Recently acquired hepatitis C virus infection among people living with human immunodeficiency virus at a university hospital in Taiwan

BACKGROUND Little is known about the engagement in hepatitis C virus(HCV)care and completion of HCV treatment in people living with human immunodeficiency virus(HIV)(PLWH)who have HCV coinfection in the Asia-Pacific region.Examining the HCV care cascade can identify barriers to the completion of HCV treatment and facilitate achievement of HCV micro-elimination in PLWH.AIM To investigate the care cascade of incident HCV infections among PLWH in Taiwan.METHODS PLWH with incident HCV infections,defined as HCV seroconversion,were retrospectively identified by sequential anti-HCV testing of all archived blood samples at National Taiwan University Hospital between 2011 and 2018.All PLWH with incident HCV infections were followed until December 31,2019.The care cascade of HCV examined included all incident HCV-infected patients,the percentages of anti-HCV antibodies detected by HIV-treating physicians in clinical care,plasma HCV RNA load tested,HCV RNA positivity diagnosed,referral to treatment assessment made,anti-HCV treatment initiated,and sustained virologic response achieved.Those who had HCV seroconversion during the interferon(IFN)era(2011–2016)and the direct-acting antiviral(DAA)era(2017–2018)were analyzed separately.The duration of HCV viremia—from the date of seroconversion to viral clearance by treatments or until the end of observation—and the incidence of sexually transmitted infections(STIs)during the HCV viremic period were estimated.RESULTS During the study period,287 of 3495(8.2%)PLWH(92.3%being men who have sex with men)who were HCV-seronegative at baseline developed HCV seroconversion by retrospective testing of all archived blood samples.Of the 287 incident HCV infections,277(96.5%)had anti-HCV antibodies detected by HIV-treating physicians,270(94.1%)had plasma HCV RNA determined and 251(87.5%)tested positive for HCV RNA.Of those with HCV viremia,226(78.7%)were referred to treatment assessment,215(74.9%)initiated anti-HCV treatment,and 202(70.4%)achieved viral clearance.Compared with that in the IFN era,the median interval from HCV seroconversion by retrospective testing to detection of HCV seropositivity by HIV-treating physicians was significantly shorter in the DAA era{179 d[interquartile range(IQR)87-434]vs 92 d(IQR 57-173);P<0.001}.The incidence rate of STIs in the DAA vs the IFN era was 50.5 per 100 person-years of follow-up(PYFU)and 38.5 per 100 PYFU,respectively,with an incidence rate ratio of 1.31(95%confidence interval 0.96-1.77),while the duration of HCV viremia was 380 d(IQR 274-554)and 735 d(IQR 391-1447)(P<0.001),respectively.CONCLUSION While anti-HCV therapies are effective in achieving viral clearance,our study suggests more efforts are needed to expedite the linkage of PLWH diagnosed with incident HCV infections to HCV treatment.

Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

Highly Accurate Golden Section Search Algorithms and Fictitious Time Integration Method for Solving Nonlinear Eigenvalue Problems

This study sets up two new merit functions,which are minimized for the detection of real eigenvalue and complex eigenvalue to address nonlinear eigenvalue problems.For each eigen-parameter the vector variable is solved from a nonhomogeneous linear system obtained by reducing the number of eigen-equation one less,where one of the nonzero components of the eigenvector is normalized to the unit and moves the column containing that component to the right-hand side as a nonzero input vector.1D and 2D golden section search algorithms are employed to minimize the merit functions to locate real and complex eigenvalues.Simultaneously,the real and complex eigenvectors can be computed very accurately.A simpler approach to the nonlinear eigenvalue problems is proposed,which implements a normalization condition for the uniqueness of the eigenvector into the eigenequation directly.The real eigenvalues can be computed by the fictitious time integration method(FTIM),which saves computational costs compared to the one-dimensional golden section search algorithm(1D GSSA).The simpler method is also combined with the Newton iterationmethod,which is convergent very fast.All the proposed methods are easily programmed to compute the eigenvalue and eigenvector with high accuracy and efficiency.

