@article{WeichWernerBucketal.2021, author = {Weich, Alexander and Werner, Rudolf A. and Buck, Andreas K. and Hartrampf, Philipp E. and Serfling, Sebastian E. and Scheurlen, Michael and Wester, Hans-J{\"u}rgen and Meining, Alexander and Kircher, Stefan and Higuchi, Takahiro and Pomper, Martin G. and Rowe, Steven P. and Lapa, Constantin and Kircher, Malte}, title = {CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas}, series = {Diagnostics}, volume = {11}, journal = {Diagnostics}, number = {4}, issn = {2075-4418}, doi = {10.3390/diagnostics11040605}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234231}, year = {2021}, abstract = {We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-na{\"i}ve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.}, language = {en} } @article{BachmannSchrederEngelhardtetal.2021, author = {Bachmann, Friederike and Schreder, Martin and Engelhardt, Monika and Langer, Christian and Wolleschak, Denise and M{\"u}gge, Lars Olof and D{\"u}rk, Heinz and Sch{\"a}fer-Eckart, Kerstin and Blau, Igor Wolfgang and Gramatzki, Martin and Liebisch, Peter and Grube, Matthias and Metzler, Ivana v. and Bassermann, Florian and Metzner, Bernd and R{\"o}llig, Christoph and Hertenstein, Bernd and Khandanpour, Cyrus and Dechow, Tobias and Hebart, Holger and Jung, Wolfram and Theurich, Sebastian and Maschmeyer, Georg and Salwender, Hans and Hess, Georg and Bittrich, Max and Rasche, Leo and Brioli, Annamaria and Eckardt, Kai-Uwe and Straka, Christian and Held, Swantje and Einsele, Hermann and Knop, Stefan}, title = {Kinetics of renal function during induction in newly diagnosed multiple myeloma: results of two prospective studies by the German Myeloma Study Group DSMM}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {6}, issn = {2072-6694}, doi = {10.3390/cancers13061322}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234139}, year = {2021}, abstract = {Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3\% at baseline to 1.9\% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49\% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined "renal complete response (CRrenal)" was achieved in 17/25 (68\%) pts after VCD, 12/19 (63\%) after RAD, and 14/27 (52\%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment "renal fitness" in the latter group.}, language = {en} } @article{EgenolfAltenschildescheKressetal.2021, author = {Egenolf, Nadine and Altenschildesche, Caren Meyer zu and Kreß, Luisa and Eggermann, Katja and Namer, Barbara and Gross, Franziska and Klitsch, Alexander and Malzacher, Tobias and Kampik, Daniel and Malik, Rayaz A. and Kurth, Ingo and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan}, title = {Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study}, series = {Therapeutic Advances in Neurological Disorders}, volume = {14}, journal = {Therapeutic Advances in Neurological Disorders}, issn = {1756-2864}, doi = {10.1177/17562864211004318}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232019}, year = {2021}, abstract = {Background and aims: Small fiber neuropathy (SFN) is increasingly suspected in patients with pain of uncertain origin, and making the diagnosis remains a challenge lacking a diagnostic gold standard. Methods: In this case-control study, we prospectively recruited 86 patients with a medical history and clinical phenotype suggestive of SFN. Patients underwent neurological examination, quantitative sensory testing (QST), and distal and proximal skin punch biopsy, and were tested for pain-associated gene loci. Fifty-five of these patients additionally underwent pain-related evoked potentials (PREP), corneal confocal microscopy (CCM), and a quantitative sudomotor axon reflex test (QSART). Results: Abnormal distal intraepidermal nerve fiber density (IENFD) (60/86, 70\%) and neurological examination (53/86, 62\%) most frequently reflected small fiber disease. Adding CCM and/or PREP further increased the number of patients with small fiber impairment to 47/55 (85\%). Genetic testing revealed potentially pathogenic gene variants in 14/86 (16\%) index patients. QST, QSART, and proximal IENFD were of lower impact. Conclusion: We propose to diagnose SFN primarily based on the results of neurological examination and distal IENFD, with more detailed phenotyping in specialized centers.