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ZusammenfassungDigitales Lernen in religiösen Bildungsprozessen befasst sich besonders mit medienethischen Fragestellungen. Sexting und Cybermobbing werden als riskantes Mediennutzungsverhalten von Jugendlichen bewertet. Im Rahmen der schulischen Präventionsarbeit wird daher vor allem die Schuldfrage thematisiert. Die besondere Herausforderung für die Religionspädagogik besteht in der Wahrnehmung der Schamerfahrungen für die Identitätsentwicklung von Mädchen und Jungen in den erweiterten sozialen Räumen der digitalen Kommunikationsmittel. In Anlehnung an die Schamethik von Klaas Huizing und der medienweltorientierten Religionsdidaktik von Manfred Pirner verfolgt eine evangelische Mediennutzungsethik der Schamsensibilisierung (Kristian Fechtner) das Ziel der Kompetenzentwicklung von Mitgefühl und Widerstandsfähigkeit.
Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe−/−, n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe−/− mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability.
Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrations in human serum, but might reach tissue concentrations similar to those of T4 and T3, at least based on data from rodent models. However, the immunoassay-based measurements in human sera revealed remarkable variations depending on antibodies used in the assays and thus need to be interpreted with caution. In clinical experimental approaches in euthyroid volunteers and hypothyroid patients using the immunoassay as the analytical tool no evidence of formation of 3,5-T2 from its putative precursors T4 or T3 was found, nor was any support found for the assumption that 3,5-T2 might represent a direct precursor for serum 3-T1-AM generated by combined deiodination and decarboxylation from 3,5-T2, as previously documented for mouse intestinal mucosa. We hypothesized that lowered endogenous production of 3,5-T2 in patients requiring T4 replacement therapy after thyroidectomy or for treatment of autoimmune thyroid disease, compared to production of 3,5-T2 in individuals with intact thyroid glands might contribute to the discontent seen in a subset of patients with this therapeutic regimen. So far, our observations do not support this assumption. However, the unexpected association between high serum 3,5-T2 and elevated urinary concentrations of metabolites related to coffee consumption requires further studies for an explanation. Elevated 3,5-T2 serum concentrations were found in several situations including impaired renal function, chronic dialysis, sepsis, non-survival in the ICU as well as post-operative atrial fibrillation (POAF) in studies using a monoclonal antibody-based chemoluminescence immunoassay. Pilot analysis of human sera using LC-linear-ion-trap-mass-spectrometry yielded 3,5-T2 concentrations below the limit of quantification in the majority of cases, thus the divergent results of both methods need to be reconciliated by further studies. Although positive anti-steatotic effects have been observed in rodent models, use of 3,5-T2 as a muscle anabolic, slimming or fitness drug, easily obtained without medical prescription, must be advised against, considering its potency in suppressing the HPT axis and causing adverse cardiac side effects. 3,5-T2 escapes regular detection by commercially available clinical routine assays used for thyroid function tests, which may be seriously disrupted in individuals self-administering 3,5-T2 obtained over-the counter or from other sources.
Overexpression of polo-like kinase 1 (PLK1) has been found in many different types of cancers. With its essential role in cell proliferation, PLK1 has been determined to be a broad-spectrum anti-cancer target. In this study, 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations were applied on a series of novel pteridinone derivatives as PLK1 inhibitors to discover anti-cancer drug candidates. In this work, three models—CoMFA (Q² = 0.67, R² = 0.992), CoMSIA/SHE (Q² = 0.69, R² = 0.974), and CoMSIA/SEAH (Q² = 0.66, R² = 0.975)—of pteridinone derivatives were established. The three models that were established gave R²(pred) = 0.683, R²(pred) = 0.758, and R²(pred) = 0.767, respectively. Thus, the predictive abilities of the three proposed models were successfully evaluated. The relations between the different champs and activities were well-demonstrated by the contour chart of the CoMFA and CoMSIA/SEAH models. The results of molecular docking indicated that residues R136, R57, Y133, L69, L82, and Y139 were the active sites of the PLK1 protein (PDB code: 2RKU), in which the more active ligands can inhibit the enzyme of PLK1. The results of the molecular dynamic MD simulation diagram were obtained to reinforce the previous molecular docking results, which showed that both inhibitors remained stable in the active sites of the PLK1 protein (PDB code: 2RKU) for 50 ns. Finally, a check of the ADME-Tox properties of the two most active molecules showed that molecular N° 28 could represent a good drug candidate for the therapy of prostate cancer diseases.
