The microRNA-183/96/182 cluster inhibits lung cancer progression and metastasis by inducing an interleukin-2-mediated antitumor CD8+ cytotoxic T-cell response.

One of the mechanisms by which cancer cells acquire hyperinvasive and migratory properties with progressive loss of epithelial markers is the epithelial-to-mesenchymal transition (EMT). We have previously reported that in different cancer types, including nonsmall cell lung cancer (NSCLC), the microRNA-183/96/182 cluster (m96cl) is highly repressed in cells that have undergone EMT. In the present study, we used a novel conditional m96cl mouse to establish that loss of m96cl accelerated the growth of Kras mutant autochthonous lung adenocarcinomas. In contrast, ectopic expression of the m96cl in NSCLC cells results in a robust suppression of migration and invasion in vitro, and tumor growth and metastasis in vivo. Detailed immune profiling of the tumors revealed a significant enrichment of activated CD8+ cytotoxic T lymphocytes (CD8+ CTLs) in m96cl-expressing tumors, and m96cl-mediated suppression of tumor growth and metastasis was CD8+ CTL-dependent. Using coculture assays with naïve immune cells, we show that m96cl expression drives paracrine stimulation of CD8+ CTL proliferation and function. Using tumor microenvironment-associated gene expression profiling, we identified that m96cl elevates the interleukin-2 (IL2) signaling pathway and results in increased IL2-mediated paracrine stimulation of CD8+ CTLs. Furthermore, we identified that the m96cl modulates the expression of IL2 in cancer cells by regulating the expression of transcriptional repressors Foxf2 and Zeb1, and thereby alters the levels of secreted IL2 in the tumor microenvironment. Last, we show that in vivo depletion of IL2 abrogates m96cl-mediated activation of CD8+ CTLs and results in loss of metastatic suppression. Therefore, we have identified a novel mechanistic role of the m96cl in the suppression of lung cancer growth and metastasis by inducing an IL2-mediated systemic CD8+ CTL immune response.

Purchases of Nontaxed Foods, Beverages, and Alcohol in a Longitudinal Cohort After Implementation of the Philadelphia Beverage Tax.

BACKGROUND: Evidence suggests that sweetened beverage taxes reduce taxed beverage purchases, but few studies have used individual-level data to assess whether these taxes affect purchases of nontaxed foods, beverages, and alcohol. Additionally, research has not examined whether sweetened beverage taxes influence restaurant purchases. OBJECTIVES: We assessed changes in individuals' purchases of taxed beverage types; low-calorie/low-added-sugar nontaxed beverages; high-calorie/high-added-sugar nontaxed beverages, foods, and alcohol; and beverages from restaurants following implementation of the 1.5 cent-per-ounce Philadelphia sweetened beverage tax. METHODS: A longitudinal cohort of adult sugar-sweetened beverage consumers in Philadelphia (n = 306; 67% female; mean age: 43.9 years) and Baltimore (n = 297; comparison city without a beverage tax; 58% female; mean age: 41.7 years) submitted all food and beverage receipts during 2-week periods at baseline and at 3, 6, and 12 months posttax. Difference-in-differences analyses compared changes in purchases from pre- to posttax in Philadelphia to changes in Baltimore. RESULTS: Purchases of taxed juice drinks [ratio of incidence rate ratios (RIRR) = 0.62; 95% CI, 0.42-0.91], but not other taxed beverage types, decreased in Philadelphia compared to Baltimore following the tax. Analyses did not find changes in purchases of low-calorie/low-added-sugar nontaxed beverages, such as water or milk. Additionally, analyses did not find increases in purchases of most high-calorie/high-added-sugar nontaxed products, including alcohol, juice, candy, sweet snacks, salty snacks, and desserts. Purchases of beverage concentrates increased in Philadelphia (RIRR = 2.22; 95% CI, 1.39-3.54). CONCLUSIONS: In this difference-in-differences analysis, the Philadelphia beverage tax was associated with reduced purchases of taxed juice drinks. Purchases of beverage concentrates increased after the tax, but no increases were observed for other high-calorie/high-added-sugar nontaxed foods, beverages, or alcohol.

Do Longitudinal Trends in Tobacco 21-Related Media Coverage Correlate with Policy Support? an Exploratory Analysis Using Supervised and Unsupervised Machine Learning Methods.