}, language = {en} } @article{KunzHirthSchweitzeretal.2021, author = {Kunz, Felix and Hirth, Matthias and Schweitzer, Tilmann and Linz, Christian and Goetz, Bernhard and Stellzig-Eisenhauer, Angelika and Borchert, Kathrin and B{\"o}hm, Hartmut}, title = {Subjective perception of craniofacial growth asymmetries in patients with deformational plagiocephaly}, series = {Clinical Oral Investigations}, volume = {25}, journal = {Clinical Oral Investigations}, issn = {1432-6981}, doi = {10.1007/s00784-020-03417-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232803}, pages = {525-537}, year = {2021}, abstract = {Objectives The present investigation aimed to evaluate the subjective perception of deformational cranial asymmetries by different observer groups and to compare these subjective perceptions with objective parameters. Materials and methods The 3D datasets of ten infants with different severities of deformational plagiocephaly (DP) were presented to 203 observers, who had been subdivided into five different groups (specialists, pediatricians, medical doctors (not pediatricians), parents of infants with DP, and laypersons). The observers rated their subjective perception of the infants' cranial asymmetries using a 4-point Likert-type scale. The ratings from the observer groups were compared with one another using a multilevel modelling linear regression analysis and were correlated with four commonly used parameters to objectively quantify the cranial asymmetries. Results No significant differences were found between the ratings of the specialists and those of the parents of infants with DP, but both groups provided significantly more asymmetric ratings than did pediatricians, medical doctors, or laypersons. Moreover, the subjective perception of cranial asymmetries correlated significantly with commonly used parameters for objectively quantifying cranial asymmetries. Conclusions Our results demonstrate that different observer groups perceive the severity of cranial asymmetries differently. Pediatricians' more moderate perception of cranial asymmetries may reduce the likelihood of parents to seek therapeutic interventions for their infants. Moreover, we identified some objective symmetry-related parameters that correlated strongly with the observers' subjective perceptions. Clinical relevance Knowledge about these findings is important for clinicians when educating parents of infants with DP about the deformity.}, language = {en} } @article{MerzMerzKirchneretal.2021, author = {Merz, Viktor and Merz, Julia and Kirchner, Maximilian and Lenhart, Julian and Marder, Todd B. and Krueger, Anke}, title = {Pyrene-Based "Turn-Off" Probe with Broad Detection Range for Cu\(^{2+}\), Pb\(^{2+}\) and Hg\(^{2+}\) Ions}, series = {Chemistry—A European Journal}, volume = {27}, journal = {Chemistry—A European Journal}, number = {31}, doi = {10.1002/chem.202100594}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256803}, pages = {8118-8126}, year = {2021}, abstract = {Detection of metals in different environments with high selectivity and specificity is one of the prerequisites of the fight against environmental pollution with these elements. Pyrenes are well suited for the fluorescence sensing in different media. The applied sensing principle typically relies on the formation of intra- and intermolecular excimers, which is however limiting the sensitivity range due to masking of e. g. quenching effects by the excimer emission. Herein we report a highly selective, structurally rigid chemical sensor based on the monomer fluorescence of pyrene moieties bearing triazole groups. This sensor can quantitatively detect Cu\(^{2+}\), Pb\(^{2+}\) and Hg\(^{2+}\) in organic solvents over a broad concentrations range, even in the presence of ubiquitous ions such as Na\(^{+}\), K\(^{+}\), Ca\(^{2+}\) and Mg\(^{2+}\). The strongly emissive sensor's fluorescence with a long lifetime of 165 ns is quenched by a 1 : 1 complex formation upon addition of metal ions in acetonitrile. Upon addition of a tenfold excess of the metal ion to the sensor, agglomerates with a diameter of about 3 nm are formed. Due to complex interactions in the system, conventional linear correlations are not observed for all concentrations. Therefore, a critical comparison between the conventional Job plot interpretation, the method of Benesi-Hildebrand, and a non-linear fit is presented. The reported system enables the specific and robust sensing of medically and environmentally relevant ions in the health-relevant nM range and could be used e. g. for the monitoring of the respective ions in waste streams.