Displaying publications 21 - 40 of 101 in total

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  1. Conen D, Alonso-Coello P, Douketis J, Chan MTV, Kurz A, Sigamani A, et al.
    Eur Heart J, 2020 02 01;41(5):645-651.
    PMID: 31237939 DOI: 10.1093/eurheartj/ehz431
    AIMS: To determine the 1-year risk of stroke and other adverse outcomes in patients with a new diagnosis of perioperative atrial fibrillation (POAF) after non-cardiac surgery.

    METHODS AND RESULTS: The PeriOperative ISchemic Evaluation (POISE)-1 trial evaluated the effects of metoprolol vs. placebo in 8351 patients, and POISE-2 compared the effect of aspirin vs. placebo, and clonidine vs. placebo in 10 010 patients. These trials included patients with, or at risk of, cardiovascular disease who were undergoing non-cardiac surgery. For the purpose of this study, we combined the POISE datasets, excluding 244 patients who were in atrial fibrillation (AF) at the time of randomization. Perioperative atrial fibrillation was defined as new AF that occurred within 30 days after surgery. Our primary outcome was the incidence of stroke at 1 year of follow-up; secondary outcomes were mortality and myocardial infarction (MI). We compared outcomes among patients with and without POAF using multivariable adjusted Cox proportional hazards models. Among 18 117 patients (mean age 69 years, 57.4% male), 404 had POAF (2.2%). The stroke incidence 1 year after surgery was 5.58 vs. 1.54 per 100 patient-years in patients with and without POAF, adjusted hazard ratio (aHR) 3.43, 95% confidence interval (CI) 2.00-5.90; P 

  2. Shang X, Peng Z, Ye Y, Asan, Zhang X, Chen Y, et al.
    EBioMedicine, 2017 Sep;23:150-159.
    PMID: 28865746 DOI: 10.1016/j.ebiom.2017.08.015
    Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.
  3. Lim KL, Wong CY, Wong WY, Loh KS, Selambakkannu S, Othman NAF, et al.
    Membranes (Basel), 2021 May 27;11(6).
    PMID: 34072048 DOI: 10.3390/membranes11060397
    This review discusses the roles of anion exchange membrane (AEM) as a solid-state electrolyte in fuel cell and electrolyzer applications. It highlights the advancement of existing fabrication methods and emphasizes the importance of radiation grafting methods in improving the properties of AEM. The development of AEM has been focused on the improvement of its physicochemical properties, including ionic conductivity, ion exchange capacity, water uptake, swelling ratio, etc., and its thermo-mechano-chemical stability in high-pH and high-temperature conditions. Generally, the AEM radiation grafting processes are considered green synthesis because they are usually performed at room temperature and practically eliminated the use of catalysts and toxic solvents, yet the final products are homogeneous and high quality. The radiation grafting technique is capable of modifying the hydrophilic and hydrophobic domains to control the ionic properties of membrane as well as its water uptake and swelling ratio without scarifying its mechanical properties. Researchers also showed that the chemical stability of AEMs can be improved by grafting spacers onto base polymers. The effects of irradiation dose and dose rate on the performance of AEM were discussed. The long-term stability of membrane in alkaline solutions remains the main challenge to commercial use.
  4. Wang Y, Van Le Q, Yang H, Lam SS, Yang Y, Gu H, et al.
    Chemosphere, 2021 Oct;281:130835.
    PMID: 33992848 DOI: 10.1016/j.chemosphere.2021.130835
    The increase in global population size over the past 100 decades has doubled the requirements for energy resources. To mitigate the limited fossil fuel available, new clean energy sources being environmental sustainable for replacement of traditional energy sources are explored to supplement the current scarcity. Biomass containing lignin and cellulose is the main raw material to replace fossil energy given its abundance and lower emission of greenhouse gases and NOx when transformed into energy. Bacteria, fungi and algae decompose lignocellulose leading to generation of hydrogen, methane, bioethanol and biodiesel being the clean energy used for heating, power generation and the automobile industry. Microbial Fuel Cell (MFC) uses microorganisms to decompose biomass in wastewater to generate electricity and remove heavy metals in wastewater. Biomass contains cellulose, hemicellulose, lignin and other biomacromolecules which need hydrolyzation for conversion into small molecules by corresponding enzymes in order to be utilized by microorganisms. This paper discusses microbial decomposition of biomass into clean energy and the five major ways of clean energy production, and its economic benefits for future renewable energy security.
  5. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Dec 29;131(26):262301.
    PMID: 38215362 DOI: 10.1103/PhysRevLett.131.262301
    Quasireal photons exchanged in relativistic heavy ion interactions are powerful probes of the gluonic structure of nuclei. The coherent J/ψ photoproduction cross section in ultraperipheral lead-lead collisions is measured as a function of photon-nucleus center-of-mass energies per nucleon (W_{γN}^{Pb}) over a wide range of 40
  6. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Jul 07;131(1):011803.
    PMID: 37478454 DOI: 10.1103/PhysRevLett.131.011803
    The first search exploiting the vector boson fusion process to probe heavy Majorana neutrinos and the Weinberg operator at the LHC is presented. The search is performed in the same-sign dimuon final state using a proton-proton collision dataset recorded at sqrt[s]=13  TeV, collected with the CMS detector and corresponding to a total integrated luminosity of 138  fb^{-1}. The results are found to agree with the predictions of the standard model. For heavy Majorana neutrinos, constraints on the squared mixing element between the muon and the heavy neutrino are derived in the heavy neutrino mass range 50 GeV-25 TeV; for masses above 650 GeV these are the most stringent constraints from searches at the LHC to date. A first test of the Weinberg operator at colliders provides an observed upper limit at 95% confidence level on the effective μμ Majorana neutrino mass of 10.8 GeV.
  7. Zhao C, Wong L, Zhu Q, Yang H
    PLoS One, 2018;13(6):e0199006.
    PMID: 29902222 DOI: 10.1371/journal.pone.0199006
    BACKGROUND: The escalating problem of multiple chronic conditions among older adults in China draws public health attention due to increasing proportion of the elderly population. This study sought to assess the prevalence of and factors associated with four chronic diseases in older adults in Haikou, the capital city of Hainan Province, China.

