Demonstration of two novel methods for predicting functional siRNA efficiency

BACKGROUND: siRNAs are small RNAs that serve as sequence determinants during the gene silencing process called RNA interference (RNAi). It is well know that siRNA efficiency is crucial in the RNAi pathway, and the siRNA efficiency for targeting different sites of a specific gene varies greatly. Therefore, there is high demand for reliable siRNAs prediction tools and for the design methods able to pick up high silencing potential siRNAs. RESULTS: In this paper, two systems have been established for the prediction of functional siRNAs: (1) a statistical model based on sequence information and (2) a machine learning model based on three features of siRNA sequences, namely binary description, thermodynamic profile and nucleotide composition. Both of the two methods show high performance on the two datasets we have constructed for training the model. CONCLUSION: Both of the two methods studied in this paper emphasize the importance of sequence information for the prediction of functional siRNAs. The way of denoting a bio-sequence by binary system in mathematical language might be helpful in other analysis work associated with fixed-length bio-sequence

Dietary quality among men and women in 187 countries in 1990 and 2010: a systematic assessment

Background Healthy dietary patterns are a global priority to reduce non-communicable diseases. Yet neither worldwide patterns of diets nor their trends with time are well established. We aimed to characterise global changes (or trends) in dietary patterns nationally and regionally and to assess heterogeneity by age, sex, national income, and type of dietary pattern. Methods In this systematic assessment, we evaluated global consumption of key dietary items (foods and nutrients) by region, nation, age, and sex in 1990 and 2010. Consumption data were evaluated from 325 surveys (71·7% nationally representative) covering 88·7% of the global adult population. Two types of dietary pattern were assessed: one refl ecting greater consumption of ten healthy dietary items and the other based on lesser consumption of seven unhealthy dietary items. The mean intakes of each dietary factor were divided into quintiles, and each quintile was assigned an ordinal score, with higher scores being equivalent to healthier diets (range 0–100). The dietary patterns were assessed by hierarchical linear regression including country, age, sex, national income, and time as exploratory variables. Findings From 1990 to 2010, diets based on healthy items improved globally (by 2·2 points, 95% uncertainty interval (UI) 0·9 to 3·5), whereas diets based on unhealthy items worsened (–2·5, –3·3 to –1·7). In 2010, the global mean scores were 44·0 (SD 10·5) for the healthy pattern and 52·1 (18·6) for the unhealthy pattern, with weak intercorrelation (r=–0·08) between countries. On average, better diets were seen in older adults compared with younger adults, and in women compared with men (p<0·0001 each). Compared with low-income nations, high-income nations had better diets based on healthy items (+2·5 points, 95% UI 0·3 to 4·1), but substantially poorer diets based on unhealthy items (–33·0, –37·8 to –28·3). Diets and their trends were very heterogeneous across the world regions. For example, both types of dietary patterns improved in high-income countries, but worsened in some low-income countries in Africa and Asia. Middle-income countries showed the largest improvement in dietary patterns based on healthy items, but the largest deterioration in dietary patterns based on unhealthy items. Interpretation Consumption of healthy items improved, while consumption of unhealthy items worsened across the world, with heterogeneity across regions and countries. These global data provide the best estimates to date of nutrition transitions across the world and inform policies and priorities for reducing the health and economic burdens of poor diet quality

Assessing global dietary habits: a comparison of national estimates from the FAO and the Global Dietary Database.

