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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]

Currently, the relationship between serum uric acid (SUA) and bone mineral density (BMD) in men remains controversial. This study aims to investigate the relationship between SUA and lumbar spine BMD in American men using data from the National Health and Nutrition Examination Survey (NHANES). A total of 6254 male subjects aged 12–80 years (mean age 35.52 ± 14.84 years) in the NHANES from 2011 to 2020 were analyzed. SUA was measured by DxC using the timed endpoint method, and lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA). Multivariate linear regression models were used to explore the relationship between SUA and BMD by adjusting for age, race/Hispanic origin, drinking behavior, smoking behavior, physical activity, body mass index (BMI), poverty-to-income ratio (PIR), total protein, serum calcium, cholesterol, serum phosphorus, and blood urea nitrogen. After correcting for the above confounders, it was found that SUA was positively associated with lumbar spine BMD in the range of SUA < 5 mg/dL (β = 0.006 95% CI 0.003–0.009, P < 0.001), and BMD of individuals in the highest quartile of SUA was 0.020 g/cm2 higher than those in the lowest quartile of SUA (β = 0.020 95% CI 0.008–0.032, P = 0.003). This study showed that SUA was positively correlated with lumbar spine BMD in American men within a certain range. This gives clinicians some insight into how to monitor SUA levels to predict BMD levels during adolescence when bone is urgently needed for growth and development and during old age when bone loss is rapid. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effects of a three-month Guolin Qigong (GQ) intervention on physical fitness and patient-reported health outcomes among patients with lung cancer. Methods: This pilot study was a non-randomized controlled trial. Eligible participants who were over 18 years of age and diagnosed with stage I–IV lung cancer were enrolled in the study and received either the GQ intervention or usual care (UC). Participants in the GQ group performed GQ at least twice a week (one hour per session) for three months. Physical fitness (chair stand, arm curl, sit and reach, back scratch, 8-foot up and go, 6-min walk test) was assessed at baseline, post-intervention, six months, and 12 months. Self-reported quality of life and sleep (European Organization for Research and Treatment of Cancer Quality of Life questionnaire and Pittsburgh Sleep Quality Index) were assessed at baseline, post-intervention, and six months. Results: Forty-nine participants (65% females, 59.1 ± 7.0 years old, ranging from 39 to 71 years old) were enrolled in the study, and 25 participants completed all tests at 12-month follow-up (13 in GQ vs. 12 in UC; 68% females, 59.3 ± 5.5 years old). Compared to the UC group, results for the chair stand and arm curl tests improved significantly in the GQ group from baseline to post-intervention (P = 0.024 and P = 0.041, respectively). Similarly, the 8-foot up and go test improved in the GQ group from baseline to post-intervention and 12 months (P = 0.004 and P = 0.008, respectively) when compared to the UC group. Between-group analyses also revealed a statistically significant improvement in global health status/quality of life from baseline to six months (P = 0.018) and quality of sleep from baseline to post-intervention (P = 0.034) in favor of the GQ group. Conclusion: GQ had a beneficial effect on lower and upper body strength, locomotor performance (speed, agility, and balance while moving), quality of sleep, and quality of life among lung cancer survivors, but further randomized controlled trials are warranted to confirm these findings. Trial registration: The trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200059145). [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]

Background: Periprosthetic joint infection (PJI) is a devastating complication after total hip arthroplasty (THA) or total knee arthroplasty (TKA). It is scarce and contradicting evidence supporting the use of serum D-dimer to diagnose PJI in revision THA and TKA. This systematic review and meta-analysis aimed to investigate the accuracy of D-dimer in the diagnosis of periprosthetic infections. Methods: The PubMed, Embase, Web of Science were systematically searched from the inception dates to August 15, 2020. We included all diagnostic studies of D-dimer in the diagnosis of periprosthetic infections. The literature's quality was evaluated by the QUADAS-2 tool, and Stata16 and Revman5.3 software carried out the meta-analysis. Results: Of 115 citations identified by the search strategy, 10 studies (comprising 1756 participants) met the inclusion criteria. The literature quality assessment results show that most of the literature is low-risk bias literature. The combined sensitivity of D-dimer in diagnosing periprosthetic infections was 0.81 (95% confidence interval [CI] 0.71–0.88), combined specificity was 0.74 (95% CI 0.61–0.84), combined positive likelihood ratio was 3.1 (95% CI 2.0–5.0), combined negative likelihood ratio 0.26 (95% CI 0.16–0.41), combined diagnosis odds ratio 12 (95% CI 5–27), area under the Summary Receiver Operator Characteristic Curve (SROC) is 0.85 (95% CI 0.81–0.88). The data are statistically significant. Conclusion: D-dimer has a high diagnostic value in diagnosing PJI and has clinical significance in diagnosing periprosthetic infection. In addition, there are relatively few studies on the threshold of D-dimer, different sampling types, different laboratory detection methods, and different races, so more prospective trials with large samples, multi-centers, and scientific design should be carried out in the future. [ABSTRACT FROM AUTHOR]

• An accurate quasi-static model considering the effect of slender ball-end milling cutter deflections on cutting forces was developed. • The correlation between cutting forces and slender ball-end milling cutter deflections were quantitatively analyzed. • The influence of slender ball-end milling cutter deflection and its compensation on machining error were systematically investigated. In this study, a quasistatic force-deflection interaction model considering cutting and elastic force was proposed to analyze and compensate for the quasistatic deflection of slender ball-end milling cutter. The theoretical waveforms and peaks of cutting force considering the force-deflection interactions were consistent with the experimental results. The deflection of slender ball-end milling cutter significantly reduces the cutting force, and the Pearson's correlation coefficient between the difference in the peak cutting force and maximum deflection in radial is larger than that of in feed directions. An analysis of the machining error of a cylindrical surface revealed that the deflection of slender ball-end milling cutter had a considerable effect on the machining error, and the compensation of slender cutter deflection effectively reduced the amplitude and fluctuation of the machining error. This work can provide a useful guidance for machining error control in the ball-end milling process of mold surfaces with deep cavities. [Display omitted] [ABSTRACT FROM AUTHOR]

Machined surface topography prediction is an important and useful tool for optimizing cutting parameters. However, accurate prediction of machined surface topography in ball-end milling operation has been extremely challenging, due to the complexity in tool-workpiece interaction induced by the trochoidal motion of cutting edge and computing burden. In this present research, a modified iterative approach was proposed to solve the intersections between the cutting-edge sweeping surface and the discrete Z-vector model of workpiece, which were used to predict the machined surface topography in ball-end milling operation. Firstly, the accurate model of cutting-edge sweeping surface was established utilizing homogeneous coordinate transformation, in which the tool runout was considered. Secondly, the cutting-edge sweeping surface was dispersed into a series of patches in accordance with equal parameter interval, and the in-cut patch was extracted by using the minimum and maximum axial immersion angle of the cutting edge. Thirdly, the intersection between each in-cut patch and discrete Z-vector was solved using the Newton's method, which was used to update the endpoint of the corresponding discrete Z-vector. Finally, ball-end milling experiments of AISI P20 steel were carried out to validate the proposed approach as well as investigate the effect of cutting parameters on the machined surface topography and roughness. The predicted machined surface topography and roughness were in good agreement with the measured results. Moreover, the proposed approach needs less computing time than the traditional iterative approaches at the same predicting accuracy. This research also provides guidance for optimizing cutting parameters to control surface quality in ball-end milling operation. [ABSTRACT FROM AUTHOR]

