Publications by authors named "Yuanjie Pang"

53 Publications

Metabolic risk factors, genetic predisposition, and risk of severe liver disease in Chinese: a prospective study of 0.5 million people.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China.

Background: Metabolic risk factors have been shown to be associated with severe liver disease (SLD) in Chinese populations. However, there is limited evidence on the combined impact of these factors, or the genetic variants associated with SLD.

Objectives: We examined the associations of combined metabolic risk factors with risks of SLD, both overall and by genetic predisposition to SLD.

Methods: The study population involved 486,828 participants of the prospective China Kadoorie Biobank aged 30-79 years from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted HRs for SLD associated with combined metabolic risk factors (central adiposity, physical inactivity, and diabetes) by stratum of genetic risk [assessed separately by a PNPLA3 variant (rs738409) and a BMI genetic risk score].

Results: During ∼10 years of follow-up, 3279 incident cases of SLD were recorded. The overall mean BMI was 23.8 kg/m2 (SD, 3.4 kg/m2), and 5.9% participants had diabetes. Compared with those with 3 metabolic factors, participants with 2, 1, and 0 metabolic factors had 31% (HR, 0.69; 95% CI: 0.65-0.73), 43% (HR, 0.57; 95% CI: 0.53-0.60), and 52% (HR, 0.48; 95% CI: 0.42-0.56) lower risks of SLD, respectively. For both BMI and nonalcoholic fatty liver disease variants, participants with fewer metabolic factors had a lower risk of SLD, lower levels of gamma-glutamyl transferase, and lower fatty liver index scores, in participants with low and high genetic risks (P value for interaction > 0.05).

Conclusions: In relatively lean Chinese adults, individuals with fewer metabolic risk factors had a lower relative risk of SLD and a more favorable profile of liver biomarkers across all strata of genetic risk.
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http://dx.doi.org/10.1093/ajcn/nqab099DOI Listing
May 2021

Pneumonia hospitalizations and the subsequent risk of incident ischaemic cardiovascular disease in Chinese adults.

Int J Epidemiol 2021 Apr 7. Epub 2021 Apr 7.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

Background: Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established.

Methods: The China Kadoorie Biobank enrolled 512 726 participants aged 30-79 years from 10 areas across China during 2004-2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia.

Results: The risk of ischaemic CVD increased during days 1-3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35) and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction < 0.05). Besides, the risk of ischaemic CVD was also higher among the participants aged ≥70 years (Pinteraction < 0.001 for IHD and 0.033 for IS).

Conclusion: Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year.
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http://dx.doi.org/10.1093/ije/dyab039DOI Listing
April 2021

Causal effects of gallstone disease on risk of gastrointestinal cancer in Chinese.

Br J Cancer 2021 May 26;124(11):1864-1872. Epub 2021 Mar 26.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.

Background: Gallstone disease (GSD) is associated with a higher risk of gastrointestinal (GI) cancer. However, it is unclear whether the associations are causal.

Methods: The prospective China Kadoorie Biobank (CKB) recorded 17,598 cases of GI cancer among 510,137 participants without cancer at baseline during 10 years of follow-up. Cox regression was used to estimate hazard ratios (HRs) for specific cancer by GSD status and duration. Mendelian randomisation was conducted to assess the genetic associations of GSD with specific cancer.

Results: Overall 6% of participants had symptomatic GSD at baseline. Compared with those without GSD, individuals with symptomatic GSD had adjusted HRs of 1.13 (1.01-1.29) for colorectal, 2.01 (1.78-2.26) for liver, 3.70 (2.88-4.87) for gallbladder, 2.31 (1.78-3.07) for biliary tract, and 1.38 (1.18-1.74) for pancreatic cancer. Compared with participants without GSD, the risks of colorectal, liver, gallbladder, biliary tract, and pancreatic cancer were highest during 0 to <5 years following disease diagnosis. There was evidence of genetic associations of GSD with these cancers, with odds ratios per 1-SD genetic score of 1.08 (1.05-1.11) for colorectal, 1.22 (1.19-1.25) for liver, 1.56 (1.49-1.64) for gallbladder, 1.39 (1.31-1.46) for biliary tract, and 1.16 (1.10-1.22) for pancreatic cancer. When meta-analysing the genetic estimates in CKB and UK Biobank, there was evidence of causal associations of GSD with colon cancer, gallbladder and biliary tract cancer (GBTC), and total GI cancer (RR per 1-SD: 1.05 [0.99-1.11], 2.00 [1.91-2.09], and 1.09 [1.05-1.13]).

Conclusions: GSD was associated with higher risks of several GI cancers, warranting future studies on the underlying mechanisms.
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http://dx.doi.org/10.1038/s41416-021-01325-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144569PMC
May 2021

Association between 4-dimension lifestyle pattern and 10-year mortality risk in Chinese individuals older than 65: a population-based cohort study.

Aging (Albany NY) 2021 03 19;13(6):8835-8848. Epub 2021 Mar 19.

Department of Global Health, Peking University School of Public Health, Haidian 100191, Beijing, China.

While the impact of a 4-dimension lifestyle pattern (4DL) on older people's mortality (aged ≥65 years) has been reported in high-income countries, few studies investigated the association between lifestyle pattern and disease-accompanied mortality, or examined the difference among different age or gender groups in low- and middle-income countries. We followed up 16,954 Chinese older participants from 2008 to 2018 and adopted the Cox proportional hazard model to evaluate the protective effect of 4DL. After adjustment for confounders, individuals with 3-4 4DL scores had a 38% reduction in all-cause mortality risk, and up to 36%, 42% and 41% reduced risk of mortality accompanied by hypertension, respiratory disease and dementia, respectively in contrast with those scored 0. Compared with octogenarians, nonagenarians, and centenarians, adhering to 3-4 4DL could further reduce the mortality risks in the younger elderly (aged 65-79 years). This study shows that among the elderly population in China, participants who adhered to 4DL had a lower all-cause mortality risk than those who did not. Additionally, hypertension, respiratory disease, or dementia accompanied mortality risk was also reduced significantly. The findings indicated that the positive effects of 4DL on longevity should be acknowledged in China's older population, especially for the younger elderly.
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http://dx.doi.org/10.18632/aging.202695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034959PMC
March 2021

Tea consumption and long-term risk of type 2 diabetes and diabetic complications: a cohort study of 0.5 million Chinese adults.

Am J Clin Nutr 2021 Mar 11. Epub 2021 Mar 11.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

Background: Evidence from epidemiological studies remains inconsistent or limited about the associations of tea consumption with incident diabetes and risk of diabetic complications and death among patients with diabetes.

