration of 3 mg/kg leptin for 6 to 8 weeks increases body temperature without affecting food intake or body weight. This is associated with increased protein expression of the thermogenic molecule uncoupling protein 1 (UCP1) and the sympathetic nerve marker tyrosine hydroxylase (TH) in BAT. These findings suggest that leptin treatment in LD stimulates BAT thermogenesis through sympathetic nerves, which might contribute to some of its metabolic benefits by providing a healthy reservoir for excess circulating nutrients.},
  language  = {en}
}
@article{ZhouBaiMeckeletal.2021,
  author    = {Zhou, Xiang and Bai, Tao and Meckel, Katharina and Song, Jun and Jin, Yu and Kort{\"u}m, Martin K. and Eisele, Hermann and Hou, Xiaohua and Rasche, Leo},
  title     = {COVID-19 infection in patients with multiple myeloma: a German-Chinese experience from W{\"u}rzburg and Wuhan},
  series = {Annals of Hematology},
  volume    = {100},
  journal   = {Annals of Hematology},
  issn      = {0939-5555},
  doi       = {10.1007/s00277-020-04184-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235108},
  pages     = {843-846},
  year      = {2021},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{HeuschmannMontellanoUngethuemetal.2021,
  author    = {Heuschmann, Peter U. and Montellano, Felipe A. and Ungeth{\"u}m, Kathrin and R{\"u}cker, Viktoria and Wiedmann, Silke and Mackenrodt, Daniel and Quilitzsch, Anika and Ludwig, Timo and Kraft, Peter and Albert, Judith and Morbach, Caroline and Frantz, Stefan and St{\"o}rk, Stefan and Haeusler, Karl Georg and Kleinschnitz, Christoph},
  title     = {Prevalence and determinants of systolic and diastolic cardiac dysfunction and heart failure in acute ischemic stroke patients: The SICFAIL study},
  series = {ESC Heart Failure},
  volume    = {8},
  journal   = {ESC Heart Failure},
  number    = {2},
  doi       = {10.1002/ehf2.13145},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225656},
  pages     = {1117-1129},
  year      = {2021},
  abstract  = {Aims Ischaemic stroke (IS) might induce alterations of cardiac function. Prospective data on frequency of cardiac dysfunction and heart failure (HF) after IS are lacking. We assessed prevalence and determinants of diastolic dysfunction (DD), systolic dysfunction (SD), and HF in patients with acute IS. Methods and results The Stroke-Induced Cardiac FAILure in mice and men (SICFAIL) study is a prospective, hospital-based cohort study. Patients with IS underwent a comprehensive assessment of cardiac function in the acute phase (median 4 days after IS) including clinical examination, standardized transthoracic echocardiography by expert sonographers, and determination of blood-based biomarkers. Information on demographics, lifestyle, risk factors, symptoms suggestive of HF, and medical history was collected by a standardized personal interview. Applying current guidelines, cardiac dysfunction was classified based on echocardiographic criteria into SD (left ventricular ejection fraction < 52\% in men or <54\% in women) and DD (≥3 signs of DD in patients without SD). Clinically overt HF was classified into HF with reduced, mid-range, or preserved ejection fraction. Between January 2014 and February 2017, 696 IS patients were enrolled. Of them, patients with sufficient echocardiographic data on SD were included in the analyses {n = 644 patients [median age 71 years (interquartile range 60-78), 61.5\% male]}. In these patients, full assessment of DD was feasible in 549 patients without SD (94\%). Prevalence of cardiac dysfunction and HF was as follows: SD 9.6\% [95\% confidence interval (CI) 7.6-12.2\%]; DD in patients without SD 23.3\% (95\% CI 20.0-27.0\%); and clinically overt HF 5.4\% (95\% CI 3.9-7.5\%) with subcategories of HF with preserved ejection fraction 4.35\%, HF with mid-range ejection fraction 0.31\%, and HF with reduced ejection fraction 0.78\%. In multivariable analysis, SD and fulfilment of HF criteria were associated with history of coronary heart disease [SD: odds ratio (OR) 3.87, 95\% CI 1.93-7.75, P = 0.0001; HF: OR 2.29, 95\% CI 1.04-5.05, P = 0.0406] and high-sensitive troponin T at baseline (SD: OR 1.78, 95\% CI 1.31-2.42, P = 0.0003; HF: OR 1.66, 95\% CI 1.17-2.33, P = 0.004); DD was associated with older age (OR 1.08, 95\% CI 1.05-1.11, P < 0.0001) and treated hypertension vs. no hypertension (OR 2.84, 95\% CI 1.23-6.54, P = 0.0405). Conclusions A substantial proportion of the study population exhibited subclinical and clinical cardiac dysfunction. SICFAIL provides reliable data on prevalence and determinants of SD, DD, and clinically overt HF in patients with acute IS according to current guidelines, enabling further clarification of its aetiological and prognostic role.},
  language  = {en}
}
@article{KamaliRajendranStadelmannetal.2021,
  author    = {Kamali, Salar and Rajendran, Ranjithkumar and Stadelmann, Christine and Karnati, Srikanth and Rajendran, Vinothkumar and Giraldo-Velasquez, Mario and Berghoff, Martin},
  title     = {Oligodendrocyte-specific deletion of FGFR2 ameliorates MOG\(_{35-55}\)-induced EAE through ERK and Akt signalling},
  series = {Brain Pathology},
  volume    = {31},
  journal   = {Brain Pathology},
  doi       = {10.1111/bpa.12916},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224354},
  pages     = {297 -- 311},
  year      = {2021},
