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BackgroundWhile the associations between individual lifestyle factors and risk of hepatocellular carcinoma (HCC) have been described previously, their combined impact on HCC risk is unknown.MethodsThe association of a composite score of healthy lifestyle factors, including body mass index, alcohol consumption, cigarette smoking, alternative Mediterranean diet, and sleep duration, and HCC risk was examined in the Singapore Chinese Health Study, an ongoing prospective cohort study of 63,257 Chinese men and women. Cox proportional hazard regression method was used to estimate HR and its 95% confidence interval (CI). Conditional logistic regression method was used to evaluate this composite lifestyle score-HCC risk association among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody.ResultsAfter a mean follow-up of 17.7 years, 561 participants developed HCC. Individuals with higher composite scores representing healthier lifestyles (range 0-8) were at significantly lower risk of HCC. Compared with the lowest composite score category (0-4), the HRs (95% CIs) for the composite scores of 5, 6, 7, and 8 were 0.67 (0.62-0.85), 0.61 (0.48-0.77), 0.49 (0.37-0.65), and 0.13 (0.06-0.30), respectively (P trend < 0.0001). A similar inverse association was observed in participants with negative HBsAg and anti-hepatitis C virus (HCV)-negative serology (HR, 0.38; 95% CI, 0.19-0.79; for the highest vs. the lowest category of the composite scores; P trend = 0.001).ConclusionsHealthy lifestyles protect against HCC development, especially for individuals without hepatitis B virus and HCV infections.ImpactThis study highlights the importance of a comprehensive lifestyle modification strategy for HCC primary prevention.

In order to optimize machined surface topography, this paper presents a novel algorithm for simulating the surface topography and predicting the surface roughness of a ball-end milling process. First, a discrete workpiece model was developed using the Z-map method, and the swept surface of a cutter edge was represented using triangular approximation. The workpiece surface was updated (i.e., material removal process) using the intersection between the vertical reference line and the triangular facet under a cutting judgement. Second, the proposed algorithm was verified by comparing the simulated 3D surface topography as well as 2D surface profile and average roughness (Sa) with experimental measurements. Then, numerical simulation examples planed by the Box–Behnken design methods were carried out to investigate the Sa in the ball-end milling operation. The correlations of Sa and cutting parameters were represented by a response surface reduced quadratic model based on the ANOVA results. Finally, the feed per tooth, radial depth of cut, and tilt and lead angles were optimized for improving the machining efficiency under the Sa constraints. This study presents an effective method for simulating surface topography and predicting the Sa to optimize the cutting parameters during ball-end milling process. [ABSTRACT FROM AUTHOR]

Background: Most of the subjects eligible for annual low‐dose computed tomography (LDCT) lung screening will not develop lung cancer for their life. It is important to identify novel biomarkers that can help identify those at risk of developing lung cancer and improve the efficiency of LDCT screening programs. Objective: This study aims to investigate the association between the morphology of the pulmonary circulatory system (PCS) and lung cancer development using LDCT scans acquired in the screening setting. Methods: We analyzed the PLuSS cohort of 3635 lung screening patients from 2002 to 2016. Circulatory structures were segmented and quantified from LDCT scans. The time from the baseline CT scan to lung cancer diagnosis, accounting for death, was used to evaluate the prognostic ability (i.e., hazard ratio (HR)) of these structures independently and with demographic factors. Five‐fold cross‐validation was used to evaluate prognostic scores. Results: Intrapulmonary vein volume had the strongest association with future lung cancer (HR = 0.63, p < 0.001). The joint model of intrapulmonary vein volume, age, smoking status, and clinical emphysema provided the strongest prognostic ability (HR = 2.20, AUC = 0.74). The addition of circulatory structures improved risk stratification, identifying the top 10% with 28% risk of lung cancer within 15 years. Conclusion: PCS characteristics, particularly intrapulmonary vein volume, are important predictors of lung cancer development. These factors significantly improve prognostication based on demographic factors and noncirculatory patient characteristics, particularly in the long term. Approximately 10% of the population can be identified with risk several times greater than average. [ABSTRACT FROM AUTHOR]

