Essential requirements for the governance and management of data trusts, data repositories, and other data collaborations.

Introduction: Around the world, many organisations are working on ways to increase the use, sharing, and reuse of person-level data for research, evaluation, planning, and innovation while ensuring that data are secure and privacy is protected. As a contribution to broader efforts to improve data governance and management, in 2020 members of our team published 12 minimum specification essential requirements (min specs) to provide practical guidance for organisations establishing or operating data trusts and other forms of data infrastructure.

Approach And Aims: We convened an international team, consisting mostly of participants from Canada and the United States of America, to test and refine the original 12 min specs.

Relationship between attentional bias and stimulus control: An observational study of real-world eating patterns.

Background: Attentional bias towards food related stimuli has been proposed as a potential target for dieting intervention, however the evidence supporting a relationship between attentional bias and food intake is mixed. Theory holds that food related attentional bias should be positively associated with measures of stimulus-controlled eating, and that implicit processes such as impulsivity moderate this association. The aim of the present study was to examine whether the proposed relationship between food-related attentional bias and stimulus control exists, and whether it is moderated by impulsivity.

Open-source Software Sustainability Models: Initial White Paper From the Informatics Technology for Cancer Research Sustainability and Industry Partnership Working Group.

Background: The National Cancer Institute Informatics Technology for Cancer Research (ITCR) program provides a series of funding mechanisms to create an ecosystem of open-source software (OSS) that serves the needs of cancer research. As the ITCR ecosystem substantially grows, it faces the challenge of the long-term sustainability of the software being developed by ITCR grantees. To address this challenge, the ITCR sustainability and industry partnership working group (SIP-WG) was convened in 2019.

Comfort eating: An observational study of affect in the hours immediately before, and after, snacking.

Objective: 'Comfort eating' has been used to explain real-world food choices, suggesting that individuals are drawn to energy-dense ('unhealthy') snacks when experiencing negative affect. However, this concept has rarely been studied, particularly in real-world settings. Similarly, the effects of snacking on subsequent affect are also poorly understood.

Comparison of Geographic Information System and Subjective Assessments of Momentary Food Environments as Predictors of Food Intake: An Ecological Momentary Assessment Study.

Background: It has been observed that eating is influenced by the presence and availability of food. Being aware of the presence of food in the environment may enable mobile health (mHealth) apps to use geofencing techniques to determine the most appropriate time to proactively deliver interventions. To date, however, studies on eating typically rely on self-reports of environmental contexts, which may not be accurate or feasible for issuing mHealth interventions.

Body Mass Index and stimulus control: Results from a real-world study of eating behaviour.

Background: Evidence suggests decisions about when, what, and how much to eat can be influenced by external (location, food outlet presence, food availability) and internal (affect) cues. Although the relationship between stimulus control and obesity is debated, it is suggested that individuals with higher BMIs are more driven by cues to eating than individuals in the healthy-weight range (HWR). This study investigates the influence of stimulus control on real-world food intake, and whether stimulus control differs by BMI.

Inter-goal conflict and facilitation as predictors of adherence to dieting goals: an ecological momentary assessment study.

To examine dieting goals within a system of individual goals, and the patterns by personally-relevant goals might interfere or facilitate each other. 94 dieters completed an assessment of goals using Little's personal project analysis. Participants identified 7 goals; one of which was pre-defined as adhering to diet.

Personal and situational predictors of everyday snacking: An application of temporal self-regulation theory.

Objectives: This study aims at testing predictions derived from temporal self-regulation theory (TST) in relation to discretionary food choices (snacks). TST combines a motivational sphere of influence (cognitions and temporal valuations resulting in intentions) with a momentary sphere (encompassing social and physical environmental cues). This dual approach differs from current health behaviour theories, but can potentially improve our understanding of the interplay of personal and environmental factors in health behaviour self-regulation.

Situational cues and momentary food environment predict everyday eating behavior in adults with overweight and obesity.

Objectives: Individual eating behavior is a risk factor for obesity and highly dependent on internal and external cues. Many studies also suggest that the food environment (i.e.

Reverse causal reasoning: applying qualitative causal knowledge to the interpretation of high-throughput data.

Background: Gene expression profiling and other genome-scale measurement technologies provide comprehensive information about molecular changes resulting from a chemical or genetic perturbation, or disease state. A critical challenge is the development of methods to interpret these large-scale data sets to identify specific biological mechanisms that can provide experimentally verifiable hypotheses and lead to the understanding of disease and drug action.

Results: We present a detailed description of Reverse Causal Reasoning (RCR), a reverse engineering methodology to infer mechanistic hypotheses from molecular profiling data.

Continuing professional development for public health: an andragogical approach.

The UK professional body for public health, the Faculty of Public Health (FPH), has a well-established approach towards continuing professional development (CPD) for its members and fellows. The FPH approach, initially designed for public health physicians, has evolved to meet CPD requirements of a workforce beyond that of public health medicine to what is now a multiprofessional public health workforce. Despite over 20 years of CPD activity in the field of public health, limited literature examines the underlying theoretical principles, or proposes the most effective approach to adopt.