}, language = {en} } @article{AnkenbrandLohrSchloetelburgetal.2021, author = {Ankenbrand, Markus Johannes and Lohr, David and Schl{\"o}telburg, Wiebke and Reiter, Theresa and Wech, Tobias and Schreiber, Laura Maria}, title = {Deep learning-based cardiac cine segmentation: Transfer learning application to 7T ultrahigh-field MRI}, series = {Magnetic Resonance in Medicine}, volume = {86}, journal = {Magnetic Resonance in Medicine}, number = {4}, doi = {10.1002/mrm.28822}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257604}, pages = {2179-2191}, year = {2021}, abstract = {Purpose Artificial neural networks show promising performance in automatic segmentation of cardiac MRI. However, training requires large amounts of annotated data and generalization to different vendors, field strengths, sequence parameters, and pathologies is limited. Transfer learning addresses this challenge, but specific recommendations regarding type and amount of data required is lacking. In this study, we assess data requirements for transfer learning to experimental cardiac MRI at 7T where the segmentation task can be challenging. In addition, we provide guidelines, tools, and annotated data to enable transfer learning approaches by other researchers and clinicians. Methods A publicly available segmentation model was used to annotate a publicly available data set. This labeled data set was subsequently used to train a neural network for segmentation of left ventricle and myocardium in cardiac cine MRI. The network is used as starting point for transfer learning to 7T cine data of healthy volunteers (n = 22; 7873 images) by updating the pre-trained weights. Structured and random data subsets of different sizes were used to systematically assess data requirements for successful transfer learning. Results Inconsistencies in the publically available data set were corrected, labels created, and a neural network trained. On 7T cardiac cine images the model pre-trained on public imaging data, acquired at 1.5T and 3T, achieved DICE\(_{LV}\) = 0.835 and DICE\(_{MY}\) = 0.670. Transfer learning using 7T cine data and ImageNet weight initialization improved model performance to DICE\(_{LV}\) = 0.900 and DICE\(_{MY}\) = 0.791. Using only end-systolic and end-diastolic images reduced training data by 90\%, with no negative impact on segmentation performance (DICE\(_{LV}\) = 0.908, DICE\(_{MY}\) = 0.805). Conclusions This work demonstrates and quantifies the benefits of transfer learning for cardiac cine image segmentation. We provide practical guidelines for researchers planning transfer learning projects in cardiac MRI and make data, models, and code publicly available.}, language = {en} } @article{MoraisPasechnikPorod2021, author = {Morais, Ant{\´o}nio P. and Pasechnik, Roman and Porod, Werner}, title = {Grand Unified origin of gauge interactions and families replication in the Standard Model}, series = {Universe}, volume = {7}, journal = {Universe}, number = {12}, issn = {2218-1997}, doi = {10.3390/universe7120461}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250237}, year = {2021}, abstract = {The tremendous phenomenological success of the Standard Model (SM) suggests that its flavor structure and gauge interactions may not be arbitrary but should have a fundamental first-principle explanation. In this work, we explore how the basic distinctive properties of the SM dynamically emerge from a unified New Physics framework tying together both flavor physics and Grand Unified Theory (GUT) concepts. This framework is suggested by a novel anomaly-free supersymmetric chiral E\(_6\)×SU(2)\(_F\)×U(1)\(_F\) GUT containing the SM. Among the most appealing emergent properties of this theory is the Higgs-matter unification with a highly-constrained massless chiral sector featuring two universal Yukawa couplings close to the GUT scale. At the electroweak scale, the minimal SM-like effective field theory limit of this GUT represents a specific flavored three-Higgs doublet model consistent with the observed large hierarchies in the quark mass spectra and mixing already at tree level.}, language = {en} } @article{WagenbrennerMayerWagnerRudertetal.2021, author = {Wagenbrenner, Mike and Mayer-Wagner, Susanne and Rudert, Maximilian and Holzapfel, Boris Michael and Weissenberger, Manuel}, title = {Combinations of hydrogels and mesenchymal stromal cells (MSCs) for cartilage tissue engineering — a review of the literature}, series = {Gels}, volume = {7}, journal = {Gels}, number = {4}, issn = {2310-2861}, doi = {10.3390/gels7040217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250177}, year = {2021}, abstract = {Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering.}, language = {en} } @article{HocheFlockMiaoetal.2021, author = {Hoche, Joscha and Flock, Marco and Miao, Xincheng and Philipp, Luca Nils and Wenzel, Michael and Fischer, Ingo and Mitric, Roland}, title = {Excimer formation dynamics in the isolated tetracene dimer}, series = {Chemical Science}, volume = {12}, journal = {Chemical Science}, number = {36}, doi = {10.1039/D1SC03214C}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251559}, pages = {11965 -- 11975}, year = {2021}, abstract = {The understanding of excimer formation and its interplay with the singlet-correlated triplet pair state \(^{1}\)(TT) is of high significance for the development of efficient organic electronics. Here, we study the photoinduced dynamics of the tetracene dimer in the gas phase by time-resolved photoionisation and photoion imaging experiments as well as nonadiabatic dynamics simulations in order to obtain mechanistic insight into the excimer formation dynamics. The experiments are performed using a picosecond laser system for excitation into the S\(_{2}\) state and reveal a biexponential time dependence. The time constants, obtained as a function of excess energy, lie in the range between ≈10 ps and 100 ps and are assigned to the relaxation of the excimer on the S\(_{1}\) surface and to its deactivation to the ground state. Simulations of the quantum-classical photodynamics are carried out in the frame of the semi-empirical CISD and TD-lc-DFTB methods. Both theoretical approaches reveal a dominating relaxation pathway that is characterised by the formation of a perfectly stacked excimer. TD-lc-DFTB simulations have also uncovered a second relaxation channel into a less stable dimer conformation in the S\(_{1}\) state. Both methods have consistently shown that the electronic and geometric relaxation to the excimer state is completed in less than 10 ps. The inclusion of doubly excited states in the CISD dynamics and their diabatisation further allowed to observe a transient population of the \(^{1}\)(TT) state, which, however, gets depopulated on a timescale of 8 ps, leading finally to the trapping in the excimer minimum.}, language = {en} } @article{StrekalovaVeniaminovaSvirinetal.2021, author = {Strekalova, Tatyana and Veniaminova, Ekaterina and Svirin, Evgeniy and Kopeikina, Ekaterina and Veremeyko, Tatyana and Yung, Amanda W. Y. and Proshin, Andrey and Tan, Shawn Zheng Kai and Khairuddin, Sharafuddin and Lim, Lee Wei and Lesch, Klaus-Peter and Walitza, Susanne and Anthony, Daniel C. and Ponomarev, Eugene D.}, title = {Sex-specific ADHD-like behaviour, altered metabolic functions, and altered EEG activity in sialyltransferase ST3GAL5-deficient mice}, series = {Biomolecules}, volume = {11}, journal = {Biomolecules}, number = {12}, issn = {2218-273X}, doi = {10.3390/biom11121759}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250071}, year = {2021}, abstract = {A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5\(^{-/-}\)) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5\(^{-/-}\) mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5\(^{-/-}\) mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5\(^{-/-}\) mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5\(^{-/-}\) mice. Together, St3gal5\(^{-/-}\) mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.}, language = {en} } @article{FussOtherHeinzeetal.2021, author = {Fuss, Carmina Teresa and Other, Katharina and Heinze, Britta and Landwehr, Laura-Sophie and Wiegering, Armin and Kalogirou, Charis and Hahner, Stefanie and Fassnacht, Martin}, title = {Expression of the chemokine receptor CCR7 in the normal adrenal gland and adrenal tumors and its correlation with clinical outcome in adrenocortical carcinoma}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {22}, issn = {2072-6694}, doi = {10.3390/cancers13225693}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250112}, year = {2021}, abstract = {Background: The chemokine receptor CCR7 is crucial for an intact immune function, but its expression is also associated with clinical outcome in several malignancies. No data exist on the expression of CCR7 in adrenocortical tumors. Methods: CCR7 expression was investigated by qRT-PCR and immunohistochemistry in 4 normal adrenal glands, 59 adrenocortical adenomas, and 181 adrenocortical carcinoma (ACC) samples. Results: CCR7 is highly expressed in the outer adrenocortical zones and medulla. Aldosterone-producing adenomas showed lower CCR7 protein levels (H-score 1.3 ± 1.0) compared to non-functioning (2.4 ± 0.5) and cortisol-producing adenomas (2.3 ± 0.6), whereas protein expression was variable in ACC (1.8 ± 0.8). In ACC, CCR7 protein expression was significantly higher in lymph node metastases (2.5 ± 0.5) compared to primary tumors (1.8±0.8) or distant metastases (2.0 ± 0.4; p < 0.01). mRNA levels of CCR7 were not significantly different between ACCs, normal adrenals, and adrenocortical adenomas. In contrast to other tumor entities, neither CCR7 protein nor mRNA expression significantly impacted patients' survival. Conclusion: We show that CCR7 is expressed on mRNA and protein level across normal adrenals, benign adrenocortical tumors, as well as ACCs. Given that CCR7 did not influence survival in ACC, it is probably not involved in tumor progression, but it could play a role in adrenocortical homeostasis.}, language = {en} } @article{Koelligan2021, author = {K{\"o}lligan, Daniel}, title = {Murmur, heat and bonds - on some words of magic and healing}, series = {Indogermanische Forschungen}, volume = {126}, journal = {Indogermanische Forschungen}, number = {1}, issn = {1613-0405}, doi = {10.1515/if-2021-006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250976}, pages = {107 -- 134}, year = {2021}, abstract = {The paper argues that a) Germanic *tauf/ƀra- (Germ. Zauber, etc.) is related to a root PIE *deu̯p- 'beat; make a hollow sound, resound' found in Greek δοῦπος 'thud', etc., b) Greek φάρμακον goes back to the root PIE *gʷʰer- 'heat' (Gk. θερμός, etc.) implying healing by fomentation, and c) Armenian hiwand 'sick', borrowed from Iranian, to PIE *sh₂ei̯- 'bind' relying on the notion of disease as a supernatural bond.}, language = {en} } @article{Koelligan2021, author = {K{\"o}lligan, Daniel}, title = {A note on Vedic cīti-}, series = {Indogermanische Forschungen}, volume = {126}, journal = {Indogermanische Forschungen}, number = {1}, issn = {1613-0405}, doi = {10.1515/if-2021-007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250986}, pages = {135 -- 140}, year = {2021}, abstract = {Vedic cīti-, attested in the Atharvaveda, is argued to be related to Av. ṣ̌āitī-, OP šiyāti- 'happiness' built to PIE *kʷi̯eh₁- 'to (come to) rest'.}, language = {en} } @article{TamihardjaLutyjKraftetal.2021, author = {Tamihardja, J{\"o}rg and Lutyj, Paul and Kraft, Johannes and Lisowski, Dominik and Weick, Stefan and Flentje, Michael and Polat, B{\"u}lent}, title = {Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis}, series = {Frontiers in Oncology}, volume = {11}, journal = {Frontiers in Oncology}, issn = {2234-943X}, doi = {10.3389/fonc.2021.764536}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250992}, year = {2021}, abstract = {Purpose Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer. Methods 338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90\%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1\%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition. Results Median follow-up was 101.8 months. 15 (4.4\%)/115 (34.0\%)/208 (61.5\%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7\% and 75.9\% for all patients. The estimated 5-year bRFS was 93.3\%, 93.4\% and 79.5\% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5\% and 70.0\%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3\% and 5.0\% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6\%/0.3\%. Conclusions Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.}, language = {en} } @article{StrilciucVecseiBoeringetal.2021, author = {Strilciuc, Stefan and V{\´e}csei, L{\´a}szl{\´o} and Boering, Dana and Pražnikar, Aleš and Kaut, Oliver and Riederer, Peter and Battistin, Leontino}, title = {Safety of Cerebrolysin for neurorecovery after acute ischemic stroke: a systematic review and meta-analysis of twelve randomized-controlled trials}, series = {Pharmaceuticals}, volume = {14}, journal = {Pharmaceuticals}, number = {12}, issn = {1424-8247}, doi = {10.3390/ph14121297}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252403}, year = {2021}, abstract = {We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed, and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis were conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95\% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p > 0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.