The Optimization Design of the Nozzle Section for theWater Jet Propulsion System Applied in Jet Skis

The performance of a water jet propulsion system is related to the inlet duct,rotor,stator,and nozzle.Generally,the flow inlet design must fit the bottom line of the hull,and the design of the inlet duct is often limited by stern space.The entire section,from the rotor to the nozzle through the stator,must be designed based on system integration in that the individual performance of these three components will influence each other.Particularly,the section from the rotor to the nozzle significantly impacts the performance of a water jet propulsion system.This study focused on nozzle design and established referable analysis results to facilitate subsequent integrated studies on the design parameters regarding nozzle contour.Most existing studies concentrate on discussions on rotor design and the tip leakage flow of rotors or have replaced the existing complex computational domain with a simple flow field.However,research has yet to implement an integrated,optimal design of the section from the rotor to the nozzle.Given the above,our program conducted preliminary research on this system integration design issue,discussed the optimal nozzle for this section in-depth,and proposed design suggestions based on the findings.This program used an existing model as the design case.This study referred to the actual trial data as the design conditions for the proposed model.Unlike prior references’simple flow field form,this study added a jet ski geometry and free surface to the computational domain.After the linear hull shape was considered,the inflow in the inlet duct would be closer to the actual condition.Based on the numerical calculation result,this study recommends that the optimal nozzle outlet area should be 37%of the inlet area and that the nozzle contour should be linear.Furthermore,for the pump head,static pressure had a more significant impact than dynamic pressure.

Optimal Shape Factor and Fictitious Radius in the MQ-RBF:Solving Ill-Posed Laplacian Problems

To solve the Laplacian problems,we adopt a meshless method with the multiquadric radial basis function(MQRBF)as a basis whose center is distributed inside a circle with a fictitious radius.A maximal projection technique is developed to identify the optimal shape factor and fictitious radius by minimizing a merit function.A sample function is interpolated by theMQ-RBF to provide a trial coefficient vector to compute the merit function.We can quickly determine the optimal values of the parameters within a preferred rage using the golden section search algorithm.The novel method provides the optimal values of parameters and,hence,an optimal MQ-RBF;the performance of the method is validated in numerical examples.Moreover,nonharmonic problems are transformed to the Poisson equation endowed with a homogeneous boundary condition;this can overcome the problem of these problems being ill-posed.The optimal MQ-RBF is extremely accurate.We further propose a novel optimal polynomial method to solve the nonharmonic problems,which achieves high precision up to an order of 10^(−11).

Understanding the molecular crossroads in acute liver failure:A pathway to new therapies

In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.

Exploring the Relationship Between Patent Forward Citation and Stock Return Rate Using Empirical Data of China Stock Market

A novel indicator called price-citation was proposed.Based on the company integrated patent database of China listed companies of common stocks(A-shares)with the stock price and the stock return rate data,more than two thousand of A-shares from 2017 to 2020 were selected.The effect of the traditional patent forward citation and the price-citation for discriminating the stock return rate was thoroughly analyzed via ANOVA.The A-shares of forward citation counts above the average showed higher stock return rate means than the A-shares having patents but receiving no forward citations.The price-citation,combining both the financial and patent attributes,defined as the multiplication of the current stock price and the currently receiving forward citation count,showed its excellence in discriminating the stock return rate.The A-shares of higher price-citation showed significantly higher stock return rate means while the A-shares of lower price-citation showed significantly lowest stock return rate means.The price-citation effect had not been changed by COVID-19 though COVID-19 affected the social and economic environment to a considerable extent in 2020.

Unveiling significant risk factors for intensive care unit-acquired weakness:Advancing preventive care

In this editorial,we discuss an article titled,“Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning,”published in a recent issue of the World Journal of Clinical Cases.Intensive care unit-acquired weakness(ICU-AW)is a debilitating condition that affects critically ill patients,with significant implications for patient outcomes and their quality of life.This study explored the use of artificial intelligence and machine learning techniques to predict ICU-AW occurrence and identify key risk factors.Data from a cohort of 1063 adult intensive care unit(ICU)patients were analyzed,with a particular emphasis on variables such as duration of ICU stay,duration of mechanical ventilation,doses of sedatives and vasopressors,and underlying comorbidities.A multilayer perceptron neural network model was developed,which exhibited a remarkable impressive prediction accuracy of 86.2%on the training set and 85.5%on the test set.The study highlights the importance of early prediction and intervention in mitigating ICU-AW risk and improving patient outcomes.

High glucose reduces Nrf2-dependent cRAGE release and enhances inflammasome-dependent IL-1βproduction in monocytes:the modulatory effects of EGCG

Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.

