Association of Serum Uric Acid with Non-Valvular Atrial Fibrillation: A Retrospective Study in China

Hua-Jing Yuan,1 Hua-Chen Jiao,2 Xiu-Juan Liu,2 Hao Hao,2 Yang Liu,2 Yi-Tao Xue,2 Yan Li2 1Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250014, People’s Republic of China; 2Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250014, People’s Republic of ChinaCorrespondence: Yi-Tao Xue; Yan Li, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shanshi East Road, Lixia District, Jinan City, Shandong Province, People’s Republic of China, Tel +86-531-82602943 ; +86-531-68611662, Email [email protected]; [email protected]: The association between serum uric acid (SUA) and atrial fibrillation (AF) has been widely focused on and studied in recent years. However, the exact association between SUA and AF is unclear, and the effect of gender on the association between SUA levels and AF has been controversial. This study aimed to investigate the association between SUA levels and non-valvular AF (NVAF) and the potential effect of gender on it.Patients and Methods: A total of 866 NVAF patients (463 males, age 69.44 ± 8.07 years) and 646 sex-matched control patients in sinus rhythm, with no history of arrhythmia were included in this study. t-test, ANOVA, and chi-square test were used for baseline data analysis. The receiver operating characteristic curve, logistic regression and Pearson correlation analysis were used for correlation analysis.Results: Compared to controls, NVAF patients exhibited higher SUA (P< 0.001). After adjusting for confounders of NVAF, SUA remained significantly associated with NVAF, regardless of gender (OR= 1.31, 95% CI 1.18– 1.43, P< 0.001). SUA demonstrated higher predictability and sensitivity in predicting the occurrence of female NVAF compared to male (area under the curve was 0.68 (95% CI 0.64– 0.72, P< 0.001), sensitivity 87.3%), with the optimal cut-off point identified as 5.72 mg/dL. Furthermore, SUA levels correlated with APOA1, Scr and NT-proBNP in NVAF patients. SUA levels varied significantly among NVAF subtypes.Conclusion: High SUA levels were independently associated with NVAF, regardless of gender. SUA exhibited higher predictability and sensitivity in predicting the occurrence of NVAF in females compared to males. High SUA levels may affect other NVAF-related factors and participate in the pathophysiological process of NVAF.Keywords: serum uric acid, non-valvular atrial fibrillation, gender difference, retrospective study, predictive indicator

FastTagger: an efficient algorithm for genome-wide tag SNP selection using multi-marker linkage disequilibrium

<p>Abstract</p> <p>Background</p> <p>Human genome contains millions of common single nucleotide polymorphisms (SNPs) and these SNPs play an important role in understanding the association between genetic variations and human diseases. Many SNPs show correlated genotypes, or linkage disequilibrium (LD), thus it is not necessary to genotype all SNPs for association study. Many algorithms have been developed to find a small subset of SNPs called tag SNPs that are sufficient to infer all the other SNPs. Algorithms based on the <it>r</it>²LD statistic have gained popularity because <it>r</it>²is directly related to statistical power to detect disease associations. Most of existing <it>r</it>²based algorithms use pairwise LD. Recent studies show that multi-marker LD can help further reduce the number of tag SNPs. However, existing tag SNP selection algorithms based on multi-marker LD are both time-consuming and memory-consuming. They cannot work on chromosomes containing more than 100 k SNPs using length-3 tagging rules.</p> <p>Results</p> <p>We propose an efficient algorithm called FastTagger to calculate multi-marker tagging rules and select tag SNPs based on multi-marker LD. FastTagger uses several techniques to reduce running time and memory consumption. Our experiment results show that FastTagger is several times faster than existing multi-marker based tag SNP selection algorithms, and it consumes much less memory at the same time. As a result, FastTagger can work on chromosomes containing more than 100 k SNPs using length-3 tagging rules.</p> <p>FastTagger also produces smaller sets of tag SNPs than existing multi-marker based algorithms, and the reduction ratio ranges from 3%-9% when length-3 tagging rules are used. The generated tagging rules can also be used for genotype imputation. We studied the prediction accuracy of individual rules, and the average accuracy is above 96% when <it>r</it>²≥ 0.9.</p> <p>Conclusions</p> <p>Generating multi-marker tagging rules is a computation intensive task, and it is the bottleneck of existing multi-marker based tag SNP selection methods. FastTagger is a practical and scalable algorithm to solve this problem.</p

Estimation and projection of the national profile of cancer mortality in China: 1991–2005

