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

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

The Office building

Import 15/01/2013Diplomová práce se zabývá návrhem teplovodního vytápění administrativní budovy nízkoenergetického standardu při použití jedné z nejrozšířenějších otopných soustav. Je navrhnuta dvoutrubková otopná soustava se spodním rozvodem a nuceným oběhem vody s umístěním strojovny v suterénu. Jako primární energie se využívá zemní plyn s důrazem na využití celého potenciálu dané energie. Soustava je navržena tak, aby pracovala v celém svém režimu jako kondenzační. Celá práce je koncipována s důrazem na její jednoduchost, nenáročnost a ekonomičnost.The thesis deals with a suggestion of water heating of an administrative building of low energy standard with application of one of the most common heating systems. Two-pipe heating system with low distribution and forced water circulation with placement of an engine room on the basement is suggested. There is used as a primary energy natural gas with emphasis on the utilization of the whole potential of the energy. The system is suggested to work in its whole mode as condensing. The whole dissertation is drawn up with focus on its simplicity, undemanding character and for the sake of economyPrezenční229 - Katedra prostředí staveb a TZBdobř

Optimalization of the external cladding insulation

Import 01/09/2009Prezenční225 - Katedra pozemního stavitelstvívelmi dobř

Optimalization of winter maintenance of ground communications in Ostrava

Diplomová práce se zabývá zimní údržbou místních komunikací s městskou hromadnou dopravou ve městě Ostrava a legislativními podmínkami pro zimní údržbu komunikací.Katedra technologie a řízení dopravyDokončená práce s úspěšnou obhajobo

Monoclonal Gammopathy of Renal Significance (MGRS): Real-World data on outcomes and prognostic factors

: Monoclonal Gammopathy of Renal Significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003-2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; non-amyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0 - 121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR&nbsp;=&nbsp;0.41, 95%CI: 0.25 - 0.69; P = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR&nbsp;=&nbsp;8.03 95%CI: 4.04 - 115.96; P &lt; 0.0001), one-fourth of patients with ≥VGPR were renal non-responders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age &gt; 65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS. This article is protected by copyright. All rights reserved