@article{AbdelhameedEltamanyHaletal.2020,
  author    = {Abdelhameed, Reda F. A. and Eltamany, Enas E. and Hal, Dina M. and Ibrahim, Amany K. and AboulMagd, Asmaa M. and Al-Warhi, Tarfah and Youssif, Khayrya A. and Abd El-kader, Adel M. and Hassanean, Hashim A. and Fayez, Shaimaa and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan},
  title     = {New cytotoxic cerebrosides from the Red Sea cucumber Holothuria spinifera supported by in-silico studies},
  series = {Marine Drugs},
  volume    = {18},
  journal   = {Marine Drugs},
  number    = {8},
  issn      = {1660-3397},
  doi       = {10.3390/md18080405},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211089},
  year      = {2020},
  abstract  = {Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC\(_{50}\) values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC\(_{50}\) 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.},
  language  = {en}
}
@article{AbdelhameedHabibEltahawyetal.2020,
  author    = {Abdelhameed, Reda F. A. and Habib, Eman S. and Eltahawy, Nermeen A. and Hassanean, Hashim A. and Ibrahim, Amany K. and Mohammed, Anber F. and Fayez, Shaimaa and Hayallah, Alaa M. and Yamada, Koji and Behery, Fathy A. and Al-Sanea, Mohammad M. and Alzarea, Sami I. and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan},
  title     = {New cytotoxic natural products from the Red Sea sponge Stylissa carteri},
  series = {Marine Drugs},
  volume    = {18},
  journal   = {Marine Drugs},
  number    = {5},
  issn      = {1660-3397},
  doi       = {10.3390/md18050241},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205795},
  year      = {2020},
  abstract  = {Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract's metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC\(_{50}\) values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC\(_{50}\) at 36.8 ± 0.16 µM for 1 and IC\(_{50}\) 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.},
  language  = {en}
}
@article{AbdelhameedHabibGodaetal.2020,
  author    = {Abdelhameed, Reda F. A. and Habib, Eman S. and Goda, Marwa S. and Fahim, John Refaat and Hassanean, Hashem A. and Eltamany, Enas E. and Ibrahim, Amany K. and AboulMagd, Asmaa M. and Fayez, Shaimaa and Abd El-kader, Adel M. and Al-Warhi, Tarfah and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan},
  title     = {Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass Thalassodendron ciliatum},
  series = {Marine Drugs},
  volume    = {18},
  journal   = {Marine Drugs},
  number    = {7},
  doi       = {10.3390/md18070354},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236085},
  year      = {2020},
  abstract  = {Thalassodendron ciliatum (Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol (1) was isolated from the methanolic extract of T. ciliatum growing in the Red Sea, along with two known first-reported sterols, namely ergosterol (2) and stigmasterol (3), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC\(_{50}\) values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol 1 explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of T. ciliatum using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides.},
  language  = {en}
}
@article{AdakuChilakaMally2020,
  author    = {Adaku Chilaka, Cynthia and Mally, Angela},
  title     = {Mycotoxin Occurrence, Exposure and Health Implications in Infants and Young Children in Sub-Saharan Africa: A Review},
  series = {Foods},
  volume    = {9},
  journal   = {Foods},
  number    = {11},
  issn      = {2304-8158},
  doi       = {10.3390/foods9111585},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219250},
  year      = {2020},
  abstract  = {Infants and young children (IYC) remain the most vulnerable population group to environmental hazards worldwide, especially in economically developing regions such as sub-Saharan Africa (SSA). As a result, several governmental and non-governmental institutions including health, environmental and food safety networks and researchers have been proactive toward protecting this group. Mycotoxins, toxic secondary fungal metabolites, contribute largely to the health risks of this young population. In SSA, the scenario is worsened by socioeconomic status, poor agricultural and storage practices, and low level of awareness, as well as the non-establishment and lack of enforcement of regulatory limits in the region. Studies have revealed mycotoxin occurrence in breast milk and other weaning foods. Of concern is the early exposure of infants to mycotoxins through transplacental transfer and breast milk as a consequence of maternal exposure, which may result in adverse health effects. The current paper presents an overview of mycotoxin occurrence in foods intended for IYC in SSA. It discusses the imperative evidence of mycotoxin exposure of this population group in SSA, taking into account consumption data and the occurrence of mycotoxins in food, as well as biomonitoring approaches. Additionally, it discusses the health implications associated with IYC exposure to mycotoxins in SSA.},
