The multiplex bead array approach to identifying serum biomarkers associated with breast cancer

Introduction Breast cancer is the most common type of cancer seen in women in western countries. Thus, diagnostic modalities sensitive to early-stage breast cancer are needed. Antibody-based array platforms of a data-driven type, which are expected to facilitate more rapid and sensitive detection of novel biomarkers, have emerged as a direct, rapid means for profiling cancer-specific signatures using small samples. In line with this concept, our group constructed an antibody bead array panel for 35 analytes that were selected during the discovery step. This study was aimed at testing the performance of this 35-plex array panel in profiling signatures specific for primary non-metastatic breast cancer and validating its diagnostic utility in this independent population. Methods Thirty-five analytes were selected from more than 50 markers through screening steps using a serum bank consisting of 4,500 samples from various types of cancer. An antibody-bead array of 35 markers was constructed using the Luminex (TM) bead array platform. A study population consisting of 98 breast cancer patients and 96 normal subjects was analysed using this panel. Multivariate classification algorithms were used to find discriminating biomarkers and validated with another independent population of 90 breast cancer and 79 healthy controls. Results Serum concentrations of epidermal growth factor, soluble CD40-ligand and proapolipoprotein A1 were increased in breast cancer patients. High-molecular-weight-kininogen, apolipoprotein A1, soluble vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, vitamin-D binding protein and vitronectin were decreased in the cancer group. Multivariate classification algorithms distinguished breast cancer patients from the normal population with high accuracy (91.8% with random forest, 91.5% with support vector machine, 87.6% with linear discriminant analysis). Combinatorial markers also detected breast cancer at an early stage with greater sensitivity. Conclusions The current study demonstrated the usefulness of the antibody-bead array approach in finding signatures specific for primary non-metastatic breast cancer and illustrated the potential for early, high sensitivity detection of breast cancer. 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Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Influence of Cation Substitutions Based on ABO₃ Perovskite Materials, Sr_1–<i>x</i>Y_<i>x</i>Ti_1–<i>y</i>Ru_<i>y</i>O_3−δ, on Ammonia Dehydrogenation

In order to screen potential catalytic materials for synthesis and decomposition of ammonia, a series of ABO₃ perovskite materials, Sr_1–<i>x</i>Y_<i>x</i>Ti_1–<i>y</i>Ru_<i>y</i>O_3−δ (<i>x</i> = 0, 0.08, and 0.16; <i>y</i> = 0, 0.04, 0.07, 0.12, 0.17, and 0.26) were synthesized and tested for ammonia dehydrogenation. The influence of A or B site substitution on the catalytic ammonia dehydrogenation activity was determined by varying the quantity of either A or B site cation, producing <b>Sr</b>_{<b>1</b>–<b><i>x</i></b>}<b>Y</b>_{<b><i>x</i></b>}Ti_0.92Ru_0.08O_3−δ and Sr_0.92Y_0.08<b>Ti</b>_{<b>1</b>–<i><b>y</b></i>}<b>Ru</b>_{<b><i>y</i></b>}O_3−δ, respectively. Characterizations of the as-synthesized materials using different analytical techniques indicated that a new perovskite phase of SrRuO₃ was produced upon addition of large amounts of Ru (≥12 mol %), and the surface Ru⁰ species were formed simultaneously to ultimately yield <b>Ru</b>_{<b><i>z</i></b>}(surface)/Sr_0.92Y_0.08<b>Ti</b>_{<b>1</b>–<b><i>y</i></b>}<b>Ru</b>_{<i><b>y</b></i>–<b><i>z</i></b>}O_3−δ and/or <b>Ru</b>_{<b><i>z</i></b>–<b><i>w</i></b>}(surface)/Sr_<i>w</i>Ru_<i>w</i>O₃/Sr_{0.92–<i>w</i>}Y_0.08<b>Ti</b>_{<b>1</b>–<b><i>y</i></b>}<b>Ru</b>_{<b><i>y</i></b>–<b><i>z</i></b>}O_3−δ. The newly generated surface Ru⁰ species at the perovskite surfaces accelerated ammonia dehydrogenation under different conditions, and Sr_0.84Y_0.16Ti_0.92Ru_0.08O_3−δ exhibited a NH₃ conversion of ca. 96% at 500 °C with a gas hourly space velocity (GHSV) of 10 000 mL g_cat^–1 h^–1. In addition, Sr_0.84Y_0.16Ti_0.92Ru_0.08O_3−δ further proved to be highly active and stable toward ammonia decomposition at different reaction temperatures and GHSVs for >275 h