We evaluated whether aflatoxin B1 (AFB1) exposure was associated with later risk of developing gallbladder cancer (GBC). We measured AFB1‐lysine albumin adducts in baseline samples from the Shanghai Cohort Study of 18 244 men aged 45 to 64 years (recruited 1986‐1989). We included 84 GBC cases with sufficient serum and 168 controls matched on age at sample collection, date of blood draw and residence. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for detectable vs non‐detectable AFB1‐lysine albumin adducts and gallbladder cancer. AFB1‐lysine albumin adducts were detected in 50.0% of GBC cases, and risk of GBC was twice as high in those with detectable vs undetectable levels (OR = 2.0, 95% CI = 1.0‐3.9). ORs ranged from 1.8 (95% CI = 0.75‐4.3) for 0.5 to <1.75 pg/mg vs undetectable adduct levels to 2.2 (95% CI = 0.91‐5.6) for >3.36 pg/mg vs undetectable, suggesting a dose‐response (Ptrend =.05). When restricted to cases diagnosed before the median time to diagnosis after blood draw (18.4 years), results were similar (OR = 2.2, 95% CI = 0.80‐5.8) to those for the entire follow‐up duration. The OR was 9.4 (95% CI = 1.7‐51.1) for individuals with detectable AFB1‐lysine albumin adducts and self‐reported gallstones compared to individuals with neither. Participants with detectable AFB1‐lysine albumin adducts at baseline had increased risk of developing GBC, replicating the previously observed association between AFB1 exposure and providing the first evidence of temporality. [ABSTRACT FROM AUTHOR]

BackgroundAlthough studies suggest that omega-3 fatty acids intake may reduce cardiovascular disease (CVD) mortality risk, few studies have differentiated dietary eicosapentaenoic/docosahexaenoic acid (EPA/DHA) from alpha-linolenic acid (ALA), and epidemiological research in Asian populations is limited.MethodsThe Singapore Chinese Health Study is a population-based cohort that recruited 63,257 Chinese adults aged 45-74 years from 1993 to 1998. Usual diet was measured at recruitment using a validated semiquantitative food-frequency questionnaire, and mortality information was identified via registry linkage up to 31 December 2011. Cox proportional hazard models were used to calculate hazard ratios (HRs) with adjustment for potential confounders.ResultsWe documented 4780 cardiovascular deaths (including 2697 coronary heart disease (CHD) deaths and 1298 stroke deaths) during 890,473 person-years of follow up. Omega-3 fatty acids intake was monotonically associated with reduced risk of cardiovascular mortality. Compared to the lowest quartile, the HR was 0.88 (95% confidence interval, CI, 0.81-0.96), 0.88 (95% CI 0.80-0.97), and 0.83 (95% CI 0.74-0.92) for the second, third, and highest quartile, respectively (p-trend = 0.003). Both EPA/DHA and ALA were independently associated with reduced risk of cardiovascular mortality: HR comparing extreme quartiles was 0.86 (95% CI 0.77-0.96, p-trend = 0.002) and 0.81 (95% CI 0.73-0.90, p-trend

BACKGROUND: Genome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), mostly among individuals of European ancestry. We tested whether previously identified T2D-associated single nucleotide polymorphisms (SNPs) replicate and whether SNPs in regions near known T2D SNPs were associated with T2D within the Singapore Chinese Health Study. METHODS: 2338 cases and 2339 T2D controls from the Singapore Chinese Health Study were genotyped for 507,509 SNPs. Imputation extended the genotyped SNPs to 7,514,461 with high estimated certainty (r(2)>0.8). Replication of known index SNP associations in T2D was attempted. Risk scores were computed as the sum of index risk alleles. SNPs in regions ± 100 kb around each index were tested for associations with T2D in conditional fine-mapping analysis. RESULTS: Of 69 index SNPs, 20 were genotyped directly and genotypes at 35 others were well imputed. Among the 55 SNPs with data, disease associations were replicated (at p

