@article{BrenzingerCostaHoetal.2021,
  author    = {Brenzinger, Kristof and Costa, Ohana Y. A. and Ho, Adrian and Koorneef, Guusje and Robroek, Bjorn and Molenaar, Douwe and Korthals, Gerard and Bodelier, Paul L. E.},
  title     = {Steering microbiomes by organic amendments towards climate-smart agricultural soils},
  series = {Biology and Fertility of Soils},
  volume    = {57},
  journal   = {Biology and Fertility of Soils},
  number    = {8},
  doi       = {10.1007/s00374-021-01599-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326930},
  pages     = {1053-1074},
  year      = {2021},
  abstract  = {We steered the soil microbiome via applications of organic residues (mix of cover crop residues, sewage sludge + compost, and digestate + compost) to enhance multiple ecosystem services in line with climate-smart agriculture. Our result highlights the potential to reduce greenhouse gases (GHG) emissions from agricultural soils by the application of specific organic amendments (especially digestate + compost). Unexpectedly, also the addition of mineral fertilizer in our mesocosms led to similar combined GHG emissions than one of the specific organic amendments. However, the application of organic amendments has the potential to increase soil C, which is not the case when using mineral fertilizer. While GHG emissions from cover crop residues were significantly higher compared to mineral fertilizer and the other organic amendments, crop growth was promoted. Furthermore, all organic amendments induced a shift in the diversity and abundances of key microbial groups. We show that organic amendments have the potential to not only lower GHG emissions by modifying the microbial community abundance and composition, but also favour crop growth-promoting microorganisms. This modulation of the microbial community by organic amendments bears the potential to turn soils into more climate-smart soils in comparison to the more conventional use of mineral fertilizers.},
  language  = {en}
}
@article{D'AndreaSoriaGrotenhuisetal.2021,
  author    = {D'Andrea, David and Soria, Francesco and Grotenhuis, Anne J. and Cha, Eugene K. and Malats, Nuria and Di Stasi, Savino and Joniau, Steven and Cai, Tommaso and Rhijn, Bas W. G. van and Irani, Jaques and Karnes, Jeffrey and Varkarakis, John and Baniel, Jack and Palou, Joan and Babjuk, Marek and Spahn, Martin and Ardelt, Peter and Colombo, Renzo and Serretta, Vincenzo and Dalbagni, Guido and Gontero, Paolo and Bartoletti, Riccardo and Larr{\´e}, Stephane and Malmstrom, Per-Uno and Sylvester, Richard and Shariat, Shahrokh F.},
  title     = {Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Gu{\´e}rin immunotherapy for T1G3/HG bladder cancer},
  series = {World Journal of Urology},
  volume    = {39},
  journal   = {World Journal of Urology},
  number    = {9},
  doi       = {10.1007/s00345-021-03653-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-344486},
  pages     = {3337-3344},
  year      = {2021},
  abstract  = {Purpose To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Gu{\´e}rin (BCG) for T1G3/HG urinary bladder cancer (UBC). Materials and methods We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95\% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression. Results A total of 2170 (82\%) males and 465 (18\%) females were available for analysis. Overall, 1090 (50\%) males and 244 (52\%) females experienced recurrence, and 391 (18\%) males and 104 (22\%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95\%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95\%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95\%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95\%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95\%CI 0.78-1.60, p = 0.55). Conclusion Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.},
  language  = {en}
}
@article{LinzBrandsKertelsetal.2021,
  author    = {Linz, Christian and Brands, Roman C. and Kertels, Olivia and Dierks, Alexander and Brumberg, Joachim and Gerhard-Hartmann, Elena and Hartmann, Stefan and Schirbel, Andreas and Serfling, Sebastian and Zhi, Yingjun and Buck, Andreas K. and K{\"u}bler, Alexander and Hohm, Julian and Lapa, Constantin and Kircher, Malte},
  title     = {Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity - initial experience and comparison to [\(^{18}\)F]FDG PET/CT and MRI},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {48},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {12},