  language  = {en}
}
@article{AkhundzadahSoltaniAich2020,
  author    = {Akhundzadah, Noor Ahmad and Soltani, Salim and Aich, Valentin},
  title     = {Impacts of climate change on the water resources of the Kunduz River Basin, Afghanistan},
  series = {Climate},
  volume    = {8},
  journal   = {Climate},
  number    = {10},
  issn      = {2225-1154},
  doi       = {10.3390/cli8100102},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213199},
  year      = {2020},
  abstract  = {The Kunduz River is one of the main tributaries of the Amu Darya Basin in North Afghanistan. Many communities live in the Kunduz River Basin (KRB), and its water resources have been the basis of their livelihoods for many generations. This study investigates climate change impacts on the KRB catchment. Rare station data are, for the first time, used to analyze systematic trends in temperature, precipitation, and river discharge over the past few decades, while using Mann-Kendall and Theil-Sen trend statistics. The trends show that the hydrology of the basin changed significantly over the last decades. A comparison of landcover data of the river basin from 1992 and 2019 shows significant changes that have additional impact on the basin hydrology, which are used to interpret the trend analysis. There is considerable uncertainty due to the data scarcity and gaps in the data, but all results indicate a strong tendency towards drier conditions. An extreme warming trend, partly above 2 °C since the 1960s in combination with a dramatic precipitation decrease by more than -30\% lead to a strong decrease in river discharge. The increasing glacier melt compensates the decreases and leads to an increase in runoff only in the highland parts of the upper catchment. The reduction of water availability and the additional stress on the land leads to a strong increase of barren land and a reduction of vegetation cover. The detected trends and changes in the basin hydrology demand an active management of the already scarce water resources in order to sustain water supply for agriculture and ecosystems in the KRB.},
  language  = {en}
}
@article{AltieriDiDatoModicaetal.2020,
  author    = {Altieri, Barbara and Di Dato, Carla and Modica, Roberta and Bottiglieri, Filomena and Di Sarno, Antonella and Pittaway, James F.H. and Martini, Chiara and Faggiano, Antongiulio and Colao, Annamaria},
  title     = {Bone metabolism and vitamin D implication in gastroenteropancreatic neuroendocrine tumors},
  series = {Nutrients},
  volume    = {12},
  journal   = {Nutrients},
  number    = {4},
  issn      = {2072-6643},
  doi       = {10.3390/nu12041021},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203823},
  year      = {2020},
  abstract  = {Patients affected by gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP-NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP-NET, focusing on vitamin D and its role in GEP-NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.},
  language  = {en}
}
@article{AltieriSbieraHerterichetal.2020,
  author    = {Altieri, Barbara and Sbiera, Silviu and Herterich, Sabine and De Francia, Silvia and Della Casa, Silvia and Calabrese, Anna and Pontecorvi, Alfredo and Quinkler, Marcus and Kienitz, Tina and Mannelli, Massimo and Canu, Letizia and Angelousi, Anna and Chortis, Vasileios and Kroiss, Matthias and Terzolo, Massimo and Fassnacht, Martin and Ronchi, Cristina L.},
  title     = {Effects of Germline CYP2W1*6 and CYP2B6*6 Single Nucleotide Polymorphisms on Mitotane Treatment in Adrenocortical Carcinoma: A Multicenter ENSAT Study},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {2},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12020359},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200565},
  pages     = {359},
  year      = {2020},