Cutting force prediction is very important for optimizing machining parameters ahead of the costly physical test. Ball-end milling operation is widely used for machining sculptured surface. Mechanistic approach can precisely predict elemental cutting force at each cutting element and integrate them into the cutter tooth with high fidelity to predict the cutting force for ball-end milling operation. However, the intersection between the cutting tool and workpiece could be complicated due to the trochoid motion trajectory of cutting edge and constantly changing workpiece geometry, making it difficult to determine the cutter-workpiece engagement (CWE) and undeformed chip thickness (UCT). In this present research, a modified cutting force prediction model was developed with considering the true trajectory of cutting edge and in-process workpiece geometry in ball-end milling operation. First, a triangular mesh model of the in-process workpiece surface was developed, and its mesh points were continuously updated by the intersection between the vertical reference line of the selected mesh point and the motion trajectory of cutting edge. Secondly, the UCT was calculated directly using the linear distance between a selected point on the cutting edge and the intersection between the radial reference line of the selected point and the triangular mesh of the in-process workpiece surface. Meanwhile, the CWE was expressed as a step function of UCT. Thirdly, a modified mechanistic approach was established by incorporation into the developed UCT and CWE models. The cutting force of ball-end milling operation was predicted with mechanistic approaches. Finally, ball-end milling experiments of AISI P20 steel were carried out for calibrating cutting force coefficients and validating cutting force model. The relative error between the predicted and measured cutting force is less than 15%, which indicates the predicted cutting force is in good agreement with measured cutting force. The works presented in this paper are one important step for optimizing machining parameters and compensating cutting force induced form error, which could improve the surface accuracy and machining efficiency. [ABSTRACT FROM AUTHOR]

Background: Diet and inflammation have been suggested to be important risk factors for lung cancer. We examined the ability of the dietary inflammatory index (DII®) to predict lung cancer in the Singapore Chinese Health Study (SCHS). The DII is a diet quality index based on the literature linking foods and nutrients with inflammatory biomarkers. Patients and methods: Using data from the SCHS for 60,232 participants, including 1851 lung cancer cases, we investigated the associations of baseline DII scores calculated from a food frequency questionnaire with risk of developing lung cancer over an average of 17.6 years of follow-up. Hazard ratios (HR) were estimated using Cox regression, adjusting for smoking status and other risk factors. Results: After excluding cancers diagnosed in the first 2 years of follow-up, the DII was non-significantly associated with risk of lung cancer (HRQ5vsQ1 = 1.13; 95% CI 0.94–1.35; P-trend = 0.24) after adjusting for age, dialect group, sex, interview year, education, body mass index, total calorie intake, physical activity and various smoking variables. In stratified analysis, stronger, statistically significant associations were evident in current smokers (HR 1.44; 95% CI 1.11–1.86; Ptrend = 0.03, P for interaction = 0.003) and in male ever-smokers (HRQ5vsQ1 = 1.37; 95% CI 1.07–1.77; P-trend = 0.03). Conclusion: A pro-inflammatory diet, as shown by higher DII scores, is associated with an elevated risk of lung cancer for subjects with a history of smoking. Public health measures should be adopted to promote consumption of a healthy, anti-inflammatory diet to reduce the risk of lung cancer, especially in current and former smokers. [ABSTRACT FROM AUTHOR]

ABO blood type is an inherited characteristic. The associations between ABO blood type and risk of all cancer and specific cancers were examined in a prospective cohort study of 18,244 Chinese men enrolled in 1986. During the 25 years of follow-up, 3,973 men developed cancer including 964 lung cancers, 624 colorectal cancers, 560 gastric cancers, 353 liver cancers, and 172 urinary bladder cancers. Hazard ratios (HR) for all cancer and specific cancers by ABO blood type were calculated using Cox proportional hazards models. Compared with blood type A, blood type B was associated with statistically significant reduced risk of all cancers (HR, 0.91, 95% CI:0.84, 0.99). Both blood types B and AB were associated with significantly lower risk of gastrointestinal cancer and colorectal cancer, respectively. Blood type B was also associated with significantly lower risk of stomach cancer and bladder cancer, while blood type AB was associated with significantly increased risk of liver cancer. By histological type, blood types B and AB were associated with lower risk of epidermoid carcinoma and adenocarcinoma, but were not associated with risk of sarcoma, lymphoma, leukemia or other cell types of cancer. The findings of this study support a role of genetic traits related to ABO blood type in the development of cancers in the gastrointestinal and urinary tracts. [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]

While epidemiologic studies suggest that bone turnover biomarkers may predict hip fracture risk, findings are inconsistent and Asian data are lacking. We conducted a matched case–control (1:1) study nested in the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women (45–74 years) recruited from 1993 to 1998 in Singapore. One hundred cases with incident hip fracture and 100 individually matched controls were randomly selected from 63,257 participants. Serum bone turnover biomarkers, namely bone alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), N-terminal and C-terminal crosslinking telopeptide of type I collagen (NTX-I and CTX-I) were measured using immunoassays. Hip fracture cases had significantly higher serum levels of OC, PINP, CTX-I and NTX-I than controls (p < 0.05). There was a dose-dependent positive relationship between OC, PINP, CTX-I and NTX-I and risk of hip fracture (all Ps for trend ≤ 0.006), where the risk was significantly increased by 4.32–8.23 folds for the respective BTM [Quartile (Q) 4 vs. Q1]. The odds ratio [OR (95% CI)] at the highest quartile (Q4) was 6.63 (2.02–21.18) for PINP and 4.92 (1.67–14.51) for CTX-I. The joint effect of PINP and CTX-I showed a 7-fold increase in risk (OR: 7.36; 95% CI: 2.53–21.41) comparing participants with higher levels of PINP (Q4) and CTX-I (Q3–Q4) to those with low levels of PINP (Q1–Q3) and CTX-I (Q1–Q2). Our data demonstrated that higher serum levels of bone turnover biomarkers were associated with increased risk of hip fracture in an Asian population. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) copy number in peripheral blood is associated with increased risk of several cancers. However, data from prospective studies on mtDNA copy number and breast cancer risk are lacking. We evaluated the association between mtDNA copy number in peripheral blood and breast cancer risk in a nested case-control study of 183 breast cancer cases with pre-diagnostic blood samples and 529 individually matched controls among participants of the Singapore Chinese Health Study. The mtDNA copy number was measured using real time PCR. Conditional logistic regression analyses showed that there was an overall positive association between mtDNA copy number and breast cancer risk (Ptrend = 0.01). The elevated risk for higher mtDNA copy numbers was primarily seen for women with <3 years between blood draw and cancer diagnosis; ORs (95% CIs) for 2nd, 3rd, 4th, and 5th quintile of mtDNA copy number were 1.52 (0.61, 3.82), 2.52 (1.03, 6.12), 3.12 (1.31, 7.43), and 3.06 (1.25, 7.47), respectively, compared with the 1st quintile (Ptrend = 0.004). There was no association between mtDNA copy number and breast cancer risk among women who donated a blood sample ≥3 years before breast cancer diagnosis (Ptrend = 0.41). This study supports a prospective association between increased mtDNA copy number and breast cancer risk that is dependent on the time interval between blood collection and breast cancer diagnosis. Future studies are warranted to confirm these findings and to elucidate the biological role of mtDNA copy number in breast cancer risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Asian populations are documenting rapid increases in the rates of diabetes and hip fracture, but there are no prospective data linking both diseases in Asian studies. We investigated this association among a cohort of Chinese in Singapore. RESEARCH DESIGN AND METHODS-- A prospective cohort of 63,257 Chinese in the Singapore Chinese Health Study, established between 1993 and 1998, was followed up for a mean duration of 12 years. Diabetes status was ascertained by baseline interviews, and incidence of hip fracture post-enrollment was identified through a nationwide hospital discharge database. RESULTS-- The risk of hip fracture, after adjustment for other risk factors, was almost double among people with diabetes compared with people without diabetes (relative risk 1.98, 95% CI 1.71-2.29). When stratified by BMI, the increase in risk of hip fracture among people with diabetes relative to people without diabetes was similar in all four strata. There was a very strong dose-dependent relationship between duration of diabetes and risk of hip fracture (P for trend <0.0001). Compared with people without diabetes, the relative risk (95% CI) among subjects with diabetes for <5 years at recruitment was 1.40 (1.08-1.82), and this risk increased to 2.66 (2.04-3.47) among individuals with diabetes for ≥ 15 years. CONCLUSIONS-- Asians with diabetes, like their Western counterparts, experience an increased risk of hip fracture. Early assessment for osteoporosis and increased fracture risk, as well as prevention of falls, should be part of the management of diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Rigid porous poly(glycidyl methacrylate–divinylbenzene) (P(GMA–DVB)) microspheres were synthesized through suspension polymerization with a mixture of isooctane and 4-methyl-2-pentonal as the porogen. The microspheres were intended to use as column packing materials for protein separation. However, irreversible adsorption of protein was found on the polymer microsphere. To circumvent the problem, polyethylene glycol (PEG) was coupled to the microspheres. The coupling reaction took place between the hydroxyl group of PEG and the epoxy group of the P(GMA–DVB) solid medium in the presence of boron trifluoride. The density of PEG immobilized onto the P(GMA–DVB) can be determined easily by saponification of modified microsphere firstly and then titration of glycerol–PEG. The effect of the cross-linker content of microsphere on the density of PEG immobilization was investigated. Molecular weight of PEG was found to influence the PEG-immobilization density, which subsequently affects the hydrophilicity of the modified P(GMA–DVB). Bovine serum albumin (BSA) and trypsin were used as model proteins to examine the adsorption and desorption properties of the modified P(GMA–DVB) microspheres. The results demonstrated that P(GMA–DVB) porous microsphere with 20% DVB and modified with PEG4000 showed excellent adsorption and desorption properties. Adsorption capacity of BSA on the modified microsphere attained to 51.6mg/g microsphere, and BSA mass recovery and trypsin activity recovery was up to 97.6% and 98.7%, respectively. The modified microsphere was demonstrated to be a promising hydrophobic interaction chromatography material for purification of protein. [Copyright &y& Elsevier]