Objectives: We aimed to investigate the associations of tea consumption with long-term risk of developing type 2 diabetes (T2D) and risks of diabetic complications and death among patients with diabetes.

Methods: This study included 482,425 diabetes-free participants and 30,300 patients with diabetes aged 30-79 y at study enrollment from the China Kadoorie Biobank. Tea consumption information was collected at baseline by interviewer-administered questionnaires. Incidences of diabetes, diabetic complications, and death were identified by linkages to the National Health Insurance system, disease registries, and death registries. Cox proportional hazard regression models were used to estimate HRs and 95% CIs.

Results: The mean ± SD age of participants free of diabetes was 51.2 ± 10.5 y and 41% were male. The mean ± SD age of patients with diabetes was 58.2 ± 9.6 y and 39% were male. Of all daily tea consumers, 85.8% preferred green tea. In the diabetes-free population, 17,434 participants developed incident T2D during 11.1 y of follow-up. Compared with participants who never consumed tea in the past year, the HR (95% CI) of T2D for daily consumers was 0.92 (0.88, 0.97). In patients with diabetes, we identified 6572 deaths, 12,677 diabetic macrovascular cases, and 2441 diabetic microvascular cases during follow-up. Compared with patients who never consumed tea in the past year, the HRs (95% CIs) of all-cause mortality and risk of microvascular complications for daily consumers were 0.90 (0.83, 0.97) and 0.88 (0.78, 1.00), respectively. Tea consumption was not associated with risk of macrovascular complications among patients with diabetes. With regard to tea consumed, the inverse associations between daily tea consumption and risks of T2D and all-cause mortality in patients with diabetes were only observed among daily green tea drinkers.

Conclusions: In Chinese adults, daily green tea consumption was associated with a lower risk of incident T2D and a lower risk of all-cause mortality in patients with diabetes, but the associations for other types of tea were less clear. In addition, daily tea consumption was associated with a lower risk of diabetic microvascular complications, but not macrovascular complications.
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http://dx.doi.org/10.1093/ajcn/nqab006DOI Listing
March 2021

Exfoliated Ultrathin ZnIn S Nanosheets with Abundant Zinc Vacancies for Enhanced CO Electroreduction to Formate.

ChemSusChem 2021 Feb 12;14(3):852-859. Epub 2021 Jan 12.

Key Laboratory of Material Chemistry for Energy Conversion and Storage (Ministry of Education) Hubei Key Laboratory of Material Chemistry and Service Failure, Wuhan National Laboratory for Optoelectronics School of Chemistry and Chemical Engineering Huazhong University of Science and Technology (HUST), 1037 Luoyu Road, Wuhan, 430074, P. R. China.

Electrocatalytic conversion of carbon dioxide (CO ) is promising for balancing carbon cycles while producing value-added feedstocks. Herein, ultrathin ZnIn S nanosheets with abundant Zn vacancies are demonstrated for electrochemically reducing CO to formate. Specifically, a partial current density of 245 mA cm with a near-unity faradaic efficiency of 94 % for formate generation was achieved over the ultrathin ZnIn S nanosheets in a flow cell configuration. Experimental and theoretical results revealed that abundant Zn vacancies in the ultrathin ZnIn S nanosheets with a high electrochemically active surface area synergistically optimized the intermediate binding energy and contributed to the boosted selectivity and activity. This work may provide useful understandings in designing efficient catalysts for selective CO electroreduction.
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http://dx.doi.org/10.1002/cssc.202002785DOI Listing
February 2021

Associations of Adiposity, Circulating Protein Biomarkers, and Risk of Major Vascular Diseases.

JAMA Cardiol 2021 Mar;6(3):276-286

Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom.

Importance: Obesity is associated with a higher risk of cardiovascular disease (CVD), but little is known about the role that circulating protein biomarkers play in this association.

Objective: To examine the observational and genetic associations of adiposity with circulating protein biomarkers and the observational associations of proteins with incident CVD.

Design, Setting, And Participants: This subcohort study included 628 participants from the prospective China Kadoorie Biobank who did not have a history of cancer at baseline. The Olink platform measured 92 protein markers in baseline plasma samples. Data were collected from June 2004 to January 2016 and analyzed from January 2019 to June 2020.

Exposures: Measured body mass index (BMI) obtained during the baseline survey and genetically instrumented BMI derived using 571 externally weighted single-nucleotide variants.

Main Outcomes And Measures: Cross-sectional associations of adiposity with biomarkers were examined using linear regression. Associations of biomarkers with CVD risk were assessed using Cox regression among those without prior cancer or CVD at baseline. Mendelian randomization was conducted to derive genetically estimated associations of BMI with biomarkers.

Findings: In observational analyses of 628 individuals (mean [SD] age, 52.2 [10.5] years; 385 women [61.3%]), BMI (mean [SD], 23.9 [3.6]) was positively associated with 27 proteins (per 1-SD higher BMI; eg, interleukin-6: 0.21 [95% CI, 0.12-0.29] SD; interleukin-18: 0.13 [95% CI, 0.05-0.21] SD; monocyte chemoattractant protein-1: 0.12 [95% CI, 0.04-0.20] SD; hepatocyte growth factor: 0.31 [95% CI, 0.24-0.39] SD), and inversely with 3 proteins (Fas ligand: -0.11 [95% CI, -0.19 to -0.03] SD; TNF-related weak inducer of apoptosis, -0.14 [95% CI, -0.23 to -0.06] SD; and carbonic anhydrase 9: (-0.14 [95% CI, -0.22 to -0.05] SD), with similar associations identified for other adiposity traits (eg, waist circumference [r = 0.96]). In mendelian randomization, the associations of genetically elevated BMI with specific proteins were directionally consistent with the observational associations. In meta-analyses of genetically elevated BMI with 8 proteins, combining present estimates with previous studies, the most robust associations were shown for interleukin-6 (per 1-SD higher BMI; 0.21 [95% CI, 0.13-0.29] SD), interleukin-18 (0.16 [95% CI, 0.06-0.26] SD), monocyte chemoattractant protein-1 (0.21 [95% CI, 0.11-0.30] SD), monocyte chemotactic protein-3 (0.12 [95% CI, 0.03-0.21] SD), TNF-related apoptosis-inducing ligand (0.23 [95% CI, 0.13-0.32] SD), and hepatocyte growth factor (0.14 [95% CI, 0.06-0.22] SD). Of the 30 BMI-associated biomarkers, 10 (including interleukin-6, interleukin-18, and hepatocyte growth factor) were nominally associated with incident CVD.