BACKGROUND: Accurate data on dietary habits are crucial for understanding impacts on disease and informing policy priorities. Nation-specific food balance sheets from the United Nations FAO provided the only available global dietary estimates but with uncertain validity. OBJECTIVES: We investigated how FAO estimates compared with nationally representative, individual-based dietary surveys from the Global Dietary Database (GDD) and developed calibration equations to improve the validity of FAO data to estimate dietary intakes. DESIGN: FAO estimates were matched to GDD data for 113 countries across the following 9 major dietary metrics for 30 y of data (1980-2009): fruit, vegetables, beans and legumes, nuts and seeds, whole grains, red and processed meats, fish and seafood, milk, and total energy. Both absolute and percentage differences in FAO and GDD mean estimates were evaluated. Linear regression was used to evaluate whether FAO estimates predicted GDD dietary intakes and whether this prediction varied according to age, sex, region, and time. Calibration equations were developed to adjust FAO estimates to approximate national dietary surveys validated by using randomly split data sets. RESULTS: For most food groups, FAO estimates substantially overestimated individual-based dietary intakes by 74.5% (vegetables) and 270% (whole grains) while underestimating beans and legumes (-50%) and nuts and seeds (-29%) (P < 0.05 for each). In multivariate regressions, these overestimations and underestimations for each dietary factor further varied by age, sex, region, and time (P < 0.001 for each). Split-data set calibration models, which accounted for country-level covariates and other sources of heterogeneity, effectively adjusted FAO estimates to approximate estimates from national survey data (r = 0.47-0.80) with small SEs of prediction (generally 1-5 g/d). CONCLUSIONS: For all food groups and total energy, FAO estimates substantially exceeded or underestimated individual-based national surveys of individual intakes with significant variation depending on age, sex, region, and time. Calibration models effectively adjusted the comprehensive, widely accessible FAO data to facilitate a more-accurate estimation of individual-level dietary intakes nationally and by age and sex.Supported by a grant from the Bill & Melinda Gates Foundation (Global Dietary Habits among Women, Price and Income Elasticities, and Validity of Food Balance Sheets; to LCDG, SH, RM, PS and DM) and the Medical Research Council Epidemiology Unit Core Support (MC_UU_12015/5; to FI).This is the final version of the article. It first appeared from the American Society for Nutrition via http://dx.doi.org/10.3945/​ajcn.114.08740

Global, regional and national consumption of major food groups in 1990 and 2010 : a systematic analysis including 266 country-specific nutrition surveys worldwide

Objective: To quantify global intakes of key foods related to non-communicable diseases in adults by region (n=21), country (n=187), age and sex, in 1990 and 2010. Design: We searched and obtained individual-level intake data in 16 age/sex groups worldwide from 266 surveys across 113 countries. We combined these data with food balance sheets available in all nations and years. A hierarchical Bayesian model estimated mean food intake and associated uncertainty for each age-sex-country-year stratum, accounting for differences in intakes versus availability, survey methods and representativeness, and sampling and modelling uncertainty. Setting/population: Global adult population, by age, sex, country and time. Results: In 2010, global fruit intake was 81.3 g/day (95% uncertainty interval 78.9–83.7), with country-specific intakes ranging from 19.2–325.1 g/day; in only 2 countries (representing 0.4% of the world's population), mean intakes met recommended targets of ≥300 g/day. Country-specific vegetable intake ranged from 34.6–493.1 g/day (global mean=208.8 g/day); corresponding values for nuts/seeds were 0.2–152.7 g/day (8.9 g/day); for whole grains, 1.3–334.3 g/day (38.4 g/day); for seafood, 6.0–87.6 g/day (27.9 g/day); for red meats, 3.0–124.2 g/day (41.8 g/day); and for processed meats, 2.5–66.1 g/day (13.7 g/day). Mean national intakes met recommended targets in countries representing 0.4% of the global population for vegetables (≥400 g/day); 9.6% for nuts/seeds (≥4 (28.35 g) servings/week); 7.6% for whole grains (≥2.5 (50 g) servings/day); 4.4% for seafood (≥3.5 (100 g) servings/week); 20.3% for red meats (≤1 (100 g) serving/week); and 38.5% for processed meats (≤1 (50 g) serving/week). Intakes of healthful foods were generally higher and of less healthful foods generally lower at older ages. Intakes were generally similar by sex. Vegetable, seafood and processed meat intakes were stable over time; fruits, nuts/seeds and red meat, increased; and whole grains, decreased. Conclusions: These global dietary data by nation, age and sex identify key challenges and opportunities for optimising diets, informing policies and priorities for improving global health.peer-reviewe