A HybridManufacturing ProcessMonitoringMethod Using Stacked Gated Recurrent Unit and Random Forest

This study proposed a new real-time manufacturing process monitoring method to monitor and detect process shifts in manufacturing operations.Since real-time production process monitoring is critical in today’s smart manufacturing.The more robust the monitoring model,the more reliable a process is to be under control.In the past,many researchers have developed real-time monitoring methods to detect process shifts early.However,thesemethods have limitations in detecting process shifts as quickly as possible and handling various data volumes and varieties.In this paper,a robust monitoring model combining Gated Recurrent Unit(GRU)and Random Forest(RF)with Real-Time Contrast(RTC)called GRU-RF-RTC was proposed to detect process shifts rapidly.The effectiveness of the proposed GRU-RF-RTC model is first evaluated using multivariate normal and nonnormal distribution datasets.Then,to prove the applicability of the proposed model in a realmanufacturing setting,the model was evaluated using real-world normal and non-normal problems.The results demonstrate that the proposed GRU-RF-RTC outperforms other methods in detecting process shifts quickly with the lowest average out-of-control run length(ARL1)in all synthesis and real-world problems under normal and non-normal cases.The experiment results on real-world problems highlight the significance of the proposed GRU-RF-RTC model in modern manufacturing process monitoring applications.The result reveals that the proposed method improves the shift detection capability by 42.14%in normal and 43.64%in gamma distribution problems.

Occupational physical activity, all-cause, cardiovascular disease, and cancer mortality in 349,248 adults: Prospective and longitudinal analyses of the MJ Cohort

Background:Evidence on the health benefits of occupational physical activity(OPA)is inconclusive.We examined the associations of baseline OPA and OPA changes with all-cause,cardiovascular disease(CVD),and cancer mortality and survival times.Methods:This study included prospective and longitudinal data from the MJ Cohort,comprising adults over 18 years recruited in 1998-2016,349,248 adults(177,314 women)with baseline OPA,of whom 105,715(52,503 women)had 2 OPA measures at 6.3±4.2 years(mean±SD)apart.Exposures were baseline OPA,OPA changes,and baseline leisure-time physical activity.Results:Over a mean mortality follow-up of 16.2±5.5 years for men and 16.4±5.4 years for women,11,696 deaths(2033 of CVD and 4631 of cancer causes)in men and 8980 deaths(1475 of CVD and 3689 of cancer causes)in women occurred.Combined moderately heavy/heavy baseline OPA was beneficially associated with all-cause mortality in men(multivariable-adjusted hazard ratio(HR)=0.93,95%confidence interval(95%CI):0.89-0.98 compared to light OPA)and women(HR=0.86,95%CI:0.79-0.93).Over a mean mortality follow-up of 12.5±4.6 years for men and 12.6±4.6 years for women,OPA decreases in men were detrimentally associated(HR=1.16,95%CI:1.01-1.33)with all-cause mortality,while OPA increases in women were beneficially(HR=0.83,95%CI:0.70-0.97)associated with the same outcome.Baseline or changes in OPA showed no associations with CVD or cancer mortality.Conclusion:Higher baseline OPA was beneficially associated with all-cause mortality risk in both men and women.Our longitudinal OPA analyses partly confirmed the prospective findings,with some discordance between sex groups.

Sonographic fatty liver and hepatitis B virus carrier status: Synergistic effect on liver damage in Taiwan Residents adults

AIM: To examine the epidemiology of hepatitis B virus carrier status (HBVC) and sonographic fatty liver (SFL) in Taiwan Residents adults, and to evaluate their possible interaction in inducing liver damage (LD). From an epidemiological viewpoint, we analyzed previous studies which indicated that fatty liver sensitizes host immune response to HBV infection and enhances liver damage.METHODS: A cross-sectional retrospective analysis of health records including medical history, physical examination, abdominal sonogram, blood biochemistry and hepatic virological tests. We utilized the Student's t-test, chi-square, multivariate logistic regression and synergy index to assess risks for LD.RESULTS: Among a total of 5406 Taiwan Residents adults (mean age 46.2 years, 51.5% males), the prevalence of LD, HBVC and SFL were 12.3%, 15.1% and 33.4%, respectively; 5.1% of participants had SFL plus HBVC. Multivariate logistic regression analysis demonstrated that male gender (odds ratio (OR) = 2.8, 95% confidence interval (CI): 2.3-3.5), overweight state (OR = 1.6, 95% CI: 1.3-2.0), HBVC (OR = 2.5, 95% CI: 2.0-3.1) and SFL (OR = 4.2, 95% CI: 2.2-5.3) were independently associated with LD. Synergism analysis showed that the adjusted OR for LD in adults with HBVC-alone was 3.3 (95% CI: 2.4-4.6), SFL-alone, 4.7 (95% CI: 3.7-6.1) and combined HBVC and SFL, 9.5 (95% CI: 6.8-13.3); the synergy index was 1.4 (95% CI: 1.001-2.0).CONCLUSION: In Taiwan Residents adults, SFL plus HBVC have a significant synergistic association with LD.