  abstract  = {Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms (SNPs) as biomarkers. A multicenter cohort study including 182 ACC patients (F/M = 121/61) treated with mitotane monotherapy after radical resection (group A, n = 103) or in not completely resectable, recurrent or advanced disease (group B, n = 79) was performed. CYP2W1*2, CYP2W1*6, CYP2B6*6 and CYP2B6 rs4803419 were genotyped in germline DNA. Mitotane blood levels were measured regularly. Response to therapy was evaluated as time to progression (TTP) and disease control rate (DCR). Among investigated SNPs, CYP2W1*6 and CYP2B6*6 correlated with mitotane treatment only in group B. Patients with CYP2W1*6 (n = 21) achieved less frequently therapeutic mitotane levels (>14 mg/L) than those with wild type (WT) allele (76.2\% vs 51.7\%, p = 0.051) and experienced shorter TTP (HR = 2.10, p = 0.019) and lower DCR (chi-square = 6.948, p = 0.008). By contrast, 55\% of patients with CYP2B6*6 vs. 28.2\% WT (p = 0.016) achieved therapeutic range. Combined, a higher rate of patients with CYP2W1*6WT+CYP2B6*6 (60.6\%) achieved mitotane therapeutic range (p = 0.034). In not completely resectable, recurrent or advanced ACC, CYP2W1*6 SNP was associated with a reduced probability to reach mitotane therapeutic range and lower response rates, whereas CYP2B6*6 correlated with higher mitotane levels. The association of these SNPs may predict individual response to mitotane.},
  language  = {en}
}
@article{AlzheimerSvenssonKoenigetal.2020,
  author    = {Alzheimer, Mona and Svensson, Sarah L. and K{\"o}nig, Fabian and Schweinlin, Matthias and Metzger, Marco and Walles, Heike and Sharma, Cynthia M.},
  title     = {A three-dimensional intestinal tissue model reveals factors and small regulatory RNAs important for colonization with Campylobacter jejuni},
  series = {PLoS Pathogens},
  volume    = {16},
  journal   = {PLoS Pathogens},
  number    = {2},
  doi       = {10.1371/journal.ppat.1008304},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229454},
  year      = {2020},
  abstract  = {The Gram-negative Epsilonproteobacterium Campylobacter jejuni is currently the most prevalent bacterial foodborne pathogen. Like for many other human pathogens, infection studies with C. jejuni mainly employ artificial animal or cell culture models that can be limited in their ability to reflect the in-vivo environment within the human host. Here, we report the development and application of a human three-dimensional (3D) infection model based on tissue engineering to study host-pathogen interactions. Our intestinal 3D tissue model is built on a decellularized extracellular matrix scaffold, which is reseeded with human Caco-2 cells. Dynamic culture conditions enable the formation of a polarized mucosal epithelial barrier reminiscent of the 3D microarchitecture of the human small intestine. Infection with C. jejuni demonstrates that the 3D tissue model can reveal isolate-dependent colonization and barrier disruption phenotypes accompanied by perturbed localization of cell-cell junctions. Pathogenesis-related phenotypes of C. jejuni mutant strains in the 3D model deviated from those obtained with 2D-monolayers, but recapitulated phenotypes previously observed in animal models. Moreover, we demonstrate the involvement of a small regulatory RNA pair, CJnc180/190, during infections and observe different phenotypes of CJnc180/190 mutant strains in 2D vs. 3D infection models. Hereby, the CJnc190 sRNA exerts its pathogenic influence, at least in part, via repression of PtmG, which is involved in flagellin modification. Our results suggest that the Caco-2 cell-based 3D tissue model is a valuable and biologically relevant tool between in-vitro and in-vivo infection models to study virulence of C. jejuni and other gastrointestinal pathogens.},
  language  = {en}
}
@article{AmeriSchiattarellaCrottietal.2020,
  author    = {Ameri, Pietro and Schiattarella, Gabriele Giacomo and Crotti, Lia and Torchio, Margherita and Bertero, Edoardo and Rodolico, Daniele and Forte, Maurizio and Di Mauro, Vittoria and Paolillo, Roberta and Chimenti, Cristina and Torella, Daniele and Catalucci, Daniele and Sciarretta, Sebastiano and Basso, Cristina and Indolfi, Ciro and Perrino, Cinzia},
  title     = {Novel basic science insights to improve the management of heart failure: Review of the working group on cellular and molecular biology of the heart of the Italian Society of Cardiology},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {4},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21041192},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285085},