}, language = {en} } @article{NguemeniHiewKoegleretal.2021, author = {Nguemeni, Carine and Hiew, Shawn and K{\"o}gler, Stefanie and Homola, Gy{\"o}rgy A. and Volkmann, Jens and Zeller, Daniel}, title = {Split-belt training but not cerebellar anodal tDCS improves stability control and reduces risk of fall in patients with multiple sclerosis}, series = {Brain Sciences}, volume = {12}, journal = {Brain Sciences}, number = {1}, issn = {2076-3425}, doi = {10.3390/brainsci12010063}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252179}, year = {2021}, abstract = {The objective of this study was to examine the therapeutic potential of multiple sessions of training on a split-belt treadmill (SBT) combined with cerebellar anodal transcranial direct current stimulation (tDCS) on gait and balance in People with Multiple Sclerosis (PwMS). Twenty-two PwMS received six sessions of anodal (PwMS\(_{real}\), n = 12) or sham (PwMS\(_{sham}\), n = 10) tDCS to the cerebellum prior to performing the locomotor adaptation task on the SBT. To evaluate the effect of the intervention, functional gait assessment (FGA) scores and distance walked in 2 min (2MWT) were measured at the baseline (T0), day 6 (T5), and at the 4-week follow up (T6). Locomotor performance and changes of motor outcomes were similar in PwMS\(_{real}\) and PwMS\(_{sham}\) independently from tDCS mode applied to the cerebellum (anodal vs. sham, on FGA, p = 0.23; and 2MWT, p = 0.49). When the data were pooled across the groups to investigate the effects of multiple sessions of SBT training alone, significant improvement of gait and balance was found on T5 and T6, respectively, relative to baseline (FGA, p < 0.001 for both time points). The FGA change at T6 was significantly higher than at T5 (p = 0.01) underlining a long-lasting improvement. An improvement of the distance walked during the 2MWT was also observed on T5 and T6 relative to T0 (p = 0.002). Multiple sessions of SBT training resulted in a lasting improvement of gait stability and endurance, thus potentially reducing the risk of fall as measured by FGA and 2MWT. Application of cerebellar tDCS during SBT walking had no additional effect on locomotor outcomes.}, language = {en} } @article{KhareDeslauriersMorinetal.2021, author = {Khare, Siddhartha and Deslauriers, Annie and Morin, Hubert and Latifi, Hooman and Rossi, Sergio}, title = {Comparing time-lapse PhenoCams with satellite observations across the boreal forest of Quebec, Canada}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {1}, issn = {2072-4292}, doi = {10.3390/rs14010100}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252213}, year = {2021}, abstract = {Intercomparison of satellite-derived vegetation phenology is scarce in remote locations because of the limited coverage area and low temporal resolution of field observations. By their reliable near-ground observations and high-frequency data collection, PhenoCams can be a robust tool for intercomparison of land surface phenology derived from satellites. This study aims to investigate the transition dates of black spruce (Picea mariana (Mill.) B.S.P.) phenology by comparing fortnightly the MODIS normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI) extracted using the Google Earth Engine (GEE) platform with the daily PhenoCam-based green chromatic coordinate (GCC) index. Data were collected from 2016 to 2019 by PhenoCams installed in six mature stands along a latitudinal gradient of the boreal forests of Quebec, Canada. All time series were fitted by double-logistic functions, and the estimated parameters were compared between NDVI, EVI, and GCC. The onset of GCC occurred in the second week of May, whereas the ending of GCC occurred in the last week of September. We demonstrated that GCC was more correlated with EVI (R\(^2\) from 0.66 to 0.85) than NDVI (R\(^2\) from 0.52 to 0.68). In addition, the onset and ending of phenology were shown to differ by 3.5 and 5.4 days between EVI and GCC, respectively. Larger differences were detected between NDVI and GCC, 17.05 and 26.89 days for the onset and ending, respectively. EVI showed better estimations of the phenological dates than NDVI. This better performance is explained by the higher spectral sensitivity of EVI for multiple canopy leaf layers due to the presence of an additional blue band and an optimized soil factor value. Our study demonstrates that the phenological observations derived from PhenoCam are comparable with the EVI index. We conclude that EVI is more suitable than NDVI to assess phenology in evergreen species of the northern boreal region, where PhenoCam data are not available. The EVI index could be used as a reliable proxy of GCC for monitoring evergreen species phenology in areas with reduced access, or where repeated data collection from remote areas are logistically difficult due to the extreme weather.