    METHOD: In this cross-sectional study, 9432 community-dwelling elderly people aged 60 years and older living in rural or urban areas in Haikou were investigated. The interviews collected self-reported information on the presence of four major chronic diseases, as well as socio-demographic characteristics, lifestyle factors and self-reported height and weight.

    FINDINGS: Overall, 31.7% (2961/9344) reported at least one of the four chronic diseases. The prevalence of hypertension, diabetes mellitus, COPD, and stroke was 26.0% (2449/9407), 8.0% (749/9371), 1.0% (95/9360), and 1.9% (175/9382), respectively. Common correlates of the four major chronic diseases were older age, being engaged in intellectual work, currently being a smoker and obesity. Gender, locality of residence, and alcohol consumptions were also found to be associated to some of the chronic conditions.

    CONCLUSION: This finding indicates that multiple chronic conditions among elderly people in Haikou are prevalent and warrant special attention to reduce diseases burden and align health care services to cater the holistic elderly patients' need.

  8. Ng SC, Kaplan GG, Tang W, Banerjee R, Adigopula B, Underwood FE, et al.
    Am J Gastroenterol, 2019 01;114(1):107-115.
    PMID: 30177785 DOI: 10.1038/s41395-018-0233-2
    INTRODUCTION: Living in an urban environment may increase the risk of developing inflammatory bowel disease (IBD). It is unclear if this observation is seen globally. We conducted a population-based study to assess the relationship between urbanization and incidence of IBD in the Asia-Pacific region.

    METHODS: Newly diagnosed IBD cases between 2011 and 2013 from 13 countries or regions in Asia-Pacific were included. Incidence was calculated with 95% confidence interval (CI) and pooled using random-effects model. Meta-regression analysis was used to assess incidence rates and their association with population density, latitude, and longitude.

    RESULTS: We identified 1175 ulcerative colitis (UC), 656 Crohn's disease (CD), and 37 IBD undetermined (IBD-U). Mean annual IBD incidence per 100 000 was 1.50 (95% CI: 1.43-1.57). India (9.31; 95% CI: 8.38-10.31) and China (3.64; 95% CI, 2.97-4.42) had the highest IBD incidence in Asia. Incidence of overall IBD (incidence rate ratio [IRR]: 2.19; 95% CI: 1.01-4.76]) and CD (IRR: 3.28; 95% CI: 1.83-9.12) was higher across 19 areas of Asia with a higher population density. In China, incidence of IBD (IRR: 2.37; 95% CI: 1.10-5.16) and UC (IRR: 2.63; 95% CI: 1.2-5.8) was positively associated with gross domestic product. A south-to-north disease gradient (IRR: 0.94; 95% CI: 0.91-0.98) was observed for IBD incidence and a west-to-east gradient (IRR: 1.14; 95% CI: 1.05-1.24) was observed for CD incidence in China. This study received IRB approval.

    CONCLUSIONS: Regions in Asia with a high population density had a higher CD and UC incidence. Coastal areas within China had higher IBD incidence. With increasing urbanization and a shift from rural areas to cities, disease incidence may continue to climb in Asia.