Mercury exposure and risk of cardiovascular disease in two U.S. cohorts

BACKGROUND: Exposure to methylmercury from fish consumption has been linked to a potentially increased risk of cardiovascular disease, but evidence from prior studies is equivocal. Beneficial effects of the ingestion of fish and selenium may also modify such effects. METHODS: Among subjects from two U.S. cohorts (a total of 51,529 men and 121,700 women) whose toenail clippings had been stored, we prospectively identified incident cases of cardiovascular disease (coronary heart disease and stroke) in 3427 participants and matched them to risk-set–sampled controls according to age, sex, race, and smoking status. Toenail mercury and selenium concentrations were assessed with the use of neutron-activation analysis. Other demographic characteristics, cardiovascular risk factors, fish consumption, and lifestyle habits were assessed by means of validated questionnaires. Associations between mercury exposure and incident cardiovascular disease were evaluated with the use of conditional logistic regression. RESULTS: Median toenail mercury concentrations were 0.23 µg per gram (interdecile range, 0.06 to 0.94) in the case participants and 0.25 µg per gram (interdecile range, 0.07 to 0.97) in the controls. In multivariate analyses, participants with higher mercury exposures did not have a higher risk of cardiovascular disease. For comparisons of the fifth quintile of mercury exposure with the first quintile, the relative risks were as follows: coronary heart disease, 0.85 (95% confidence interval [CI], 0.69 to 1.04; P = 0.10 for trend); stroke, 0.84 (95% CI, 0.62 to 1.14; P = 0.27 for trend); and total cardiovascular disease, 0.85 (95% CI, 0.72 to 1.01; P = 0.06 for trend). Findings were similar in analyses of participants with low selenium concentrations or low overall fish consumption and in several additional sensitivity analyses. CONCLUSIONS: We found no evidence of any clinically relevant adverse effects of mercury exposure on coronary heart disease, stroke, or total cardiovascular disease in U.S. adults at the exposure levels seen in this study. (Funded by the National Institutes of Health.

Global, regional, and national consumption levels of dietary fats and oils in 1990 and 2010: a systematic analysis including 266 country-specific nutrition surveys

Objectives: To quantify global consumption of key dietary fats and oils by country, age, and sex in 1990 and 2010. Design: Data were identified, obtained, and assessed among adults in 16 age- and sex-specific groups from dietary surveys worldwide on saturated, omega 6, seafood omega 3, plant omega 3, and trans fats, and dietary cholesterol. We included 266 surveys in adults (83% nationally representative) comprising 1 630 069 unique individuals, representing 113 of 187 countries and 82% of the global population. A multilevel hierarchical Bayesian model accounted for differences in national and regional levels of missing data, measurement incomparability, study representativeness, and sampling and modelling uncertainty. Setting and population Global adult population, by age, sex, country, and time. Results: In 2010, global saturated fat consumption was 9.4%E (95%UI=9.2 to 9.5); country-specific intakes varied dramatically from 2.3 to 27.5%E; in 75 of 187 countries representing 61.8% of the world’s adult population, the mean intake was <10%E. Country-specific omega 6 consumption ranged from 1.2 to 12.5%E (global mean=5.9%E); corresponding range was 0.2 to 6.5%E (1.4%E) for trans fat; 97 to 440 mg/day (228 mg/day) for dietary cholesterol; 5 to 3,886 mg/day (163 mg/day) for seafood omega 3; and <100 to 5,542 mg/day (1,371 mg/day) for plant omega 3. Countries representing 52.4% of the global population had national mean intakes for omega 6 fat ≥5%E; corresponding proportions meeting optimal intakes were 0.6% for trans fat (≤0.5%E); 87.6% for dietary cholesterol (<300 mg/day); 18.9% for seafood omega 3 fat (≥250 mg/day); and 43.9% for plant omega 3 fat (≥1,100 mg/day). Trans fat intakes were generally higher at younger ages; and dietary cholesterol and seafood omega 3 fats generally higher at older ages. Intakes were similar by sex. Between 1990 and 2010, global saturated fat, dietary cholesterol, and trans fat intakes remained stable, while omega 6, seafood omega 3, and plant omega 3 fat intakes each increased. Conclusions: These novel global data on dietary fats and oils identify dramatic diversity across nations and inform policies and priorities for improving global health

Dietary quality among men and women in 187 countries in 1990 and 2010: a systematic assessment.