40-Year Longitudinal Caries Development in German Adolescents in the Light of New Caries Measures
(2019)
This study assessed the 40-year longitudinal caries development in German adolescents in the light of the sixth National Oral Health Survey in Children (NOHSC, 2016) employing initial DMFT (IDMFT), Significant Caries Index (SiC) and Specific Affected Caries Index (SaC). On the basis of the current NOHSC (randomized cluster selection using school list or regional community school surveys, 55,956 12-year-old sixth-graders examined by 482 calibrated community/study dentists) DMFT, SiC, a novel IDMFT including initial lesions (IT) and the recently introduced SaC were calculated and also recalculated for national and international surveys from the last 4 decades. In 2016, 78.8% of children were caries-free (DMFT = 0), 65.5% including IT lesions. The mean DMFT was 0.44 (single components: DT = 0.14, MT = 0.02, FT = 0.29, IT = 0.52) showing a clear association with the school type as marker for the socio-economic status. The mean number of affected teeth in children with DMFT >0 was 2.07 (SaC) in comparison to almost 9 teeth in the 1970s. The current care index on the tooth level was 66.3%, leaving only 7.7% of children with restorative treatment needs. Longitudinally, a continuous caries decline of more than 80%, including the risk groups (SiC/SaC), to an internationally extremely low level was observed. In conclusion, the National Oral Health Surveys reveal a continuous caries decline to a very low caries level in 12-year-old 6th-graders in Germany even if IT lesions are included (IDMFT). In spite of proportional reductions in the risk groups (SiC/SaC), the polarized caries distribution according to socio-economic parameters reveals the need for targeted preventive programmes.
Abstract
Amphidiploid fungal Verticillium longisporum strains Vl43 and Vl32 colonize the plant host Brassica napus but differ in their ability to cause disease symptoms. These strains represent two V. longisporum lineages derived from different hybridization events of haploid parental Verticillium strains. Vl32 and Vl43 carry same‐sex mating‐type genes derived from both parental lineages. Vl32 and Vl43 similarly colonize and penetrate plant roots, but asymptomatic Vl32 proliferation in planta is lower than virulent Vl43. The highly conserved Vl43 and Vl32 genomes include less than 1% unique genes, and the karyotypes of 15 or 16 chromosomes display changed genetic synteny due to substantial genomic reshuffling. A 20 kb Vl43 lineage‐specific (LS) region apparently originating from the Verticillium dahliae‐related ancestor is specific for symptomatic Vl43 and encodes seven genes, including two putative transcription factors. Either partial or complete deletion of this LS region in Vl43 did not reduce virulence but led to induction of even more severe disease symptoms in rapeseed. This suggests that the LS insertion in the genome of symptomatic V. longisporum Vl43 mediates virulence‐reducing functions, limits damage on the host plant, and therefore tames Vl43 from being even more virulent.
Oral mucositis is the most common and severe non-hematological complication associated with cancer radiotherapy, chemotherapy, or their combination. Treatment of oral mucositis focuses on pain management and the use of natural anti-inflammatory, sometimes weakly antiseptic mouth rinses in combination with optimal oral cavity hygiene. To prevent negative effects of rinsing, accurate testing of oral care products is necessary. Due to their ability to mimic realistic in-vivo conditions, 3D models may be an appropriate option in compatibility testing of anti-inflammatory and antiseptically effective mouth rinses. We present a 3D model of oral mucosa based on the cell line TR-146 with a physical barrier, characterized by high transepithelial electrical resistance (TEER) and confirmed cell integrity. Histological characterization of the 3D mucosa model showed a stratified, non-keratinized multilayer of epithelial cells similar to that of human oral mucosa. By means of immuno-staining, tissue-specific expression of cytokeratin 13 and 14 was shown. Incubation of the 3D mucosa model with the rinses had no effects on cell viability, but TEER decreased 24h after incubation in all solutions except ProntOral®. Analogous to skin models, the established 3D model meets the quality control criteria of OECD guidelines and may therefore be suitable for comparing the cytocompatibility of oral rinses.