Media coverage can impact support for health policies and, ultimately, compliance with those policies. Prior research found consistent, high support for Tobacco 21 policies, which raise the minimum legal age of tobacco purchase to 21, among adults and nonsmoking youth. However, a recent study found support (i.e., agreement with the statement: "The legal age to buy tobacco cigarettes should be increased from 18 to 21") among 13-20-year-old smokers increased from 2014 until mid-2016 and then declined steadily through mid-2017. To assess whether media coverage could be related to young smokers' changing support, we conducted an exploratory content analysis to identify texts about Tobacco 21 in a large corpus of tobacco texts (N = 135,691) published in four popular media sources from 2014 to 2017. For this content analysis, we developed a novel methodological approach that combined supervised and unsupervised machine learning methods and could be useful in other areas of communication research. We found that the prevalence of Tobacco 21 media coverage and Tobacco 21 support among young smokers exhibited similar temporal patterns for much of the study period. These findings highlight the need for continued research into the effects of media coverage on Tobacco 21 support among young smokers, a group that must comply with Tobacco 21 policies in order to ensure maximum effectiveness. This research is of particular utility following the 2019 passage of a federal Tobacco 21 regulation, as the public health impact of this regulation could be limited by low public support, and thus low rates of policy compliance.

Rating the Valence of Media Content about Electronic Cigarettes Using Crowdsourcing: Testing Rater Instructions and Estimating the Optimal Number of Raters.

Electronic cigarettes (e-cigarettes) are a controversial public health topic due to their increasing popularity among youth and the uncertainty about their risks and benefits. Researchers have started to assess the valence of media content about e-cigarette use, mostly using expert coding. The current study aims to offer a methodological framework and guideline when using crowdsourcing to rate the valence of e-cigarette media content. Specifically, we present (1) an experiment to determine rating instructions that would result in reliable valence ratings and (2) an analysis to identify the optimal number of raters needed to replicate these ratings. Specifically, we compared ratings produced by crowdsourced raters instructed to rate from several different perspectives (e.g., objective vs. subjective) and determined the instructions that led to reliable ratings. We then used bootstrapping methods and a set of criteria to identify the minimum number of raters needed to replicate these ratings. Results suggested that when rating e-cigarette valence, instructing raters to rate from their own subjective perspective produced reliable results, and nine raters were deemed the optimal number of raters. We expect these findings to inform future content analyses of e-cigarette valence. The study procedures can be applied to crowdsourced content analyses of other health-related media content to determine appropriate rating instructions and the number of raters.

Valence of Media Coverage About Electronic Cigarettes and Other Tobacco Products From 2014 to 2017: Evidence From Automated Content Analysis.

INTRODUCTION: As media exposure can influence people's opinions and perceptions about vaping and smoking, analyzing the valence of media content about tobacco products (ie, overall attitude toward tobacco, cigars, electronic cigarettes, etc.) is an important issue. This study advances the field by analyzing a large amount of media content about multiple tobacco products across six different media sources. AIMS AND METHODS: From May 2014 to December 2017, we collected all English-language media items about tobacco products that U.S. young people might see from mass media and websites (long-form) and social media (Twitter and YouTube). We used supervised machine learning to develop validated algorithms to label the valence of these media items. Using the labeled results, we examined the impact of product type (e-cigarettes vs. other tobacco products), source (long-form vs. social media), and time (by month) on the valence of coverage. RESULTS: We obtained 152 886 long-form media texts (20% with more than a passing mention), nearly 86 million tweets, and 12 262 YouTube videos about tobacco products. Most long-form media content opposed, while most social media coverage supported, the use of e-cigarettes and other tobacco products. Over time, within-source valence proportions were stable, though in aggregate, the amount of media coverage against the use of tobacco products decreased. CONCLUSIONS: This study describes the U.S. public communication environment about vaping and smoking for young people and offers a novel big data approach to analyzing media content. Results suggest that content has gradually become less negative toward the use of e-cigarettes and other tobacco products. IMPLICATIONS: This study is the first to examine how the valence of media coverage differs for e-cigarettes versus other tobacco products, across several media sources, and over time using a large corpus of media items. Unlike prior studies, these data allow us to draw conclusions about relative support and opposition for these two categories of products in a variety of media coverage because the same coding scheme was used across products and media sources.

Breadth of Media Scanning Leads to Vaping among Youth and Young Adults: Evidence of Direct and Indirect Pathways from a National Longitudinal Survey.