Conclusions And Relevance: Mendelian randomization shows adiposity to be associated with a range of protein biomarkers, with some biomarkers also showing association with CVD risk. Future studies are warranted to validate these findings and assess whether proteins may be mediators between adiposity and CVD.
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http://dx.doi.org/10.1001/jamacardio.2020.6041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711564PMC
March 2021

Association of healthy lifestyle with cognitive function among Chinese older adults.

Eur J Clin Nutr 2021 Feb 28;75(2):325-334. Epub 2020 Oct 28.

Department of Epidemiology & Biostatistics, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Road, 100191, Beijing, China.

Background/objectives: Dietary patterns and daily life habits have been reported to be associated with cognitive function in European populations. We aimed to examine the associations of dietary patterns and daily life habits with cognitive function among Chinese old people.

Subjects/methods: We used 2011-2014 longitudinal data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) comprising 5716 participants with an average age of 82 years. Cognitive function was measured in 2014 based on the results of Mini-Mental Status Examination. Data on participants' dietary patterns and daily life habits were collected during baseline survey. Logistic regression models and general linear models were adopted to estimate the associations of dietary pattern and daily life habit with cognitive function.

Results: Compared with participants in the lowest quartile of lifestyle score, those in the highest quartile had a lower risk of cognitive impairment after controlling for all covariates (OR = 0.52, 95% confidence interval (CI), 0.41-0.65, P < 0.001). Higher lifestyle score was associated with better cognitive function (β = 0.74, 95% CI, 0.55-0.93, P < 0.001). Participants with top quartile of dietary pattern had a lower risk of cognitive impairment (OR = 0.65, 95% CI, 0.51-0.81, P < 0.001). Similar trends were observed in daily life habit, showing that more exercises, moderate alcohol consumption, and non-smoking were associated with improved cognition status (OR = 0.64, 95% CI, 0.53-0.77, P < 0.001).

Conclusions: Our findings suggest that maintaining a healthy dietary pattern and carrying out outdoor exercises is associated with a lower risk of cognitive impairment among Chinese old people.
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http://dx.doi.org/10.1038/s41430-020-00785-2DOI Listing
February 2021

Observational and Genetic Associations of Body Mass Index and Hepatobiliary Diseases in a Relatively Lean Chinese Population.

JAMA Netw Open 2020 10 1;3(10):e2018721. Epub 2020 Oct 1.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Big Data Institute University of Oxford, Oxford, United Kingdom.

Importance: There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower.

Objectives: To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases differed by hepatitis B virus infection status.

Design, Setting, And Participants: This cohort study used data from the prospective China Kadoorie Biobank, including 473 938 adults aged 30 to 79 years without hepatobiliary diseases at baseline from 10 diverse areas in China from June 25, 2004, to July 15, 2008. A random sample of 75 736 participants with genotyping data was included in the Mendelian randomization analysis. Follow-up was completed January 1, 2017 (median [interquartile range] length of follow-up, 10.2 [9.2-11.1] years). Data were analyzed from January to October 2019.

Exposures: Measured BMI obtained during the baseline survey and genetically instrumented BMI derived using 92 single-nucleotide variations.

Main Outcomes And Measures: Incident cases of hepatobiliary diseases, liver enzymes, fatty liver index, and fibrosis score.

Results: Among 473 938 individuals (276 041 [58.2%] women), the mean (SD) age was 52 (10.9) years and mean (SD) BMI was 23.8 (3.4). Baseline BMI was associated with higher risks of chronic liver disease (adjusted risk ratio per 1-SD increase, 1.14; 95% CI, 1.11 to 1.17) and gallbladder disease (adjusted risk ratio per 1-SD increase, 1.29; 95% CI, 1.27 to 1.31), with heterogeneity by disease subtype (P < .001). Genetically instrumented BMI was associated with higher risks of chronic liver disease (risk ratio per 1-SD increase, 1.55; 95% CI, 1.08 to 2.24) and gallbladder disease (risk ratio per 1-SD increase, 1.40; 95% CI, 1.11 to 1.76), with no heterogeneity between subtypes. A meta-analysis of the genetic associations in China Kadoorie Biobank and those calculated in UK Biobank gave a risk ratio of 1.55 (95% CI, 1.30 to 1.84) for chronic liver disease and 1.42 (95% CI, 1.22 to 1.64) for gallbladder disease. In the China Kadoorie Biobank study, there were positive genetic associations of BMI with liver enzymes, steatosis, and fibrosis scores, consistent with observational associations. The genetic associations of BMI with liver diseases and biomarkers did not differ by hepatitis B virus infection status.

Conclusions And Relevance: In this cohort study of a relatively lean Chinese population, there were positive genetic associations of BMI with hepatobiliary diseases. These results suggest that maintaining a healthy weight through diet and physical activity may help prevent hepatobiliary diseases.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.18721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532388PMC
October 2020

Association of physical activity with risk of hepatobiliary diseases in China: a prospective cohort study of 0.5 million people.

Br J Sports Med 2020 Aug 21. Epub 2020 Aug 21.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China

Objective: There is limited prospective evidence on the association of physical activity with hepatobiliary cancer subtypes and other major hepatobiliary diseases, especially in China. We aimed to quantify the associations with risk of these diseases.

Methods: The study population involved 460 937 participants of the prospective China Kadoorie Biobank aged 30-79 years from 10 diverse areas in China without history of cancer or hepatobiliary disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with self-reported total and domain-specific physical activity (occupational and non-occupational, ie, leisure time, household and commuting).

Results: During ~10 years of follow-up, 22 012 incident cases of hepatobiliary diseases were recorded. The overall mean (SD) total physical activity was 21.2 (13.9) metabolic equivalent of task (MET)-hours/day, with 62% from occupational activity. Total physical activity was inversely associated with hospitalised non-alcoholic fatty liver disease (HR comparing top vs bottom quintile: 0.62, 95% confidence interval (CI) 0.53 to 0.72), viral hepatitis (0.73, 95% CI 0.62 to 0.87), cirrhosis (0.76, 95% CI 0.66 to 0.88) and liver cancer (0.81, 95% CI 0.71 to 0.93), as well as gallstone disease (0.86, 95% CI 0.81 to 0.90), gallbladder cancer (0.51, 95% CI 0.32 to 0.80) and biliary tract cancer (0.55, 95% CI 0.38 to 0.78). The associations for occupational physical activity were similar to those for total physical activity, but for non-occupational physical activity they differed by disease subtype. For leisure-time physical activity, there was an inverse association with liver cancer and an inverse trend for gallstone disease (HR comparing ≥7.5 MET-hours/day with none: 0.83, 95% CI 0.75 to 0.91 and 0.82, 95% CI 0.66 to 1.01).