Abstract
Environmentally‐friendly processes for the manufacturing of valuable industrial compounds like ω‐hydroxy fatty acids (ω‐OHFAs) are highly desirable. Herein, we present such an approach by establishing a two‐step enzymatic cascade reaction for the production of 2,15,16‐trihydroxy hexadecanoic acid (THA). Starting with the easily accessible natural compound ustilagic acid (UA) that is secreted by the corn smut fungus Ustilago maydis, the recombinantly expressed esterase BS2 from Bacillus subtilis and the commercial β‐glucosidase from almonds were applied yielding 86 % product. Both hydrolases do not require expensive cofactors, making the process economically attractive. Additionally, no harmful solvents are required, so that the product THA can be labelled natural to be used in food and cosmetic products.
Introduction: It has been shown that Alzheimer’s disease (AD) is accompanied by marked structural brain changes that can be detected several years before clinical diagnosis via structural magnetic resonance (MR) imaging. In this study, we developed a structural MR-based biomarker for in vivo detection of AD using a supervised machine learning approach. Based on an individual’s pattern of brain atrophy a continuous AD score is assigned which measures the similarity with brain atrophy patterns seen in clinical cases of AD.
Methods: The underlying statistical model was trained with MR scans of patients and healthy controls from the Alzheimer’s Disease Neuroimaging Initiative (ADNI-1 screening). Validation was performed within ADNI-1 and in an independent patient sample from the Open Access Series of Imaging Studies (OASIS-1). In addition, our analyses included data from a large general population sample of the Study of Health in Pomerania (SHIP-Trend).
Results: Based on the proposed AD score we were able to differentiate patients from healthy controls in ADNI-1 and OASIS-1 with an accuracy of 89% (AUC = 95%) and 87% (AUC = 93%), respectively. Moreover, we found the AD score to be significantly associated with cognitive functioning as assessed by the Mini-Mental State Examination in the OASIS-1 sample after correcting for diagnosis, age, sex, age·sex, and total intracranial volume (Cohen’s f2 = 0.13). Additional analyses showed that the prediction accuracy of AD status based on both the AD score and the MMSE score is significantly higher than when using just one of them. In SHIP-Trend we found the AD score to be weakly but significantly associated with a test of verbal memory consisting of an immediate and a delayed word list recall (again after correcting for age, sex, age·sex, and total intracranial volume, Cohen’s f2 = 0.009). This association was mainly driven by the immediate recall performance.
Discussion: In summary, our proposed biomarker well differentiated between patients and healthy controls in an independent test sample. It was associated with measures of cognitive functioning both in a patient sample and a general population sample. Our approach might be useful for defining robust MR-based biomarkers for other neurodegenerative diseases, too.
Our goal was to provide a comprehensive overview of the antibody response to Staphylococcus aureus antigens in the general population as a basis for defining disease-specific profiles and diagnostic signatures. We tested the specific IgG and IgA responses to 79 staphylococcal antigens in 996 individuals from the population-based Study of Health in Pomerania. Using a dilution-based multiplex suspension array, we extended the dynamic range of specific antibody detection to seven orders of magnitude, allowing the precise quantification of high and low abundant antibody specificities in the same sample. The observed IgG and IgA antibody responses were highly heterogeneous with differences between individuals as well as between bacterial antigens that spanned several orders of magnitude. Some antigens elicited significantly more IgG than IgA and vice versa. We confirmed a strong influence of colonization on the antibody response and quantified the influence of sex, smoking, age, body mass index, and serum glucose on anti-staphylococcal IgG and IgA. However, all host parameters tested explain only a small part of the extensive variability in individual response to the different antigens of S. aureus.