Background We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. Methods We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided. Results The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (P difference =.001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model. Conclusion Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is a major contributor to the rising incidence of hepatocellular carcinoma (HCC). Magnesium is a major cation in cellular activities. Epidemiological data on magnesium level and its relation to HCC are sparse. This study aimed to examine the associations between serum levels of magnesium and the risk of HCC among patients with NAFLD. Methods: A total of 26,053 patients with NAFLD were identified in the University of Pittsburgh Medical Center Electronic Health Records from 2004 through 2018. After an average of 5.15 years of follow‐up, 395 patients developed HCC after the first measurement of serum magnesium. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs of HCC incidence associated with quartile levels of serum magnesium after adjustment for age, sex, race, body mass index, diuretics use, history of type 2 diabetes, history of hypertension, history of hyperlipidemia, and tobacco smoking. Results: Patients with NAFLD who developed HCC had a significantly lower mean (± standard deviation) serum magnesium (0.769 ± 0.131 mmol/L) than those who remained free of HCC (0.789 ± 0.125 mmol/L; p =.003). Compared with the lowest quartile, the HRs (95% CIs) of HCC second, third, and fourth quartiles of serum magnesium were 0.87 (0.67–1.12), 0.77 (0.57–1.04), and 0.73 (0.56–0.96), respectively, after adjustment for multiple potential confounders (Ptrend =.02). Conclusion: This finding suggests higher levels of serum magnesium were significantly associated with decreased risk of HCC among patients with NAFLD. Monitoring serum magnesium levels among those with nonalcoholic fatty liver disease may be beneficial in hepatocellular carcinoma primary prevention. [ABSTRACT FROM AUTHOR]

Background: There is an urgent need to identify biomarkers for advanced adenoma, an important precursor of colorectal cancer (CRC). We aimed to determine alterations in ileal juice bile acids associated with colorectal advanced adenoma. Methods: We quantified a comprehensive panel of primary and secondary bile acids and their conjugates using an ultraperformance liquid chromatography triple-quadrupole mass spectrometric assay in ileal juice collected at colonoscopy from 46 study subjects (i.e., 14 biopsy-confirmed advanced adenomas and 32 controls free of adenoma or cancer). Using analysis of covariance (ANCOVA), we examined the differences in bile acid concentrations by disease status, adjusting for age, sex, body mass index, smoking status and type 2 diabetes. Results: The concentrations of hyodeoxycholic acid (HCA) species in ileal juice of the advanced adenoma patients (geometric mean = 4501.9 nM) were significantly higher than those of controls (geometric mean = 1292.3 nM, p = 0.001). The relative abundance of ursodeoxycholic acid (UDCA) in total bile acids was significantly reduced in cases than controls (0.73% in cases vs. 1.33% in controls; p = 0.046). No significant difference between cases and controls was observed for concentrations of total or specific primary bile acids (i.e., cholic acid (CA), chenodeoxycholic acid (CDCA) and their glycine- and taurine-conjugates) and total and specific major secondary bile acids (i.e., deoxycholic acid and lithocholic acid). Conclusions: Colorectal advanced adenoma was associated with altered bile acids in ileal juice. The HCA species may promote the development of colorectal advanced adenoma, whereas gut microbiota responsible for the conversion of CDCA to UDCA may protect against it. Our findings have important implications for the use of bile acids as biomarkers in early detection of colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Peri-prosthetic joint infection (PJI) is the most serious complication after prosthetic joint replacement. However, the diagnosis of PJI remains challenging for clinicians because of the lack of a gold standard. The purpose of this study was to investigate the diagnostic significance of serum globulin, albumin/globulin, and other biomarkers in acute and chronic periprosthetic infections. Patients and Methods: A retrospective study of 162 patients with PJI and aseptic loosening between January 2016 and March 2021 at our institution was performed in three groups. There were 20 patients with acute infection in group A, 36 patients with chronic infection in group B, and 106 patients with aseptic loosening in group C. Globulin, albumin/globulin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet count (PLT), mean platelet volume (MPV), d-dimer, and platelet count/mean platelet volume ratio (PMR) levels were recorded. The area under the curve (AUC) was used to measure the diagnostic value of globulin and albumin/globulin with other biomarkers for PJI. Results: Compared with the aseptic loosening group, the acute and chronic PJI group had higher levels of CRP, ESR, d-dimer, globulin, PLT, and PMR (p < 0.01) and lower levels of albumin/globulin and MPV (p < 0.01). The optimal cutoff, AUC, sensitivity, and specificity of CRP, albumin/globulin, ESR, and globulin were: CRP, 8.3 mg/L, 0.903, 78.57%, and 88.68%; albumin/globulin, 1.31, 0.899, 91.07%, and 73.58%; ESR, 32 mm/h, 0.888, 75.%, and 85.85%; globulin, 29.5 g/L, 0.880, 91.07%, and 72.64%. Conclusions: Globulin and albumin/globulin have excellent diagnostic value for acute and chronic PJI and are promising potential biomarkers for the diagnosis of PJI. The diagnostic performance of albumin/globulin is superior to that of ESR and similar to that of CRP. [ABSTRACT FROM AUTHOR]