BACKGROUND: Healthy dietary patterns are a global priority to reduce non-communicable diseases. Yet neither worldwide patterns of diets nor their trends with time are well established. We aimed to characterise global changes (or trends) in dietary patterns nationally and regionally and to assess heterogeneity by age, sex, national income, and type of dietary pattern. METHODS: In this systematic assessment, we evaluated global consumption of key dietary items (foods and nutrients) by region, nation, age, and sex in 1990 and 2010. Consumption data were evaluated from 325 surveys (71·7% nationally representative) covering 88·7% of the global adult population. Two types of dietary pattern were assessed: one reflecting greater consumption of ten healthy dietary items and the other based on lesser consumption of seven unhealthy dietary items. The mean intakes of each dietary factor were divided into quintiles, and each quintile was assigned an ordinal score, with higher scores being equivalent to healthier diets (range 0-100). The dietary patterns were assessed by hierarchical linear regression including country, age, sex, national income, and time as exploratory variables. FINDINGS: From 1990 to 2010, diets based on healthy items improved globally (by 2·2 points, 95% uncertainty interval (UI) 0·9 to 3·5), whereas diets based on unhealthy items worsened (-2·5, -3·3 to -1·7). In 2010, the global mean scores were 44·0 (SD 10·5) for the healthy pattern and 52·1 (18·6) for the unhealthy pattern, with weak intercorrelation (r=-0·08) between countries. On average, better diets were seen in older adults compared with younger adults, and in women compared with men (p<0·0001 each). Compared with low-income nations, high-income nations had better diets based on healthy items (+2·5 points, 95% UI 0·3 to 4·1), but substantially poorer diets based on unhealthy items (-33·0, -37·8 to -28·3). Diets and their trends were very heterogeneous across the world regions. For example, both types of dietary patterns improved in high-income countries, but worsened in some low-income countries in Africa and Asia. Middle-income countries showed the largest improvement in dietary patterns based on healthy items, but the largest deterioration in dietary patterns based on unhealthy items. INTERPRETATION: Consumption of healthy items improved, while consumption of unhealthy items worsened across the world, with heterogeneity across regions and countries. These global data provide the best estimates to date of nutrition transitions across the world and inform policies and priorities for reducing the health and economic burdens of poor diet quality. FUNDING: The Bill & Melinda Gates Foundation and Medical Research Council.The study was sponsored by The Bill & Melinda Gates Foundation, and and FI was supported by Medical Research Council Unit Programme number MC_UU_125015/5.This paper was originally published in Lancet Global Health (Imamura F, Micha R, Khatibzadeh S, Fahimi S, Shi P, Powles J, Mozaffarian D, Lancet Global Health 2015, 3 e132–142, doi:10.1016/S2214-109X(14)70381-X)

Mastering Complex Control in MOBA Games with Deep Reinforcement Learning

We study the reinforcement learning problem of complex action control in the Multi-player Online Battle Arena (MOBA) 1v1 games. This problem involves far more complicated state and action spaces than those of traditional 1v1 games, such as Go and Atari series, which makes it very difficult to search any policies with human-level performance. In this paper, we present a deep reinforcement learning framework to tackle this problem from the perspectives of both system and algorithm. Our system is of low coupling and high scalability, which enables efficient explorations at large scale. Our algorithm includes several novel strategies, including control dependency decoupling, action mask, target attention, and dual-clip PPO, with which our proposed actor-critic network can be effectively trained in our system. Tested on the MOBA game Honor of Kings, our AI agent, called Tencent Solo, can defeat top professional human players in full 1v1 games.Comment: AAAI 202