Health Belief Model Predicts Likelihood of Eating Nutrient-Rich Foods among U.S. Adults.

Despite decades of messaging, most Americans still consume excess fats and sugars, but inadequate fiber, potassium, and calcium. Nutrient-rich foods (NRFs) have a high density of favorable nutrients related to calories. Choosing NRFs could lower risk of nutrition-related chronic diseases and aid in their control. We hypothesized that having greater knowledge of NRFs, the presence of a nutrition-related chronic disease or risk factor, and positive Health Belief Model (HBM) views would be predictive of the likelihood of eating NRFs. Through a national online survey panel, 976 adults aged 18-80 completed demographic, health, NRF knowledge, attitudes, and HBM construct questions. Participants were 77% White, 52% women, and 55% had a nutrition-related disease or risk factor. Multivariable HBM scales were generated by theory, principal components, and reliability analysis. NRF knowledge was significantly higher for women, Whites, households without children, and persons without a nutrition-related disease (all p ≤ 0.015). 'Likelihood of eating NRFs' was significantly higher for persons with a nutrition-related disease, Whites, married participants, main food shoppers, and households with children (all p ≤ 0.022). Regressing demographic and HBM constructs on the 'likelihood of eating NRFs' resulted in R2 of 0.435. Nutrition-related disease and HBM constructs of self-efficacy, perceived benefits, and cues to action were predictive of the likelihood of eating NRFs, but higher NRF knowledge was negatively associated.

ICAT: a novel algorithm to robustly identify cell states following perturbations in single-cell transcriptomes.

MOTIVATION: The detection of distinct cellular identities is central to the analysis of single-cell RNA sequencing (scRNA-seq) experiments. However, in perturbation experiments, current methods typically fail to correctly match cell states between conditions or erroneously remove population substructure. Here, we present the novel, unsupervised algorithm Identify Cell states Across Treatments (ICAT) that employs self-supervised feature weighting and control-guided clustering to accurately resolve cell states across heterogeneous conditions. RESULTS: Using simulated and real datasets, we show ICAT is superior in identifying and resolving cell states compared with current integration workflows. While requiring no a priori knowledge of extant cell states or discriminatory marker genes, ICAT is robust to low signal strength, high perturbation severity, and disparate cell type proportions. We empirically validate ICAT in a developmental model and find that only ICAT identifies a perturbation-unique cellular response. Taken together, our results demonstrate that ICAT offers a significant improvement in defining cellular responses to perturbation in scRNA-seq data. AVAILABILITY AND IMPLEMENTATION: https://github.com/BradhamLab/icat.

Impairment of regulatory T-cell function in autoimmune thyroid disease.

BACKGROUND: Autoimmune thyroid disease (AITD) pathogenesis may result from a loss of immune tolerance to thyroid antigens. Regulatory T cells (Tregs) control immune responses, prevent excessive inflammation, and may be dysfunctional in AITD. We investigated the role of Tregs in Hashimoto's thyroiditis (HT) and Graves' disease (GD), complicated by Down syndrome (DS). Our goal was to identify differences in CD4(+)CD25(high) Treg function or number in patients with GD and HT, compared to healthy controls (HC). METHODS: Treg number was assessed by flow cytometric analysis in samples from 20 AITD patients (seven GD, 13 HT), nine HC, and seven individuals with DS, a genetic disorder associated with multiple autoimmune disorders including AITD. Treg function was assessed by the inhibition of proliferation (radioactive thymidine incorporation into DNA) of blood-derived T effector (Teff) cells by Tregs in a coculture. Various methods of stimulation were contrasted. Cytokine levels were determined in conditioned media from the co-cultures. RESULTS: No differences were found in the frequency of Tregs as a percentage of CD4(+) cells between AITD and HC. AITD Tregs were less capable of inhibiting the proliferation of Teff cells when compared to HC; however, the impairment was dependent on the type of stimulation used. DS patients without AITD exhibited normal Treg function. We observed few differences in cytokine production between HC and AITD patients. CONCLUSIONS: Tregs from AITD patients are partly dysfunctional, possibly explaining their autoimmunity. Future work will elucidate the diagnostic potential and pathophysiology of Tregs in AITD.

ATP depletion triggers acute myeloid leukemia differentiation through an ATR/Chk1 protein-dependent and p53 protein-independent pathway.

Despite advances in oncology drug development, most commonly used cancer therapeutics exhibit serious adverse effects. Often the toxicities of chemotherapeutics are due to the induction of significant DNA damage that is necessary for their ability to kill cancer cells. In some clinical situations, the direct induction of significant cytotoxicity is not a requirement to meet clinical goals. For example, differentiation, growth arrest, and/or senescence is a valuable outcome in some cases. In fact, in the case of acute myeloid leukemia (AML), the use of the differentiation agent all-trans-retinoic acid (ATRA) has revolutionized the therapy for a subset of leukemia patients and led to a dramatic survival improvement. Remarkably, this therapeutic approach is possible even in many elderly patients, who would not be able to tolerate therapy with traditional cytotoxic chemotherapy. Because of the success of ATRA, there is widespread interest in identifying differentiation strategies that may be effective for the 90-95% of AML patients who do not clinically respond to ATRA. Utilizing an AML differentiation agent that is in development, we found that AML differentiation can be induced through ATP depletion and the subsequent activation of DNA damage signaling through an ATR/Chk1-dependent and p53-independent pathway. This study not only reveals mechanisms of AML differentiation but also suggests that further investigation is warranted to investigate the potential clinical use of low dose chemotherapeutics to induce differentiation instead of cytotoxicity. This therapeutic approach may be of particular benefit to patients, such as elderly AML patients, who often cannot tolerate traditional AML chemotherapy.