  year      = {2020},
  abstract  = {Despite important advances in diagnosis and treatment, heart failure (HF) remains a syndrome with substantial morbidity and dismal prognosis. Although implementation and optimization of existing technologies and drugs may lead to better management of HF, new or alternative strategies are desirable. In this regard, basic science is expected to give fundamental inputs, by expanding the knowledge of the pathways underlying HF development and progression, identifying approaches that may improve HF detection and prognostic stratification, and finding novel treatments. Here, we discuss recent basic science insights that encompass major areas of translational research in HF and have high potential clinical impact.},
  language  = {en}
}
@article{AndreskaLueningschroerSendtner2020,
  author    = {Andreska, Thomas and L{\"u}ningschr{\"o}r, Patrick and Sendtner, Michael},
  title     = {Regulation of TrkB cell surface expression — a mechanism for modulation of neuronal responsiveness to brain-derived neurotrophic factor},
  series = {Cell and Tissue Research},
  volume    = {382},
  journal   = {Cell and Tissue Research},
  doi       = {10.1007/s00441-020-03224-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235055},
  pages     = {5-14},
  year      = {2020},
  abstract  = {Neurotrophin signaling via receptor tyrosine kinases is essential for the development and function of the nervous system in vertebrates. TrkB activation and signaling show substantial differences to other receptor tyrosine kinases of the Trk family that mediate the responses to nerve growth factor and neurotrophin-3. Growing evidence suggests that TrkB cell surface expression is highly regulated and determines the sensitivity of neurons to brain-derived neurotrophic factor (BDNF). This translocation of TrkB depends on co-factors and modulators of cAMP levels, N-glycosylation, and receptor transactivation. This process can occur in very short time periods and the resulting rapid modulation of target cell sensitivity to BDNF could represent a mechanism for fine-tuning of synaptic plasticity and communication in complex neuronal networks. This review focuses on those modulatory mechanisms in neurons that regulate responsiveness to BDNF via control of TrkB surface expression.},
  language  = {en}
}
@article{AngermannAssmusAnkeretal.2020,
  author    = {Angermann, Christiane E. and Assmus, Birgit and Anker, Stefan D. and Asselbergs, Folkert W. and Brachmann, Johannes and Brett, Marie-Elena and Brugts, Jasper J. and Ertl, Georg and Ginn, Greg and Hilker, Lutz and Koehler, Friedrich and Rosenkranz, Stephan and Zhou, Qian and Adamson, Philip B. and B{\"o}hm, Michael},
  title     = {Pulmonary artery pressure-guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF)},
  series = {European Journal of Heart Failure},
  volume    = {22},
  journal   = {European Journal of Heart Failure},
  number    = {10},
  doi       = {10.1002/ejhf.1943},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218061},
  pages     = {1891 -- 1901},
  year      = {2020},
  abstract  = {Aims Heart failure (HF) leads to repeat hospitalisations and reduces the duration and quality of life. Pulmonary artery pressure (PAP)-guided HF management using the CardioMEMS™ HF system was shown to be safe and reduce HF hospitalisation (HFH) rates in New York Heart Association (NYHA) class III patients. However, these findings have not been replicated in health systems outside the United States. Therefore, the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland. Methods and results A total of 234 NYHA class III patients (68 ± 11 years, 22\% female, ≥1 HFH in the preceding year) from 31 centres were implanted with a CardioMEMS sensor and underwent PAP-guided HF management. One-year rates of freedom from device- or system-related complications and from sensor failure (co-primary outcomes) were 98.3\% [95\% confidence interval (CI) 95.8-100.0] and 99.6\% (95\% CI 97.6-100.0), respectively. Survival rate was 86.2\%. For the 12 months post- vs. pre-implant, HFHs decreased by 62\% (0.60 vs. 1.55 events/patient-year; hazard ratio 0.38, 95\% CI 0.31-0.48; P < 0.0001). After 12 months, mean PAP decreased by 5.1 ± 7.4 mmHg, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall/clinical summary scores increased from 47.0 ± 24.0/51.2 ± 24.8 to 60.5 ± 24.3/62.4 ± 24.1 (P < 0.0001), and the 9-item Patient Health Questionnaire sum score improved from 8.7 ± 5.9 to 6.3 ± 5.1 (P < 0.0001). Conclusion Haemodynamic-guided HF management proved feasible and safe in the health systems of Germany, The Netherlands, and Ireland. Physician-directed treatment modifications based on remotely obtained PAP values were associated with fewer HFH, sustainable PAP decreases, marked KCCQ improvements, and remission of depressive symptoms.},
