Serum protein fingerprinting by PEA immunoassay coupled with a pattern-recognition algorithms distinguishes MGUS and multiple myeloma

Serum protein fingerprints associated with MGUS and MM and their changes in MM after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored. Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, P-corr=.0004), Growth differentiation factor 15 (GDF15, P-corr=.003), and soluble Major histocompatibility complex class I-related chain A (sMICA, P-corr=.023), all prosurvival and chemoprotective factors for myeloma cells, were detected in MM comparing to MGUS. Comparison of MGUS and healthy subjects revealed elevation of angiogenic and antia-poptotic midkine (P-corr=.0007) and downregulation of Transforming growth factor beta 1 (TGFB1, P-corr=.005) in MGUS. Importantly, altered serum pattern was associated with MM-ASCT compared to paired MM at the diagnosis as well as to healthy controls, namely by upregulated B-Cell Activating Factor (sBAFF) (P-corr<.006) and sustained elevation of other pro-tumorigenic factors. In conclusion, the serum fingerprints of MM and MM-ASCT were characteristic by elevated levels of prosurvival and chemoprotective factors for myeloma cells.Web of Science841694216940

Next-generation optical mapping reveals numerous previously unrecognizable structural variants in multiple myeloma

Web of Science1910E64E6

Cross-linked gelatine by modified dextran as a potential bioink prepared by a simple and non-toxic process

Essential features of well-designed materials intended for 3D bioprinting via microextrusion are the appropriate rheological behavior and cell-friendly environment. Despite the rapid development, few materials are utilizable as bioinks. The aim of our work was to design a novel cytocompatible material facilitating extrusion-based 3D printing while maintaining a relatively simple and straightforward preparation process without the need for harsh chemicals or radiation. Specifically, hydrogels were prepared from gelatines coming from three sources-bovine, rabbit, and chicken-cross-linked by dextran polyaldehyde. The influence of dextran concentration on the properties of hydrogels was studied. Rheological measurements not only confirmed the strong shear-thinning behavior of prepared inks but were also used for capturing cross-linking reaction kinetics and demonstrated quick achievement of gelation point (in most cases < 3 min). Their viscoelastic properties allowed satisfactory extrusion, forming a self-supported multi-layered uniformly porous structure. All gelatin-based hydrogels were non-cytototoxic. Homogeneous cells distribution within the printed scaffold was confirmed by fluorescence confocal microscopy. In addition, no disruption of cells structure was observed. The results demonstrate the great potential of the presented hydrogels for applications related to 3D bioprinting.RP/CPS/2022/001; CZ.02.2.69/0.0/0.0/19_073/0016941; Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT: CZ.1.05/2.1.00/19.0376, RP/CPS/2022/003; Grantová Agentura České Republiky, GA ČR: 20-28732SMinistry of Education, Youth and Sports of the Czech republic-DKRVO [RP/CPS/2022/003, RP/CPS/2022/001]; project OP RDE Junior Grants of TBU in Zlin [CZ.02.2.69/0.0/0.0/19_073/0016941]; CEBIA-Tech Instrumentation [CZ.1.05/2.1.00/19.0376]; Czech Science FoundationGrant Agency of the Czech Republic [20-28732S

Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities

Extramedullary disease (EMM) represents a rare, aggressive and mostly resistant phenotype of multiple myeloma (MM). EMM is frequently associated with high-risk cytogenetics, but their complex genomic architecture is largely unexplored. We used whole-genome optical mapping (Saphyr, Bionano Genomics) to analyse the genomic architecture of CD138+ cells isolated from bone-marrow aspirates from an unselected cohort of newly diagnosed patients with EMM (n=4) and intramedullary MM (n=7). Large intrachromosomal rearrangements (>5 Mbp) within chromosome 1 were detected in all EMM samples. These rearrangements, predominantly deletions with/without inversions, encompassed hundreds of genes and led to changes in the gene copy number on large regions of chromosome 1. Compared with intramedullary MM, EMM was characterised by more deletions (size range of 500 bp-50 kbp) and fewer interchromosomal translocations, and two EMM samples had copy number loss in the 17p13 region. Widespread genomic heterogeneity and novel aberrations in the high-risk IGH/IGK/IGL, 8q24 and 13q14 regions were detected in individual patients but were not specific to EMM/MM. Our pilot study revealed an association of chromosome 1 abnormalities in bone marrow myeloma cells with extramedullary progression. Optical mapping showed the potential for refining the complex genomic architecture in MM and its phenotypes.Web of Science111art. no. 1467

Ixazomib-lenalidomide-dexamethasone in routine clinical practice: Effectiveness in relapsed/refractory multiple myeloma

[Aim]: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed.[Results]: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events.[Conclusion]: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1.This work was supported by Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited

Monitoring jakosti vody na vybraných přítocích řeky Svratky

The aim of this thesis with the topic "Monitoring water quality in selected affluents of the river Svratka" has been monitoring water quality during one year in selected affluents of the river Svratka, including the sample collection from river Svratka itself before the first monitored affluent joins the river and after the last monitored affluent joins in. For the monitoring was chosen river Nedvědička in the township Nedvědice river Loučka (Bobrůvka), stream Besének in the township Predklasteri and stream Lubě that joins river Svratka in the village Brezina. The first part of this thesis deals with the literature review on the topic of surface water. The second part characterizes the interest flows. The last part of the thesis deals with the methodology and results. There were interpreted readings of conductivity, pH, dissolved oxygen, temperature and the determined concentration of sulfates, nitrates and total phosphorus. These values were compared with ČSN 75 7221 classification of surface water quality and Annex 3 of the Government Regulation No. 61/2003 Coll. on the characteristics and values of acceptable pollution of surface water and wastewater

Vyhodnocení ohroženosti pozemků vodní erozí na vybraném území

This thesis on the topic Evaluation of the endangerment of land by water erosion in the selected area describes the determination of endangerment of land by water erosion in the catchment area of creek of Čebín, in the district Brno-venkov. The first literary part of thesis marginally describes the land issues which continues with major issues of soil erosion. The next part of thesis describes the characteristic of selected area. The main part of thesis is based on calculations of factors of the universal equation to determine the long term average soil loss by water erosion according to Wischmeier and Smith. Calculations were made in the programs ArcGIS, USLE2D and LS converter. Based on the evaluation of endangerment of land by water erosion were designed erosion control steps according to the current conditions of farming. The thesis is supported by map documentation which is processed in the program ArcGIS

Návrh posklizňové linky

Grains are one of the most important elements in the human and animal nutrition. The grain is seasonal product. Therefore, it is important to conserve a sufficient amount of grains for year nutrition consumption. These stocks are post-harvest treated before storage. In the post-harvest treatment belongs intake of grain, grain cleaning, grain drying and storage of grains in good conditions. Quality of product is important in terms of market value. This thesis deals with the most widely used post-harvest processing technologies in the Czech Republic. Also requirements for the quality of grains according to standards are explained. The parameters of chosen harvest line and the suggestions of improvements are described in practical part of this thesis. Final part is devoted to the economic, investment and technical evaluation of suggested solutions