Influence of rice straw burning on the levels of polycyclic aromatic hydrocarbons in agricultural county of Taiwan

Atmospheric particulate and polycyclic aromatic hydrocarbons （PAHs） size distribution were measured at Jhu-Shan （a rural site） and Sin-Gang （a town site） in central Taiwan during the rice straw burning and non-burning periods. The concentrations of total PAHs accounting for a roughly 58% （34%） increment in the concentrations of total PAHs due to rice-straw burning. Combustion-related PAHs during burning periods were 1.54-2.57 times higher than those during non-burning periods. The mass median diameter （MMD） of 0.88-1.21 μm in the particulate phase suggested that rice-straw burning generated the increase in coarse particle number. Chemical mass balance （CMB） receptor model analyses showed that the primary pollution sources at the two sites were similar. However, ricestraw burning emission was specifically identified as a significant source of PAH during burning periods at the two sites. Open burning of rice straws was estimated to contribute approximately 6.3%-24.6% to total atmospheric PAHs at the two sites.

Peanut consumption and reduced risk of colorectal cancer in women:A prospective study in Taiwan

瞄准：检验花生消费是否与肤色的减少的风险被联系在有 10 年的后续的一个未来的队的表面的癌症。方法：在 1990-1992，在 7 个镇区的居民(30 ～ 65 年的 12026 个男人和 11917 个女人) ，台湾，被会见并且招募并且每年列在后面起来进一个屏蔽癌症的队。在这个队的 Colorectal 癌症诉讼从癌症登记和死亡证被识别。在 2001 底的这疾病的发生率被性为主要学习变量和 covariates 计算。饮食的吸入借助于每周的食物频率措施被估计，包括包括甘薯，豆子产品，花生产品， pickled 食品， nitrated 或吸的食品的经常消费的食物组和民间盘子。结果：在学习经期期间， 107 新肤色表面的癌症盒子(68 个男人和 39 个女人) 被证实。多，变量考克斯的比例的危险模型证明花生消费的相对风险(RR ) 是 0.73 [95% 信心间隔(CI )= 0.44-1.21 ] 为男人并且 0.42 (95% CI = 0.21-0.84 ) 为女人。然而， pickled 食品的经常的吸入为女人是有害的(RR = 2.15， 95% CI = 0.99-4.65 ) 。表面的癌症也是的颜色的风险在香烟吸烟者之中提高了然而并非重要(P【0.05 ) 。结论：这研究建议花生和它的产品的经常的吸入可以减少表面的癌症在女人冒的风险的颜色，表明花生吸入的增殖反的效果。

Enhancing Partnership Between Rural Schools and Communities for Geoheritage Conservation—A Case Study of Taiwan

Academics in Taiwan have been working on geo-conservation for 20 years.Numerous studies focus on investigation,assessment,monitoring and education of special scientific important geoheritages. However,few researches have been done on the issues of local stakeholder participation and community development.The authors choose one of the national-level geoheritages,the Lichi Badland

Population genetics of red imported fire ant in Taiwan

In the case of recently established populations of Solenopsis invicta in Taiwan,analysis of genetic variation may provide various dimensions regarding the historical demographic events of this invasive species,which represents a novel opportunity to study the genetic consequences of invasiveness over an ex- tremely short time period.Here we describe genetic structure of two introduced S.invicta populations, Taoyuan and Chiayi,in Taiwan using two classes of markers,nuclear(microsatellites)and mitochondrial (mtDNA)genomes.Pronounced regional differentiation inferred from either AMOVA or Bayesian clustering approach at both genomes suggests that the two populations most likely originate from separate introductions. Furthermore,significant mtDNA but not nuclear differentiation between sympatric social forms suggests two scenarios that interform gene flow is mainly mediated by males,and queens of each form commonly fail to become egg-layers of alternate form.Isolation by distance(IBD)obtained from microsatellites is absent in monogynes,indicating sexuals of this form retain the superior dispersal ability to homogenize the nuclear sig- nature among spatially isolated areas;however,lack of IBD in less vagile polygyne may result from frequent human mediated jump dispersal that erodes the geographical restrictions of genetic exchange.The patterns observed here not only provide insights into how social organization influences the interform gene flow but also reinforce different breeding strategies pursued by two forms in the character of shaping the genetic varia- tion at two levels of genomes.