  language  = {en}
}
@article{AppeltshauserBrunderHeiniusetal.2020,
  author    = {Appeltshauser, Luise and Brunder, Anna-Michelle and Heinius, Annika and K{\"o}rtv{\´e}lyessy, Peter and Wandinger, Klaus-Peter and Junker, Ralf and Villmann, Carmen and Sommer, Claudia and Leypoldt, Frank and Doppler, Kathrin},
  title     = {Antiparanodal antibodies and IgG subclasses in acute autoimmune neuropathy},
  series = {Neurology: Neuroimmunology \& Neuroinflammation},
  volume    = {7},
  journal   = {Neurology: Neuroimmunology \& Neuroinflammation},
  number    = {5},
  doi       = {10.1212/NXI.0000000000000817},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230079},
  year      = {2020},
  abstract  = {Objective To determine whether IgG subclasses of antiparanodal autoantibodies are related to disease course and treatment response in acute- to subacute-onset neuropathies, we retrospectively screened 161 baseline serum/CSF samples and 66 follow-up serum/CSF samples. Methods We used ELISA and immunofluorescence assays to detect antiparanodal IgG and their subclasses and titers in serum/CSF of patients with Guillain-Barre syndrome (GBS), recurrent GBS (R-GBS), Miller-Fisher syndrome, and acute- to subacute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). We evaluated clinical data retrospectively. Results We detected antiparanodal autoantibodies with a prevalence of 4.3\% (7/161), more often in A-CIDP (4/23, 17.4\%) compared with GBS (3/114, 2.6\%). Longitudinal subclass analysis in the patients with GBS revealed IgG2/3 autoantibodies against Caspr-1 and against anti-contactin-1/Caspr-1, which disappeared at remission. At disease onset, patients with A-CIDP had IgG2/3 anti-Caspr-1 and anti-contactin-1/Caspr-1 or IgG4 anti-contactin-1 antibodies, IgG3 being associated with good response to IV immunoglobulins (IVIg). In the chronic phase of disease, IgG subclass of one patient with A-CIDP switched from IgG3 to IgG4. Conclusion Our data (1) confirm and extend previous observations that antiparanodal IgG2/3 but not IgG4 antibodies can occur in acute-onset neuropathies manifesting as monophasic GBS, (2) suggest association of IgG3 to a favorable response to IVIg, and (3) lend support to the hypothesis that in some patients, an IgG subclass switch from IgG3 to IgG4 may be the correlate of a secondary progressive or relapsing course following a GBS-like onset.},
  language  = {en}
}
@article{Appelt‐MenzelOerterMathewetal.2020,
  author    = {Appelt-Menzel, Antje and Oerter, Sabrina and Mathew, Sanjana and Haferkamp, Undine and Hartmann, Carla and Jung, Matthias and Neuhaus, Winfried and Pless, Ole},
  title     = {Human iPSC-Derived Blood-Brain Barrier Models: Valuable Tools for Preclinical Drug Discovery and Development?},
  series = {Current Protocols in Stem Cell Biology},
  volume    = {55},
  journal   = {Current Protocols in Stem Cell Biology},
  number    = {1},
  doi       = {10.1002/cpsc.122},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218509},
  year      = {2020},
  abstract  = {Translating basic biological knowledge into applications remains a key issue for effectively tackling neurodegenerative, neuroinflammatory, or neuroendocrine disorders. Efficient delivery of therapeutics across the neuroprotective blood-brain barrier (BBB) still poses a demanding challenge for drug development targeting central nervous system diseases. Validated in vitro models of the BBB could facilitate effective testing of drug candidates targeting the brain early in the drug discovery process during lead generation. We here review the potential of mono- or (isogenic) co-culture BBB models based on brain capillary endothelial cells (BCECs) derived from human-induced pluripotent stem cells (hiPSCs), and compare them to several available BBB in vitro models from primary human or non-human cells and to rodent in vivo models, as well as to classical and widely used barrier models [Caco-2, parallel artificial membrane permeability assay (PAMPA)]. In particular, we are discussing the features and predictivity of these models and how hiPSC-derived BBB models could impact future discovery and development of novel CNS-targeting therapeutics.},