There are no national-level data on cancer mortality in China since two surveys in 1973-1975 and 1990-1992 (a 10% sample), but ongoing surveillance systems, based on nonrandom selected populations, give an indication as to the trends for major cancers. Based on a log-linear regression model with Poisson errors, the annual rates of change for 10 cancers and all other cancers combined, by age, sex and urban/rural residence were estimated from the data of the surveillance system of the Center for Health Information and Statistics, covering about 10% of the national population. These rates of change were applied to the survey data of 1990-1992 to estimate national mortality in the year 2000, and to make projections for 2005. Mortality rates for all cancers combined, adjusted for age, are predicted to change little between 1991 and 2005 (-0.8% in men and +2.5% in women), but population growth and ageing will result in an increasing number of deaths, from 1.2 to 1.8 million. The largest predicted increases are for the numbers of female breast (+155.4%) and lung cancers (+112.1% in men, +153.5% in women). For these two sites, mortality rates will almost double. Cancer will make an increasing contribution to the burden of diseases in China in the 21st century. The marked increases in risk of cancers of the lung, female breast and large bowel indicate priorities for prevention and control. The increasing trends in young age groups for cancers of the cervix, lung and female breast suggest that their predicted increases may be underestimated, and that more attention should be paid to strategies for their prevention and control

A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency

BackgroundOncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance.ResultsIn reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5-100x more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels.ConclusionThese new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.Peer reviewe

Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways

Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKɛ, requires interaction with adapter proteins such as TRAF associated NF-κB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKɛ/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity.Peer reviewe

Inhibition of Proliferation and Induction of Apoptosis in Multiple Myeloma Cell Lines by CD137 Ligand Signaling

BACKGROUND: Multiple myeloma (MM) is a malignancy of terminally-differentiated plasma cells, and the second most prevalent blood cancer. At present there is no cure for MM, and the average prognosis is only three to five years. Current treatments such as chemotherapy are able to prolong a patient's life but rarely prevent relapse of the disease. Even hematopoietic stem cell transplants and novel drug combinations are often not curative, underscoring the need for a continued search for novel therapeutics. CD137 and its ligand are members of the Tumor Necrosis Factor (TNF) receptor and TNF superfamilies, respectively. Since CD137 ligand cross-linking enhances proliferation and survival of healthy B cells we hypothesized that it would also act as a growth stimulus for B cell cancers. METHODOLOGY/PRINCIPAL FINDINGS: Proliferation and survival of B cell lymphoma cell lines were not affected or slightly enhanced by CD137 ligand agonists in vitro. But surprisingly, they had the opposite effects on MM cells, where CD137 ligand signals inhibited proliferation and induced cell death by apoptosis. Furthermore, secretion of the pro-inflammatory cytokines, IL-6 and IL-8 were also enhanced in MM but not in non-MM cell lines in response to CD137 ligand agonists. The secretion of these cytokines in response to CD137 ligand signaling was consistent with the observed activation of the classical NF-kappaB pathway. We hypothesize that the induction of this pathway results in activation-induced cell death, and that this is the underlying mechanism of CD137-induced MM cell death and growth arrest. CONCLUSIONS/SIGNIFICANCE: These data point to a hitherto unrecognized role of CD137 and CD137 ligand in MM cell biology. The selective inhibition of proliferation and induction of cell death in MM cells by CD137 ligand agonists may also warrant a closer evaluation of their therapeutic potential

Tracing the legacy of the early Hainan Islanders - a perspective from mitochondrial DNA

<p>Abstract</p> <p>Background</p> <p>Hainan Island is located around the conjunction of East Asia and Southeast Asia, and during the Last Glacial Maximum (LGM) was connected with the mainland. This provided an opportunity for the colonization of Hainan Island by modern human in the Upper Pleistocene. Whether the ancient dispersal left any footprints in the contemporary gene pool of Hainan islanders is debatable.</p> <p>Results</p> <p>We collected samples from 285 Li individuals and analyzed mitochondrial DNA (mtDNA) variations of hypervariable sequence I and II (HVS-I and II), as well as partial coding regions. By incorporating previously reported data, the phylogeny of Hainan islanders was reconstructed. We found that Hainan islanders showed a close relationship with the populations in mainland southern China, especially from Guangxi. Haplotype sharing analyses suggested that the recent gene flow from the mainland might play important roles in shaping the maternal pool of Hainan islanders. More importantly, haplogroups M12, M7e, and M7c1* might represent the genetic relics of the ancient population that populated this region; thus, 14 representative complete mtDNA genomes were further sequenced.</p> <p>Conclusions</p> <p>The detailed phylogeographic analyses of haplogroups M12, M7e, and M7c1* indicated that the early peopling of Hainan Island by modern human could be traced back to the early Holocene and/or even the late Upper Pleistocene, around 7 - 27 kya. These results correspond to both Y-chromosome and archaeological studies.</p