  issn      = {1619-7070},
  doi       = {10.1007/s00259-021-05422-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307246},
  pages     = {3951-3960},
  year      = {2021},
  abstract  = {Purpose While [\(^{18}\)F]-fluorodeoxyglucose ([\(^{18}\)F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. Methods Ten consecutive, treatment-na{\"i}ve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [\(^{18}\)F]FDG and [\(^{68}\)Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUV\(_{max}\)) and peak (SUV\(_{peak}\) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. Results [\(^{18}\)F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([\(^{18}\)F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3\% vs. 87.5\%; P = 0.32) and specificity (93.3\% vs. 81.3\%; P = 0.16) to [\(^{18}\)F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. Conclusion FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.},
  language  = {en}
}
@article{GieselKratochwilSchlittenhardtetal.2021,
  author    = {Giesel, Frederik L. and Kratochwil, Clemens and Schlittenhardt, Joel and Dendl, Katharina and Eiber, Matthias and Staudinger, Fabian and Kessler, Lukas and Fendler, Wolfgang P. and Lindner, Thomas and Koerber, Stefan A. and Cardinale, Jens and Sennung, David and Roehrich, Manuel and Debus, Juergen and Sathekge, Mike and Haberkorn, Uwe and Calais, Jeremie and Serfling, Sebastian and Buck, Andreas L.},
  title     = {Head-to-head intra-individual comparison of biodistribution and tumor uptake of \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG PET/CT in cancer patients},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {48},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {13},
  issn      = {1619-7070},
  doi       = {10.1007/s00259-021-05307-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307252},
  pages     = {4377-4385},
  year      = {2021},
  abstract  = {Purpose FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of \(^{68}\)Ga-FAPI versus standard-of-care \(^{18}\)F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. Material and Methods This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). Results A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. \(^{68}\)Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for \(^{68}\)Ga-FAPI than \(^{18}\)F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, \(^{68}\)Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases. Conclusion Quantitative tumor uptake is comparable between \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for \(^{68}\)Ga-FAPI. Thus, \(^{68}\)Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological \(^{18}\)F-FDG uptake.},
  language  = {en}
}
@article{PennigHoyerKrauskopfetal.2021,
  author    = {Pennig, Lenhard and Hoyer, Ulrike Cornelia Isabel and Krauskopf, Alexandra and Shahzad, Rahil and J{\"u}nger, Stephanie T. and Thiele, Frank and Laukamp, Kai Roman and Grunz, Jan-Peter and Perkuhn, Michael and Schlamann, Marc and Kabbasch, Christoph and Borggrefe, Jan and Goertz, Lukas},
  title     = {Deep learning assistance increases the detection sensitivity of radiologists for secondary intracranial aneurysms in subarachnoid hemorrhage},
  series = {Neuroradiology},
  volume    = {63},
  journal   = {Neuroradiology},
  number    = {12},
  issn      = {0028-3940},
  doi       = {10.1007/s00234-021-02697-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308117},
  pages     = {1985-1994},
  year      = {2021},
  abstract  = {Purpose To evaluate whether a deep learning model (DLM) could increase the detection sensitivity of radiologists for intracranial aneurysms on CT angiography (CTA) in aneurysmal subarachnoid hemorrhage (aSAH). Methods Three different DLMs were trained on CTA datasets of 68 aSAH patients with 79 aneurysms with their outputs being combined applying ensemble learning (DLM-Ens). The DLM-Ens was evaluated on an independent test set of 104 aSAH patients with 126 aneuryms (mean volume 129.2 ± 185.4 mm3, 13.0\% at the posterior circulation), which were determined by two radiologists and one neurosurgeon in consensus using CTA and digital subtraction angiography scans. CTA scans of the test set were then presented to three blinded radiologists (reader 1: 13, reader 2: 4, and reader 3: 3 years of experience in diagnostic neuroradiology), who assessed them individually for aneurysms. Detection sensitivities for