  9. Choi JR, Liu Z, Hu J, Tang R, Gong Y, Feng S, et al.
    Anal Chem, 2016 06 21;88(12):6254-64.
    PMID: 27012657 DOI: 10.1021/acs.analchem.6b00195
    In nucleic acid testing (NAT), gold nanoparticle (AuNP)-based lateral flow assays (LFAs) have received significant attention due to their cost-effectiveness, rapidity, and the ability to produce a simple colorimetric readout. However, the poor sensitivity of AuNP-based LFAs limits its widespread applications. Even though various efforts have been made to improve the assay sensitivity, most methods are inappropriate for integration into LFA for sample-to-answer NAT at the point-of-care (POC), usually due to the complicated fabrication processes or incompatible chemicals used. To address this, we propose a novel strategy of integrating a simple fluidic control strategy into LFA. The strategy involves incorporating a piece of paper-based shunt and a polydimethylsiloxane (PDMS) barrier to the strip to achieve optimum fluidic delays for LFA signal enhancement, resulting in 10-fold signal enhancement over unmodified LFA. The phenomena of fluidic delay were also evaluated by mathematical simulation, through which we found the movement of fluid throughout the shunt and the tortuosity effects in the presence of PDMS barrier, which significantly affect the detection sensitivity. To demonstrate the potential of integrating this strategy into a LFA with sample-in-answer-out capability, we further applied this strategy into our prototype sample-to-answer LFA to sensitively detect the Hepatitis B virus (HBV) in clinical blood samples. The proposed strategy offers great potential for highly sensitive detection of various targets for wide application in the near future.
  10. Yan L, Le QV, Sonne C, Yang Y, Yang H, Gu H, et al.
    J Hazard Mater, 2021 04 05;407:124771.
    PMID: 33388721 DOI: 10.1016/j.jhazmat.2020.124771
    Soil and water contaminated with radionuclides threaten the environment and public health during leaks from nuclear power plants. Remediation of radionuclides at the contaminated sites uses mainly physical and chemical methods such as vitrification, chemical immobilization, electro-kinetic remediation and soil excavation, capping and washing being among the preferred methods. These traditional technologies are however costly and less suitable for dealing with large-area pollution. In contrast to this, cost-effective and environment-friendly alternatives such as phytoremediation using plants to remove radionuclides from polluted sites in situ represent promising alternatives for environmental cleanup. Understanding the physiology and molecular mechanisms of radionuclides accumulation in plants is essential to optimize and improve this new remediation technology. Here, we give an overview of radionuclide contamination in the environment and biochemical characteristics for uptake, transport, and compartmentation of radionuclides in plants that characterize phytoextraction and its efficiency. Phytoextraction is an eco-friendly and efficient method for environmental removal of radionuclides at contaminated sites such as mine tailings. Selecting the most proper plant for the specific purpose, however, is important to obtain the best result together with, for example, applying soil amendments such as citric acid. In addition, using genetic engineering and optimizing agronomic management practices including regulation of atmospheric CO2 concentration, reasonable measures of fertilization and rational water management are important as well. For future application, the technique needs commercialization in order to fully exploit the technique at mining activities and nuclear industries.
  11. Sun Y, Chen G, Wang L, Li N, Srisurapanont M, Hong JP, et al.
    Front Psychiatry, 2019;10:321.
    PMID: 31156476 DOI: 10.3389/fpsyt.2019.00321
    Stigma of major depressive disorder (MDD) is an important public health problem. This study aimed to examine the level of perceived stigma and its associated factors in MDD patients in five Asian countries, including China, Korea, Malaysia, Singapore, and Thailand. A total of 547 outpatients with MDD were included from Asian countries. We used the stigma scale of the Explanatory Model Interview Catalogue (EMIC) to assess stigma. The Montgomery-Asberg Depression Rating Scale (MADRS), Symptoms Checklist 90-Revised (SCL-90-R), Fatigue Severity Scale (FSS), Sheehan Disability Scale (SDS), 36-Item Short-Form Health Survey (SF-36), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to assess symptoms, clinical features, functional impairment, health status, and social support. The stigma scores of patients under 55 years old were significantly higher than those equal to or greater than 55 years old (P < 0.001). The stigma scores exhibited significant negative correlation with age; MSPSS scores of family, friends, and others; and SF-36 subscale of mental health, but significant positive correlation with MADRS, FSS, SDS, and SCL-90-R subscale scores of depression, interpersonal sensitivity, obsession-compulsion, psychoticism, and somatization. Multivariate regression analysis revealed that age, SCL-90-R interpersonal sensitivity, obsession-compulsion, psychoticism, MSPSS scores of friends and others, and SF-36 of mental health were significantly associated with the level of perceived stigma. These findings suggest that MDD patients who are young, have a high degree of interpersonal sensitivity and psychoticism, have low health-related quality of life, and have low social support are the target population for stigma interventions in Asia.