Differential Expression of miRNAs in Colorectal Cancer: Comparison of Paired Tumor Tissue and Adjacent Normal Mucosa Using High-Throughput Sequencing

We present the results of a global study of dysregulated miRNAs in paired samples of normal mucosa and tumor from eight patients with colorectal cancer. Although there is existing data of miRNA contribution to colorectal tumorigenesis, these studies are typically small to medium scale studies of cell lines or non-paired tumor samples. The present study is to our knowledge unique in two respects. Firstly, the normal and adjacent tumor tissue samples are paired, thus taking into account the baseline differences between individuals when testing for differential expression. Secondly, we use high-throughput sequencing, thus enabling a comprehensive survey of all miRNAs expressed in the tissues. We use Illumina sequencing technology to perform sequencing and two different tools to statistically test for differences in read counts per gene between samples: edgeR when using the pair information and DESeq when ignoring this information, i.e., treating tumor and normal samples as independent groups. We identify 37 miRNAs that are significantly dysregulated in both statistical approaches, 19 down-regulated and 18 up-regulated. Some of these miRNAs are previously published as potential regulators in colorectal adenocarcinomas such as miR-1, miR-96 and miR-145. Our comprehensive survey of differentially expressed miRNAs thus confirms some existing findings. We have also discovered 16 dysregulated miRNAs, which to our knowledge have not previously been associated with colorectal carcinogenesis: the following significantly down-regulated miR-490-3p, -628-3p/-5p, -1297, -3151, -3163, -3622a-5p, -3656 and the up-regulated miR-105, -549, -1269, -1827, -3144-3p, -3177, -3180-3p, -4326. Although the study is preliminary with only eight patients included, we believe the results add to the present knowledge on miRNA dysregulation in colorectal carcinogenesis. As such the results would serve as a robust training set for validation of potential biomarkers in a larger cohort study. Finally, we also present data supporting the hypothesis that there are differences in miRNA expression between adenocarcinomas and neuroendocrine tumors of the colon

Pyrosequencing the Bemisia tabaci Transcriptome Reveals a Highly Diverse Bacterial Community and a Robust System for Insecticide Resistance

BACKGROUND: Bemisia tabaci (Gennadius) is a phloem-feeding insect poised to become one of the major insect pests in open field and greenhouse production systems throughout the world. The high level of resistance to insecticides is a main factor that hinders continued use of insecticides for suppression of B. tabaci. Despite its prevalence, little is known about B. tabaci at the genome level. To fill this gap, an invasive B. tabaci B biotype was subjected to pyrosequencing-based transcriptome analysis to identify genes and gene networks putatively involved in various physiological and toxicological processes. METHODOLOGY AND PRINCIPAL FINDINGS: Using Roche 454 pyrosequencing, 857,205 reads containing approximately 340 megabases were obtained from the B. tabaci transcriptome. De novo assembly generated 178,669 unigenes including 30,980 from insects, 17,881 from bacteria, and 129,808 from the nohit. A total of 50,835 (28.45%) unigenes showed similarity to the non-redundant database in GenBank with a cut-off E-value of 10-5. Among them, 40,611 unigenes were assigned to one or more GO terms and 6,917 unigenes were assigned to 288 known pathways. De novo metatranscriptome analysis revealed highly diverse bacterial symbionts in B. tabaci, and demonstrated the host-symbiont cooperation in amino acid production. In-depth transcriptome analysis indentified putative molecular markers, and genes potentially involved in insecticide resistance and nutrient digestion. The utility of this transcriptome was validated by a thiamethoxam resistance study, in which annotated cytochrome P450 genes were significantly overexpressed in the resistant B. tabaci in comparison to its susceptible counterparts. CONCLUSIONS: This transcriptome/metatranscriptome analysis sheds light on the molecular understanding of symbiosis and insecticide resistance in an agriculturally important phloem-feeding insect pest, and lays the foundation for future functional genomics research of the B. tabaci complex. Moreover, current pyrosequencing effort greatly enriched the existing whitefly EST database, and makes RNAseq a viable option for future genomic analysis