A Trustable and Secure Usage-Based Insurance Policy Auction Mechanism and Platform Using Blockchain and Smart Contract Technologies.

This study presents an architectural framework for the blockchain-based usage-based insurance (UBI) policy auction mechanism in the internet of vehicles (IoV) applications. The main objective of this study is to analyze and design the specific blockchain architecture and management considerations for the UBI environment. An auction mechanism is developed for the UBI blockchain platform to enhance consumer trust. The study identifies correlations between driving behaviors and associated risks to determine a driver's score. A decentralized bidding algorithm is proposed and implemented on a blockchain platform using elliptic curve cryptography and first-price sealed-bid auctions. Additionally, the model incorporates intelligent contract functionality to prevent unauthorized modifications and ensure that insurance prices align with the prevailing market value. An experimental study evaluates the system's efficacy by expanding the participant pool in the bidding process to identify the winning bidder and is investigated under scenarios where varying numbers of insurance companies submit bids. The experimental results demonstrate that as the number of insurance companies increases exponentially, the temporal overhead incurred by the system exhibits only marginal growth. Moreover, the allocation of bids is accomplished within a significantly abbreviated timeframe. These findings provide evidence that supports the efficiency of the proposed algorithm.

[Analysis of time trend of hepatocellular carcinoma mortality in Haimen city of Jiangsu province from 1993 to 2006].

OBJECTIVE: To predict the trend of hepatocellular carcinoma (HCC) mortality and investigate the features of its mortality including age, period, and birth cohort in males living in Haimen city of Jiangsu province, China. METHODS: Grey model (GM) was modeled using standardized mortality rate (SMR) of HCC from 1993 to 2006, and was applied to predicting SMR until 2012. Based on the mortality density (MD) for a four-year period, the goodness-of-fit of models and comparisons between models were evaluated so as to obtain the best one among these models including the effects of intercept, age-period-cohort (APC), age-period (AP), age-cohort (AC), period-cohort(PC), and APC. Both APC full model and the best model were used to estimate effects of age, period, and cohort on HCC mortality. In addition, MD form 2005 to 2012 was predicted by the best model. RESULTS: Predictions based on GM (1,1) showed that SMR was 48.578 pre 100 000 population (relative error=-1.267%) in 2007 year, which declined between 2008 and 2012. The lowest value was 45.578 pre 100 000 people (in the 2012 year). The results of fitted models and comparisons between models showed that AP model was the best one (ΔG(2) = 9.065, AIC = 202.544). The curvatures of the effects of the three factors from APC model suggested that significances existed in changes of curvatures of 36.5 - 40.5 years old-(-0.368) and 64.5 - 68.5 years old-(-0.489) as well as in the change of 1956 - 1959 birth cohort (C(2)(1949.5, 1967.5) = -0.492). The estimation of relative risks for AP model showed that the age effects were upward to 64.5 - 68.5 years old-, then downward; and that the period effects were found to be declined between 1993 and 2004. Predictions based on AP model suggested the decrease of HCC mortality. CONCLUSION: The slightly decreasing trend of HCC mortality for males might be explained by age, period and a minor birth cohort effects in Haimen of China.

Blood folate levels and risk of liver damage and hepatocellular carcinoma in a prospective high-risk cohort.

BACKGROUND: Studies in experimental animals suggest that low folate levels may play a role in liver damage and hepatocarcinogenesis. To examine this association in humans, folate levels in blood and risk for subsequent liver damage and hepatocellular carcinoma (HCC) were assessed in a population at high risk of liver cancer in China. METHODS: Four hundred fifteen hepatitis B surface antigen-positive participants of the Haimen City Cohort were prospectively followed between 1998 and 2002. Serum and RBC folate levels were determined at baseline. Alanine aminotransferase (ALT) and hepatitis B virus DNA levels were measured semiannually. Logistic regression modeling was used to examine the presence of hepatitis B virus DNA and HCC, whereas linear regression with a log-link function was used to examine ALT levels. RESULTS: There was a statistically significant inverse association between serum folate level and ALT level. ALT levels decreased with each quartile increase in serum folate (adjusted odds ratio, 0.86; 95% confidence interval, 0.76-0.97 for the highest compared with the lowest quartile; Ptrend = 0.002). After exclusion of three persons with prevalent HCC, 20 (4.9%) of the 412 study participants developed HCC during follow-up, with a median time between enrollment and HCC diagnosis of 2.66 years (interquartile range, 1.8-4.1). When comparing persons in the lowest quartile RBC folate to persons in all other quartiles, the analysis found that higher RBC folate levels were associated with reduced risk of hepatocarcinogenesis (odds ratio, 0.33, 95% confidence interval, 0.13-0.86; P(trend) = 0.02). CONCLUSIONS: This study suggests that increased folate levels in humans may be inversely associated with the development of liver damage and HCC.

Toenail selenium and risk of hepatocellular carcinoma mortality in Haimen City, China.