  language  = {en}
}
@article{ApsemidouFuellerIdelevichetal.2020,
  author    = {Apsemidou, Athanasia and F{\"u}ller, Miriam Antonie and Idelevich, Evgeny A. and Kurzai, Oliver and Tragiannidis, Athanasios and Groll, Andreas H.},
  title     = {Candida lusitaniae breakthrough fungemia in an immuno-compromised adolescent: case report and review of the literature},
  series = {Journal of Fungi},
  volume    = {6},
  journal   = {Journal of Fungi},
  number    = {4},
  issn      = {2309-608X},
  doi       = {10.3390/jof6040380},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220125},
  year      = {2020},
  abstract  = {Candida lusitaniae is a rare cause of candidemia that is known for its unique capability to rapidly acquire resistance to amphotericin B. We report the case of an adolescent with grade IV graft-vs.-host disease after hematopoietic cell transplantation who developed catheter-associated C. lusitaniae candidemia while on therapeutic doses of liposomal amphotericin B. We review the epidemiology of C. lusitaniae bloodstream infections in adult and pediatric patients, the development of resistance, and its role in breakthrough candidemia. Appropriate species identification, in vitro susceptibility testing, and source control are pivotal to optimal management of C. lusitaniae candidemia. Initial antifungal therapy may consist of an echinocandin and be guided by in vitro susceptibility and clinical response.},
  language  = {en}
}
@article{ArgentieroSolimandoKrebsetal.2020,
  author    = {Argentiero, Antonella and Solimando, Antonio Giovanni and Krebs, Markus and Leone, Patrizia and Susca, Nicola and Brunetti, Oronzo and Racanelli, Vito and Vacca, Angelo and Silvestris, Nicola},
  title     = {Anti-angiogenesis and immunotherapy: novel paradigms to envision tailored approaches in renal cell-carcinoma},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {5},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9051594},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205846},
  year      = {2020},
  abstract  = {Although decision making strategy based on clinico-histopathological criteria is well established, renal cell carcinoma (RCC) represents a spectrum of biological ecosystems characterized by distinct genetic and molecular alterations, diverse clinical courses and potential specific therapeutic vulnerabilities. Given the plethora of drugs available, the subtype-tailored treatment to RCC subtype holds the potential to improve patient outcome, shrinking treatment-related morbidity and cost. The emerging knowledge of the molecular taxonomy of RCC is evolving, whilst the antiangiogenic and immunotherapy landscape maintains and reinforces their potential. Although several prognostic factors of survival in patients with RCC have been described, no reliable predictive biomarkers of treatment individual sensitivity or resistance have been identified. In this review, we summarize the available evidence able to prompt more precise and individualized patient selection in well-designed clinical trials, covering the unmet need of medical choices in the era of next-generation anti-angiogenesis and immunotherapy.},
  language  = {en}
}
@article{ArnholdtKamawalHorasetal.2020,
  author    = {Arnholdt, J{\"o}rg and Kamawal, Yama and Horas, Konstantin and Holzapfel, Boris M. and Gilbert, Fabian and Ripp, Axel and Rudert, Maximilian and Steinert, Andre F.},
  title     = {Accurate implant fit and leg alignment after cruciate-retaining patient-specific total knee arthroplasty},
  series = {BMC Musculoskeletal Disorders},
  volume    = {21},
  journal   = {BMC Musculoskeletal Disorders},
  doi       = {10.1186/s12891-020-03707-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230012},
  year      = {2020},