Dengue virus (DV) is a positive-strand RNA virus of the Flavivirus genus. It is one of the most prevalent mosquito-borne viruses, infecting globally 390 million individuals per year. The clinical spectrum of DV infection ranges from an asymptomatic course to severe complications such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), the latter because of severe plasma leakage. Given that the outcome of infection is likely determined by the kinetics of viral replication and the antiviral host cell immune response (HIR) it is of importance to understand the interaction between these two parameters. In this study, we use mathematical modeling to characterize and understand the complex interplay between intracellular DV replication and the host cells' defense mechanisms. We first measured viral RNA, viral protein, and virus particle production in Huh7 cells, which exhibit a notoriously weak intrinsic antiviral response. Based on these measurements, we developed a detailed intracellular DV replication model. We then measured replication in IFN competent A549 cells and used this data to couple the replication model with a model describing IFN activation and production of IFN stimulated genes (ISGs), as well as their interplay with DV replication. By comparing the cell line specific DV replication, we found that host factors involved in replication complex formation and virus particle production are crucial for replication efficiency. Regarding possible modes of action of the HIR, our model fits suggest that the HIR mainly affects DV RNA translation initiation, cytosolic DV RNA degradation, and naïve cell infection. We further analyzed the potential of direct acting antiviral drugs targeting different processes of the DV lifecycle in silico and found that targeting RNA synthesis and virus assembly and release are the most promising anti-DV drug targets.
Background: Previous studies suggest that blood donation impacts blood donors’ psychological state, with either positive or negative effects, such as feeling more energetic or more exhausted. It has not yet been described how long these effects last. Materials and Methods: This prospective cohort study consisted of a qualitative and a quantitative part: (1) Psychological characteristics which changed after blood donation were identified by structured interviews of regular whole blood donors (n = 42). Based on this, a questionnaire addressing 7 psychological dimensions was established. (2) The psychological state of 100 blood donors was assessed after blood donation by applying the questionnaire 15–30 min before and during donation, as well as 15–30 min, 6 h, 24 h, 72 h, 1 week, and 8 weeks after donation. The resulting changes were summarized to a score. Furthermore, potential correlations of the score with pre-donation blood pressure, hemoglobin, or body mass index were calculated. Results: Seven items were identified which changed in at least 25% of blood donors (mood, concentration, satisfaction, resilience, spirit of initiative, physical well-being, energy level). In the 100 blood donors, the well-being score increased (positive effects, n = 23), showed minor changes (n = 53), or decreased (negative effects, n = 24). The positive effects lasted for about 1 week and the negative effects for 3 days. Conclusion: While the frequency of psychological effects following blood donation identified by our study was comparable to others, the changes of the psychological state in our donors were traceable for a longer period than previously acknowledged.
We introduce PVSC-DTM (Parallel Vectorized Stencil Code for Dirac and Topological Materials), a library and code generator based on a domain-specific language tailored to implement the specific stencil-like algorithms that can describe Dirac and topological materials such as graphene and topological insulators in a matrix-free way. The generated hybrid-parallel (MPI+OpenMP) code is fully vectorized using Single Instruction Multiple Data (SIMD) extensions. It is significantly faster than matrix-based approaches on the node level and performs in accordance with the roofline model. We demonstrate the chip-level performance and distributed-memory scalability of basic building blocks such as sparse matrix-(multiple-) vector multiplication on modern multicore CPUs. As an application example, we use the PVSC-DTM scheme to (i) explore the scattering of a Dirac wave on an array of gate-defined quantum dots, to (ii) calculate a bunch of interior eigenvalues for strong topological insulators, and to (iii) discuss the photoemission spectra of a disordered Weyl semimetal.
Background
The Federal Ministry of Education and Research of Germany (BMBF) funds a network of university medicines (NUM) to support COVID-19 and pandemic research at national level. The “COVID-19 Data Exchange Platform” (CODEX) as part of NUM establishes a harmonised infrastructure that supports research use of COVID-19 datasets. The broad consent (BC) of the Medical Informatics Initiative (MII) is agreed by all German federal states and forms the legal base for data processing. All 34 participating university hospitals (NUM sites) work upon a harmonised infrastructural as well as legal basis for their data protection-compliant collection and transfer of their research dataset to the central CODEX platform. Each NUM site ensures that the exchanged consent information conforms to the already-balloted HL7 FHIR consent profiles and the interoperability concept of the MII Task Force “Consent Implementation” (TFCI). The Independent Trusted Third-Party (TTP) of the University Medicine Greifswald supports data protection-compliant data processing and provides the consent management solutions gICS.