}, language = {en} } @article{Dosoo2021, author = {Dosoo, Korshi}, title = {Healing traditions in Coptic magical texts}, series = {Trends in Classics}, volume = {13}, journal = {Trends in Classics}, number = {1}, issn = {1866-7473}, doi = {10.1515/tc-2021-0003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251219}, pages = {44 -- 94}, year = {2021}, abstract = {Within the 'market of healing' of Christian Egypt (here broadly considered as the fourth through twelfth centuries CE), 'magical' practitioners represent an elusive yet recurrent category. This article explores the evidence for magical healing from three perspectives - first, literary texts which situate 'magicians' in competition with medical and ecclesiastical healing; second, the papyrological evidence of Coptic-language magical texts, which provide evidence for concepts of disease, wellness, and their mediation; and finally confronting the question of how these healing traditions might be understood within the methodologically materialistic framework of academic history, using the concepts of placebo and healing as a performance.}, language = {en} } @article{SchmidtJakubietzGilbertetal.2021, author = {Schmidt, Karsten and Jakubietz, Michael Georg and Gilbert, Fabian and Fenwick, Annabel and Meffert, Reiner Heribert and Jakubietz, Rafael Gregor}, title = {Muscle cuff in distal pedicled adipofascial sural artery flaps: a retrospective case control study}, series = {PRS Global Open}, volume = {9}, journal = {PRS Global Open}, number = {3}, doi = {10.1097/GOX.0000000000003464}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259875}, year = {2021}, abstract = {Background: Amputation after open tibial fracture occurs in 3\% of cases. The rate increases when flap reconstruction is required. The standard care involves microsurgical tissue transfer although the pedicled reverse sural artery adipofascial flap (PRSAF) is a local alternative in patients endangered by a prolonged operative time. Incorporation of a gastrocnemius muscle cuff in this flap can be used to fill dead space and increase healing potential. Literature shows superior survival rates for both PRSAF and inclusion of a muscle cuff in comparison with the cutaneous version. The aim of the study was to compare the outcome of the PRSAF and the musculoadipofascial version (PRSMAF). We hypothesize that the PRSMAF provides similar lap viability and flap-related complication rates as does the adipofascial version. The muscle component may reduce the long-term osteomyelitis rate. Methods: Patients were evaluated retrospectively after reconstruction with either PRSAF or PRSMAF. Preoperative osteomyelitis, flap survival, complications and osteomyelitis clearance were analyzed. Results: The study shows preliminary results supporting the potential use of the PRSMAF. We compare either 23 PRSMAF or 20 PRSAF flaps. We found no statistically significant differences in flap survival or in complication rate. Conclusions: Although the anatomical situation may sometimes dictate the use of a free flap, a technically less-complicated option may in some cases offer a viable alternative. This study shows that the PRSMAF can serve as an alternative for complex bone defects in the limb, though it does not provide statistical improvement to the PRSAF.}, language = {en} } @article{HojsgaardSchartl2021, author = {Hojsgaard, Diego and Schartl, Manfred}, title = {Skipping sex: A nonrecombinant genomic assemblage of complementary reproductive modules}, series = {BioEssays}, volume = {43}, journal = {BioEssays}, number = {1}, doi = {10.1002/bies.202000111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225818}, year = {2021}, abstract = {The unusual occurrence and developmental diversity of asexual eukaryotes remain a puzzle. De novo formation of a functioning asexual genome requires a unique assembly of sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and to affect discrete components of sexuality and produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, that is, a nonrecombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.}, language = {en} }