  abstract  = {Background For improved outcomes in total knee arthroplasty (TKA) correct implant fitting and positioning are crucial. In order to facilitate a best possible implant fitting and positioning patient-specific systems have been developed. However, whether or not these systems allow for better implant fitting and positioning has yet to be elucidated. For this reason, the aim was to analyse the novel patient-specific cruciate retaining knee replacement system iTotal (TM) CR G2 that utilizes custom-made implants and instruments for its ability to facilitate accurate implant fitting and positioning including correction of the hip-knee-ankle angle (HKA). Methods We assessed radiographic results of 106 patients who were treated with the second generation of a patient-specific cruciate retaining knee arthroplasty using iTotal\(^{TM}\) CR G2 (ConforMIS Inc.) for tricompartmental knee osteoarthritis (OA) using custom-made implants and instruments. The implant fit and positioning as well as the correction of the mechanical axis (hip-knee-ankle angle, HKA) and restoration of the joint line were determined using pre- and postoperative radiographic analyses. Results On average, HKA was corrected from 174.4 degrees +/- 4.6 degrees preoperatively to 178.8 degrees +/- 2.2 degrees postoperatively and the coronal femoro-tibial angle was adjusted on average 4.4 degrees. The measured preoperative tibial slope was 5.3 degrees +/- 2.2 degrees (mean +/- SD) and the average postoperative tibial slope was 4.7 degrees +/- 1.1 degrees on lateral views. The joint line was well preserved with an average modified Insall-Salvati index of 1.66 +/- 0.16 pre- and 1.67 +/- 0.16 postoperatively. The overall accuracy of fit of implant components was decent with a measured medial overhang of more than 1 mm (1.33 mm +/- 0.32 mm) in 4 cases only. Further, a lateral overhang of more than 1 mm (1.8 mm +/- 0.63) (measured in the anterior-posterior radiographs) was observed in 11 cases, with none of the 106 patients showing femoral notching. Conclusion The patient-specific iTotal\(^{TM}\) CR G2 total knee replacement system facilitated a proper fitting and positioning of the implant components. Moreover, a good restoration of the leg axis towards neutral alignment was achieved as planned. Nonetheless, further clinical follow-up studies are necessary to validate our findings and to determine the long-term impact of using this patient- specific system.},
  language  = {en}
}
@article{ArnoldMuellerOerlinghausenHemrichetal.2020,
  author    = {Arnold, Michaela Maria and M{\"u}ller-Oerlinghausen, Bruno and Hemrich, Norbert and B{\"o}nsch, Dominikus},
  title     = {Effects of Psychoactive Massage in Outpatients with Depressive Disorders: A Randomized Controlled Mixed-Methods Study},
  series = {Brain Sciences},
  volume    = {10},
  journal   = {Brain Sciences},
  number    = {10},
  issn      = {2076-3425},
  doi       = {10.3390/brainsci10100676},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213385},
  year      = {2020},
  abstract  = {The clinical picture of depressive disorders is characterized by a plethora of somatic symptoms, psychomotor retardation, and, particularly, anhedonia. The number of patients with residual symptoms or treatment resistance is high. Touch is the basic communication among humans and animals. Its application professionally in the form of, e.g., psychoactive massage therapy, has been shown in the past to reduce the somatic and mental symptoms of depression and anxiety. Here, we investigated the effects of a specially developed affect-regulating massage therapy (ARMT) vs. individual treatment with a standardized relaxation procedure, progressive muscle relaxation (PMR), in 57 outpatients with depression. Patients were given one ARMT or PMR session weekly over 4 weeks. Changes in somatic and cognitive symptoms were assessed by standard psychiatric instruments (Hamilton Depression Scale (HAMD) and the Bech-Rafaelsen-Melancholia-Scale (BRMS)) as well as a visual analogue scale. Furthermore, oral statements from all participants were obtained in semi-structured interviews. The findings show clear and statistically significant superiority of ARMT over PMR. The results might be interpreted within various models. The concept of interoception, as well as the principles of body psychotherapy and phenomenological aspects, offers cues for understanding the mechanisms involved. Within a neurobiological context, the significance of C-tactile afferents activated by special touch techniques and humoral changes such as increased oxytocin levels open additional ways of interpreting our findings.},
  language  = {en}
}
@article{AssfalgSeligTolksdorfetal.2020,