Cigarette smoking and alcohol drinking and esophageal cancer risk in Taiwan Residents women

AIM:To investigate the etiology of esophageal cancer among Taiwan Residents women.METHODS:This is a multi-center,hospital-based,case-control study.Case patients consisted of women who were newly diagnosed and pathology-proven to have esophageal squamous cell carcinoma(ESCC) from three large medical centers(one from Northern and two from Southern Taiwan,respectively)between August 2000 and December 2008.Each ESCC patient was matched with 4 healthy women based on age(within 3 years)and hospital of origin,from the Department of Preventive Medicine in each hospital.A total of 51 case patients and 204 controls,all women,were studied.RESULTS:Frequencies of smokers and drinkers among ESCC patients were 19.6%and 21.6%,respectively,which were significantly higher than smokers(4.4%) and drinkers(4.4%)among controls(OR=4.07,95%CI:1.36-12.16,P=0.01;OR=3.55,95%CI:1.03-12.27,P=0.04).Women who drank an amount of alcohol more than 158 g per week had a 20.58-fold greater risk(95%CI:1.72-245.62,P=0.02)of ESCC than those who never drank alcohol after adjusting for other covariates,although the sample size was small.CONCLUSION:Cigarette smoking and alcohol drinking,especially heavy drinking,are the major risks for developing ESCC in Taiwan Residents women.

Impacts of Regional Network Dynamics on Taiwan’s Foreign Trade and OFDI

The purpose of this study is to explore the impact of regional network(regional economies integration)dynamics(integration of free trade agreements[FTAs]/regional trade agreements[RTAs]in Asia-Pacific economies)on Taiwan’s trade(export)and outward foreign direct investment(OFDI)flows.This study uses two models to estimate export and FDI respectively to investigate the impact of regional network dynamics on individuals,and the impact of trade effects on FDI.Research period is 2001-2016.Estimated findings indicate that Taiwan’s exports are highly dependent on major Asian countries,and the GDP growth of major trading countries has no significant effect on Taiwan’s exports,but the GDP growth of major Asian countries has positive and significant effects on Taiwan’s FDIs.Exports have no significant effects mostly on FDI,which implies that Taiwan’s main OFDIs have no significant correlation with export orientation.In terms of regional network integration,the impact of the initial regional network integration(ASEAN plus three countries)has no significant effects mostly on the export flows of Taiwan’s trading countries,but has relatively significant effects on the FDI flows of Taiwan’s FDI countries;the impact of the relatively mature regional network integration(ASEAN plus six countries)has negative effects on the export and FDI flows of Taiwan’s major trading and FDI countries,especially Association of Southeast Asian Nations(ASEAN)and Japan.The impact of the bilateral economic agreement(Economic Cooperation Framework Agreement[ECFA])has positive and significant effects on the export flows of Taiwan’s major trading countries,especially in Asian countries;while for FDI countries has only a positive and significant effect on China,but has a negative and significant effect on ASEAN.According to the analysis results,regional network integration appears to have significant negative effects on Taiwan’s major trading and FDI partners.

Vegetation Landscape,Ecological Characteristics and Soil Fixation for Riverbank in Taiwan,China

This study is aimed to investigate and analyze the vegetation landscape around Rivers of Hou-lung, Fa-tz, Da-li, Ching-shuei and Gau- ping, and to select the suitable plant species that could be applied for the area of riverbank ecological engineering in Taiwan. Studying the vegetation established the key point and procedure of ecological engineering in the riverside and revetment, to compile and edit the dominant plants＇ types, life form, propagating method, root systems＇ characteristics and functions for soil conservation. This research choses three dominant plants for roots strength test. The fitting models of plants pulling resistance（Rp, kg） between plant height （H, cm）, diameter near ground （Dn, mm）, diameter above ground 100 mm （Da, mm）, The research finished the relative abundant, types and cluster analysis of riverbank dominant plants that generalize vegetative distribution and ecological restoration for different river types to apply and manage in Taiwan.

Blood DNA methylation markers in prospectively identifiedhepatocellular carcinoma cases and controls from Taiwan

AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarkers of HCC susceptibility but should be replicated in additional prospective studies.