Understanding dietary patterns is vital to reducing the number of people experiencing hunger (about 795 million), micronutrient deficiencies (2 billion), and overweight or obesity (2.1 billion). We ...characterize global trends in dietary quality by estimating micronutrient density of the food supply, prevalence of inadequate intake of 14 micronutrients, and average prevalence of inadequate intake of these micronutrients for all countries between 1961 and 2011. Over this 50-year period, the estimated prevalence of inadequate intakes of micronutrients has declined in all regions due to increased total production of food and/or micronutrient density. This decline has been particularly strong in East and Southeast Asia and weaker in South Asia and sub-Saharan Africa. Sub-Saharan Africa is the only region where dietary micronutrient density has declined over this 50-year period. At the global level, micronutrients with the lowest levels of adequate estimated intake are calcium, iron, vitamin A, and zinc, but there are strong differences between countries and regions. Fortification has reduced the estimated prevalence of inadequate micronutrient intakes in all low-income regions, except South Asia. The food supply in many countries is still far below energy requirements, which suggests a need to increase the availability and accessibility of nutritious foods. Countries where the food energy supply is adequate show a very large variation in dietary quality, and in many of these countries people would benefit from more diverse diets with a greater proportion of micronutrient-dense foods. Dietary quality can be improved through fortification, biofortification, and agricultural diversification, as well as efforts to improve access to and use of micronutrient-dense foods and nutritional knowledge. Reducing poverty and increasing education, especially of women, are integral to sustainably addressing malnutrition.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Among men with nonmetastatic prostate cancer who had a rapid PSA doubling time and were receiving androgen-deprivation therapy, the median metastasis-free survival was 40.5 months with apalutamide ...versus 16.2 months with placebo. Rash occurred in 24% of men receiving apalutamide.
Standard therapy for metastatic, hormone-sensitive prostate cancer is androgen-deprivation therapy, usually with docetaxel. A large, multinational, phase 3 trial assessed the addition of the ...androgen-receptor blocker darolutamide to standard therapy. At 4 years, survival was higher with darolutamide than with placebo (62.7% vs. 50.4%), with no major differences in the frequency of adverse events.
Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to ...evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories. Analyses of 519 autism spectrum disorder families did not identify association with any categories after correction for 4,123 effective tests. Without appropriate correction, biologically plausible associations are observed in both cases and controls. Despite excluding previously identified gene-disrupting mutations, coding regions still exhibited the strongest associations. Thus, in autism, the contribution of de novo noncoding variation is probably modest in comparison to that of de novo coding variants. Robust results from future WGS studies will require large cohorts and comprehensive analytical strategies that consider the substantial multiple-testing burden.
Quantifying changes in Earth’s ice sheets and identifying the climate drivers are central to improving sea level projections. We provide unified estimates of grounded and floating ice mass change ...from 2003 to 2019 using NASA’s Ice, Cloud and land Elevation Satellite (ICESat) and ICESat-2 satellite laser altimetry. Our data reveal patterns likely linked to competing climate processes: Ice loss from coastal Greenland (increased surface melt), Antarctic ice shelves (increased ocean melting), and Greenland and Antarctic outlet glaciers (dynamic response to ocean melting) was partially compensated by mass gains over ice sheet interiors (increased snow accumulation). Losses outpaced gains, with grounded-ice loss from Greenland (200 billion tonnes per year) and Antarctica (118 billion tonnes per year) contributing 14 millimeters to sea level. Mass lost from West Antarctica’s ice shelves accounted for more than 30% of that region’s total.
Glycans have essential roles in biology and the etiology of many diseases. A major hurdle in studying glycans through functional glycomics is the lack of methods to release glycans from diverse types ...of biological samples. Here we describe an oxidative strategy using household bleach to release all types of free reducing N-glycans and O-glycan-acids from glycoproteins, and glycan nitriles from glycosphingolipids. Released glycans are directly useful in glycomic analyses and can be derivatized fluorescently for functional glycomics. This chemical method overcomes the limitations in glycan generation and promotes archiving and characterization of human and animal glycomes and their functions.