Conclusion: Among Chinese adults, high total physical activity, particularly occupational physical activity, was inversely associated with risk of major hepatobiliary cancers and diseases, including non-alcoholic fatty liver disease, cirrhosis and certain types of cancer.
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http://dx.doi.org/10.1136/bjsports-2020-102174DOI Listing
August 2020

Influenza Vaccination and Hospitalization Outcomes Among Older Patients With Cardiovascular or Respiratory Diseases.

J Infect Dis 2021 Apr;223(7):1196-1204

Department of Global Health, School of Public Health, Peking University Health Science Center, Beijing, China.

Background: Influenza vaccination has been suggested to protect against death and recurrent events among patients with cardiovascular disease or chronic obstructive respiratory disease, but there is limited evidence in older adults, who have higher risks of influenza-associated hospitalization and mortality.

Methods: Patients aged ≥60 years hospitalized for cardiovascular or respiratory diseases from the Beijing Urban Employee Basic Medical Insurance database during 3 influenza seasons (2013-2014 through 2015-2016) were pooled to estimate the effects of influenza vaccination on hospitalization outcomes. Vaccination status was ascertained through cross-referencing the Beijing Elderly Influenza Vaccination database. The summer months (June-August) were used as a reference period to adjust for unmeasured confounders during influenza seasons.

Results: After adjustment for both measured and unmeasured confounders, influenza vaccination was associated with lower risks of in-hospital deaths among patients hospitalized for cardiovascular (odds ratio [95% confidence interval], 0.85 [.68-1.06]) or respiratory diseases (0.66 [.54-.82]). Influenza vaccination was associated with a lower risk of readmission among patients with cardiovascular (odds ratio [95% confidence interval], 0.81 [.69-.95]) but not respiratory diseases (1.12 [.92-1.35]). Influenza vaccination was also associated with lower direct medical costs, but not with length of stay.

Conclusions: Influenza vaccination protected against hospitalization outcomes among older adults with cardiovascular or respiratory diseases.
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http://dx.doi.org/10.1093/infdis/jiaa493DOI Listing
April 2021

Accelerated discovery of CO electrocatalysts using active machine learning.

Nature 2020 05 13;581(7807):178-183. Epub 2020 May 13.

Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada.

The rapid increase in global energy demand and the need to replace carbon dioxide (CO)-emitting fossil fuels with renewable sources have driven interest in chemical storage of intermittent solar and wind energy. Particularly attractive is the electrochemical reduction of CO to chemical feedstocks, which uses both CO and renewable energy. Copper has been the predominant electrocatalyst for this reaction when aiming for more valuable multi-carbon products, and process improvements have been particularly notable when targeting ethylene. However, the energy efficiency and productivity (current density) achieved so far still fall below the values required to produce ethylene at cost-competitive prices. Here we describe Cu-Al electrocatalysts, identified using density functional theory calculations in combination with active machine learning, that efficiently reduce CO to ethylene with the highest Faradaic efficiency reported so far. This Faradaic efficiency of over 80 per cent (compared to about 66 per cent for pure Cu) is achieved at a current density of 400 milliamperes per square centimetre (at 1.5 volts versus a reversible hydrogen electrode) and a cathodic-side (half-cell) ethylene power conversion efficiency of 55 ± 2 per cent at 150 milliamperes per square centimetre. We perform computational studies that suggest that the Cu-Al alloys provide multiple sites and surface orientations with near-optimal CO binding for both efficient and selective CO reduction. Furthermore, in situ X-ray absorption measurements reveal that Cu and Al enable a favourable Cu coordination environment that enhances C-C dimerization. These findings illustrate the value of computation and machine learning in guiding the experimental exploration of multi-metallic systems that go beyond the limitations of conventional single-metal electrocatalysts.
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http://dx.doi.org/10.1038/s41586-020-2242-8DOI Listing
May 2020

Publisher Correction: Copper adparticle enabled selective electrosynthesis of n-propanol.

Nat Commun 2020 Feb 20;11(1):1034. Epub 2020 Feb 20.

Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, M5S 3G8, Canada.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-14883-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033088PMC
February 2020

Socioeconomic Status in Relation to Risks of Major Gastrointestinal Cancers in Chinese Adults: A Prospective Study of 0.5 Million People.

Cancer Epidemiol Biomarkers Prev 2020 04 27;29(4):823-831. Epub 2020 Jan 27.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Background: Low socioeconomic status (SES) is associated with higher risk of certain gastrointestinal (e.g., colorectal, pancreatic, and liver) cancers in Western populations. Evidence is very limited in China, where correlates and determinants of SES differ from those in the West.

Methods: The prospective China Kadoorie Biobank recruited 512,715 adults (59% women, mean age 51 years) from 10 (5 urban, 5 rural) regions. During 10 years of follow-up, 27,940 incident cancers (including 3,061 colorectal, 805 pancreatic, and 2,904 liver) were recorded among 510,131 participants without prior cancer at baseline. Cox regression was used to estimate adjusted HRs for specific cancers associated with area-level (e.g., per capita gross domestic product, disposable income) and individual-level (e.g., education, household income) SES.

Results: Area-level SES and household income showed positive associations with incident colorectal and pancreatic cancers and inverse associations with liver cancer ( < 0.05). Education showed no association with colorectal cancer but inverse associations with pancreatic and liver cancers, with adjusted HRs comparing university to no formal schooling being 1.05 [95% confidence interval (CI), 0.85-1.29], 0.49 (95% CI, 0.28-0.85), and 0.61 (95% CI, 0.47-0.81), respectively. Potential risk factors (e.g., smoking, alcohol) partly explained the inverse associations of education with pancreatic and liver cancers (17.6% and 60.4%), respectively.

Conclusions: Among Chinese adults, the associations of SES with gastrointestinal cancers differed by cancer type and SES indicator. Potential risk factors partially explained the inverse associations of education with pancreatic and liver cancers.

Impact: The different associations between SES with gastrointestinal cancers may inform cancer prevention strategies.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242093PMC
April 2020

Efficient upgrading of CO to C fuel using asymmetric C-C coupling active sites.

Nat Commun 2019 11 29;10(1):5186. Epub 2019 Nov 29.