aneurysms of the readers with and without the assistance of the DLM were compared. Results In the test set, the detection sensitivity of the DLM-Ens (85.7\%) was comparable to the radiologists (reader 1: 91.2\%, reader 2: 86.5\%, and reader 3: 86.5\%; Fleiss κ of 0.502). DLM-assistance significantly increased the detection sensitivity (reader 1: 97.6\%, reader 2: 97.6\%,and reader 3: 96.0\%; overall P=.024; Fleiss κ of 0.878), especially for secondary aneurysms (88.2\% of the additional aneurysms provided by the DLM). Conclusion Deep learning significantly improved the detection sensitivity of radiologists for aneurysms in aSAH, especially for secondary aneurysms. It therefore represents a valuable adjunct for physicians to establish an accurate diagnosis in order to optimize patient treatment.},
  language  = {en}
}
@article{FeketeEgbertsPreissleretal.2021,
  author    = {Fekete, Stefanie and Egberts, K. and Preissler, T. and Wewetzer, C. and Mehler-Wex, C. and Romanos, M. and Gerlach, M.},
  title     = {Estimation of a preliminary therapeutic reference range for children and adolescents with tic disorders treated with tiapride},
  series = {European Journal of Clinical Pharmacology},
  volume    = {77},
  journal   = {European Journal of Clinical Pharmacology},
  number    = {2},
  doi       = {10.1007/s00228-020-03000-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279893},
  pages     = {163-170},
  year      = {2021},
  abstract  = {Purpose Tiapride is commonly used in Europe for the treatment of tics. The aim of this study was to examine the relationship between dose and serum concentrations of tiapride and potential influential pharmacokinetic factors in children and adolescents. In addition, a preliminary therapeutic reference range for children and adolescents with tics treated with tiapride was calculated. Methods Children and adolescents treated with tiapride at three university hospitals and two departments of child and adolescents psychiatry in Germany and Austria were included in the study. Patient characteristics, doses, serum concentrations, and therapeutic outcome were assessed during clinical routine care using standardised measures. Results In the 49 paediatric patients (83.7\% male, mean age = 12.5 years), a positive correlation was found between tiapride dose (median 6.9 mg/kg, range 0.97-19.35) and serum concentration with marked inter-individual variability. The variation in dose explained 57\% of the inter-patient variability in tiapride serum concentrations; age, gender, and concomitant medication did not contribute to the variability. The symptoms improved in 83.3\% of the patients. 27.1\% of the patients had mild or moderate ADRs. No patient suffered from severe ADRs. Conclusions This study shows that tiapride treatment was effective and safe in most patients with tics. Compared with the therapeutic concentration range established for adults with Chorea Huntington, our data hinted at a lower lower limit (560 ng/ml) and similar upper limit (2000 ng/ml).},
  language  = {en}
}
@article{BarileBerryBlaauboeretal.2021,
  author    = {Barile, Frank A. and Berry, Colin and Blaauboer, Bas and Boobis, Alan and Bolt, Herrmann M. and Borgert, Christopher and Dekant, Wolfgang and Dietrich, Daniel and Domingo, Jose L. and Galli, Corrado L. and Gori, Gio Batta and Greim, Helmut and Hengstler, Jan G. and Heslop-Harrison, Pat and Kacew, Sam and Marquardt, Hans and Mally, Angela and Pelkonen, Olavi and Savolainen, Kai and Testai, Emanuela and Tsatsakis, Aristides and Vermeulen, Nico P.},
  title     = {The EU chemicals strategy for sustainability: in support of the BfR position},
  series = {Archives of Toxicology},
  volume    = {95},
  journal   = {Archives of Toxicology},
  number    = {9},
  issn      = {0340-5761},
  doi       = {10.1007/s00204-021-03125-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307154},
  pages     = {3133-3136},
  year      = {2021},
  abstract  = {The EU chemicals strategy for sustainability (CSS) asserts that both human health and the environment are presently threatened and that further regulation is necessary. In a recent Guest Editorial, members of the German competent authority for risk assessment, the BfR, raised concerns about the scientific justification for this strategy. The complexity and interdependence of the networks of regulation of chemical substances have ensured that public health and wellbeing in the EU have continuously improved. A continuous process of improvement in consumer protection is clearly desirable but any initiative directed towards this objective must be based on scientific knowledge. It must not confound risk with other factors in determining policy. This conclusion is fully supported in the present Commentary including the request to improve both, data collection and the time-consuming and bureaucratic procedures that delay the publication of regulations.},