The kinetics of hydride transfer from Re(Rbpy)(CO)3H (bpy = 4,4′-R-2,2′-bipyridine; R = OMe, tBu, Me, H, Br, COOMe, CF3) to CO2 and seven different cationic N-heterocycles were determined. ...Additionally, the thermodynamic hydricities of complexes of the type Re(Rbpy)(CO)3H were established primarily using computational methods. Linear free-energy relationships (LFERs) derived by correlating thermodynamic and kinetic hydricities indicate that, in general, the rate of hydride transfer increases as the thermodynamic driving force for the reaction increases. Kinetic isotope effects range from inverse for hydride transfer reactions with a small driving force to normal for reactions with a large driving force. Hammett analysis indicates that hydride transfer reactions with greater thermodynamic driving force are less sensitive to changes in the electronic properties of the metal hydride, presumably because there is less buildup of charge in the increasingly early transition state. Bronsted α values were obtained for a range of hydride transfer reactions and along with DFT calculations suggest the reactions are concerted, which enables the use of Marcus theory to analyze hydride transfer reactions involving transition metal hydrides. It is notable, however, that even slight perturbations in the steric properties of the Re hydride or the hydride acceptor result in large deviations in the predicted rate of hydride transfer based on thermodynamic driving forces. This indicates that thermodynamic considerations alone cannot be used to predict the rate of hydride transfer, which has implications for catalyst design.
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IJS, KILJ, NUK, PNG, UL, UM
Summary Background Anthropogenic declines of animal pollinators and the associated effects on human nutrition are of growing concern. We quantified the nutritional and health outcomes associated with ...decreased intake of pollinator-dependent foods for populations around the world. Methods We assembled a database of supplies of 224 types of food in 156 countries. We quantified nutrient composition and pollinator dependence of foods to estimate the size of possible reductions in micronutrient and food intakes for different national populations, while keeping calorie intake constant with replacement by staple foods. We estimated pollinator-decline-dependent changes in micronutrient-deficient populations using population-weighted estimated average requirements and the cutpoint method. We estimated disease burdens of non-communicable, communicable, and malnutrition-related diseases with the Global Burden of Disease 2010 comparative risk assessment framework. Findings Assuming complete removal of pollinators, 71 million (95% uncertainty interval 41–262) people in low-income countries could become newly deficient in vitamin A, and an additional 2·2 billion (1·2–2·5) already consuming below the average requirement would have further declines in vitamin A supplies. Corresponding estimates for folate were 173 million (134–225) and 1·23 billion (1·12–1·33). A 100% decline in pollinator services could reduce global fruit supplies by 22·9% (19·5–26·1), vegetables by 16·3% (15·1–17·7), and nuts and seeds by 22·1% (17·7–26·4), with significant heterogeneity by country. In sum, these dietary changes could increase global deaths yearly from non-communicable and malnutrition-related diseases by 1·42 million (1·38–1·48) and disability-adjusted life-years (DALYs) by 27·0 million (25·8–29·1), an increase of 2·7% for deaths and 1·1% for DALYs. A 50% loss of pollination services would be associated with 700 000 additional annual deaths and 13·2 million DALYs. Interpretation Declines in animal pollinators could cause significant global health burdens from both non-communicable diseases and micronutrient deficiencies. Funding Winslow Foundation , Bill & Melinda Gates Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma ...protein levels. Here we estimated the effects of 1,002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130 (31.5%) were not supported by results of colocalization analyses, suggesting that genetic confounding due to linkage disequilibrium is widespread in naïve phenome-wide association studies of proteins. Combining MR and colocalization evidence in cis-only analyses, we identified 111 putatively causal effects between 65 proteins and 52 disease-related phenotypes ( https://www.epigraphdb.org/pqtl/ ). Evaluation of data from historic drug development programs showed that target-indication pairs with MR and colocalization support were more likely to be approved, evidencing the value of this approach in identifying and prioritizing potential therapeutic targets.
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