The manufacturing industry consumes a considerable amount of energy every year, which poses a major challenge to resource consumption and environment problem. To overcome these difficulties, it is necessary to understand the machine tools' power characteristics. The current research aims to investigate the energy consumption of the machine tool and to establish a cutting power model for ball-end milling process. First, a cutting power theoretical model for a ball-end milling cutter was established based on the infinitesimal cutting force. Secondly, a series of experiments were conducted to reveal and validate the mathematical function of spindle power and feed power. Finally, slotting milling experiments were conducted, and a cutting power empirical model was proposed by analyzing the correlation between cutting forces and cutting power. The results showed that the spindle power, feed power, and cutting power could be exactly predicted by the proposed method. Furthermore, the Z-axis's feed power characteristic was revealed that the gravity made the Z-axis's motor transform to the generator when Z-axis moved in the downward direction. For cutting power model, the theoretical model and empirical model had the same predictive accuracy, while the empirical model had a simpler form and could be easier applied. The proposed power investigation method provided technical support for the research of the machine tools' energy consumption characteristics. [ABSTRACT FROM AUTHOR]

Simple Summary: Serine and glycine have an important role in the folate-dependent one-carbon metabolism. No prior epidemiologic study has evaluated the associations for serum levels of serine and glycine with pancreatic cancer risk. We performed a nested case-control study of 129 incident pancreatic cancer cases and 258 individually matched controls within the Shanghai Cohort Study, a prospective cohort study involving 18,244 male residents in Shanghai, China. We found that the risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of serine and glycine in serum collected, on average, more than 10 years prior to cancer diagnosis. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for pancreatic cancer prevention. Background. Serine and glycine play an important role in the folate-dependent one-carbon metabolism. The metabolism of serine and glycine has been shown to be associated with cancer cell proliferation. No prior epidemiologic study has investigated the associations for serum levels of serine and glycine with pancreatic cancer risk. Methods. We conducted a nested case-control study involved 129 incident pancreatic cancer cases and 258 individually matched controls within a prospective cohort study of 18,244 male residents in Shanghai, China. Glycine and serine and related metabolites in pre-diagnostic serum were quantified using gas chromatography-tandem mass spectrometry. A conditional logistic regression method was used to evaluate the associations for serine, glycine, and related metabolites with pancreatic cancer risk with adjustment for potential confounders. Results: Odds ratios (95% confidence intervals) of pancreatic cancer for the highest quartile of serine and glycine were 0.33 (0.14–0.75) and 0.25 (0.11–0.58), respectively, compared with their respective lowest quartiles (both p's < 0.01). No significant association with risk of pancreatic cancer was observed for other serine- or glycine related metabolites including cystathionine, cysteine, and sarcosine. Conclusion. The risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of glycine and serine in serum collected, on average, more than 10 years prior to cancer diagnosis in a prospectively designed case-control study. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for cancer prevention. [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]

Introduction: Telomeres and telomerase play important role in maintaining chromosome integrity and genomic stability. Recent epidemiologic data showed inconsistent findings which suggested that both short and long leukocyte telomeres could be associated with increased risk of pancreatic cancer. We prospectively examined the association between telomere length and pancreatic cancer risk in a population-based cohort study. Methods: The Singapore Chinese Health Study recruited 63,257 Chinese aged 45 to 74 years from 1993 to 1998 in Singapore. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction method in 26,540 participants, including 116 participants who later developed pancreatic cancer after an average of 13 years of follow-up. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and its 95% confidence interval (CI) of pancreatic cancer risk associated with telomere length, with adjustment for confounding factors. Results: Longer telomeres were significantly associated with higher risk of pancreatic cancer (Ptrend = 0.02). Compared with lowest quartile, subjects with highest quartile of telomere length had an HR of 2.18 (95% CI: 1.25–3.80) for developing pancreatic cancer. In stratified analysis, this association remained among pancreatic adenocarcinoma patients but not among pancreatic non-adenocarcinoma patients. In continuous scale, the HRs and 95% CIs were 3.08 (1.17–8.11) for adenocarcinoma patients and 1.47 (0.43–5.06) for non-adenocarcinoma patients. The HRs and 95% CIs of the highest quartile of telomere length, compared with the lowest quartile, for adenocarcinoma and non-adenocarcinoma were 2.50 (1.22–5.13) and 1.63 (0.66–4.03), respectively. The length of follow-up from the collection of blood for the measurement of telomere length to the diagnosis of cancer (median = 8.0, range: from 5.0 months to 16.2 years) had no significant impact on the association between telomere length and pancreatic cancer risk. Conclusions: The present study demonstrates that longer telomeres are associated with increased risk of overall pancreatic cancer. [ABSTRACT FROM AUTHOR]