Electronic cigarette use among youth and young adults has reached an epidemic proportion of growth. This study examined the direct and indirect effects of the breadth of media scanning about e-cigarette use on subsequent vaping behavior through interpersonal communication and changes in descriptive norm perceptions. We conducted a nationally representative longitudinal phone survey of 13- to 25-year-olds from June 2014 to March 2017, with 11,013 respondents who completed a baseline survey, among which 3,212 completed a follow-up 6 months later. The results from both cross-sectional and lagged analyses provided robust evidence to suggest that passive routine exposure to e-cigarette use content from more media outlets predicted increased likelihood of vaping among youth and young adults. High scanners were about twice as likely to vape as non-scanners (17% versus 9%). Mediation models using bootstrapping procedures found that breadth of scanning predicted higher descriptive norm perceptions which were associated with subsequent vaping; in addition, interpersonal communication mediated the relationship between breadth of scanning and changes in descriptive norm perceptions. These findings highlight the important roles of scanning, norm perceptions and interpersonal discussions in shaping cognition and behavior changes. The results also suggest an overall pro-e-cigarette public communication environment, which warrants further examination.

Combining Crowd-Sourcing and Automated Content Methods to Improve Estimates of Overall Media Coverage: Theme Mentions in E-cigarette and Other Tobacco Coverage.

Exposure to media content can shape public opinions about tobacco. Accurately describing content is a first step to showing such effects. Historically, content analyses have hand-coded tobacco-focused texts from a few media sources which ignored passing mention coverage and social media sources, and could not reliably capture over-time variation. By using a combination of crowd-sourced and automated coding, we labeled the population of all e-cigarette and other tobacco-related (including cigarettes, hookah, cigars, etc.) 'long-form texts' (focused and passing coverage, in mass media and website articles) and social media items (tweets and YouTube videos) collected May 2014-June 2017 for four tobacco control themes. Automated coding of theme coverage met thresholds for item-level precision and recall, event validation, and weekly-level reliability for most sources, except YouTube. Health, Policy, Addiction and Youth themes were frequent in e-cigarette long-form focused coverage (44%-68%), but not in long-form passing coverage (5%-22%). These themes were less frequent in other tobacco coverage (long-form focused (13-32%) and passing coverage (4-11%)). Themes were infrequent in both e-cigarette (1-3%) and other tobacco tweets (2-4%). Findings demonstrate that passing e-cigarette and other tobacco long-form coverage and social media sources paint different pictures of theme coverage than focused long-form coverage. Automated coding also allowed us to code the amount of data required to estimate reliable weekly theme coverage over three years. E-cigarette theme coverage showed much more week-to-week variation than did other tobacco coverage. Automated coding allows accurate descriptions of theme coverage in passing mentions, social media, and trends in weekly theme coverage.

Type of E-Cigarette Device Used Among Adolescents and Young Adults: Findings From a Pooled Analysis of Eight Studies of 2166 Vapers.

Background: A recent study of adult smokers who vape found that disposable/cigalike electronic (e-) cigarette devices were more commonly used than later generation devices. However, whether these trends reflect patterns among adolescents and young adults, many of whom have limited or no history of combustible cigarette use, has not been studied. Methods: Participants were drawn from eight locally, regionally, and US nationally representative studies. Surveys took place between Fall 2014 and Spring 2016; participants were residents of California (3 studies), Texas (2 studies), Connecticut (1 study), or randomly selected from the US population (2 studies). Data were collected from middle and high school students (4 studies), young adults under 30 (3 studies), or a mixture (1 study) to assess type of e-cigarette device used among past-30 day e-cigarette users: disposable/cigalike, or later generation e-cigarette device. Results: Fewer than 15% of participants in each study reported primarily using a disposable/cigalike device in the past month (across all studies: 7.5%; 95%CI: 4.9%, 10.5%). The proportion using later generation devices ranged from 58% to 86% across studies; overall, 77.0% (95%CI: 70.5%, 82.9%) reported primary use of a later generation device. Combined, 13.2% (95%CI: 5.9%, 22.8%) reported "don't know" or were missing data. Conclusions: Among adolescent and young adult e-cigarette users, primary use of disposable/cigalike devices was rare. Future research should continue to evaluate the type of device used by adolescents and young adults, as these data may be relevant to regulatory oversight of e-cigarettes recently acquired by the Food and Drug Administration Center for Tobacco Products. Implications: In this pooled analysis of adolescent and young adult vapers, primary use of later generation e-cigarette devices was substantially more common than use of disposable/cigalike devices. The type of device predominantly used by adolescents and young adults has regulatory implications for policy to reduce adolescent use of e-cigarettes.

The effects of breastfeeding on childhood BMI: a propensity score matching approach.