Department of Electrical and Computer Engineering, University of Toronto, 35 St George Street, Toronto, ON, M5S 1A4, Canada.

The electroreduction of C feedgas to high-energy-density fuels provides an attractive avenue to the storage of renewable electricity. Much progress has been made to improve selectivity to C and C products, however, the selectivity to desirable high-energy-density C products remains relatively low. We reason that C electrosynthesis relies on a higher-order reaction pathway that requires the formation of multiple carbon-carbon (C-C) bonds, and thus pursue a strategy explicitly designed to couple C with C intermediates. We develop an approach wherein neighboring copper atoms having distinct electronic structures interact with two adsorbates to catalyze an asymmetric reaction. We achieve a record n-propanol Faradaic efficiency (FE) of (33 ± 1)% with a conversion rate of (4.5 ± 0.1) mA cm, and a record n-propanol cathodic energy conversion efficiency (EE) of 21%. The FE and EE represent a 1.3× improvement relative to previously-published CO-to-n-propanol electroreduction reports.
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http://dx.doi.org/10.1038/s41467-019-13190-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882816PMC
November 2019

Physical Activity, Sedentary Leisure Time, Circulating Metabolic Markers, and Risk of Major Vascular Diseases.

Circ Genom Precis Med 2019 09 28;12(9):386-396. Epub 2019 Aug 28.

Clinical Trial Service Unit and Epidemiological Studies Unit (Y.P., C.K., H.D., I.Y.M., Y.C., L.Y., R.W., F.B., R.P., R. Clarke, R. Collins, D.A.B., L.L., M.V.H., Z.C.), Nuffield Department of Population Health, University of Oxford, United Kingdom.

Background: Physical inactivity and sedentary behavior are associated with higher risk of cardiovascular disease (CVD). Little is known about the relevance of circulating metabolites for these associations.

Methods: A nested case-control study within the prospective China Kadoorie Biobank included 3195 incident CVD cases (2057 occlusive CVD and 1138 intracerebral hemorrhage) and 1465 controls aged 30 to 79 years without prior CVD or statin use at baseline. Nuclear magnetic resonance spectroscopy was used to measure 225 metabolic markers and derived traits in baseline plasma samples. Linear regression was used to relate self-reported physical activity and sedentary leisure time to biomarkers, adjusting for potential confounders. These were contrasted with associations of biomarkers with occlusive CVD risk.

Results: Physical activity and sedentary leisure time were associated with >100 metabolic markers, with patterns of associations generally mirroring each other. Physical activity was inversely associated with very low and low-density and positively with large and very large HDL (high-density lipoprotein) particle concentrations. Physical activity was also inversely associated with alanine, glucose, lactate, acetoacetate, and the inflammatory marker glycoprotein acetyls. In general, associations of physical activity and sedentary leisure time with specific metabolic markers were directionally consistent with the associations of these metabolic markers with occlusive CVD risk. Overall, metabolic markers potentially explained ≈70% of the protective associations of physical activity and ≈50% of the positive associations of sedentary leisure time with occlusive CVD.

Conclusions: Among Chinese adults, physical activity and sedentary behavior have opposing associations with a diverse range of circulating metabolites, which may partially explain their associations with CVD risk.
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http://dx.doi.org/10.1161/CIRCGEN.118.002527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752700PMC
September 2019

Mendelian Randomization and the Environmental Epigenetics of Health: a Systematic Review.

Curr Environ Health Rep 2019 03;6(1):38-51

Area of Cardiometabolic and Renal Risk, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Av. Menendez Pelayo 4 accesorio, 46010, Valencia, Spain.

Purpose Of Review: Epigenetic modifications are environmentally responsive and may play a mechanistic role in the development of disease. Mendelian randomization uses genetic variation to assess the causal effect of modifiable exposures on health outcomes. We conducted a systematic review of Mendelian randomization studies evaluating the causal role of DNA methylation (DNAm) changes on the development of health states, emphasizing on studies that formally evaluate exposure-DNAm, in addition to DNAm-outcome, causal associations.

Recent Findings: We identified 15 articles, 4 of them including an environmental determinant of DNAm, including self-reported tobacco smoke exposure, in utero tobacco smoke exposure, measured vitamin B, and glycemia. Selected articles suggest a causal association of DNAm with some cardiometabolic endpoints. DNAm seemed to partly explain the association of postnatal and prenatal exposure to tobacco smoke and vitamin B with inflammation biomarkers, birth weight, and cognitive outcomes, respectively. However, the current evidence is not sufficient to infer causality. Additional Mendelian randomization studies from large epidemiologic samples are needed to support the causal role of environmental factors as determinants of health-related epigenetic modifications.
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http://dx.doi.org/10.1007/s40572-019-0226-3DOI Listing
March 2019

Adiposity in relation to risks of fatty liver, cirrhosis and liver cancer: a prospective study of 0.5 million Chinese adults.

Sci Rep 2019 01 28;9(1):785. Epub 2019 Jan 28.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Adiposity is an increasing public health problem in China. We aimed to examine the associations of adiposity with non-alcoholic fatty liver disease (NAFLD) and other chronic liver diseases in Chinese adults. The prospective China Kadoorie Biobank recruited 512,891 adults aged 30-79 years from 10 areas. During 10 years of follow-up, 7,386 incident liver disease cases were recorded among 503,991 participants without prior cancer or chronic liver disease at baseline. The mean body mass index (BMI) (SD) was 23.7 (3.3) kg/m and mean waist circumference (WC) 80.3 (9.8) cm, with 33% having BMI ≥25 kg/m. Throughout the range examined (BMI 15-50) BMI showed a log-linear positive association with NAFLD (n = 1,298), with adjusted HR per 5 kg/m of 2.81 (95% CI 2.63-3.01), adjusting for regression dilution. There were also positive associations of percent body fat, WC, and waist-to-hip ratio with NAFLD, with HRs per 1-SD of 2.27 (2.14-2.41), 2.60 (2.44-2.76), and 1.84 (1.76-1.92). BMI was unrelated to viral hepatitis (n = 1,477), and had a U-shaped association with cirrhosis (n = 2,082) and an inverse association with liver cancer (n = 2,568), which disappeared after excluding the first 5 years of follow-up. Among Chinese adults, adiposity was a major risk factor for NAFLD but not other chronic liver diseases.
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http://dx.doi.org/10.1038/s41598-018-36460-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349919PMC
January 2019

Central adiposity in relation to risk of liver cancer in Chinese adults: A prospective study of 0.5 million people.

Int J Cancer 2019 09 13;145(5):1245-1253. Epub 2019 Feb 13.