Selenium (Se) is an essential trace mineral with known anticarcinogenic properties in humans. However, few studies have examined the association between Se nutrient status and risk of liver cancer. We conducted a nested case-control study comparing the Se content in toenail clippings of 166 individuals (154 men, 12 women) with hepatocellular carcinoma (HCC) to 394 healthy controls (360 men, 34 women) in Haimen City, China, where HCC is a leading cause of mortality. Toenail Se concentration was measured by inductively coupled plasma-optical emission spectroscopy. Median toenail Se was lower for HCC cases than controls (p = 0.03). Adjusted odds ratios and 95% confidence intervals for HCC mortality by increasing quartile of toenail Se were 1.00 (reference), 0.58 (0.32-1.03), 0.83 (0.48-1.42) and 0.50 (0.28-0.90), with a marginally significant trend in risk observed (p for trend = 0.06). This inverse association appeared stronger among those who did not consume alcohol and among women. Future studies are needed to examine the interrelationship between Se, viral hepatitis infection and HCC in order to better understand the etiologic mechanisms involved and evaluate the true chemopreventive potential of Se compounds for liver diseases.

Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic carriers.

The role of quantitative viral load in development of hepatocellular carcinoma (HCC) among chronic hepatitis B virus (HBV) carriers was evaluated using real-time PCR (TaqMan PCR), a highly sensitive method for quantitative detection of HBV DNA. Serum samples collected at study entry from HCC cases and matched controls were chosen separately from ongoing prospective cohort studies in Senegal, West Africa, and Haimen City, China. For 14 HCC cases and 28 controls from Senegal, the relative risk (RR, 95% CI) of HCC was 15.6 (2.0-124.3) for those positive by the TaqMan PCR assay. Average length of follow-up (study entry to death from HCC) among cases was 2.8 (+/-1.6) years. The paired median difference between cases and controls was 3.8 x 10(4) virions/ml, with cases higher (P = 0.09). In order to clarify the relationship with lower-titer viremia, we selected 55 cases and 55 matched controls from the Chinese cohort all negative for serum HBV DNA by conventional dot blot hybridization. In this group, the RR associated with HBV DNA positivity by TaqMan PCR was 3.1 (1.1-9.2), with an average duration of follow-up of 3.3 (+/-2.1) years. The median difference in quantitative viremia between cases and controls was 6.0 x 10(4) virions/ml, with cases higher (P < 0.0001). Increased risk appeared to be confined to subjects with viral loads >2.3 x 10(4) virions/ml. In conclusion, HBV viremia, except perhaps at extremely low levels, is associated with increased risk for HCC in prospective studies of chronic carriers in two disparate populations.

Segregation analysis of hepatocellular carcinoma in a moderately high-incidence area of East China.

AIM: To explore the mode of inheritance of hepatocellular carcinoma (HCC) in a moderately high-incidence area of East China. METHODS: A pedigree survey was conducted in 210 families (3315 individuals) ascertained through 210 HCC probands in Haimen, Jiangsu Province. Simple segregation analysis was conducted using SEGRANB software. The probability of ascertainment (pi), segregation ratio (p), and the proportion of sporadic cases (x) were estimated. Complex segregation analysis was performed using the REGTL program of S.A.G.E. Models were fitted on the data of 3212 individuals that allowed for personal HBsAg status and variable age of onset in REGTL program. RESULTS: The estimate of segregation ratio was 0.191 by SEGRANB. The probability of ascertainment was 0.0266, and the proportion of sporadic cases was 0.465. The results of complex segregation analysis showed that Mendelian autosomal recessive inheritance of a major gene that influenced the age of onset distribution of HCC, provided the best fit to the data. In the best-fitting recessive model, the frequency of the disease allele was 0.11138. HBsAg seropositive status would significantly increase the risk of developing HCC. CONCLUSION: These results suggest that at least one major gene is involved in the genetic predisposition to develop HCC at an earlier age of onset. The seropositive HBsAg status can significantly increase the risk of developing HCC, which provides strong support for the interaction between genetic and environmental risk factors.

[A study on the relationship of birth order hepatocellular carcinoma].

OBJECTIVE: To explore the association of hepatocellular carcinoma (HCC) with environmental factors through analyzing birth order data from pedigree sibships. METHODS: A birth order study was conducted based on the methods of Greenwood and Haldane for 100 probands and 22 affected siblings from 100 pedigrees in a cohort which was followed up for 8 years in Haimen, Jiangsu, China. RESULTS: The findings from the Greenwood method suggested that there was a tendency for cases of HCC to concentrate at lower birth orders of 1 to 3. With the effects of hepatitis B virus on the birth orders being controlled, the same tendency was also observed. The results from Haldane method showed that difference between actual value and expected value of 6A was more than the double standard deviation. Sigma 6A(actual value) = 1,806, Sigma 6A(expected value) = 1,988, the absolute value of (Sigma 6A(actual value) - Sigma 6A(expected value))/the square root of Sigma V6A = 2.1657 (0.02 < P < 0.05). The actual value of 6A was lower than the expected value of 6A suggesting that individuals at lower birth orders were at a higher risk of suffering from HCC. In addition, through data from ecologic research, there was a decreasing tendency of mortality of HCC within 10 years after the prevalence of tap water in Haimen city. The correlation coefficient by Spearman test was -0.818 (P < 0.01). The contribution of the quality of drinking water in the locality to the onset of HCC was found among people born in earlier period. CONCLUSIONS: There was a tendency that the onset of HCC cases concentrating was at lower birth orders in this research, which was inconsistent with several reports of foreign authors' which showed a reverse tendency. According to the ecological results, it was suggested that long-term drinking of ditch-water was responsible for the tendency of cases of HCC concentrating at lower birth orders. There were also certain effects of environmental factors exerted on the onset of HCC being discovered.