  12. Keun Seon J, Anwar Ayob K, Giun Noh M, Yeol Yang H
    Acta Orthop Traumatol Turc, 2024 Jan;58(1):68-72.
    PMID: 38525513 DOI: 10.5152/j.aott.2024.23115
    Oxidized zirconium (OxiniumTM) prostheses, made up of a metallic alloy of zirconium with a ceramic surface formed by oxidizing the outer layer, were developed as an alternative bearing surface to reduce polyethylene wear and decrease failure of total knee arthroplasty (TKA). We report a unique catastrophic failure of an Oxinium TKA with consequent accelerated wear and severe metallosis. Intraoperatively, we observed extensive wear grooving of the femoral component with exposure of the underlying silver layers and the complete wear of polyethylene on the medial side. Metallic debris had a peculiar arthrogram appearance, noted within the cut surface of the femur and tibia, indicative of the osteolysis that occurred, leading up to the failure of the implants. The histopathologic examination revealed a collection of macrophages with foreign-body reactions and black-pigmented metal-induced wear particles. Oxinium has clear benefits regarding superior wear properties; however, surgeons need to be aware that there is a risk of exposure to the underlying layers that may precede accelerated wear, deformation, and metallosis. Uncovering the deeper layers could result in the appearance of an arthrogram on plain radiographs. Early identification of polyethylene wear and prompt revision is crucial to avoid the rapid progression of subsequent metallosis and catastrophic implant failure, specifically when using oxidized zirconium components for TKA. To the best of our knowledge, this is the first report presenting a detailed histologic analysis to provide insight into the mechanisms of the failed Oxinium components.
  13. Choi JR, Hu J, Wang S, Yang H, Wan Abas WA, Pingguan-Murphy B, et al.
    Crit Rev Biotechnol, 2017 Feb;37(1):100-111.
    PMID: 26912259
    Dengue endemic is a serious healthcare concern in tropical and subtropical countries. Although well-established laboratory tests can provide early diagnosis of acute dengue infections, access to these tests is limited in developing countries, presenting an urgent need to develop simple, rapid, and robust diagnostic tools. Point-of-care (POC) devices, particularly paper-based POC devices, are typically rapid, cost-effective and user-friendly, and they can be used as diagnostic tools for the prompt diagnosis of dengue at POC settings. Here, we review the importance of rapid dengue diagnosis, current dengue diagnostic methods, and the development of paper-based POC devices for diagnosis of dengue infections at the POC.
  14. Ma YC, Gao MR, Yang H, Jiang JY, Xie W, Su WP, et al.
    Appl Biochem Biotechnol, 2023 Jun;195(6):3628-3640.
    PMID: 36648604 DOI: 10.1007/s12010-023-04319-x
    C50 carotenoids, as unique bioactive molecules, have many biological properties, including antioxidant, anticancer, and antibacterial activity, and have a wide range of potential uses in the food, cosmetic, and biomedical industries. The majority of C50 carotenoids are produced by the sterile fermentation of halophilic archaea. This study aims to look at more cost-effective and manageable ways of producing C50 carotenoids. The basic medium, carbon source supplementation, and optimal culture conditions for Halorubrum sp. HRM-150 C50 carotenoids production by open fermentation were examined in this work. The results indicated that Halorubrum sp. HRM-150 grown in natural brine medium grew faster than artificial brine medium. The addition of glucose, sucrose, and lactose (10 g/L) enhanced both biomass and carotenoids productivity, with the highest level reaching 4.53 ± 0.32 μg/mL when glucose was added. According to the findings of orthogonal studies based on the OD600 and carotenoids productivity, the best conditions for open fermentation were salinity 20-25%, rotation speed 150-200 rpm, and pH 7.0-8.2. The up-scaled open fermentation was carried out in a 7 L medium under optimum culture conditions. At 96 h, the OD600 and carotenoids productivity were 9.86 ± 0.51 (dry weight 10.40 ± 1.27 g/L) and 7.31 ± 0.65 μg/mL (701.40 ± 21.51 μg/g dry weight, respectively). When amplified with both universal bacterial primer and archaeal primer in the open fermentation, Halorubrum remained the dominating species, indicating that contamination was kept within an acceptable level. To summarize, open fermentation of Halorubrum is a promising method for producing C50 carotenoids.