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Central adiposity is associated with liver cancer risk beyond general adiposity in Western populations. However, there is little prospective evidence in East Asian populations who are more likely to have central adiposity at given BMI levels. The prospective China Kadoorie Biobank recruited 512,713 adults aged 30-79 years from 10 diverse areas. During 10 years follow-up, 2,847 incident cases of liver cancer were identified. Cox regression was used to estimate adjusted hazard ratios (HR) for liver cancer associated with central adiposity, excluding individuals with cancers and liver diseases at baseline and the first 5 years of follow-up (1,049 incident liver cancer cases). Overall, mean waist circumference (WC) was 82.2 (SD 9.8) cm in men and 79.1 (9.5) cm in women. Central adiposity showed positive associations with liver cancer risk. Associations were strongest for WC and waist-to-hip ratio (WHR), with adjusted HRs per 1-SD of 1.09 (95%CI 1.01-1.18) and 1.12 (1.02-1.23), respectively. The positive associations became stronger when additionally adjusting for BMI (1.26 [1.09-1.46] and 1.14 [1.02-1.28]). The positive association of central obesity (WC ≥90 cm in men and ≥ 80 cm in women) with liver cancer increased progressively with the number of other presenting metabolic risk factors (physical inactivity, diabetes, and hypertension), with HRs of 1.07 (0.90-1.28), 1.17 (1.00-1.38), and 1.91 (1.40-2.59) in those with one, two, and three factors (p for trend 0.006). In this relatively lean Chinese population, there were positive associations of central adiposity with risk of liver cancer, with WHR and WC showing the strongest associations.
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http://dx.doi.org/10.1002/ijc.32148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767784PMC
September 2019

A review of lifestyle, metabolic risk factors, and blood-based biomarkers for early diagnosis of pancreatic ductal adenocarcinoma.

J Gastroenterol Hepatol 2019 Feb 17;34(2):330-345. Epub 2019 Jan 17.

Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

We aimed to review the epidemiologic literature examining lifestyle and metabolic risk factors, and blood-based biomarkers including multi-omics (genomics, proteomics, and metabolomics) and to discuss how these predictive markers can inform early diagnosis of pancreatic ductal adenocarcinoma (PDAC). A search of the PubMed database was conducted in June 2018 to review epidemiologic studies of (i) lifestyle and metabolic risk factors for PDAC, genome-wide association studies, and risk prediction models incorporating these factors and (ii) blood-based biomarkers for PDAC (conventional diagnostic markers, metabolomics, and proteomics). Prospective cohort studies have reported at least 20 possible risk factors for PDAC, including smoking, heavy alcohol drinking, adiposity, diabetes, and pancreatitis, but the relative risks and population attributable fractions of individual risk factors are small (mostly < 10%). High-throughput technologies have continued to yield promising genetic, metabolic, and protein biomarkers in addition to conventional biomarkers such as carbohydrate antigen 19-9. Nonetheless, most studies have utilized a hospital-based case-control design, and the diagnostic accuracy is low in studies that collected pre-diagnostic samples. Risk prediction models incorporating lifestyle and metabolic factors as well as other clinical parameters have shown good discrimination and calibration. Combination of traditional risk factors, genomics, and blood-based biomarkers can help identify high-risk populations and inform clinical decisions. Multi-omics investigations can provide valuable insights into disease etiology, but prospective cohort studies that collect pre-diagnostic samples and validation in independent studies are warranted.
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http://dx.doi.org/10.1111/jgh.14576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378598PMC
February 2019

Copper adparticle enabled selective electrosynthesis of n-propanol.

Nat Commun 2018 11 5;9(1):4614. Epub 2018 Nov 5.

Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, M5S 3G8, Canada.

The electrochemical reduction of carbon monoxide is a promising approach for the renewable production of carbon-based fuels and chemicals. Copper shows activity toward multi-carbon products from CO reduction, with reaction selectivity favoring two-carbon products; however, efficient conversion of CO to higher carbon products such as n-propanol, a liquid fuel, has yet to be achieved. We hypothesize that copper adparticles, possessing a high density of under-coordinated atoms, could serve as preferential sites for n-propanol formation. Density functional theory calculations suggest that copper adparticles increase CO binding energy and stabilize two-carbon intermediates, facilitating coupling between adsorbed *CO and two-carbon intermediates to form three-carbon products. We form adparticle-covered catalysts in-situ by mediating catalyst growth with strong CO chemisorption. The new catalysts exhibit an n-propanol Faradaic efficiency of 23% from CO reduction at an n-propanol partial current density of 11 mA cm.
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http://dx.doi.org/10.1038/s41467-018-07032-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218481PMC
November 2018

Copper-on-nitride enhances the stable electrosynthesis of multi-carbon products from CO.

Nat Commun 2018 09 20;9(1):3828. Epub 2018 Sep 20.

Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Road, Toronto, ON, M5S 3G4, Canada.

Copper-based materials are promising electrocatalysts for CO reduction. Prior studies show that the mixture of copper (I) and copper (0) at the catalyst surface enhances multi-carbon products from CO reduction; however, the stable presence of copper (I) remains the subject of debate. Here we report a copper on copper (I) composite that stabilizes copper (I) during CO reduction through the use of copper nitride as an underlying copper (I) species. We synthesize a copper-on-nitride catalyst that exhibits a Faradaic efficiency of 64 ± 2% for C products. We achieve a 40-fold enhancement in the ratio of C to the competing CH compared to the case of pure copper. We further show that the copper-on-nitride catalyst performs stable CO reduction over 30 h. Mechanistic studies suggest that the use of copper nitride contributes to reducing the CO dimerization energy barrier-a rate-limiting step in CO reduction to multi-carbon products.
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http://dx.doi.org/10.1038/s41467-018-06311-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148248PMC
September 2018

Metabolic and lifestyle risk factors for acute pancreatitis in Chinese adults: A prospective cohort study of 0.5 million people.

PLoS Med 2018 08 1;15(8):e1002618. Epub 2018 Aug 1.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Background: Little prospective evidence exists about risk factors and prognosis of acute pancreatitis in China. We examined the associations of certain metabolic and lifestyle factors with risk of acute pancreatitis in Chinese adults.