Background: Many studies have found a statistical association between breastfeeding and childhood adiposity. This paper investigates whether breastfeeding has an effect on subsequent childhood body mass index (BMI) using propensity scores to account for confounding. Methods: We use data from the Millennium Cohort Study, a nationally representative UK cohort survey, which contains detailed information on infant feeding and childhood BMI. Propensity score matching is used to investigate the mean BMI in children breastfed exclusively and partially for different durations of time. Results: We find statistically significant influences of breastfeeding on childhood BMI, particularly in older children, when breastfeeding is prolonged and exclusive. At 7 years, children who were exclusively breastfed for 16 weeks had a BMI 0.28 kg/m2 (95% confidence interval 0.07 to 0.49) lower than those who were never breastfed, a 2% reduction from the mean BMI of 16.6 kg/m2. Conclusions: For this young cohort, even small effects of breastfeeding on BMI could be important. In order to reduce BMI, breastfeeding should be encouraged as part of wider lifestyle intervention. This evidence could help to inform public health bodies when creating public health guidelines and recommendations.

Recall of "The Real Cost" Anti-Smoking Campaign Is Specifically Associated With Endorsement of Campaign-Targeted Beliefs.

Though previous research suggests the FDA's "The Real Cost" anti-smoking campaign has reduced smoking initiation, the theorized pathway of effects (through targeted beliefs) has not been evaluated. This study assesses the relationship between recall of campaign television advertisements and ad-specific anti-smoking beliefs. Respondents in a nationally representative survey of nonsmoking youths age 13-17 (n = 4,831) reported exposure to four The Real Cost advertisements and a fake ad, smoking-relevant beliefs, and nonsmoking intentions. Analyses separately predicted each targeted belief from specific ad recall, adjusting for potential confounders and survey weights. Parallel analyses with non-targeted beliefs showed smaller effects, strengthening claims of campaign effects. Recall of four campaign ads (but not the fake ad) significantly predicted endorsement of the ad-targeted belief (Mean ß = .13). Two-sided sign tests indicated stronger ad recall associations with the targeted belief relative to the non-targeted belief (p < .05). Logistic regression analyses indicated that respondents who endorsed campaign-targeted beliefs were more likely to have no intention to smoke (p < .01). This study is the first to demonstrate a relationship between recall of ads from The Real Cost campaign and the theorized pathway of effects (through targeted beliefs). These analyses also provide a methodological template for showing campaign effects despite limitations of available data.

Suppression of RAF/MEK or PI3K synergizes cytotoxicity of receptor tyrosine kinase inhibitors in glioma tumor-initiating cells.

BACKGROUND: The majority of glioblastomas have aberrant receptor tyrosine kinase (RTK)/RAS/phosphoinositide 3 kinase (PI3K) signaling pathways and malignant glioma cells are thought to be addicted to these signaling pathways for their survival and proliferation. However, recent studies suggest that monotherapies or inappropriate combination therapies using the molecular targeted drugs have limited efficacy possibly because of tumor heterogeneities, signaling redundancy and crosstalk in intracellular signaling network, indicating necessity of rationale and methods for efficient personalized combination treatments. Here, we evaluated the growth of colonies obtained from glioma tumor-initiating cells (GICs) derived from glioma sphere culture (GSC) in agarose and examined the effects of combination treatments on GICs using targeted drugs that affect the signaling pathways to which most glioma cells are addicted. METHODS: Human GICs were cultured in agarose and treated with inhibitors of RTKs, non-receptor kinases or transcription factors. The colony number and volume were analyzed using a colony counter, and Chou-Talalay combination indices were evaluated. Autophagy and apoptosis were also analyzed. Phosphorylation of proteins was evaluated by reverse phase protein array and immunoblotting. RESULTS: Increases of colony number and volume in agarose correlated with the Gompertz function. GICs showed diverse drug sensitivity, but inhibitions of RTK and RAF/MEK or PI3K by combinations such as EGFR inhibitor and MEK inhibitor, sorafenib and U0126, erlotinib and BKM120, and EGFR inhibitor and sorafenib showed synergy in different subtypes of GICs. Combination of erlotinib and sorafenib, synergistic in GSC11, induced apoptosis and autophagic cell death associated with suppressed Akt and ERK signaling pathways and decreased nuclear PKM2 and ß-catenin in vitro, and tended to improve survival of nude mice bearing GSC11 brain tumor. Reverse phase protein array analysis of the synergistic treatment indicated involvement of not only MEK and PI3K signaling pathways but also others associated with glucose metabolism, fatty acid metabolism, gene transcription, histone methylation, iron transport, stress response, cell cycle, and apoptosis. CONCLUSION: Inhibiting RTK and RAF/MEK or PI3K could induce synergistic cytotoxicity but personalization is necessary. Examining colonies in agarose initiated by GICs from each patient may be useful for drug sensitivity testing in personalized cancer therapy.

