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Abstract: The lack of reliable biomarkers in response to anti-TNFα biologicals hinders personalized therapy for Crohn’s disease (CD) patients. The motivation behind our study is to shift the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression signals, which may be masked due to the treatment or ongoing inflammation; Methods: The singlecell RNA sequencing was performed on PBMC samples from CD patients either naïve to biological therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and independent cohort genomic profiling. Replication and meta-analyses were performed using publicly available raw RNA sequencing files of sorted immune cells and an association analysis summary. Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found PLCB1 in CD4+ T cells and CRTAM in double-negative T cells, which met the stringent statistical thresholds throughout the analyses. An additional assessment proved causal inference of both genes in response to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy or inflammation.
Keywords: inflammatory bowel diseases, Crohn’s disease, tumor necrosis factor alpha, adalimumab, single-cell gene expression analysis
Published in DKUM: 10.12.2024; Views: 0; Downloads: 3
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Abstract: This paper introduces a new method for the region segmentation of images. The approach is based on the raster-scan paradigm and builds the segments incrementally. The pixels are processed in the raster-scan order, while the construction of the segments is based on a distance metric in regard to the already segmented pixels in the neighbourhood. The segmentation procedure operates in linear time according to the total number of pixels. The proposed method, named the RSM (raster-scan segmentation method), was tested on selected images from the popular benchmark datasets MS COCO and DIV2K. The experimental results indicate that our method successfully extracts regions with similar pixel values. Furthermore, a comparison with two of the well-known segmentation methods—Watershed and DBSCAN—demonstrates that the proposed approach is superior in regard to efficiency while yielding visually similar results.
Keywords: segment, image analysis, distance metric, Watershed, DBSCAN
Published in DKUM: 05.12.2024; Views: 0; Downloads: 2
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Abstract: The content of this paper presents the research results of a three-year research project in which a multi-criteria evaluation model (according to the DEX methodology) was developed for the evaluation of three different food sectors (represented by a cattle breeding chain, a pig farming chain, and a milk production chain) with added value in Slovenia. Indicators for the assessment of the economically, socially, and environmentally sustainable development of food chains were taken into account. The data for the analysis, such as prices and costs of food, wage levels by sector, food miles and others, were obtained from various public services between 2020 and 2023. The final qualitative assessment of the food sectors was uniform (“average”), while the longest analysis of the results using the plus-minus-1 analysis method showed the reasons for such an assessment in individual sectors (such as the ratio between the price of agricultural products and the price of agricultural inputs is poor, the ratio between average gross salary in the individual food sector and gross salary in the agricultural sector is poor, etc.). In addition to the results already mentioned, recommendations or suggestions for building a sustainable food chain were made using the results of the modelling. The research results contributed to a better understanding of the importance of stable relationships between different groups of indicators and later showed their importance for improving the functioning of agri-food chains. The results of the research will help various stakeholders (such as the agricultural advisory service, decision-makers at the level of agricultural policy, researchers in further analyses, and especially the international professional public interested in various case studies from EU countries) to further analyse and plan for the organisation of the agricultural sector.
Keywords: food sectors, value added, DEX methodology, plus-minus-1 analysis, Slovenia
Published in DKUM: 29.11.2024; Views: 0; Downloads: 4
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Abstract: The static and dynamic loading capacities of components depend on the stress level to which the material is exposed. The fatigue behavior of materials manufactured using additive technology is accompanied by a pronounced scatter between the number of cycles at the same stress level, which is significantly greater than the scatter from a material with the same chemical composition, e.g., AISI 316L, but produced by rolling or forging. An important reason lies in the fact that fatigue cracks are initiated almost always below the material surface of the loaded specimen. Thus, in the article, assuming that a crack will always initiate below the surface, we analyzed the fatigue behavior of specimens with the same bearing cross section but with a different number of bearing rods. With a larger number of rods, the circumference around the supporting part of the rods was 1.73 times larger. Thus, experimental fatigue of specimens with different sizes showed that the dynamic loading capacity of components with a smaller number of bars is significantly greater and can be monitored by individual stress levels. Although there are no significant differences in loading capacity under static and low-cycle loading of materials manufactured with additive technologies, in high-cycle fatigue it has been shown that the ratio between the circumference and the loading cross section of tensile-loaded rods plays an important role in the lifetime. This finding is important for setting a strategy for manufacturing components with additive technologies. It shows that a better dynamic loading capacity can be obtained with a larger loading cross section.
Keywords: AISI 316L stainless steel, additive manufacturing, FEM, high-cycle fatigue, fractography analysis
Published in DKUM: 25.11.2024; Views: 0; Downloads: 8
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Abstract: Many details of glucose-stimulated intracellular calcium changes in [beta] cells during activation, activity, and deactivation, as well as their concentration-dependence, remain to be analyzed. Classical physiological experiments indicated that in islets, functional differences between individual cells are largely attenuated, but recent findings suggest considerable intercellular heterogeneity, with some cells possibly coordinating the collective responses. To address the above with an emphasis on heterogeneity and describing the relations between classical physiological and functional network properties, we performed functional multicellular calcium imaging in mouse pancreas tissue slices over a wide range of glucose concentrations. During activation, delays to activation of cells and any-cell-to-first-responder delays are shortened, and the sizes of simultaneously responding clusters increased with increasing glucose concentrations. Exactly the opposite characterized deactivation. The frequency of fast calcium oscillations during activity increased with increasing glucose up to 12 mM glucose concentration, beyond which oscillation duration became longer, resulting in a homogenous increase in active time. In terms of functional connectivity, islets progressed from a very segregated network to a single large functional unit with increasing glucose concentration. A comparison between classical physiological and network parameters revealed that the first-responders during activation had longer active times during plateau and the most active cells during the plateau tended to deactivate later. Cells with the most functional connections tended to activate sooner, have longer active times, and deactivate later. Our findings provide a common ground for recent differing views on [beta] cell heterogeneity and an important baseline for future studies of stimulus-secretion and intercellular coupling. NEW & NOTEWORTHY: We assessed concentration-dependence in coupled [beta] cells, degree of functional heterogeneity, and uncovered possible specialized subpopulations during the different phases of the response to glucose at the level of many individual cells. To this aim, we combined acute mouse pancreas tissue slices with functional multicellular calcium imaging over a wide range from threshold (7 mM) and physiological (8 and 9 mM) to supraphysiological (12 and 16 mM) glucose concentrations, classical physiological, and advanced network analyses.
Keywords: beta cells, calcium imaging, glucose-dependence, network analysis
Published in DKUM: 15.10.2024; Views: 0; Downloads: 6
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