Spontaneous clearance of high-titer serum HBV DNA and risk of hepatocellular carcinoma in a Chinese population.

Chronic hepatitis B virus (HBV) carriers with high-titer viremia (>10(5) virions/ml) are at increased risk for hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between clearance of high-titer viremia and subsequent risk of HCC. The study population was a prospective cohort of 114 adults from Haimen City, China, all HBV DNA(+) at study entry and followed for 797.8 person-years in total. During follow-up, 54 (47.4%) subjects spontaneously cleared high-titer viremia at least once. Of these, 27 were considered to have undergone stable seroconversion, 16 were considered unstable (12 reversions to HBV DNA positivity and 4 multiple clearances), and 11 did not have sufficient follow-up to determine stability. Of the 114 persons, 26 (22.8%) died during follow-up, 21 (18.4%) from HCC. Using Cox proportional hazards models, the RR of HCC death associated with seroconversion was 2.8 (95% CI = 1.1-7.4), controlling for age, sex, family HCC history, history of acute hepatitis, alcohol use and cigarette smoking. In conclusion, fluctuations of high-titer viremia may indicate increased hepatocellular damage and at least short-term increases in HCC risk. Long-term longitudinal studies are needed to clarify this relationship and its potential usefulness as a prognostic marker in chronic HBV infection.

A phylogenetic analysis identifies heterogeneity among hepatocellular carcinomas.

Primary hepatocellular carcinoma (HCC) is a significant cause of cancer morbidity and mortality on the global scale. Although epidemiologic studies have identified major risk factors for HCC, the sequence of oncogenic events at the molecular level remains poorly understood. While genetic allele loss appears to be a common event, the significance of the loss is not clear. In order to determine whether allele loss appears to be a random event among HCCs or whether patterns of loss cluster in groups of tumors, a phylogenetic approach was used to examine 32 tumors for genome-wide loss of heterozygosity employing 391 markers. Clusters identified by the phylogenetic analysis were then contrasted to compare candidate locus variation among individuals and to determine whether certain clusters exhibited higher loss rates than other clusters. The analysis found that 3 major and 1 minor cluster of loss could be identified and, further, these clusters were distinguished by variable rates of loss (cluster 1, 29%; cluster 2, 21%; cluster 3, 16%). The analyses also indicated that the allele loss rates in HCC were not insignificant and that the patterns of allele loss were complex. In addition, the results indicated that an individual's constitutional genotype at the EPHX1 locus may be a critical factor in determining the path of tumor evolution. In conclusion, it appears that in HCC, allele loss is not random, but clusters into definable groups that are characterized by distinctive rates of loss.

Eight-year follow-up of the 90,000-person Haimen City cohort: I. Hepatocellular carcinoma mortality, risk factors, and gender differences.

In an 8-year follow-up of a prospective cohort study in Haimen City, China, we sought to identify hepatocellular carcinoma (HCC) risk factors in addition to hepatitis B virus (HBV) infection. Two cohorts of adults between ages 25 and 64 years at study entry were followed from 1992-1993 to 2000. The male cohort included 58,545 men, 15.0% of whom were HBV carriers. The female cohort included 25,340 women, 10.7% of whom were HBV carriers. 434,718 person-years of follow-up were accumulated, and 1092 deaths from HCC occurred. The relationship of potential risk factors measured at study entry to HCC mortality was analyzed using Cox proportional hazards models. For males, HCC mortality was significantly associated with HBV infection [relative risk (RR) 18.8; 95% confidence interval (CI), 15.7-22.5], history of acute hepatitis (RR, 2.3; 95% CI, 2.0-2.7), family history of HCC (RR, 2.3; 95% CI, 1.9-2.7), and occupation as a peasant (RR, 1.5; 95% CI, 1.3-1.8). For females, HCC mortality was significantly associated with HBV infection (RR, 33.5; 95% CI, 17.1-65.5) and acute hepatitis history (RR, 4.7; 95% CI, 3.0-7.5). HCC risk was not significantly associated with alcohol consumption, water source, or staple foods in either sex. There was no association with smoking in males, but there was a positive association for females. Environmental and genetic risk factors besides HBV infection play a significant role in HCC mortality in this extremely high-risk population. Gender differences in HCC mortality and known risk factors are substantial and warrant further study. Identification of risk factors amenable to intervention should be a high priority in the prevention of HCC.