Life cycle exposure of the frog Silurana tropicalis to arsenate: Steroid- and thyroid hormone-related genes are differently altered throughout development.

Arsenic contaminates water surface and groundwater worldwide. Several studies have suggested that arsenic acts as an endocrine disruptor in mammalian and non-mammalian species, although its chronic effect during development remains largely unknown. To address this question, life cycle exposures to 0, 0.3 and 0.8ppm of arsenate (pentavalent arsenic; As(V)) were performed in the Western clawed frog (Silurana tropicalis) from the gastrulae stage (developmental stage Nieuwkoop-Faber; NF12) until metamorphosis (NF66). Tissue samples were collected at the beginning of feeding (NF46; whole body), sexual development (NF56; liver), and at metamorphosis completion (NF66; liver and gonadal mesonephros complex). Real-time RT-PCR analysis quantified decreases in mRNA levels of genes related to estrogen- (estrogen receptor alpha and aromatase), androgen- (androgen receptor and steroid 5-alpha-reductase type 2), and cholesterol metabolism- (steroidogenic acute regulatory protein) at stage NF46. Similarly, arsenate decreased steroid 5-alpha-reductase type 2 expression in stage NF56 livers, but transcript increases were observed for both estrogen receptor alpha and steroidogenic acute regulatory protein at this stage. Given the changes observed in the expression of genes essential for proper sexual development, gonadal histological analysis was carried out in stage NF66 animals. Arsenate treatments did not alter sex ratio or produce testicular oocytes. On the other hand, arsenate interfered with thyroid hormone-related transcripts at NF66. Specifically, thyroid hormone receptor beta and deiodinase type 2 mRNA levels were significantly reduced after arsenate treatment in the gonadal mesonephros complex. This reduction in thyroid hormone-related gene expression, however, was not accompanied by any morphological changes measured. In summary, environmentally relevant concentrations of As(V) altered steroidogenesis-, sex steroid signaling- and thyroid hormone-related gene expression, although transcriptional changes varied among tissues and developmental stages.

A positive correlation between mercury and oxidative stress-related gene expression (GPX3 and GSTM3) is measured in female Double-crested Cormorant blood.

Mercury (Hg) is a widespread contaminant that has been shown to induce a wide range of adverse health effects in birds including reproductive, physiological and neurological impairments. Here we explored the relationship between blood total Hg concentrations ([THg]) and oxidative stress gene induction in the aquatic piscivorous Double-crested Cormorants (Phalacrocorax auritus) using a non-lethal technique, i.e., blood gene expression analysis. P. auritus blood was sampled at five sites across the Great Lakes basin, Ontario, Canada and was analyzed for [THg]. To assess cellular stress, the expression of glutathione peroxidases 1 and 3 (GPX1, GPX3), superoxide dismutase 1 (SOD1), heat-shock protein 70 kd-8 (HSP70-8) and glutathione S-transferase µ3 (GSTM3) were measured in whole blood samples using real-time RT-PCR. Results showed a significantly positive correlation between female blood [THg] and both GPX3 and GSTM3 expression. Different levels of oxidative stress experienced by males and females during the breeding season may be influencing the differential oxidative stress responses to blood [THg] observed in this study. Overall, these results suggest that Hg may lead to oxidative stress as some of the cellular stress-related genes were altered in the blood of female P. auritus and that blood gene expression analysis is a successful approach to assess bird health condition.

Advertising and Stocking at Small Retailers: A Sweetened Beverage Excise Tax in Philadelphia.