  author    = {Assfalg, Volker and Selig, Katharina and Tolksdorf, Johanna and van Meel, Marieke and de Vries, Erwin and Ramsoebhag, Anne-Marie and Rahmel, Axel and Renders, Lutz and Novotny, Alexander and Matevossian, Edouard and Schneeberger, Stefan and Rosenkranz, Alexander R. and Berlakovich, Gabriela and Ysebaert, Dirk and Knops, No{\"e}l and Kuypers, Dirk and Weekers, Laurent and Muehlfeld, Anja and Rump, Lars-Christian and Hauser, Ingeborg and Pisarski, Przemyslaw and Weimer, Rolf and Fornara, Paolo and Fischer, Lutz and Kliem, Volker and Sester, Urban and Stippel, Dirk and Arns, Wolfgang and Hau, Hans-Michael and Nitschke, Martin and Hoyer, Joachim and Thorban, Stefan and Weinmann-Menke, Julia and Heller, Katharina and Banas, Bernhard and Schwenger, Vedat and Nadalin, Silvio and Lopau, Kai and H{\"u}ser, Norbert and Heemann, Uwe},
  title     = {Repeated kidney re-transplantation—the Eurotransplant experience: a retrospective multicenter outcome analysis},
  series = {Transplant International},
  volume    = {33},
  journal   = {Transplant International},
  number    = {6},
  doi       = {10.1111/tri.13569},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214161},
  pages     = {617 -- 631},
  year      = {2020},
  abstract  = {In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0\% vs. 84.5\%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7\%) than in 1st DDRT (7.1\%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.},
  language  = {en}
}
@article{AuerHuegelschaefferFischeretal.2020,
  author    = {Auer, Daniela and H{\"u}gelsch{\"a}ffer, Sophie D. and Fischer, Annette B. and Rudel, Thomas},
  title     = {The chlamydial deubiquitinase Cdu1 supports recruitment of Golgi vesicles to the inclusion},
  series = {Cellular Microbiology},
  volume    = {22},
  journal   = {Cellular Microbiology},
  number    = {5},
  doi       = {10.1111/cmi.13136},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208675},
  pages     = {e13136},
  year      = {2020},
  abstract  = {Chlamydia trachomatis is the main cause of sexually transmitted diseases worldwide. As obligate intracellular bacteria Chlamydia replicate in a membrane bound vacuole called inclusion and acquire nutrients for growth and replication from their host cells. However, like all intracellular bacteria, Chlamydia have to prevent eradication by the host's cell autonomous system. The chlamydial deubiquitinase Cdu1 is secreted into the inclusion membrane, facing the host cell cytosol where it deubiquitinates cellular proteins. Here we show that inactivation of Cdu1 causes a growth defect of C. trachomatis in primary cells. Moreover, ubiquitin and several autophagy receptors are recruited to the inclusion membrane of Cdu1-deficient Chlamydia . Interestingly, the growth defect of cdu1 mutants is not rescued when autophagy is prevented. We find reduced recruitment of Golgi vesicles to the inclusion of Cdu1 mutants indicating that vesicular trafficking is altered in bacteria without active deubiquitinase (DUB). Our work elucidates an important role of Cdu1 in the functional preservation of the chlamydial inclusion surface.},
  language  = {en}
}
@article{AverdunkBernhagenFehnleetal.2020,
  author    = {Averdunk, Luisa and Bernhagen, J{\"u}rgen and Fehnle, Karl and Surowy, Harald and L{\"u}decke, Hermann-Josef and Mucha, S{\"o}ren and Meybohm, Patrick and Wieczorek, Dagmar and Leng, Lin and Marx, Gernot and Leaf, David E. and Zarbock, Alexander and Zacharowski, Kai and Bucala, Richard and Stoppe, Christian},
  title     = {The Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms (rs3063368, rs755622) predict acute kidney injury and death after cardiac surgery},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {9},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9092936},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213126},
  year      = {2020},
  abstract  = {Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT\(_{5-7}\) (rs5844572/rs3063368,"-794") and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT\(_7\)) had a significantly higher risk of acute kidney injury (AKI) compared to others (23\% vs. 13\%; OR 2.01 (1.40-2.88), p = 0.0001). Carriers of CATT\(_7\) were also at higher risk of death (1.8\% vs. 0.4\%; OR 5.12 (0.99-33.14), p = 0.026). The GC genotype was associated with AKI (20\% vs. GG/CC:13\%, OR 1.71 (1.20-2.43), p = 0.003). Multivariate analyses identified CATT\(_7\) predictive for AKI (OR 2.13 (1.46-3.09), p < 0.001) and death (OR 5.58 (1.29-24.04), p = 0.021). CATT\(_7\) was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT\(_7\) allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.},
  language  = {en}
}