Predicting anticancer hyperfoods with graph convolutional networks.

BACKGROUND: Recent efforts in the field of nutritional science have allowed the discovery of disease-beating molecules within foods based on the commonality of bioactive food molecules to FDA-approved drugs. The pioneering work in this field used an unsupervised network propagation algorithm to learn the systemic-wide effect on the human interactome of 1962 FDA-approved drugs and a supervised algorithm to predict anticancer therapeutics using the learned representations. Then, a set of bioactive molecules within foods was fed into the model, which predicted molecules with cancer-beating potential.The employed methodology consisted of disjoint unsupervised feature generation and classification tasks, which can result in sub-optimal learned drug representations with respect to the classification task. Additionally, due to the disjoint nature of the tasks, the employed approach proved cumbersome to optimize, requiring testing of thousands of hyperparameter combinations and significant computational resources.To overcome the technical limitations highlighted above, we represent each drug as a graph (human interactome) with its targets as binary node features on the graph and formulate the problem as a graph classification task. To solve this task, inspired by the success of graph neural networks in graph classification problems, we use an end-to-end graph neural network model operating directly on the graphs, which learns drug representations to optimize model performance in the prediction of anticancer therapeutics. RESULTS: The proposed model outperforms the baseline approach in the anticancer therapeutic prediction task, achieving an F1 score of 67.99%±2.52% and an AUPR of 73.91%±3.49%. It is also shown that the model is able to capture knowledge of biological pathways to predict anticancer molecules based on the molecules' effects on cancer-related pathways. CONCLUSIONS: We introduce an end-to-end graph convolutional model to predict cancer-beating molecules within food. The introduced model outperforms the existing baseline approach, and shows interpretability, paving the way to the future of a personalized nutritional science approach allowing the development of nutrition strategies for cancer prevention and/or therapeutics.

High-throughput LC-MS method to investigate postprandial lipemia: considerations for future precision nutrition research.

Elevated postprandial lipemia is an independent risk factor for cardiovascular disease, yet methods to quantitate postmeal handling of dietary lipids in humans are limited. This study tested a new method to track dietary lipid appearance using a stable isotope tracer (2H11-oleate) in liquid meals containing three levels of fat [low fat (LF), 15 g; moderate fat (MF), 30 g; high fat (HF), 60 g]. Meals were fed to 12 healthy men [means ± SD, age 31.3 ± 9.2 yr, body mass index (BMI) 24.5 ± 1.9 kg/m2] during four randomized study visits; the HF meal was administered twice for reproducibility. Blood was collected over 8 h postprandially, triglyceride (TG)-rich lipoproteins (TRL), and particles with a Svedberg flotation rate >400 (Sf > 400, n = 8) were isolated by ultracentrifugation, and labeling of two TG species (54:3 and 52:2) was quantified by LC-MS. Total plasma TRL-TG concentrations were threefold greater than Sf > 400-TG. Both Sf > 400- and TRL-TG 54:3 were present at higher concentrations than 52:2, and singly labeled TG concentrations were higher than doubly labeled. Furthermore, TG 54:3 and the singly labeled molecules demonstrated higher plasma absolute entry rates differing significantly across fat levels within a single TG species (P < 0.01). Calculation of fractional entry showed no significant differences in label handling supporting the utility of either TG species for appearance rate calculations. These data demonstrate the utility of labeling research meals with stable isotopes to investigate human postprandial lipemia while simultaneously highlighting the importance of examining individual responses. Meal type and timing, control of prestudy activities, and effects of sex on outcomes should match the research goals. The method, optimized here, will be beneficial to conduct basic science research in precision nutrition and clinical drug development.NEW & NOTEWORTHY A novel method to test human intestinal lipid handling using stable isotope labeling is presented and, for the first time, plasma appearance and lipid turnover were quantified in 12 healthy men following meals with varying amounts of fat. The method can be applied to studies in precision nutrition characterizing individual response to support basic science research or drug development. This report discusses key questions for consideration in precision nutrition that were highlighted by the data.

Errors in the implementation, analysis, and reporting of randomization within obesity and nutrition research: a guide to their avoidance.