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: The majority of hepatocellular carcinoma (HCC) cases occur in the presence of cirrhosis. Biomarkers of cirrhosis-associated immune dysfunction such as CD8+ T cell cytokines could aid HCC risk assessment. Methods: CD8+ T cell cytokines were determined in pre-diagnostic serum in two studies including 315 HCC case–control pairs in the Shanghai Cohort Study (SCS) and 197 pairs in the Singapore Chinese Health Study (SCHS). Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for HCC with levels of five cytokines—soluble CD137 (sCD137), soluble Fas (sFas), perforin, macrophage inflammatory protein 1-beta (MIP-1β), and tumour necrosis factor alpha (TNF-α). Results: sCD137 levels were significantly higher in HCC cases than controls in both cohorts (Ps < 0.001). Compared with the lowest quartile, multivariable-adjusted ORs (95% CI) of HCC for the highest sCD137 quartile were 3.79 (1.73, 8.30) in the SCS and 3.49 (1.44, 8.48) in the SCHS. The sCD137-HCC association was independent of hepatitis B seropositivity and follow-up time. No other cytokine was consistently associated with HCC risk. Conclusion: sCD137 was associated with higher risk of HCC in two studies nested in general population cohorts. sCD137 may be a long-term risk marker of HCC development. [ABSTRACT FROM AUTHOR]

It has been hypothesized that the pathogenesis of lung cancer induced by cigarette smoking involves oxidative damage by free radicals. Epidemiological data on biomarkers of oxidative damage and risk of lung cancer development are sparse. A nested case-control study of 610 lung cancer cases and 610 matched controls was conducted within a prospective cohort of 18 244 Chinese men in Shanghai, China. The concentrations of 8-epi-prostaglandin F2 (8-epiPGF2), a biomarker of oxidative stress, were determined in baseline urine samples using a validated mass-spectrometry assay. Current smokers had significantly higher level of 8-epiPGF2 than former smokers or never smokers (P < 0.001). 8-epiPGF2 levels were significantly higher in lung cancer cases than their smoking-matched controls in former and current smokers, but not different in never smokers (P for interaction = 0.019). The relative risks of developing lung cancer for former and current smokers in the highest relative to the lowest quartile of 8-epiPGF2 were 5.25 (P trend = 0.035) and 1.99 (P trend =0.007), respectively. The effect of 8-epiPGF2 and biomarkers of cigarette smoke exposure on lung cancer risk was additive; the relative risk was 5.33 (95% confidence interval = 2.65-7.51) for current smokers with the highest thirds of 8-epiPGF2 and total cotinine compared with their lowest thirds. Smokers with a heightened state of oxidative stress in response to the insults of cigarette smoking may be more susceptible to smoking-induced lung carcinogenesis. [ABSTRACT FROM AUTHOR]

Purpose To investigate whether the vessels surrounding a nodule depicted on non-contrast, low-dose computed tomography (LDCT) can discriminate benign and malignant screen detected nodules. Materials and Methods We collected a dataset consisting of LDCT scans acquired on 100 subjects from the Pittsburgh Lung Screening study (PLuSS). Fifty subjects were diagnosed with lung cancer and 50 subjects had suspicious nodules later proven benign. For the lung cancer cases, the location of the malignant nodule in the LDCT scans was known; while for the benign cases, the largest nodule in the LDCT scan was used in the analysis. A computer algorithm was developed to identify surrounding vessels and quantify the number and volume of vessels that were connected or near the nodule. A nonparametric receiver operating characteristic (ROC) analysis was performed based on a single nodule per subject to assess the discriminability of the surrounding vessels to provide a lung cancer diagnosis. Odds ratio (OR) were computed to determine the probability of a nodule being lung cancer based on the vessel features. Results The areas under the ROC curves (AUCs) for vessel count and vessel volume were 0.722 (95% CI = 0.616-0.811, p < 0.01) and 0.676 (95% CI = 0.565-0.772), respectively. The number of vessels attached to a nodule was significantly higher in the lung cancer group 9.7 (±9.6) compared to the non-lung cancer group 4.0 (±4.3) Conclusion Our preliminary results showed that malignant nodules are often surrounded by more vessels compared to benign nodules, suggesting that the surrounding vessel characteristics could serve as lung cancer biomarker for indeterminate nodules detected during LDCT lung cancer screening using only the information collected during the initial visit. [ABSTRACT FROM AUTHOR]

Background: Blood neutrophil to lymphocyte ratio (NLR) or lymphocyte count may be important markers for immune function. Previous work has shown higher NLR was associated with higher risk of hepatitis B‐related hepatocellular carcinoma (HCC). However, studies in non‐alcoholic fatty liver disease (NAFLD) patients are lacking. Methods: Utilizing the University of Pittsburgh Medical Center (UPMC) electronic health records, we created a retrospective cohort of 27,834 patients diagnosed with NAFLD from 2004 to 2018 with complete NLR data. After an average 5.5 years of follow‐up, 203 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence associated with different levels of NLR and lymphocyte count. Results: Compared with the lowest tertile of NLR (<1.97), the highest tertile of NLR (≥3.09) was statistically significantly associated with a 43% higher risk of HCC incidence (HR = 1.43, 95% CI: 1.01–2.03, ptrend = 0.031) after adjustment for age, sex, race, body mass index, smoking status, history of type 2 diabetes, hyperlipidemia, hypertension, and fibrosis‐4 score category. Conversely the highest tertile of lymphocyte count (≥2.15 K/ul) was significantly associated with a 36% lower risk of HCC (HR = 0.64, 95% CI: 0.43–0.94, ptrend = 0.028) compared to the lowest tertile (<1.55 K/ul). There was no association between neutrophil count and HCC risk. Conclusions: Higher NLR and lower lymphocyte count are associated with significantly higher risk of HCC among NAFLD patients. These findings warrant further investigation of immune response and surveillance in association with HCC development in NAFLD patients. [ABSTRACT FROM AUTHOR]