Methods
Based on a stakeholder dialogue a required set of FHIR-functionalities was identified and technically specified supported by official FHIR experts. Next, a “TTP-FHIR Gateway” for the HL7 FHIR-compliant exchange of consent information using gICS was implemented. A last step included external integration tests and the development of a pre-configured consent template for the BC for the NUM sites.
Results
A FHIR-compliant gICS-release and a corresponding consent template for the BC were provided to all NUM sites in June 2021. All FHIR functionalities comply with the already-balloted FHIR consent profiles of the HL7 Working Group Consent Management. The consent template simplifies the technical BC rollout and the corresponding implementation of the TFCI interoperability concept at the NUM sites.
Conclusions
This article shows that a HL7 FHIR-compliant and interoperable nationwide exchange of consent information could be built using of the consent management software gICS and the provided TTP-FHIR Gateway. The initial functional scope of the solution covers the requirements identified in the NUM-CODEX setting. The semantic correctness of these functionalities was validated by project-partners from the Ludwig-Maximilian University in Munich. The production rollout of the solution package to all NUM sites has started successfully.
Diagenetic illite growth in porous sandstones leads to significant modifications of the initial pore system which result in tight reservoirs. Understanding and quantifying these changes provides insight into the porosity-permeability history of the reservoir and improves predictions on petrophysical behavior. To characterize the various stages of diagenetic alteration, a focused ion beam – scanning electron microscopy (FIB-SEM) study was undertaken on aeolian sandstones from the Bebertal outcrop of the Parchim Formation (Early Permian Upper Rotliegend group). Based on 3D microscopic reconstructions, three different textural types of illite crystals occur, common to many tight Rotliegend sandstones, namely (1) feldspar grain alterations and associated illite meshworks, (2) tangential grain coats, and (3) pore-filling laths and fibers. Reaction textures, pore structure quantifications, and numerical simulations of fluid transport have revealed that different generations of nano-porosity are connected to the diagenetic alteration of feldspars and the authigenic growth of pore-filling illites. The latter leads to the formation of microstructures that range from authigenic compact tangential grain coatings to highly porous, pore-filling structures. K-feldspar replacement and initial grain coatings of illite are composed primarily of disordered 1Md illite whereas the epitaxially grown illite lath- and fiber-shaped crystals occurring as pore-filling structures are of the trans-vacant 1Mtv polytype. Although all analyzed 3D structures offer connected pathways, the largest reduction in sandstone permeability occurred during the initial formation of the tangential illite coatings that sealed altered feldspars and the subsequent growth of pore-filling laths and fibrous illites. Analyses of both illite pore-size and crystallite-size distributions indicate that crystal growth occurred by a continuous nucleation and growth mechanism probably controlled by the multiple influx of potassium-rich fluids during late Triassic and Jurassic times. The detailed insight into the textural varieties of illite crystal growth and its calculated permeabilities provides important constraints for understanding the complexities of fluid-flow in tight reservoir sandstones.
Lacewings (Neuroptera) have predatory larvae with highly specialised mouthparts. Larvae of many groups within Neuroptera are well represented as fossils preserved in ambers; however, larvae of some groups are less often reported in the literature. Here we report such a rare case, a larva of the group Hemerobiidae, an aphidlion, preserved in a piece of Eocene Baltic amber (about 40 million years old). It is preserved together with three possible prey items, wingless aphids, most likely representatives of Germaraphis (or at least closely related to this group). The aphidlion can be identified based on the morphology of the antennae, simple curved and toothless stylets, well developed labial palps, and the absence of other mouth-part structures such as a protruding labrum or maxillary palps. A long, club-shaped distal element of the labial palps identifies the specimen as a larva of Hemerobiidae. The aphids can be identified based on their very long, beak-like mouth parts. This find is, to our knowledge, the first example of a lacewing larva preserved together with its potential prey. We briefly discuss other cases in which fossils preserved in amber allow us to reconstruct aspects of behaviour and interactions of fossil lacewing larvae.