Randomization is an important tool used to establish causal inferences in studies designed to further our understanding of questions related to obesity and nutrition. To take advantage of the inferences afforded by randomization, scientific standards must be upheld during the planning, execution, analysis, and reporting of such studies. We discuss ten errors in randomized experiments from real-world examples from the literature and outline best practices for their avoidance. These ten errors include: representing nonrandom allocation as random, failing to adequately conceal allocation, not accounting for changing allocation ratios, replacing subjects in nonrandom ways, failing to account for non-independence, drawing inferences by comparing statistical significance from within-group comparisons instead of between-groups, pooling data and breaking the randomized design, failing to account for missing data, failing to report sufficient information to understand study methods, and failing to frame the causal question as testing the randomized assignment per se. We hope that these examples will aid researchers, reviewers, journal editors, and other readers to endeavor to a high standard of scientific rigor in randomized experiments within obesity and nutrition research.

News from NHLBI: Nutrition Research at the National Heart, Lung, and Blood Institute and Future Opportunities.

BACKGROUND: Nutrition plays a major role in the prevention and treatment of cardiovascular and other chronic diseases; hence, nutrition research is a priority for the National Heart, Lung, and Blood Institute (NHLBI). The purpose of this analysis is to describe the scope of NHLBI-funded extramural nutrition research grants over the past decade and offer insights into future opportunities for nutrition research relevant to NHLBI's mission. METHODS: Data were extracted using the Research, Condition, and Disease Categorization spending categories from the publicly available NIH Research Portfolio Online Reporting Tool Expenditures and Results. New 2018 and 2019 grants were coded into categories and mapped to the 2016 NHLBI Strategic Vision priorities. RESULTS: Approximately 90% of nutrition research funds supported extramural grants, particularly through investigator-initiated R series grants (69.6%). Of these, 19.8% were classified as clinical trials. Consistent nutrition-related topics, including physical activity, weight loss, fatty acids, metabolic syndrome, childhood obesity, and other topics such as gut microbiota, arterial stiffness, sleep duration, and meal timing, emerged in 2014-2019.  Mapping of the NHLBI Strategic Vision objectives revealed that 32% of newly funded grants focused on pathobiological mechanisms important to the onset and progression of heart, lung, blood, and sleep disorders, with opportunities including developing novel diagnostic and therapeutic strategies and clinical and implementation science research. DISCUSSION: The findings show the breadth of NHLBI-funded nutrition research and highlight potential research opportunities for nutrition scientists.

Toward the Definition of Personalized Nutrition: A Proposal by The American Nutrition Association.

Personalized nutrition holds tremendous potential to improve human health. Despite exponential growth, the field has yet to be clearly delineated and a consensus definition of the term "personalized nutrition" (PN) has not been developed. Defining and delineating the field will foster standardization and scalability in research, data, training, products, services, and clinical practice; and assist in driving favorable policy. Building on the seminal work of pioneering thought leaders across disciplines, we propose that personalized nutrition be defined as: a field that leverages human individuality to drive nutrition strategies that prevent, manage, and treat disease and optimize health, and be delineated by three synergistic elements: PN science and data, PN professional education and training, and PN guidance and therapeutics. Herein we describe the application of PN in these areas and discuss challenges and solutions that the field faces as it evolves. This and future work will contribute to the continued refinement and growth of the field of PN.Teaching pointsPN approaches can be most effective when there is consensus regarding its definition and applications.PN can be delineated into three main areas of application: PN science and data, PN education and training, PN guidance and therapeutics.PN science and data foster understanding about the impact of genetic, phenotypic, biochemical and nutritional inputs on an individual's health.PN education and training equip a variety of healthcare professionals to apply PN strategies in many healthcare settings.PN professionals have greater ability to tailor interventions via PN guidance and therapeutics.Favorable policy allows PN to be more fully integrated into the healthcare system.

Is nutrition science ready for the twenty-first century? Moving towards transdisciplinary impacts in a changing world.

Malnutrition in an obese world was the fitting title of the 13th Federation of European Nutrition Societies (FENS) conference held in October 2019. Many individuals do not eat a healthy, well-balanced diet, and this is now understood to be a major driver of increased disease risk and illness. Moreover, both our current eating patterns and the food system as a whole are environmentally unsustainable, threatening the planetary systems we depend on for survival. As we attempt to feed a growing global population, food systems will increasingly be confronted with their environmental impacts, with the added challenge of climate change-induced threats to food production. As we move into the third decade of the twenty-first century, these challenges demand that the nutrition research community reconsider its scope, concepts, methods, and societal role. At a pre-meeting workshop held at the FENS conference, over 70 researchers active in the field explored ways to advance the discipline's capacity to address cross-cutting issues of personal, public and planetary health. Using the world cafe method, four themed discussion tables explored (a) the breadth of scientific domains needed to meet the current challenges, (b) the nature and definition of the shifting concepts in nutrition sciences, (c) the next-generation methods required and (d) communication and organisational challenges and opportunities. As a follow-up to earlier work [1], here we report the highlights of the discussions, and propose the next steps to advance responsible research and innovation in the domain of nutritional science.