Identifying risk factors for future change in sleep duration can clarify whether, and if so how, sleep and morbidity are bidirectionally related. To date, only limited longitudinal evidence exists characterizing changes to sleep duration among older adults. This study aimed to identify factors associated with change in sleep duration in a large sample of older adults (≥ 60 years) residing in Singapore ( n = 10 335). These adults were monitored as part of the Singapore Chinese Health Study, which collected information regarding daily sleep duration at baseline (assessed in 1993-1998) and at a follow-up wave conducted over a mean of 12.7 years later (assessed in 2006-2010). Among adults sleeping 6-8 h at baseline ( n = 8265), most participants (55.6%) remained 6-8 h sleepers at follow-up, while 8.4% became short (< 6 h) and 36.0% became long (> 8 h) sleepers. A history of stroke, diabetes, cancer, hip fracture and greater age all independently increased the odds of having long sleep duration at follow-up, while greater educational attainment and weekly physical activity were both associated with reduced odds of becoming a long sleeper. Other than greater baseline age, the only factor related to higher odds of becoming a short sleeper was concurrent stomach/duodenal ulcer at follow-up. Long sleep duration among older adults may therefore reflect longstanding disease processes, whereas the aetiology of short sleep may predominately involve factors other than those examined. Future research is needed to distinguish if/when long sleep duration serves the disease recovery process, and when long sleep duration complicates disease and requires sleep medicine interventions. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of Endometrial cancer (EC) has grown substantially in Asia over the past decade. However, few studies have addressed risk factors associated with EC incidence in Asian populations. We explored the association between reproductive and dietary risk factors and EC in the Singapore Chinese Health Study (SCHS), one of the largest prospective cohort studies in Asia.Methods: Data were collected from 34,028 ethnically Chinese women aged 45-74 residing in Singapore, enrolled between 1993 and 1998. Baseline demographic, dietary, and reproductive factors were collected via structured questionnaires. EC cases were identified from the Singapore Cancer Registry (n = 126) up to 2010. Cox proportional hazard models were used to analyze association between EC and personal, reproductive, and dietary factors.Results: The incidence of EC in this population was 28.8 per 100,000 person-years. Regardless of menopausal status, obesity (BMI ≥ 27) was associated with increased EC risk (HR = 2.22, 95% CI 1.26-3.92), while later age at menarche was associated with decreased EC risk (HR = 0.14, 95% CI 0.04-0.46). In postmenopausal women, later age at menopause was associated with increased EC risk (HR = 2.82, 95% CI 1.24-6.43). Lifestyle and nutritional factors were not associated with risk of EC in this cohort.Conclusions: This study is one of the largest cohort studies exploring EC risk factors in Asian populations. Our study identified similarities in EC risk factors for European and Asian populations, which potentially suggests that strategies developed for EC prevention in Western populations can be potentially appropriate for the Singapore Chinese population due to risk factor similarities. [ABSTRACT FROM AUTHOR]

Dietary catechins are phytochemicals with both antioxidative and prooxidative stress properties. Green tea is a major source of catechins and may be associated with hepatocellular carcinoma (HCC) risk, but the catechin-HCC relationship has not been evaluated using a biomarker-based approach. A nested case-control study of HCC (211 cases and 1,067 matched controls) was conducted within the Shanghai Cohort Study, which enrolled 18,244 men between 1986 and 1989. Concentrations of specific catechins, including epicatechin, epigallocatechin (EGC), and 4′-O-methyl-epigallocatechin, were measured in urine specimens that had been collected prior to HCC diagnosis. None of the catechins measured were associated with HCC risk. In stratified analyses, there was a statistically significant trend for an association of higher urinary EGC with increased HCC risk among subjects with positive serology for hepatitis B surface antigen (P for trend = 0.02). This positive EGC-HCC association became stronger for hepatitis B surface antigen–positive persons who also had low serum retinol levels (for detectable levels vs. undetectable levels, odds ratio = 2.62, 95% confidence interval: 1.25, 5.51). There was no evidence supporting a protective role of catechins in the development of HCC. Instead, exposure to high levels of catechins may increase the risk of developing HCC for high-risk individuals. [ABSTRACT FROM PUBLISHER]

Lung cancer is unusually common among non-smoking women in Southeastern Asia but the causes of this frequently fatal disease are not well understood. Several epidemiology studies indicate that inhalation of fumes from high temperature Chinese style cooking with a wok may be a cause. Only one previous study investigated uptake of potential toxicants and carcinogens by women who cook with a wok. We enrolled three-hundred twenty-eight non-smoking women from Singapore for this study. Each provided a spot urine sample and answered a questionnaire concerning their cooking habits and other factors. The urine samples were analyzed by liquid chromatography-tandem mass spectrometry for mercapturic acid metabolites of acrolein (3-hydroxypropylmercapturic acid), crotonaldehyde (3-hydroxy-1-methylpropylmercapturic acid), and benzene (S-phenylmercapturic acid), accepted biomarkers of uptake of these toxic and carcinogenic compounds. We observed statistically significant effects of wok cooking frequency on levels of 3-hydroxypropylmercapturic acid and 3-hydroxy-1-methylpropylmercapturic acid, but not S-phenylmercapturic acid. Women who cooked greater than 7 times per week had a geometric mean of 2600 (95% CI, 2189-3090) pmol/mg creatinine 3-hydroxypropylmercapturic acid compared to 1901 (95% CI, 1510-2395) pmol/mg creatinine when cooking less than once per week (P for trend 0.018). The corresponding values for 3-hydroxy-1-methylpropylmercapturic acid were 1167 (95% CI, 1022-1332) and 894 (95% CI, 749-1067) pmol/mg creatinine (P for trend 0.008). We conclude that frequent wok cooking leads to elevated exposure to the toxicants acrolein and crotonaldehyde, but not benzene. Kitchens should be properly ventilated to decrease exposure to potentially toxic and carcinogenic fumes produced during Chinese style wok cooking. [ABSTRACT FROM AUTHOR]

Besides polycyclic aromatic hydrocarbons (PAH) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which are established lung carcinogens, tobacco smoke also contains relatively large quantities of volatile organic carcinogens and toxicants, including 1,3-butadiene, ethylene oxide, benzene, acrolein and crotonaldehyde. Although animal experiments showed that some of these compounds can induce tumors in multiple organs including the lung, epidemiological studies of their relationship with lung cancer in smokers have not been reported. Therefore, in this study, we quantified urinary mercapturic acid metabolites of 1,3-butadiene, ethylene oxide, benzene, acrolein and crotonaldehyde in addition to urinary biomarkers for PAH, NNK and nicotine in 343 lung cancer cases and 392 matched controls among a cohort of 18 244 Chinese men in Shanghai, China, followed from 1986 to 2006. Compared with the lowest quartiles, highest quartiles of all measured mercapturic acids were associated with statistically significantly ∼2-fold increased risk for lung cancer (all P’s for trend <0.01) after adjustment for smoking intensity and duration. The positive associations between biomarkers of ethylene oxide, benzene or acrolein and lung cancer risk remained statistically significant after adjustment for biomarkers of PAH and NNK, whereas urinary total cotinine completely explained the mercapturic acid metabolites and lung cancer associations (all P’s for trend ≥0.39). We conclude that mercapturic acid metabolites of 1,3-butadiene, ethylene oxide, benzene, acrolein and crotonaldehyde may not be independent risk predictors of lung cancer among Shanghai smokers, in contrast to biomarkers of PAH, NNK and nicotine exposure. [ABSTRACT FROM AUTHOR]

N′-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are tobacco-specific nitrosamines. NNN and NNK can induce cancers of the esophagus and lung, respectively, in laboratory animals, but data on human esophageal cancer are lacking. The association between levels of NNN and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), an NNK metabolite, in urine samples collected before diagnosis and risk of esophageal cancer was examined in 77 patients with esophageal cancer and 223 individually matched controls, all current smokers, from a cohort of 18244 Chinese men in Shanghai, China, followed from 1986 to 2008. Urinary total NNN (free NNN plus NNN-N-glucuronide) was significantly higher, whereas the percentage of its detoxification product NNN-N-glucuronide was significantly lower in cases than controls. Odds ratios (95% confidence intervals) of esophageal cancer for the second and third tertiles of total NNN were 3.99 (1.25–12.7) and 17.0 (3.99–72.8), respectively, compared with the first tertile after adjustment for urinary total NNAL and total cotinine and smoking intensity and duration (Ptrend < 0.001). The corresponding figures for the percentage of NNN-N-glucuronides were 0.37 (0.17–0.80) and 0.27 (0.11–0.62) (Ptrend = 0.001). Urinary total NNN and the percentage of NNN-N-glucuronides almost completely accounted for the observed association for urinary total NNAL (free NNAL plus its glucuronides), urinary total cotinine and smoking intensity with esophageal cancer risk. These findings along with results of previous studies in laboratory animals support a significant and unique role of NNN in esophageal carcinogenesis in humans. [ABSTRACT FROM AUTHOR]