Methods And Findings: The prospective China Kadoorie Biobank (CKB) recruited 512,891 adults aged 30 to 79 years from 5 urban and 5 rural areas between 25 June 2004 and 15 July 2008. During 9.2 years of follow-up (to 1 January 2015), 1,079 cases of acute pancreatitis were recorded. Cox regression was used to estimate adjusted hazard ratios (HRs) for acute pancreatitis associated with various metabolic and lifestyle factors among all or male (for smoking and alcohol drinking) participants. Overall, the mean waist circumference (WC) was 82.1 cm (SD 9.8) cm in men and 79.0 cm (SD 9.5) cm in women, 6% had diabetes, and 6% had gallbladder disease at baseline. WC was positively associated with risk of acute pancreatitis, with an adjusted HR of 1.35 (95% CI 1.27-1.43; p < 0.001) per 1-SD-higher WC. Individuals with diabetes or gallbladder disease had HRs of 1.34 (1.07-1.69; p = 0.01) and 2.42 (2.03-2.88; p < 0.001), respectively. Physical activity was inversely associated with risk of acute pancreatitis, with each 4 metabolic equivalent of task (MET) hours per day (MET-h/day) higher physical activity associated with an adjusted HR of 0.95 (0.91-0.99; p = 0.03). Compared with those without any metabolic risk factors (i.e., obesity, diabetes, gallbladder disease, and physical inactivity), the HRs of acute pancreatitis for those with 1, 2, or ≥3 risk factors were 1.61 (1.47-1.76), 2.36 (2.01-2.78), and 3.41 (2.46-4.72), respectively (p < 0.001). Among men, heavy alcohol drinkers (≥420 g/week) had an HR of 1.52 (1.11-2.09; p = 0.04, compared with abstainers), and current regular smokers had an HR of 1.45 (1.28-1.64; p = 0.02, compared with never smokers). Following a diagnosis of acute pancreatitis, there were higher risks of pancreatic cancer (HR = 8.26 [3.42-19.98]; p < 0.001; 13 pancreatic cancer cases) and death (1.53 [1.17-2.01]; p = 0.002; 89 deaths). Other diseases of the pancreas had similar risk factor profiles and prognosis to acute pancreatitis. The main study limitations are ascertainment of pancreatitis using hospital records and residual confounding.

Conclusions: In this relatively lean Chinese population, several modifiable metabolic and lifestyle factors were associated with higher risks of acute pancreatitis, and individuals with acute pancreatitis had higher risks of pancreatic cancer and death.
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http://dx.doi.org/10.1371/journal.pmed.1002618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070164PMC
August 2018

E-cigarettes in airports and on flights: Europe and the US.

Adicciones 2019 Jul 1;31(3):196-200. Epub 2019 Jul 1.

Agència de Salut Pública de Barcelona.

Background: While progress has been made to create smoke-free airports, sales of e-cigarettes at airports and airplanes and the presence of advertisements might detract from these smoke-free policies. The objective of this study is to describe the presence of policies, advertising, sales and use of e-cigarettes in airports and on flights in Europe and the US.

Methods: A cross-sectional study was conducted between March-May, 2014. The study included 21 large and mid-sized airports of Europe and the US as well as 19 flights. A standardised protocol was used to observe points of sales and advertisements and to collect information on the implementation of policies on e-cigarette use. In addition, a series of questions were developed to obtain policy details from airport personnel and flight attendants.

Results: Retail outlets selling e-cigarettes in airports were present in approximately 20% and 40% of the observed pre and post-security areas, respectively. In post-security, 27.8% of the airport staff reported that the use of e-cigarettes indoors was not allowed, 22.2% reported that they did not know, 27.8% reported that it was only allowed in the smoking room, and 22.2% reported that it was allowed anywhere. Smoking ban announcements were made on all flights. However, only 15.8% of the flights made a specific announcement regarding the ban of using e-cigarettes. Conclusions. In light of our results, it seems necessary to reinforce in-flight e-cigarette smoking ban announcements and to instruct airport employees about the existence of e-cigarette smoking policies. Furthermore, airports themselves should also be encouraged to adopt smoke-free policies.
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http://dx.doi.org/10.20882/adicciones.1001DOI Listing
July 2019

Diabetes, plasma glucose and incidence of colorectal cancer in Chinese adults: a prospective study of 0.5 million people.

J Epidemiol Community Health 2018 10 3;72(10):919-925. Epub 2018 Jul 3.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Diabetes is associated with higher risk of colorectal cancer (CRC). Uncertainty remains about the relevance of duration of diabetes and about the association of blood glucose with CRC risk among individuals without diabetes.

Methods: The prospective China Kadoorie Biobank recruited 512 713 participants in 2004-2008 from 10 diverse areas in China. After 10 years of follow-up, 3024 incident cases of CRC (1745 colon, 1716 rectal) were recorded among 510 136 participants without prior cancer at baseline. Cox regression was used to estimate adjusted HRs for CRC associated with diabetes (previously diagnosed or screen-detected) and, among those without previously diagnosed diabetes, with levels of random plasma glucose (RPG).

Results: Overall 5.8% of participants had diabetes at baseline. Individuals with diabetes had an adjusted HR of 1.18 (95% CI 1.04 to 1.33) for CRC, with similar risk for colon and rectal cancer (1.19 [1.01 to 1.39] vs 1.14 [0.96 to 1.35]). The HRs decreased with longer duration of diabetes ( for trend 0.03). Among those without previously diagnosed diabetes, RPG was positively associated with CRC, with adjusted HRs per 1 mmol/L higher baseline RPG of 1.04 (1.02 to 1.05) for CRC, again similar for colon and rectal cancer (1.03 [1.01to 1.05] and 1.04 [1.02 to 1.06], respectively). The associations of diabetes and RPG appeared stronger in men than in women, but the differences were non-significant ( for heterogeneity 0.3 and 0.2).

Discussion: Among Chinese adults, diabetes and higher blood glucose levels among those without known diabetes are associated with higher risk of CRC.
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http://dx.doi.org/10.1136/jech-2018-210651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161653PMC
October 2018

Adiposity and risks of colorectal and small intestine cancer in Chinese adults: a prospective study of 0.5 million people.

Br J Cancer 2018 07 6;119(2):248-250. Epub 2018 Jun 6.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Uncertainty remains about the associations of adiposity with intestinal cancer in China and by its anatomical subtype.

Methods: The prospective China Kadoorie Biobank recorded 3024 incident cases of colorectal (CRC) and 143 cases of small intestine (SIC) cancer during a 10-year follow-up among 509 568 participants without prior cancer at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for specific cancers associated with adiposity.