[Anthroponutriciology: the development of the ideas of the founders of a new scientific direction].

The most outstanding Russian anatomists and anthropologists D.A. Zhdanov and B.A. Nikityuk and the leading nutritionist A.A. Pokrovsky were the founders of the Anthroponutritiology, which arose at the junction of Anthropological Anatomy and Nutrition Science and represented a new stage in the integration of these two sciences. Both Sciences, enriching each other with facts, existing methodology and established traditions, implementing modern innovative approaches, bring the physical and nutritional status of individuals closer to the standard (the "gold standard"). One of the applied tasks of Anthroponutritiology is the identification of the constitutional dependence of morphophysiological characters and determination of anthropological and clinical associations. Solving problems of Anthroponutritiology is a primary public concern, the most crucial state task. This issue is under the mandate of Federal Research Centre of Nutrition and Biotechnology and biotechnology, which implements this new branch of Science.

Translational and Implementation Research to Bridge Evidence and Implementation.

BACKGROUND: The role of science in guiding interventions and programs and contributing to progress in achieving global targets is undeniable. In public health nutrition, biological research in the past century focused largely on single nutrients and provided the basis for addressing nutritional deficiencies. This focus has now expanded to consider evidence including, but not limited, to knowledge about food, diet, behavior, context, and culture. The complex double burden of malnutrition will need to be addressed through a wider lens that appreciates the multiple and interrelated facets that underpin it. SUMMARY: Despite the acknowledged importance of translational research in improving nutritional outcomes, significant gaps remain in the process leading from science to practice. This article sheds light on 2 examples that demonstrate this, namely, anemia and stunting. Further, much work is still required to translate the current evidence base into effective actions that result in impact at scale, pointing toward the need for more implementation research in nutrition. Key Messages: While discoveries may take time to surface and implementers are impatient to address the challenge at hand, it is essential to identify and deploy the best available evidence while continuously advancing the evidence base, and to seek the right balance between action and inaction.

21st century toolkit for optimizing population health through precision nutrition.

Scientific, technological, and economic progress over the last 100 years all but eradicated problems of widespread food shortage and nutrient deficiency in developed nations. But now society is faced with a new set of nutrition problems related to energy imbalance and metabolic disease, which require new kinds of solutions. Recent developments in the area of new analytical tools enable us to systematically study large quantities of detailed and multidimensional metabolic and health data, providing the opportunity to address current nutrition problems through an approach called Precision Nutrition. This approach integrates different kinds of "big data" to expand our understanding of the complexity and diversity of human metabolism in response to diet. With these tools, we can more fully elucidate each individual's unique phenotype, or the current state of health, as determined by the interactions among biology, environment, and behavior. The tools of precision nutrition include genomics, metabolomics, microbiomics, phenotyping, high-throughput analytical chemistry techniques, longitudinal tracking with body sensors, informatics, data science, and sophisticated educational and behavioral interventions. These tools are enabling the development of more personalized and predictive dietary guidance and interventions that have the potential to transform how the public makes food choices and greatly improve population health.

The 3Rs in research: a contemporary approach to replacement, reduction and refinement.

First promulgated in 1959, the 3Rs of Replacement, Reduction and Refinement have evolved as fundamental principles underlying the use of animals and alternatives in science throughout the modern world. This review describes a contemporary approach to delivering the 3Rs through acknowledging the contribution of new technologies and emphasising that applying the 3Rs can be beneficial to good science as well as to animal welfare. This science-led approach moves the concept of the 3Rs out of an ethical silo where they were often considered by scientists to be an inconvenient obligation. On the contrary, relevant examples demonstrate the opportunity to practise better science using 3Rs technologies which deliver faster, more reproducible and more cost-effective results. Indeed, methods harnessing Replacement approaches may permit discoveries which are simply not feasible using animals and frequently are more flexible and agile since compliance with regulatory oversight requirements is simplified. Although the necessity for rigorous oversight is well recognised, it is important that the associated bureaucracy is not allowed to become prohibitive, causing scientists to avoid pursuing justifiable and important research involving animals. Public support for research is conditional - animals should not suffer unnecessarily and sufficient potential benefit should accrue from the research. However, society also actively seeks pioneering medical and scientific advances which can only be achieved through research. Therefore, a balance must be struck between safeguarding animal welfare whilst enabling high-quality science. It is this balance which promotes and sustains public confidence that animal based research is acceptable and being appropriately managed.