BACKGROUND: [ABSTRACT FROM AUTHOR]

Although there is some epidemiologic evidence that soy may reduce risk of osteoporotic fracture in women, it is not known whether this risk reduction also occurs for men. The authors examined gender-specific associations between soy intake and hip fracture risk in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese living in Singapore. At recruitment between 1993 and 1998, each subject was administered a food frequency questionnaire and questions on medical history and lifestyle factors. As of December 31, 2006, 276 incident cases of hip fracture in men and 692 cases in women were identified via linkage with hospital discharge databases. For both genders, hip fracture risk was positively associated with cigarette smoking and was inversely associated with body mass index. There was a statistically significant association of tofu equivalents, soy protein, and isoflavones with hip fracture risk among women but not among men. Compared with women in the lowest quartile of intakes for tofu equivalents (<49.4 g/day), soy protein (<2.7 g/day), and isoflavones (<5.8 mg/1,000 kcal/day), those in the second–fourth quartiles exhibited 21%–36% reductions in risk (all P < 0.036). Risk levels were comparable across the second, third, and fourth quartiles of soy intake categories. [ABSTRACT FROM PUBLISHER]

Prospective data on environmental exposures, especially with respect to alcohol, tobacco, and diet, in relation to the risk of esophageal cancer in high-risk populations are sparse. We analyzed data from a population-based cohort of 18,244 middle-aged and older men in Shanghai to identify risk factors for esophageal cancer in this high-risk population. The cohort was followed through 2006, and 101 incident esophageal cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and their corresponding 95% confidence intervals (CI) for associations between exposures and esophageal cancer risk. With adjustment for tobacco use and other potential confounders, regular drinkers vs. nondrinkers of alcoholic beverages had a twofold risk of developing esophageal cancer (HR = 2.02, 95% CI = 1.31-3.12). With adjustment for alcohol and other potential confounders, long-term smokers (40+ yr) vs. nonsmokers of cigarettes showed a twofold risk of developing esophageal cancer (HR = 2.06, 95% CI = 1.11-3.82). Increased consumption of fruits (including oranges/tangerines), seafood, and milk were found to be protective against the development of esophageal cancer; HRs were decreased by 40-60% for high vs. low consumers after adjustment for cigarette smoking, alcohol drinking, and other confounders. [ABSTRACT FROM AUTHOR]

Few data exist regarding the association of risk factor burden in middle age with lifetime risks for cardiovascular disease (CVD) and non-CVD death. In this study, participants in the Chicago Heart Association Detection Project in Industry aged 40 to 59 years in 1967 to 1973 were stratified into 5 groups on the basis of risk factor burden: favorable risk factor profile (untreated blood pressure ≤120/≤80 mm Hg, total cholesterol <200 mg/dl, nonsmoking, and body mass index <25 kg/m2); 0 elevated but ≥1 unfavorable; or any 1, any 2, or ≥3 elevated (systolic ≥140 mm Hg or diastolic ≥90 mm Hg or treated hypertension; total cholesterol ≥240 mg/dl; current smoking; or body mass index ≥30 kg/m2). Remaining lifetime risks for CVD and non-CVD death were estimated through the age of 85 years. Eight thousand thirty-three men and 6,493 women were followed for 409,987 person-years; 2,582 died of CVD, and 3,955 died of non-CVD causes. A greater risk factor burden was associated with a higher incidence of CVD and non-CVD death. Compared with participants with ≥3 risk factors, those with favorable profiles had substantially lower lifetime risks for CVD death (20.5% vs 35.2% in men, 6.7% vs 31.9% in women) and markedly longer median Kaplan-Meier survival (>35 vs 26 years in men, >35 vs 28 years in women). In conclusion, having favorable risk factors in middle age is associated with a lower lifetime risk for CVD death and markedly longer survival. These results should encourage efforts aimed at preventing the development of risk factors in younger subjects to decrease CVD mortality and promote longevity. [Copyright &y& Elsevier]

Simple Summary: Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. The increasing incidence rate of HCC in developed countries has been linked to increasing prevalence of metabolic dysfunction-associated fatty liver disease, which has characteristics of altered bile acid metabolism that may predate hepatocarcinogenesis. The aim of the present study was to assess the association of circulating bile acid levels in pre-diagnostic serum with the risk of developing HCC in a general population in Singapore. Primary conjugated bile acids were most strongly associated with increased risk of HCC whereas the ratios of secondary over primary bile acids were significantly associated with reduced risk. These results support a contributing role of dysmetabolism of bile acids in the development of HCC. The modulation of bile acid metabolism through alteration of gut microbiota may be an effective strategy for primary prevention against HCC in individuals with metabolic dysfunction-associated fatty liver disease. Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy with poor prognosis. Rising incidence of HCC may be due to rising prevalence of metabolic dysfunction-associated fatty liver disease, where altered bile acid metabolism may be implicated in HCC development. Thirty-five bile acids were quantified using ultra-performance liquid chromatography triple-quadrupole mass spectrometry assays in pre-diagnostic serum of 100 HCC cases and 100 matched controls from the Singapore Chinese Health Study. Conditional logistic regression was used to assess associations for bile acid levels with risk of HCC. Conjugated primary bile acids were significantly elevated whereas the ratios of secondary bile acids over primary bile acids were significantly lower in HCC cases than controls. The respective odds ratios and 95% confidence intervals of HCC were 6.09 (1.75–21.21) for highest vs. lowest tertile of cholic acid species and 30.11 (5.88–154.31) for chenodeoxycholic acid species. Doubling ratio of taurine-over glycine-conjugated chenodeoxycholic acid was associated significantly with 40% increased risk of HCC whereas doubling ratio of secondary over primary bile acid species was associated with 30–40% reduced risk of HCC. In conclusion, elevated primary bile acids and taurine over glycine-conjugated ratios were strongly associated with HCC risk whereas the ratios of secondary bile acids over primary bile acids were inversely associated with HCC risk. [ABSTRACT FROM AUTHOR]

Background: The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC.Methods: We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status.Results: During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26).Conclusions: This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12-16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions. [ABSTRACT FROM AUTHOR]

The role of low frequency variants associated with telomere length homeostasis in chronic diseases and mortalities is relatively understudied in the East-Asian population. Here we evaluated low frequency variants, including 1,915,154 Asian specific variants, for leukocyte telomere length (LTL) associations among 25,533 Singapore Chinese samples. Three East Asian specific variants in/near POT1, TERF1 and STN1 genes are associated with LTL (Meta-analysis P 2.49×10−14–6.94×10−10). Rs79314063, a missense variant (p.Asp410His) at POT1, shows effect 5.3 fold higher and independent of a previous common index SNP. TERF1 (rs79617270) and STN1 (rs139620151) are linked to LTL-associated common index SNPs at these loci. Rs79617270 is associated with cancer mortality [HR95%CI = 1.544 (1.173, 2.032), PAdj = 0.018] and 4.76% of the association between the rs79617270 and colon cancer is mediated through LTL. Overall, genetically determined LTL is particularly associated with lung adenocarcinoma [HR95%CI = 1.123 (1.051, 1.201), Padj = 0.007]. Ethnicity-specific low frequency variants may affect LTL homeostasis and associate with certain cancers. Xuling Chang et al. study whether low frequency variants are associated with leukocyte telomere length and whether these variants predispose to incident cancers and mortalities among East Asians. They find that three East Asian specific variants at POT1, TERF1 and STN1 loci are associated with leukocyte telomere length and report a mechanistic pathway linking TERF1, leukocyte telomere length and incident colon cancer. [ABSTRACT FROM AUTHOR]