  15. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Oct 13;131(15):151803.
    PMID: 37897747 DOI: 10.1103/PhysRevLett.131.151803
    We present an observation of photon-photon production of τ lepton pairs in ultraperipheral lead-lead collisions. The measurement is based on a data sample with an integrated luminosity of 404  μb^{-1} collected by the CMS experiment at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02  TeV. The γγ→τ^{+}τ^{-} process is observed for τ^{+}τ^{-} events with a muon and three charged hadrons in the final state. The measured fiducial cross section is σ(γγ→τ^{+}τ^{-})=4.8±0.6(stat)±0.5(syst)  μb, where the second (third) term corresponds to the statistical (systematic) uncertainty in σ(γγ→τ^{+}τ^{-}) in agreement with leading-order QED predictions. Using σ(γγ→τ^{+}τ^{-}), we estimate a model-dependent value of the anomalous magnetic moment of the τ lepton of a_{τ}=0.001_{-0.089}^{+0.055}.
  16. Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2023 Sep 01;131(9):091903.
    PMID: 37721839 DOI: 10.1103/PhysRevLett.131.091903
    A search for the rare η→μ^{+}μ^{-}μ^{+}μ^{-} double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb^{-1}. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ^{+}μ^{-} decay as normalization, the branching fraction B(η→μ^{+}μ^{-}μ^{+}μ^{-})=[5.0±0.8(stat)±0.7(syst)±0.7(B_{2μ})]×10^{-9} is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions.
  17. Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Mar 22;132(12):121901.
    PMID: 38579207 DOI: 10.1103/PhysRevLett.132.121901
    The observation of WWγ production in proton-proton collisions at a center-of-mass energy of 13 TeV with an integrated luminosity of 138  fb^{-1} is presented. The observed (expected) significance is 5.6 (5.1) standard deviations. Events are selected by requiring exactly two leptons (one electron and one muon) of opposite charge, moderate missing transverse momentum, and a photon. The measured fiducial cross section for WWγ is 5.9±0.8(stat)±0.8(syst)±0.7(modeling)  fb, in agreement with the next-to-leading order quantum chromodynamics prediction. The analysis is extended with a search for the associated production of the Higgs boson and a photon, which is generated by a coupling of the Higgs boson to light quarks. The result is used to constrain the Higgs boson couplings to light quarks.
  18. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Sep 01;131(9):091803.
    PMID: 37721845 DOI: 10.1103/PhysRevLett.131.091803
    The first observation of the production of W^{±}W^{±} bosons from double parton scattering processes using same-sign electron-muon and dimuon events in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 138  fb^{-1} recorded at a center-of-mass energy of 13 TeV using the CMS detector at the CERN LHC. Multivariate discriminants are used to distinguish the signal process from the main backgrounds. A binned maximum likelihood fit is performed to extract the signal cross section. The measured cross section for production of same-sign W bosons decaying leptonically is 80.7±11.2(stat) _{-8.6}^{+9.5}(syst)±12.1(model)  fb, whereas the measured fiducial cross section is 6.28±0.81(stat)±0.69(syst)±0.37(model)  fb. The observed significance of the signal is 6.2 standard deviations above the background-only hypothesis.
  19. Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Mar 15;132(11):111901.
    PMID: 38563916 DOI: 10.1103/PhysRevLett.132.111901
    A search is reported for near-threshold structures in the J/ψJ/ψ invariant mass spectrum produced in proton-proton collisions at sqrt[s]=13  TeV from data collected by the CMS experiment, corresponding to an integrated luminosity of 135  fb^{-1}. Three structures are found, and a model with quantum interference among these structures provides a good description of the data. A new structure is observed with a local significance above 5 standard deviations at a mass of 6638_{-38}^{+43}(stat)_{-31}^{+16}(syst)  MeV. Another structure with even higher significance is found at a mass of 6847_{-28}^{+44}(stat)_{-20}^{+48}(syst)  MeV, which is consistent with the X(6900) resonance reported by the LHCb experiment and confirmed by the ATLAS experiment. Evidence for another new structure, with a local significance of 4.7 standard deviations, is found at a mass of 7134_{-25}^{+48}(stat)_{-15}^{+41}(syst)  MeV. Results are also reported for a model without interference, which does not fit the data as well and shows mass shifts up to 150 MeV relative to the model with interference.
  20. Kar SP, Tyrer JP, Li Q, Lawrenson K, Aben KK, Anton-Culver H, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Oct;24(10):1574-84.
    PMID: 26209509 DOI: 10.1158/1055-9965.EPI-14-1270
    BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.

    METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).

    RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.

    CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.

    IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.

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