National Institute of Nutrition: 100 years of empowering the nation through nutrition.

The National Institute of Nutrition (NIN) has reached a remarkable milestone of completing 100 years of exemplary service to the nation. The long journey that started in a humble one-room laboratory at Coonoor (now in Tamil Nadu) in 1918 to a colossus of the nutrition research in the country today is dotted with several interesting vignettes. The NIN has always been at the forefront of need-based, pragmatic research. Its large-scale community-based interventions have been of great practical value in the nation's fight against malnutrition. The evolution of nutrition as a modern science almost coincides with the growth of the Institute. Being the oldest in the fraternity of institutes under the Indian Council of Medical Research (ICMR), the NIN has grown from strength to strength due to the sheer relevance of its contributions in furthering nutrition science and promoting public health in the country. This article provides a historical overview of the evolution and contributions of ICMR-NIN in the areas of nutrition, food safety, public health and policy.

Why Food System Transformation Is Essential and How Nutrition Scientists Can Contribute.

BACKGROUND: The International Union of Nutritional Sciences held its 21st International Congress of Nutrition in October 2017 in Buenos Aires, Argentina under the theme - From Sciences to Nutrition Security. In addition to multiple sessions on food systems and their links to diet, nutrition and health, the Congress closing lecture focused on the need to transform food systems so as to increase their capacity to provide healthy diets, making a call for greater involvement of nutrition scientists. SUMMARY: This article presents the main messages of that lecture, providing (i) an overview of global nutrition trends and their links to diets, food environments and food systems, (ii) a synopsis of the current global momentum for food system transformation and (iii) the need for nutrition scientists to leverage this momentum in terms of increased evidence generation and policy advocacy. Key Messages: Poor quality diets are increasingly leading to the compromising of human health as never before; the prevalence of undernutrition persists and remains acute in vulnerable regions, and hunger is increasing concomitantly with an unprecedented rise in overweight, obesity and nutrition-related non-communicable diseases. Increasing access to healthy diets through faster, stronger implementation of supply and demand-side strategies that address the underlying drivers of today's faulty food systems is imperative to solve these problems, as well as to address related environmental and economic costs. The global momentum for such action is increasing, but the evidence base needed to galvanize governments and hold stakeholders accountable remains yet a fledgling. To date, inputs from nutrition scientists to this reform agenda have been weak, especially given the unique contributions the field can make in terms of rigorous analysis and technical advice. Strengthened participation will require innovations in metrics and methodologies, combined with new thinking on what constitutes viable evidence and a greater willingness to engage with private sector agri-food actors.

Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review.

Suboptimal nutrition is a leading cause of poor health. Nutrition and policy science have advanced rapidly, creating confusion yet also providing powerful opportunities to reduce the adverse health and economic impacts of poor diets. This review considers the history, new evidence, controversies, and corresponding lessons for modern dietary and policy priorities for cardiovascular diseases, obesity, and diabetes mellitus. Major identified themes include the importance of evaluating the full diversity of diet-related risk pathways, not only blood lipids or obesity; focusing on foods and overall diet patterns, rather than single isolated nutrients; recognizing the complex influences of different foods on long-term weight regulation, rather than simply counting calories; and characterizing and implementing evidence-based strategies, including policy approaches, for lifestyle change. Evidence-informed dietary priorities include increased fruits, nonstarchy vegetables, nuts, legumes, fish, vegetable oils, yogurt, and minimally processed whole grains; and fewer red meats, processed (eg, sodium-preserved) meats, and foods rich in refined grains, starch, added sugars, salt, and trans fat. More investigation is needed on the cardiometabolic effects of phenolics, dairy fat, probiotics, fermentation, coffee, tea, cocoa, eggs, specific vegetable and tropical oils, vitamin D, individual fatty acids, and diet-microbiome interactions. Little evidence to date supports the cardiometabolic relevance of other popular priorities: eg, local, organic, grass-fed, farmed/wild, or non-genetically modified. Evidence-based personalized nutrition appears to depend more on nongenetic characteristics (eg, physical activity, abdominal adiposity, gender, socioeconomic status, culture) than genetic factors. Food choices must be strongly supported by clinical behavior change efforts, health systems reforms, novel technologies, and robust policy strategies targeting economic incentives, schools and workplaces, neighborhood environments, and the food system. Scientific advances provide crucial new insights on optimal targets and best practices to reduce the burdens of diet-related cardiometabolic diseases.

Diet, Nutrition, and Cancer Epigenetics.