To probe the impact of Darrieus–Landau (DL) instability on turbulent premixed flame propagation at various burner sizes, methane–air premixed flames from five Bunsen-type burners with different nozzle diameters (4 mm, 6 mm, 8 mm, 10 mm, and 12 mm) were investigated at Reynolds numbers ranging from 1000 to 8500. The flame curvatures used to identify DL instability were determined using Mie scatter images captured by a particle image velocimetry system. The flame speed was further derived by applying an asymmetric hypothesis to the images. The energy-frequency spectrum of the inflow disturbance was determined using a hot-wire anemometry system, and specific wavelet transform analysis was performed to investigate the dependence of DL instability on the proportion of effective disturbances (Ped) and quantify the role of DL instability in determining the turbulent flame speed. The results showed that the burner diameter had an obvious effect on the presence of DL instability and its role in flame propagation. The ability of DL instability to enhance the flame curvature skewness and the turbulent flame speed was closely related to Ped. Ped increased when the burner diameter increased from 6 mm to 12 mm, thus enhancing the DL instability. Changing the burner diameter also affected the interplay between DL instability and turbulence. The above interactions and their effects on the flame speed during the change of inflow disturbances could be formulated by Ped. Finally, a Ped-based correlation was proposed to describe the dependence of the turbulent flame speed on the burner size. [ABSTRACT FROM AUTHOR]

Background: Tea and coffee are widely consumed beverages. Tea flavonoids have been shown to inhibit lung tumorigenesis using in vitro and in vivo models. Conversely, coffee contains complex mixtures of biochemically active compounds, some of which may have genotoxic and mutagenic properties. However, previous epidemiologic studies have shown inconsistent results on tea and coffee in relation to lung cancer risk. Methods: The Singapore Chinese Health Study is a population-based prospective cohort of 63,257 Singaporean Chinese men and women, with an average of 17.7 years of follow-up. Information on tea and coffee consumption and other lifestyle factors was collected through in-person interviews at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations with adjustment for potential confounders. Results: There were 1486 incident lung cancer cases. Compared to non-daily coffee drinkers, HRs (95% CIs) of lung cancer risk for those consuming one, two, and three or more cups of coffee per day were 1.18 (1.02–1.36), 1.21 (1.05–1.40), and 1.32 (1.08–1.62) respectively (P for trend = 0.0034). The highest category of black tea consumption (at least 2 cups per day) was inversely associated with risk of lung cancer [HR (95% CI) = 0.73 (0.53–0.99)], particularly among men [HR (95% CI) = 0.67 (0.47–0.95)], compared to less-than-weekly black tea drinkers, although the interaction by sex was not statistically significant. Conclusions: Coffee beverage consumption was associated with higher risk of developing lung cancer. On the other hand, black tea intake was associated with lower risk of lung cancer among men in our cohort, and further studies are needed to confirm this association. [ABSTRACT FROM AUTHOR]

Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of hepatocellular carcinoma (HCC). We conducted a nested case–control study of 347 HCC cases and 691 matched controls within a prospective cohort of 18 244 Chinese men in Shanghai, China. The concentrations of 8- epi -prostaglandin F2α (8- epi -PGF2α), a biomarker of oxidative stress, and prostaglandin E2 (PGE2) metabolite (PGE-M), a biomarker of the inflammation mediator PGE2, were determined in baseline urine samples using validated mass spectrometry assays. 8- epi- PGF2α levels were significantly higher in HCC cases than control subjects (geometric means 0.92 versus 0.80 pmol/mg creatinine, P < 0.001). The relative risks of developing HCC for the highest relative to the lowest quartile of 8- epi- PGF2α were 2.55 (95% confidence interval = 1.62–4.01, P trend < 0.001). This positive 8- epi -PGF2α–HCC risk association was independent of smoking status, alcohol consumption and hepatitis B or liver cirrhosis and was present 10 years before the clinical manifestation of HCC. This study did not find any significant association between urinary PEG-M and HCC risk. This study provides direct evidence in support of the critical role of oxidative stress in the development of HCC regardless of its underlying causes. [ABSTRACT FROM AUTHOR]

Background: Consumption of green tea has been associated with reduced risk of breast cancer. Hormonal modulation has been suggested as one of the potential underlying mechanisms; however, it has yet to be fully elucidated in large, long-term human clinical trials.Objective: We investigated the effects of decaffeinated green tea extract (GTE) on circulating sex hormones and insulin-like growth factor (IGF) proteins.Methods: We conducted a placebo-controlled double-blind randomized clinical trial recruiting from 8 clinical centers in Minnesota. Participants were 538 healthy postmenopausal women randomly assigned to the GTE group (463 completed the study; mean age = 60.0 y) and 537 to the placebo group (474 completed; mean age = 59.7 y). Women in the GTE group orally took 4 decaffeinated capsules containing 1315 mg total catechins including 843 mg epigallocatechin-3-gallate daily for 1 y, whereas women in the placebo group took similar capsules containing no tea catechins. Blood sex hormones (estrone, estradiol, androstenedione, testosterone, and sex hormone-binding globulin) and IGF proteins (IGF-1 and IGF binding protein-3) were quantified at baseline and months 6 (for IGF proteins only) and 12, and were assessed as secondary outcomes of the study using a mixed-effect repeated-measures ANOVA model.Results: Women in the GTE group had significantly higher blood total estradiol (16%; P = 0.02) and bioavailable estradiol (21%; P = 0.03) than in the placebo group at month 12. There was a statistically significant interaction between GTE supplementation and duration of treatment on estradiol and bioavailable estradiol (both Ps for interaction = 0.001). The catechol-O-methyltransferase genotype did not influence blood sex hormones before or after GTE supplementation. The circulating concentrations of IGF proteins were comparable between GTE and placebo groups at all 3 time points.Conclusion: These results suggest that a 12-mo GTE supplementation significantly increases circulating estradiol concentrations in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00917735. [ABSTRACT FROM AUTHOR]