Results: Overall mean body mass index (BMI) was 23.7  kg/m. BMI was positively associated with CRC (HR per SD 1.10 [95% CI 1.06-1.14]), colon (1.13 [1.07-1.18]), and rectal (1.07 [1.02-1.13]) cancer. For waist circumference, the corresponding HRs per SD were 1.14 (1.10-1.18), 1.18 (1.13-1.24), and 1.11 (1.05-1.16), respectively. The adjusted HRs were somewhat greater in men than women. Adiposity was positively, but non-significantly, associated with SIC risk.

Conclusions: Among relatively lean Chinese adults, adiposity was associated with risks of colon and rectal cancer, with the associations somewhat stronger in men than women.
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http://dx.doi.org/10.1038/s41416-018-0124-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048138PMC
July 2018

CO electroreduction to ethylene via hydroxide-mediated copper catalysis at an abrupt interface.

Science 2018 05;360(6390):783-787

Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Road, Toronto, ON M5S 3G4, Canada.

Carbon dioxide (CO) electroreduction could provide a useful source of ethylene, but low conversion efficiency, low production rates, and low catalyst stability limit current systems. Here we report that a copper electrocatalyst at an abrupt reaction interface in an alkaline electrolyte reduces CO to ethylene with 70% faradaic efficiency at a potential of -0.55 volts versus a reversible hydrogen electrode (RHE). Hydroxide ions on or near the copper surface lower the CO reduction and carbon monoxide (CO)-CO coupling activation energy barriers; as a result, onset of ethylene evolution at -0.165 volts versus an RHE in 10 molar potassium hydroxide occurs almost simultaneously with CO production. Operational stability was enhanced via the introduction of a polymer-based gas diffusion layer that sandwiches the reaction interface between separate hydrophobic and conductive supports, providing constant ethylene selectivity for an initial 150 operating hours.
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http://dx.doi.org/10.1126/science.aas9100DOI Listing
May 2018

Diabetes, Plasma Glucose, and Incidence of Fatty Liver, Cirrhosis, and Liver Cancer: A Prospective Study of 0.5 Million People.

Hepatology 2018 10;68(4):1308-1318

Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

The prevalence of diabetes is increasing rapidly in China. However, evidence is limited about its effects on chronic liver diseases and liver cancer. We examined the associations of diabetes with chronic liver diseases and liver cancer and of random plasma glucose (RPG) with these liver diseases among participants without diabetes in Chinese adults and the possible interaction by hepatitis B virus (HBV) infection. The prospective China Kadoorie Biobank recruited 512,891 adults. During 10 years of follow-up, 2,568 liver cancer, 2,082 cirrhosis, 1,298 hospitalized nonalcoholic fatty liver disease (NAFLD), and 244 hospitalized alcoholic liver disease (ALD) cases were recorded among 503,993 participants without prior history of cancer or chronic liver diseases at baseline. Cox regression was used to estimate hazard ratios (HRs) for each disease by diabetes status (previously diagnosed or screen-detected) and, among those without previously diagnosed diabetes, by levels of RPG. Overall 5.8% of participants had diabetes at baseline. Compared to those without diabetes, individuals with diabetes had adjusted HRs of 1.49 (95% confidence interval 1.30-1.70) for liver cancer, 1.81 (1.57-2.09) for cirrhosis, 1.76 (1.47-2.16) for NAFLD, and 2.24 (1.42-3.54) for ALD. The excess risks decreased but remained elevated in those with longer duration. Among those without previously diagnosed diabetes, RPG was positively associated with liver diseases, with adjusted HRs per 1 mmol/L higher RPG of 1.04 (1.03-1.06) for liver cancer, 1.07 (1.05-1.09) for cirrhosis, 1.07 (1.05-1.10) for NAFLD, and 1.10 (1.05-1.15) for ALD. These associations did not differ by HBV infection.

Conclusion: In Chinese adults, diabetes and higher blood glucose levels among those without known diabetes are associated with higher risks of liver cancer and major chronic liver diseases.
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http://dx.doi.org/10.1002/hep.30083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220764PMC
October 2018

High-sensitivity cardiac troponin and natriuretic peptide with risk of lower-extremity peripheral artery disease: the Atherosclerosis Risk in Communities (ARIC) Study.

Eur Heart J 2018 07;39(25):2412-2419

Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, 1830 East Monument St., Baltimore, MD, USA.

Aims: Cardiac troponin T (cTnT) is suggested as a predictor of amputation in patients with peripheral artery disease (PAD). However, cTnT-PAD association has not been systematically studied in a large study. This study evaluated the association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also explored whether natriuretic peptide (NT-proBNP), another representative cardiac marker, predicts PAD risk.

Methods And Results: Among 12 288 middle-aged adults, the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss considered as critical limb ischaemia (CLI)]) were quantified with multivariable Cox regression models. The risk discrimination was assessed by c-statistic. During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases). In demographically adjusted models, the highest category of hs-cTnT (≥14 vs. <3 ng/L) and NT-proBNP (≥258.3 vs. <51.5 pg/mL) showed ∼8- and 10-20-fold higher risk of PAD and CLI, respectively. Even after adjusting for potential confounders and each other, hazard ratios were greater for CLI than for PAD (7.74 95% confidence interval [95% CI 4.43-13.55] vs. 2.84 [2.02-4.00] for the highest vs. reference hs-cTnT category and 4.63 [2.61-8.23] vs. 3.16 [2.23-4.49] for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI.

Conclusion: High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.
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http://dx.doi.org/10.1093/eurheartj/ehy106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031056PMC
July 2018

Fluorescence in sub-10 nm channels with an optical enhancement layer.

Lab Chip 2018 02;18(4):568-573

Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario M5S 3G8, Canada.

Fluorescence microscopy uniquely enables physical and biological research in micro- and nanofluidic systems. However, in channels with depths below 10 nm, the limited number of fluorophores results in fluorescence intensity below the detection limit of optical microscopes. To overcome this barrier, we applied Fabry-Pérot interference to enhance fluorescence intensity with a silicon nitride layer below the sub-10 nm channel. A silicon nitride layer of suitable thickness can selectively enhance both absorption and emission wavelengths, leading to a fluorescent signal that is enhanced 20-fold and readily imaged with traditional microscopes. To demonstrate this method, we studied the mass transport of a binary solution of ethanol and Rhodamin B in 8 nm nanochannels. The large molecular size of Rhodamin B (∼1.8 nm) relative to the channel depth results in both separation and reduced diffusivity, deviating from behavior at larger scales. This method extends the widely available suite of fluorescence analysis tools and infrastructure to unprecedented sub-10 nm scale with relevance to a wide variety of biomolecular interactions.
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http://dx.doi.org/10.1039/c7lc01193hDOI Listing
February 2018