Rheumatoid arthritises biobankkal szerzett tapasztalataink: 204 beteg biológiai mintáinak és klinikai adatainak összevetése | Experience with a rheumatoid arthritis biobank: analysis of biological samples and clinical data of 204 patients

Absztrakt: Bevezetés: A biobank a betegektől származó biológiai minták mellett a genetikai eltérések, klinikai adatok rögzítésére is alkalmas. Számos biobankot hoztak létre világszerte, amelyek jelentősen hozzájárultak a betegségek és genetikai polimorfizmusok szerepének jobb megismeréséhez, illetve a különböző kórképek kezelési hatékonyságának növeléséhez. Célkitűzés: A munka során az volt a célunk, hogy létrehozzunk egy internetes biobankot, amelyben rheumatoid arthritises betegekre vonatkozó laborparaméterek, genetikai jellegzetességek, társbetegségek rendszerezése megoldható, megkönnyítve a kutatómunkát, a betegség jobb megismerését, illetve megakadályozva az adatvesztést. Betegek és módszer: Összesen 204 rheumatoid arthritises beteg esetében rendelkezünk biológiai mintákkal, és a 204 beteg adatait sikerült a biobankban rögzíteni, amely a http://rheuma.biobank.eu honlapon található. Az adatok felhasználásával az SPSS20 program segítségével elvégeztük a leíró statisztikai vizsgálatokat és a korrelációk elemzését. Eredmények: A 204 beteg adatait és biológiai mintáit tartalmazó biobank megalkotásával létrehoztunk egy olyan adatbázist, amelynek segítségével rendelkezésünkre állnak a rheumatoid arthritisre vonatkozó legfontosabb paraméterek, amelyek segítséget nyújtanak majd a kórfolyamat jobb megismerésében, gyógyításában. Következtetés: A biobank alkalmas a betegek vérmintáinak és klinikai adatainak együttes elemzésére. Orv. Hetil., 2017, 158(7), 270–277. | Abstract: Introduction: A biobank is a registry, which is suitable for the storage of biological samples (e.g. tissues, DNA, protein), genetical abnormalities and clinical data. Several biobanks have been created worldwide, which contribute to research and the better understanding of disease pathogenesis, genetical polymorphisms. Biobanking also helps to improve the efficacy of therapies. Aim: Our purpose was to create an internet-based biobank, in which laboratory test results, genetic alterations and related disorders of rheumatoid arthritis (RA) patients can be registered. This biobank would be able to make the research easier and it can help to improve our knowledge about diseases and it can inhibit loss of data. Patients and method: We have biological samples from 204 RA patients and we have entered their data in the biobank which can be found on the website http://rheuma.biobank.eu. Statistical analysis was performed by SPSS20 statistical programme. Results: By the creation of biobank that contains clinical data and biological samples of 204 RA patients, we have a database which can help to improve our knowledge about the disease and help to develop new treatment strategies. Conclusion: Biobanking is suitable to analyze blood samples and clinical data together. Orv. Hetil., 2017, 158(7), 270–277

Relationship between atomic structure and excellent glass forming ability in Pd42.5Ni7.5Cu30P20 metallic glass

International audienceTo understand the relation of the glass-forming ability (GFA) to the local atomic configurations of a PdNiCuP (PNCP) metallic glass having the best GFA at present, the local structures were investigated by combining data obtained from anomalous X-ray scattering, X-ray and neutron diffraction, and applying reverse Monte Carlo modeling. By comparing the results of PNCP with PdNiP (PNP) and PdCuP (PCP) having a slightly and much worse GFAs, respectively, characteristic features were observed in the hyper-ordered atomic structures. Firstly, the concentration inhomogeneity of Ni/Cu in PNCP is larger than that of Ni in PNP and Cu in PCP. Secondly, a Voronoi tessellation showed that the fraction of pure icosahedral arrangements around the Cu atoms increases significantly in PNCP by adding icosahedral-preferred Ni atoms in PCP. Finally, a persistent homology (PH) analysis reveals the largest intermediate-size Cu PH rings in PNCP among the PH rings in these Pd-based BMGs. The structural heterogeneity for the excellent GFA of PNCP would be considered by an incompatible mixture of specific Pd-P configurations and icosahedral clusters around the secondary Ni and Cu metals

Partial structure investigation of the traditional bulk metallic glass Pd40Ni40 P20

Local structures of Pd40Ni40P20 bulk metallic glass were investigated by combining anomalous x-ray scattering close to the Pd and Ni K absorption edges, x-ray diffraction, neutron diffraction, and reverse Monte Carlo modeling, from which partial structure factors Sij(Q) and partial pair distribution functions gij(r) as well as three-dimensional atomic configurations were carefully obtained around the constituent elements. A disagreement is found in the local structures with an ab initio molecular dynamics simulation by Guan et al., i.e., the existence of the P-P nearest-neighboring configurations is clarified in the present experimental result. From the Voronoi tessellation analysis, a preference of the pure icosahedral configurations is observed around the Ni atoms, whereas the local configurations around the Pd and P atoms are rather distorted icosahedra. A persistent homology analysis was carried out to identify meaningful shape characteristics of the intermediate-range atomic configuration of large rings.</p

Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis

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Partial structure investigation of the traditional bulk metallic glass Pd40Ni40 P20

Local structures of Pd 40 Ni 40 P 20 bulk metallic glass were investigated by combining anomalous x-ray scattering close to the Pd and Ni K absorption edges, x-ray diffraction, neutron diffraction, and reverse Monte Carlo modeling, from which partial structure factors S i j (Q) and partial pair distribution functions g i j (r) as well as threedimensional atomic configurations were carefully obtained around the constituent elements. A disagreement is found in the local structures with an ab initio molecular dynamics simulation by Guan et al., i.e., the existence of the P-P nearest-neighboring configurations is clarified in the present experimental result. From the Voronoi tessellation analysis, a preference of the pure icosahedral configurations is observed around the Ni atoms, whereas the local configurations around the Pd and P atoms are rather distorted icosahedra. A persistent homology analysis was carried out to identify meaningful shape characteristics of the intermediate-range atomic configuration of large rings

Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis

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Gene expression analysis of vascular pathophysiology related to anti-TNF treatment in rheumatoid arthritis

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Angiotensin Converting Enzyme Activity in Anti-TNF-Treated Rheumatoid Arthritis and Ankylosing Spondylitis Patients

Angiotensin-converting enzyme (ACE) and ACE2 have been implicated in the regulation of vascular physiology. Elevated synovial and decreased or normal ACE or ACE2 levels have been found in rheumatoid arthritis (RA). Very little is known about the effects of tumor necrosis factor α (TNF-α) inhibition on ACE or ACE2 homeostasis. In this study, we assessed the effects of one-year anti-TNF therapy on ACE and ACE2 production in RA and ankylosing spondylitis (AS) in association with other biomarkers. Patients and Methods Forty patients including 24 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 16 AS patients treated with ETN were included in a 12-month follow-up study. Serum ACE levels were determined by commercial ELISA, while serum ACE2 activity was assessed using a specific quenched fluorescent substrate. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. In addition, CRP, rheumatoid factor (RF) and ACPA were also measured. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results Anti-TNF therapy increased ACE levels in the full cohort, as well as in the RA and AS subsets. ACE2 activity increased in the full cohort, while the ACE/ACE2 ratio increased in the full cohort and in the RA subset (p < 0.05). Uni- and multivariable regression analyses determined associations between ACE or ACE/ACE2 ratios at different time points and disease duration, CRP, RF, FMD and IMT (p < 0.05). ACE2 activity correlated with CRP. The changes of ACE or ACE2 over 12 months were determined by treatment together with either RF or FMD (p < 0.05). Conclusions Anti-TNF treatment may increase ACE and ACE2 in the sera of RA and AS patients. ACE and ACE2 may be associated with disease duration, markers of inflammation and vascular pathophysiology. The effects of TNF inhibition on ACE and ACE2 may reflect, in part, the effects of these biologics on the cardiovascular system

Microarray-Based Class Discovery for Molecular Classification of Breast Cancer: Analysis of Interobserver Agreement

Background Breast cancers can be classified by hierarchical clustering using an "intrinsic" gene list into one of at least five molecular subtypes: basal-like, HER2, luminal A, luminal B, and normal breast-like. Five different intrinsic gene lists composed of varying numbers of genes have been used for molecular subtype identification and classification of breast cancers. The aim of this study was to determine the objectivity and interobserver reproducibility of the assignment of molecular subtype classes by hierarchical cluster analysis. Methods Three publicly available breast cancer datasets (n = 779) were subjected to two-way average-linkage hierarchical cluster analysis using five distinct intrinsic gene lists. We used free-marginal Kappa statistics to analyze interobserver agreement among five breast cancer researchers for the whole classification and for each molecular subtype separately according to each intrinsic gene list for each breast cancer dataset. Results None of the classification systems tested produced almost perfect agreement (Kappa >= 0.81) among observers. However, substantial interobserver agreement (70.8% to 76.1% of the samples and free-marginal Kappa scores from 0.635 to 0.701) was consistently observed in all datasets for four molecular subtypes (luminal, basal-like, HER2, and normal breast-like). When luminal cancers were subdivided (luminal A, B, and C), none of the classification systems produced substantial agreement (Kappa >= 0.61) in all the datasets analyzed. Analysis of each subtype separately revealed that only two (basal-like and HER2) could be reproducibly identified by independent observers (Kappa >= 0.81). Conclusions Assignment of molecular subtype classes of breast cancer based on the analysis of dendrograms obtained with hierarchical cluster analysis is subjective and shows modest interobserver reproducibility. For the development of a molecular taxonomy, objective definitions for each molecular subtype and standardized methods for their identification are required