Comparative transcriptional network modeling of three PPAR-α/γ co-agonists reveals distinct metabolic gene signatures in primary human hepatocytes.

Aims: To compare the molecular and biologic signatures of a balanced dual peroxisome proliferator-activated receptor (PPAR)-α/γ agonist, aleglitazar, with tesaglitazar (a dual PPAR-α/γ agonist) or a combination of pioglitazone (Pio; PPAR-γ agonist) and fenofibrate (Feno; PPAR-α agonist) in human hepatocytes.

Methods And Results: Gene expression microarray profiles were obtained from primary human hepatocytes treated with EC(50)-aligned low, medium and high concentrations of the three treatments. A systems biology approach, Causal Network Modeling, was used to model the data to infer upstream molecular mechanisms that may explain the observed changes in gene expression.

Chemogenetic analysis of human protein methyltransferases.

A survey of the human genome was performed to understand the constituency of protein methyltransferases (both protein arginine and lysine methyltransferases) and the relatedness of their catalytic domains. We identified 51 protein lysine methyltransferase proteins based on similarity to the canonical Drosophila Su(var)3-9, enhancer of zeste (E(z)), and trithorax (trx) domain. Disruptor of telomeric silencing-1-like, a known protein lysine methyltransferase, did not fit within the protein lysine methyltransferase family, but did group with the protein arginine methyltransferases, along with 44 other proteins, including the METTL and NOP2/Sun domain family proteins.

Causal reasoning identifies mechanisms of sensitivity for a novel AKT kinase inhibitor, GSK690693.

Background: Inappropriate activation of AKT signaling is a relatively common occurrence in human tumors, and can be caused by activation of components of, or by loss or decreased activity of inhibitors of, this signaling pathway. A novel, pan AKT kinase inhibitor, GSK690693, was developed in order to interfere with the inappropriate AKT signaling seen in these human malignancies. Causal network modeling is a systematic computational analysis that identifies upstream changes in gene regulation that can serve as explanations for observed changes in gene expression.

Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo.

Background: Calorie restriction (CR) produces a number of health benefits and ameliorates diseases of aging such as type 2 diabetes. The components of the pathways downstream of CR may provide intervention points for developing therapeutics for treating diseases of aging. The NAD+-dependent protein deacetylase SIRT1 has been implicated as one of the key downstream regulators of CR in yeast, rodents, and humans.

SIRT1 promotes differentiation of normal human keratinocytes.

Sir2 regulates lifespan in model organisms, which has stimulated interest in understanding human Sir2 homolog functions. The human Sir2 gene family comprises seven members (SIRT1-SIRT7). SIRT1, the human ortholog of the yeast Sir2 by closest sequence similarity, is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase with enzymatic properties indistinguishable from the yeast enzyme.

Applying a causal framework to system modeling.

The emerging field of systems biology represents a revolution in our ability to understand biology. Perhaps for the first time in history we have the capacity to pursue biological understanding using a computer-aided integrative approach in conjunction with classical reductionist approaches. Technology has given us not only the ability to identify and measure the individual molecules of life and the way they change, but also the power to study these molecules and their changes in the context of a big picture.

Inferring gene regulatory networks from raw data--a molecular epistemics approach.

Biopathways play an important role in the functional understanding and interpretation of gene function. In this paper we present the results of an iterative algorithm for automatically generating gene regulatory networks from raw data. The algorithm is based on an epistemics approach of conjecture (hypothesis formation) and refutation (hypothesis testing).

The Merck Gene Index browser: an extensible data integration system for gene finding, gene characterization and EST data mining.

Motivation: To make effective use of the vast amounts of expressed sequence tag (EST) sequence data generated by the Merck-sponsored EST project and other similar efforts, sequences must be organized into gene classes, and scientists must be able to 'mine' the gene class data in the context of related genomic data.

Results: This paper presents the Merck Gene Index browser, an easily extensible, World Wide Web-based system for mining the Merck Gene Index (MGI) and related genomic data. The MGI is a non-redundant set of clones and sequences, each representing a distinct gene, constructed from all high-quality 3' EST sequences generated by the Merck-sponsored EST project.

Evolutionary relationship of the ligand-gated ion channels and the avermectin-sensitive, glutamate-gated chloride channels.

Two cDNAs, GluClalpha and GluClbeta, encoding glutamate-gated chloride channel subunits that represent targets of the avermectin class of antiparasitic compounds, have recently been cloned from Caenorhabditis elegans (Cully et al., Nature, 371, 707-711, 1994). Expression studies in Xenopus oocytes showed that GluClalpha and GluClbeta have pharmacological profiles distinct from the glutamate-gated cation channels as well as the gamma-aminobutyric acid (GABA)- and glycine-gated chloride channels.

Structural organization of a multifunctional polyketide synthase involved in the biosynthesis of the macrolide immunosuppressant FK506.

The immunosuppressant FK506 is a 23-membered macrocyclic polyketide produced by several Streptomyces species. Sequencing of a 19.5-kb contiguous segment of DNA from the FK506 gene cluster of Streptomyces sp.