Background: Extreme telomere length has been previously reported to be associated with increased risk of gastric cancer. However, evidence from prospective studies on a relative large sample size with long-term follow-up to further corroborate previous study findings is meager.Methods: The association between peripheral blood leukocyte telomere length and risk of gastric adenocarcinoma was prospectively examined in a cohort of 26,540 middle-aged or older Chinese nested in the Singapore Chinese Health Study. Telomere length was determined using a validated qPCR-based method. The Cox proportional regression method was used to estimate hazard ratio (HR) and its 95% confidence interval (CI) of gastric adenocarcinoma associated with telomere length after adjustment for potential confounders. Restricted cubic spline analysis was applied to assess the nonlinear relationship between telomere length and gastric cancer risk.Results: A U-shaped association was found between telomere length and risk of gastric adenocarcinoma (Pnonlinearity = 0.020). Compared with the second quintile of telomere length, a statistically significant higher risk of gastric adenocarcinoma was associated with either the lowest quintile (HR = 1.63, 95% CI, 1.07-2.47) or the highest quintile (HR = 1.55, 95% CI, 0.97-2.47) of telomere length. This U-shaped relationship was more apparent in men and younger individuals.Conclusions: This is the first prospective study demonstrating a higher risk of gastric cancer to be associated with either extremely short or extremely long telomere length. Short and long telomere length may function differently in the early and late stages of gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Serum pyridoxal 5’-phosphate (PLP), the active form of vitamin B6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B6 status and risk of pancreatic cancer is lacking. Methods: A nested case-control study involving 187 incident cases of pancreatic cancer and 362 individually matched controls were conducted within two prospective cohorts to evaluate the associations between kynurenine metabolites in pre-diagnostic serum samples and risk of pancreatic cancer. Results: Higher serum concentrations of 3-hydroxyanthranilic acid (HAA) and the HAA:3-hydroxykynurenine (HK) ratio (a measure for in vivo functional status of PLP) were significantly associated with reduced risk of pancreatic cancer. Compared with the lowest tertile, odds ratios (95% confidence intervals) of pancreatic cancer for the highest tertile was 0.62 (0.39, 1.01) for HAA, and 0.59 (0.35–0.98) for the HAA:HK ratio, after adjustment for potential confounders and serum PLP (both Ps for trend<0.05). The kynurenine:tryptophan ratio or neopterin was not significantly associated with pancreatic cancer risk. Conclusions: The inverse association between HAA or the HAA:HK ratio and risk of pancreatic cancer supports the notion that functional status of PLP may be a more important measure than circulating PLP alone for the development of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Incidence of gastric cancer is the highest in Eastern Asia. Multiple modifiable lifestyle factors have been identified as risk factors for gastric cancer. However, their aggregated effect on the risk of gastric cancer has not been examined among populations with high prevalence of Helicobacter pylori.Methods: A study was conducted to examine the association between multiple lifestyle factors together and the risk of developing gastric adenocarcinoma in the Singapore Chinese Health Study, a prospective cohort of 63 257 men and women between 45 and 74 years enroled during 1993-1998. Composite score of cigarette smoking, alcohol consumption, obesity, dietary pattern, and sodium intake at baseline was assessed with hazard ratio (HR) and 95% confidence interval (CI) of gastric adenocarcinoma using Cox regression method.Results: Higher healthy composite lifestyle scores were significantly associated with reduced risk of gastric adenocarcinoma in a dose-dependent manner. Hazard ratios (95% CIs) for total, cardia, and non-cardia gastric adenocarcinoma for the highest (score 5) vs lowest composite score (score 0/1/2) were 0.42 (0.31-0.57), 0.22 (0.10-0.47), and 0.55 (0.39-0.78), respectively (all Ptrend<0.001). These lifestyles together accounted for 48% of total gastric adenocarcinoma cases in the study population. The inverse association was observed in both genders, and remained after exclusion of first 5 years of follow-up.Conclusions: The inverse association between the aggregated healthy lifestyle factors and the risk of gastric adenocarcinoma is in dose-dependent manner in this highly H. pylori-exposed population. These lifestyle factors together may account for up to half of disease burden in this study population. [ABSTRACT FROM AUTHOR]

Background: Lung cancer in never smokers is a significant contributor of cancer mortality worldwide. In this analysis, we explored the role of nine human polyomaviruses, including JC virus (JCV), BK virus (BKV) and Merkel cell virus (MCV), in lung cancer development in never smokers as there are data to support that polyomaviruses are potentially carcinogenic in the human lung.Methods: We used multiplex serology to detect serum antibodies to polyomaviruses in a nested case-control design combining lung cancer cases and controls from four cohort studies - NYU Women's Health Study (NYU-WHS), Janus Serum Bank, Shanghai Women's Health Study and Singapore Chinese Health Study (SCHS).Results: The final analyses included 511 cases and 508 controls. Seroprevalence for each polyomavirus showed significant heterogeneity by study, but overall there were no statistically significant differences between cases and controls. In total, 69.1% of the cases and 68.7% of the controls were seropositive for JCV VP1 antibody. Seropositivity for BKV was higher at 89.0% in cases and 89.8% in controls and lower for MCV at 59.3% in cases and 61.6% in controls. Similar results were obtained after adding an additional retrospective case-control study (Xuanwei study) to the analysis.Conclusions: Our results do not support the hypothesis that seropositivity for polyomaviruses is associated with increased lung cancer risk in never smokers. Future research to evaluate relationship between polyomavirus infection and lung carcinogenesis should focus more on evaluating the presence of virus or viral nucleic acids (DNA or RNA) in lung tumour samples. [ABSTRACT FROM AUTHOR]

Background While elevated systolic blood pressure (SBP) is related to cardiovascular disease (CVD) mortality, it is unclear if the optimal SBP level may differ by age or the presence of underlying CVD. Objective We investigated the association between SBP categories and CVD mortality among middle-aged and elderly adults with and without CVD history. Methods We used data from 30,692 participants of the population-based Singapore Chinese Health Study who had blood pressures measured using a standard protocol at ages 48–85 years between 1994 and 2005. Information on lifestyle factors were collected at recruitment (1993–1998) and during follow-up interviews (1999 and 2004). Mortality was identified via nationwide registry linkage up to 31 December 2014. Results SBP 120–139 mm Hg category was associated with lowest risk of CVD mortality in both age-groups of < 60 and 60 + years, as well as in those with and without underlying coronary heart disease or stroke. Overall, compared to this category, CVD risk was non-significantly increased in lower SBP categories and significantly increased in the higher SBP categories. The risk estimates associated with elevated SBP were higher among those < 60 years compared to their older counterparts, but less distinct between those with and without underlying CVD. Conclusion SBP 120–139 mm Hg was associated with the lowest risk of CVD mortality in middle aged and elderly adults, regardless of underlying CVD. Although risks in both adult groups were similar, there is a greater risk associated with higher SBP among those aged below 60 years, highlighting a greater urgency of treatment in this younger group. [ABSTRACT FROM AUTHOR]

Background & Aim Lipidomic signature of lipid metabolism suggests that omega-6 polyunsaturated fatty acids ( PUFA) may play a role in oncogenesis of hepatocellular carcinoma ( HCC). Hence, we examined the association between dietary fatty acids and risk of HCC. Methods We used data from the Singapore Chinese Health Study, a population-based prospective cohort of 63 257 Chinese men and women aged 45-74 years enrolled between 1993 and 1998. Information on current diet assessed via a validated semi-quantitative food frequency questionnaire, medical history and lifestyle factors were obtained through in-person interview, and incidence of HCC recorded through 31 Dec 2010. We also examined the association between dietary fatty acids and HCC risk using a case-control set of 92 cases and 274 controls with available serological biomarkers of chronic infections with hepatitis B virus ( HBV) and hepatitis C virus ( HCV) nested within this cohort. Results Among the dietary fat components examined, which included saturated, monounsaturated, omega-3 and omega-6 PUFA, only omega-6 PUFA intake displayed a dose-dependent, positive association with HCC risk (p for trend = 0.02). Compared to the lowest quartile, the hazard ratio for the highest quartile intake was 1.49 [(95% confidence interval ( CI):1.08-2.07)]. In the nested case-control study, only among individuals negative for serology markers of chronic infection with HBV or HCV, those who consumed above median levels of dietary omega-6 PUFA had increased HCC risk (odds ratio = 4.36, 95% CI = 1.59-11.94) compared to those with lower intake. Conclusion Dietary omega-6 PUFA may be implicated in the risk of non-viral hepatitis related HCC. [ABSTRACT FROM AUTHOR]