The search for a connection between diet and human cancer has a long history in cancer research, as has interest in the mechanisms by which dietary factors might increase or decrease cancer risk. The realization that altering diet can alter the epigenetic state of genes and that these epigenetic alterations might increase or decrease cancer risk is a more modern notion, driven largely by studies in animal models. The connections between diet and epigenetic alterations, on the one hand, and between epigenetic alterations and cancer, on the other, are supported by both observational studies in humans as well as animal models. However, the conclusion that diet is linked directly to epigenetic alterations and that these epigenetic alterations directly increase or decrease the risk of human cancer is much less certain. We suggest that true and measurable effects of diet or dietary supplements on epigenotype and cancer risk are most likely to be observed in longitudinal studies and at the extremes of the intersection of dietary risk factors and human population variability. Careful analysis of such outlier populations is most likely to shed light on the molecular mechanisms by which suspected environmental risk factors drive the process of carcinogenesis.

Nutritional Ecology and Human Health.

In contrast to the spectacular advances in the first half of the twentieth century with micronutrient-related diseases, human nutrition science has failed to stem the more recent rise of obesity and associated cardiometabolic disease (OACD). This failure has triggered debate on the problems and limitations of the field and what change is needed to address these. We briefly review the two broad historical phases of human nutrition science and then provide an overview of the main problems that have been implicated in the poor progress of the field with solving OACD. We next introduce the field of nutritional ecology and show how its ecological-evolutionary foundations can enrich human nutrition science by providing the theory to help address its limitations. We end by introducing a modeling approach from nutritional ecology, termed nutritional geometry, and demonstrate how it can help to implement ecological and evolutionary theory in human nutrition to provide new direction and to better understand and manage OACD.

Driving Along the Zinc Road.

After having written hundreds of research articles, reviews, and book chapters, I find it awkward to pen an autobiography. I still do use a pen. As stated by others in the nutrition field who have written of their own experiences in a perspective article for the Annual Review of Nutrition, my course through this field of science has been serendipitous. My interest in nutrition developed during my experiences with horses and then Angus cattle and entry into an animal science degree program. As the age of molecular biology was unfolding, I pursued a PhD in nutritional biochemistry with Hamilton Eaton at the University of Connecticut followed by postdoctoral work with Hector DeLuca at the University of Wisconsin, working on vitamins A and D, respectively. At Rutgers University, one of the two institutions where I have served on the faculty, I started my research program on trace elements with a focus on cadmium toxicity but soon thereafter began my research on zinc metabolism and function. I moved to the University of Florida in 1982 for an endowed position and have been a Florida Gator ever since. At the University of Florida, research expanded to include identification of zinc-responsive genes and physiological outcomes of zinc transport influencing health and disease, particularly as related to inflammation. I had the opportunity to contribute national science policy as president of both the Federation of American Societies for Experimental Biology and the American Society for Nutrition. As the time of this writing, I maintain an active laboratory.

The Macronutrients, Appetite, and Energy Intake.

Each of the macronutrients-carbohydrate, protein, and fat-has a unique set of properties that influences health, but all are a source of energy. The optimal balance of their contribution to the diet has been a long-standing matter of debate. Over the past half century, thinking has progressed regarding the mechanisms by which each macronutrient may contribute to energy balance. At the beginning of this period, metabolic signals that initiated eating events (i.e., determined eating frequency) were emphasized. This was followed by an orientation to gut endocrine signals that purportedly modulate the size of eating events (i.e., determined portion size). Most recently, research attention has been directed to the brain, where the reward signals elicited by the macronutrients are viewed as potentially problematic (e.g., contribute to disordered eating). At this point, the predictive power of the macronutrients for energy intake remains limited.

Behavioral Nutrition Interventions Using e- and m-Health Communication Technologies: A Narrative Review.

e- and m-Health communication technologies are now common approaches to improving population health. The efficacy of behavioral nutrition interventions using e-health technologies to decrease fat intake and increase fruit and vegetable intake was demonstrated in studies conducted from 2005 to 2009, with approximately 75% of trials showing positive effects. By 2010, an increasing number of behavioral nutrition interventions were focusing on body weight. The early emphasis on interventions that were highly computer tailored shifted to personalized electronic interventions that included weight and behavioral self-monitoring as key features. More diverse target audiences began to participate, and mobile components were added to interventions. Little progress has been made on using objective measures rather than self-reported measures of dietary behavior. A challenge for nutritionists is to link with the private sector in the design, use, and evaluation of the many electronic devices that are now available in the marketplace for nutrition monitoring and behavioral change.