OPUS THD (Technischen Hochschule Deggendorf)
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Humoral immune response and live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant after COVID-19 mRNA vaccination in children and young adults with chronic kidney disease
Background
Data on humoral immune response to standard COVID-19 vaccination are scarce in adolescent patients and lacking for children below 12 years of age with chronic kidney disease including kidney transplant recipients.
Methods
We therefore investigated in this retrospective two-center study (DRKS00024668; registered 23.03.2021) the humoral immune response to a standard two-dose mRNA vaccine regimen in 123 CKD patients aged 5–30 years. A live-virus assay was used to assess the serum neutralizing activity against the SARS-CoV-2 omicron (BA.1) variant.
Results
Children aged 5–11 years had a comparable rate and degree of immune response to adolescents despite lower vaccine doses (10 µg vs. 30 µg BNT162b2). Treatment with two (odds ratio 9.24) or three or more (odds ratio 17.07) immunosuppressants was an independent risk factor for nonresponse. The immune response differed significantly among three patient cohorts: 48 of 77 (62.3%) kidney transplant recipients, 21 of 26 (80.8%) patients on immunosuppressive therapy, and 19 of 20 (95.0%) patients with chronic kidney disease without immunosuppressive therapy responded. In the kidney transplant recipients, immunosuppressive regimens comprising mycophenolate mofetil, an eGFR of < 60 mL/min/1.73 m2, and female sex were independent risk factors for nonresponse. Two of 18 (11.1%) and 8 of 16 (50.0%) patients with an anti-S1-RBD IgG of 100–1411 and 1411 BAU/mL, respectively, showed a neutralization activity against the omicron variant.
Conclusion
A standard mRNA vaccine regimen in immunosuppressed children and adolescents with kidney disease elicits an attenuated humoral immune response with effective live virus neutralization against the omicron variant in approximately 10% of the patients, underlying the need for omicron-adapted vaccination
A 3D In Vivo Model for Studying Human Renal Cystic Tissue and Mouse Kidney Slices
(1) Background: Autosomal dominant polycystic kidney disease (ADPKD) is a frequent monogenic disorder that leads to progressive renal cyst growth and renal failure. Strategies to inhibit cyst growth in non-human cyst models have often failed in clinical trials. There is a significant need for models that enable studies of human cyst growth and drug trials.
(2) Methods: Renal tissue from ADPKD patients who received a nephrectomy as well as adult mouse kidney slices were cultured on a chorioallantoic membrane (CAM) for one week. The cyst volume was monitored by microscopic and CT-based applications. The weight and angiogenesis were quantified. Morphometric and histological analyses were performed after the removal of the tissues from the CAM.
(3) Results: The mouse and human renal tissue mostly remained vital for about one week on the CAM. The growth of cystic tissue was evaluated using microscopic and CT-based volume measurements, which correlated with weight and an increase in angiogenesis, and was accompanied by cyst cell proliferation.
(4) Conclusions: The CAM model might bridge the gap between animal studies and clinical trials of human cyst growth, and provide a drug-testing platform for the inhibition of cyst enlargement. Real-time analyses of mouse kidney tissue may provide insights into renal physiology and reduce the need for animal experiments
Professionalization and Corporate Social Responsibility: A Comparative Study on German and US Job Requirements in CSR
Given the steady interest in corporate social responsibility (CSR), this study explores the process of professionalization of CSR. Drawing upon the literature on ‘organizational’ professionals, explicit and implicit CSR, as well as varieties of capitalism, professionalization of CSR is explored in order to trace processes of explicitization and potential cross-national differences between the United States and Germany. In a comparative longitudinal study, we analyse job announcements in the field of CSR and find that although the hybridity of explicit and implicit CSR between the US and Germany is starting to unfold, job characteristics and job requirements in CSR in Germany and the US are still not the same. Our results suggest there is a more distinct trend in professionalization in the US than in Germany in terms of the manifestation of explicit CSR and that the institutional context is linked to how employers drive professionalization processes in non-traditional professions
Loss of Gene Information: Discrepancies between RNA Sequencing, cDNA Microarray, and qRT-PCR
Molecular analyses of normal and diseased cells give insight into changes in gene expression and help in understanding the background of pathophysiological processes. Years after cDNA microarrays were established in research, RNA sequencing (RNA-seq) became a key method of quantitatively measuring the transcriptome. In this study, we compared the detection of genes by each of the transcriptome analysis methods: cDNA array, quantitative RT-PCR, and RNA-seq. As expected, we found differences in the gene expression profiles of the aforementioned techniques. Here, we present selected genes that exemplarily demonstrate the observed differences and calculations to reveal that a strong RNA secondary structure, as well as sample preparation, can affect RNA-seq. In summary, this study addresses an important issue with a strong impact on gene expression analysis in general. Therefore, we suggest that these findings need to be considered when dealing with data from transcriptome analyses
Virtual Description of Non-Crimp Fabrics at the Scale of Filaments Including Orientation Variability in the Fibrous Layers
A numerical description of dry non-crimp fabrics is proposed at the scale of the filaments using a commercially available finite element software package. Deviations in the filament orientation of the fibrous layer is a dominant factor in the occurrence of local defects, which influences the mechanical response of the textile. Therefore, the introduction of variability in the orientation distribution is proposed in this paper. This approach enables to capture the entanglement of the filaments and models all interaction mechanisms. A stepwise generation of the numerical non-crimp fabric is proposed considering the main manufacturing steps to reproduce the local defects in the fibrous mat appropriately. Averaged periodic boundary conditions are developed ensuring an overall periodicity of the model while allowing reorientation at the scale of the filaments. Two various non-crimp fabrics are investigated and modelled. The distribution of the filaments in the simulation results correlate well with measurements of the filament orientation performed on the textiles. Moreover, a detailed comparison of the local defects shows a good agreement with measurements on the specimens. The presented approach can be used to generate geometries for subsequent virtual characterization
On the one-to-one pickup-and-delivery problem with time windows and trailers
This paper studies an extension of the well-known one-to-one pickup-and-delivery problem with time windows. In the latter problem, requests to transport goods from pickup to delivery locations must be fulfilled by a set of vehicles with limited capacity subject to time window constraints. Goods are not interchangeable: what is picked up at one particular location must be delivered to one particular other location. The discussed extension consists in the consideration of a heterogeneous vehicle fleet comprising lorries with detachable trailers. Trailers are advantageous as they increase the overall vehicle capacity. However, some locations may be accessible only by lorries. Therefore, special locations are available where trailers can be parked while lorries visit accessibility-constrained locations. This induces a nontrivial tradeoff between an enlarged vehicle capacity and the necessity of scheduling detours for parking and reattaching trailers. The contribution of the paper is threefold: (i) it studies a practically relevant generalization of the one-to-one pickup-and-delivery problem with time windows. (ii) It develops an exact amortized constant-time procedure for testing the feasibility of an insertion of a transport task into a given route with regard to time windows and lorry and trailer capacities. (iii) It provides a comprehensive set of new benchmark instances on which the runtime of the constant-time test is compared with a naïve one that requires linear time by embedding both tests in an adaptive large neighbourhood search algorithm. Computational experiments show that the constant-time test outperforms its linear-time counterpart by one order of magnitude on average