  language  = {en}
}
@article{GuthHueserRothetal.2021,
  author    = {Guth, Sabine and H{\"u}ser, Stephanie and Roth, Angelika and Degen, Gisela and Diel, Patrick and Edlund, Karolina and Eisenbrand, Gerhard and Engel, Karl-Heinz and Epe, Bernd and Grune, Tilman and Heinz, Volker and Henle, Thomas and Humpf, Hans-Ulrich and J{\"a}ger, Henry and Joost, Hans-Georg and Kulling, Sabine E. and Lampen, Alfonso and Mally, Angela and Marchan, Rosemarie and Marko, Doris and M{\"u}hle, Eva and Nitsche, Michael A. and R{\"o}hrdanz, Elke and Stadler, Richard and van Thriel, Christoph and Vieths, Stefan and Vogel, Rudi F. and Wascher, Edmund and Watzl, Carsten and N{\"o}thlings, Ute and Hengstler, Jan G.},
  title     = {Contribution to the ongoing discussion on fluoride toxicity},
  series = {Archives of Toxicology},
  volume    = {95},
  journal   = {Archives of Toxicology},
  number    = {7},
  issn      = {0340-5761},
  doi       = {10.1007/s00204-021-03072-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307161},
  pages     = {2571-2587},
  year      = {2021},
  abstract  = {Since the addition of fluoride to drinking water in the 1940s, there have been frequent and sometimes heated discussions regarding its benefits and risks. In a recently published review, we addressed the question if current exposure levels in Europe represent a risk to human health. This review was discussed in an editorial asking why we did not calculate benchmark doses (BMD) of fluoride neurotoxicity for humans. Here, we address the question, why it is problematic to calculate BMDs based on the currently available data. Briefly, the conclusions of the available studies are not homogeneous, reporting negative as well as positive results; moreover, the positive studies lack control of confounding factors such as the influence of well-known neurotoxicants. We also discuss the limitations of several further epidemiological studies that did not meet the inclusion criteria of our review. Finally, it is important to not only focus on epidemiological studies. Rather, risk analysis should consider all available data, including epidemiological, animal, as well as in vitro studies. Despite remaining uncertainties, the totality of evidence does not support the notion that fluoride should be considered a human developmental neurotoxicant at current exposure levels in European countries.},
  language  = {en}
}
@article{ChumduriTurco2021,
  author    = {Chumduri, Cindrilla and Turco, Margherita Y.},
  title     = {Organoids of the female reproductive tract},
  series = {Journal of Molecular Medicine},
  volume    = {99},
  journal   = {Journal of Molecular Medicine},
  number    = {4},
  doi       = {10.1007/s00109-020-02028-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-328374},
  pages     = {531-553},
  year      = {2021},
  abstract  = {Healthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.},
  language  = {en}
}
@article{PinkawaAebersoldBoehmeretal.2021,
  author    = {Pinkawa, Michael and Aebersold, Daniel M. and B{\"o}hmer, Dirk and Flentje, Michael and Ghadjar, Pirus and Schmidt-Hegemann, Nina-Sophie and H{\"o}cht, Stefan and H{\"o}lscher, Tobias and M{\"u}ller, Arndt-Christian and Niehoff, Peter and Sedlmayer, Felix and Wolf, Frank and Zamboglou, Constantinos and Zips, Daniel and Wiegel, Thomas},
  title     = {Radiotherapy in nodal oligorecurrent prostate cancer},
  series = {Strahlentherapie und Onkologie},
  volume    = {197},
  journal   = {Strahlentherapie und Onkologie},
  number    = {7},
  issn      = {0179-7158},
  doi       = {10.1007/s00066-021-01778-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307763},
  pages     = {575-580},
  year      = {2021},
  abstract  = {Objective The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results Metastasis-directed radiotherapy results in high local control (often > 90\% within a follow-up of 1-2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.},
  language  = {en}
}