  abstract  = {Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies including multiple sclerosis (MS). In our recent study, oligodendrocyte-specific deletion of FGFR1 resulted in a milder disease course, less inflammation, reduced myelin and axon damage in EAE. The objective of this study was to elucidate the role of oligodendroglial FGFR2 in MOG\(_{35-55}\)-induced EAE. Oligodendrocyte-specific knockout of FGFR2 (Fgfr2\(^{ind-/-}\)) was achieved by application of tamoxifen; EAE was induced using the MOG\(_{35-55}\) peptide. EAE symptoms were monitored over 62 days. Spinal cord tissue was analysed by histology, immunohistochemistry and western blot. Fgfr2\(^{ind-/-}\) mice revealed a milder disease course, less myelin damage and enhanced axonal density. The number of oligodendrocytes was not affected in demyelinated areas. However, protein expression of FGFR2, FGF2 and FGF9 was downregulated in Fgfr2\(^{ind-/-}\) mice. FGF/FGFR dependent signalling proteins were differentially regulated; pAkt was upregulated and pERK was downregulated in Fgfr2\(^{ind-/-}\) mice. The number of CD3(+) T cells, Mac3(+) cells and B220(+) B cells was less in demyelinated lesions of Fgfr2\(^{ind-/-}\) mice. Furthermore, expression of IL-1β, TNF-α and CD200 was less in Fgfr2\(^{ind-/-}\) mice than controls. Fgfr2ind-/- mice showed an upregulation of PLP and downregulation of the remyelination inhibitors SEMA3A and TGF-β expression. These data suggest that cell-specific deletion of FGFR2 in oligodendrocytes has anti-inflammatory and neuroprotective effects accompanied by changes in FGF/FGFR dependent signalling, inflammatory cytokines and expression of remyelination inhibitors. Thus, FGFRs in oligodendrocytes may represent potential targets for the treatment of inflammatory and demyelinating diseases including MS.},
  language  = {en}
}
@article{KimpelBedroseMegerleetal.2021,
  author    = {Kimpel, Otilia and Bedrose, Sara and Megerle, Felix and Berruti, Alfredo and Terzolo, Massimo and Kroiss, Matthias and Mai, Knut and Dekkers, Olaf M. and Habra, Mouhammed Amir and Fassnacht, Martin},
  title     = {Adjuvant platinum-based chemotherapy in radically resected adrenocortical carcinoma: a cohort study},
  series = {British Journal of Cancer},
  volume    = {125},
  journal   = {British Journal of Cancer},
  number    = {9},
  issn      = {1532-1827},
  doi       = {10.1038/s41416-021-01513-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-273000},
  pages     = {1233-1238},
  year      = {2021},
  abstract  = {Background After radical resection, patients with adrenocortical carcinoma (ACC) frequently experience recurrence and, therefore, effective adjuvant treatment is urgently needed. The aim of the study was to investigate the role of adjuvant platinum-based therapy. Methods In this retrospective multicentre cohort study, we identified patients treated with adjuvant platinum-based chemotherapy after radical resection and compared them with patients without adjuvant chemotherapy. Recurrence-free and overall survival (RFS/OS) were investigated in a matched group analysis and by applying a propensity score matching using the full control cohort (n = 268). For both approaches, we accounted for immortal time bias. Results Of the 31 patients in the platinum cohort (R0 n = 25, RX n = 4, R1 n = 2; ENSAT Stage II n = 11, III n = 16, IV n = 4, median Ki67 30\%, mitotane n = 28), 14 experienced recurrence compared to 29 of 31 matched controls (median RFS after the landmark at 3 months 17.3 vs. 7.3 months; adjusted HR 0.19 (95\% CI 0.09-0.42; P < 0.001). Using propensity score matching, the HR for RFS was 0.45 (0.29-0.89, P = 0.021) and for OS 0.25 (0.09-0.69; P = 0.007). Conclusions Our study provides the first evidence that adjuvant platinum-based chemotherapy may be associated with prolonged recurrence-free and overall survival in patients with ACC and a very high risk for recurrence.},
  language  = {en}
}
@article{JanzZinkCirnuetal.2021,
  author    = {Janz, Anna and Zink, Miriam and Cirnu, Alexandra and Hartleb, Annika and Albrecht, Christina and Rost, Simone and Klopocki, Eva and G{\"u}nther, Katharina and Edenhofer, Frank and Erg{\"u}n, S{\"u}leyman and Gerull, Brenda},
  title     = {CRISPR/Cas9-edited PKP2 knock-out (JMUi001-A-2) and DSG2 knock-out (JMUi001-A-3) iPSC lines as an isogenic human model system for arrhythmogenic cardiomyopathy (ACM)},
  series = {Stem Cell Research},
  volume    = {53},
  journal   = {Stem Cell Research},
  doi       = {10.1016/j.scr.2021.102256},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259846},
  pages     = {102256},
  year      = {2021},
  abstract  = {Arrhythmogenic cardiomyopathy (ACM) is characterized by fibro-fatty replacement of the myocardium, heart failure and life-threatening ventricular arrhythmias. Causal mutations were identified in genes encoding for proteins of the desmosomes, predominantly plakophilin-2 (PKP2) and desmoglein-2 (DSG2). We generated gene-edited knock-out iPSC lines for PKP2 (JMUi001-A-2) and DSG2 (JMUi001-A-3) using the CRISPR/Cas9 system in a healthy control iPSC background (JMUi001A). Stem cell-like morphology, robust expression of pluripotency markers, embryoid body formation and normal karyotypes confirmed the generation of high quality iPSCs to provide a novel isogenic human in vitro model system mimicking ACM when differentiated into cardiomyocytes.},
  language  = {en}
}