INTRODUCTION: In 2017, Philadelphia enacted a $0.015 per ounce excise tax on SBs that covered both sugar-sweetened beverages and artificially-sweetened beverages, which reduced purchasing and consumption. This study assessed whether the tax also changed beverage advertising or stocking practices that could influence consumer behavior among stores in Philadelphia, Baltimore, and Philadelphia-adjacent counties not subject to the tax. METHODS: Using a longitudinal difference-in-differences approach, beverage advertising and availability changes were evaluated from 4-month pretax to 6-, 12-, and 24-month post-implementation in small independent stores in Philadelphia (n=34) and Philadelphia-adjacent counties (n=38) versus Baltimore (n=43), a demographically similar city without a tax. Mixed effects models tested whether beverage advertising/availability increased in Philadelphia and surrounding counties after implementation versus Baltimore, included store-level random intercepts, and were stratified by beverage tax status, type, size, and store ZIP code income. Data were collected from 2016 to 2018, and analyses were performed in 2022-2023. RESULTS: SB advertising increased post-tax in Philadelphia (6 months= +1.04 advertisements/store [95% CI=0.27, 1.80]; 12 months= +1.54 [95% CI=0.57, 2.52]; 24 months= +0.91 [95% CI=0.09, 1.72]) relative to Baltimore. This was driven by increased advertising of sweetened beverages in low-income ZIP codes. Marketing of SBs increased significantly in Philadelphia-adjacent counties relative to Baltimore. Although SB availability in Philadelphia did not change, it increased in surrounding county stores (6 months= +0.20 [95% CI=0.15, 0.25]; 12 months= +0.08 [95% CI=0.03, 0.12]) relative to Baltimore. CONCLUSIONS: Marketing of SBs, especially in low-income neighborhoods and in surrounding counties, increased following Philadelphia's beverage tax among small, independent retailers. These increases in advertising might have dampened the tax's effect on purchasing behaviors, although estimated effects on sales remained large.

Comparison of Sales From Vending Machines With 4 Different Food and Beverage Messages: A Randomized Trial.

Importance: Point-of-sale food messaging can encourage healthier purchases, but no studies have directly compared multiple interventions in the field. Objective: To examine which of 4 food and beverage messages would increase healthier vending machine purchases. Design, Setting, and Participants: This randomized trial assessed 13 months (February 1, 2019, to February 29, 2020) of vending sales data from 267 machines and 1065 customer purchase assessments from vending machines on government property in Philadelphia, Pennsylvania. Data analysis was performed from March 5, 2020, to November 8, 2022. Interventions: Study interventions were 4 food and beverage messaging systems: (1) beverage tax posters encouraging healthy choices because of the Philadelphia tax on sweetened drinks; (2) green labels for healthy products; (3) traffic light labels: green (healthy), yellow (moderately healthy), or red (unhealthy); or (4) physical activity equivalent labels (minutes of activity to metabolize product calories). Main Outcomes and Measures: Sales data were analyzed separately for beverages and snacks. The main outcomes analyzed at the transaction level were calories sold and the health status (using traffic light criteria) of each item sold. Additional outcomes were analyzed at the monthly machine level: total units sold, calories sold, and units of each health status sold. The customer purchase assessment outcome was calories purchased per vending trip. Results: Monthly sales data came from 150 beverage and 117 snack vending machines, whereas 1065 customers (558 [52%] male) contributed purchase assessment data. Traffic light labels led to a 30% decrease in the mean monthly number of unhealthy beverages sold (mean ratio [MR], 0.70; 95% CI, 0.55-0.88) compared with beverage tax posters. Physical activity labels led to a 34% (MR, 0.66; 95% CI, 0.51-0.87) reduction in the number of unhealthy beverages sold at the machine level and 35% (MR, 0.65; 95% CI, 0.50-0.86) reduction in mean calories sold. Traffic light labels also led to a 30-calorie reduction (b = -30.46; 95% CI, -49.36 to -11.56) per customer trip in the customer purchase analyses compared to physical activity labels. There were very few significant differences for snack machines. Conclusions and Relevance: In this 13-month randomized trial of 267 vending machines, the traffic light and physical activity labels encouraged healthier beverage purchases, but no change in snack sales, compared with a beverage tax poster. Corporations and governments should consider such labeling approaches to promote healthier beverage choices. Trial Registration: ClinicalTrials.gov Identifier: NCT06260176.

Impact of the Philadelphia Beverage Tax on Perceived Beverage Healthfulness, Tax Awareness, and Tax Opinions.

OBJECTIVE: To assess the impact of the Philadelphia Beverage Tax on perceived beverage healthfulness, and awareness and opinions of the tax. DESIGN: Natural experiment SETTING: Small independent stores in Philadelphia (n = 61) and Baltimore (untaxed control site; n = 65) PARTICIPANTS: Shoppers in Philadelphia (n = 2,731) and Baltimore (n = 4,600) pre- and post-tax implementation. MAIN OUTCOME MEASURES: Perceptions of 4 beverages (unhealthy vs healthy/neutral), tax awareness, and tax opinions (oppose vs favor/neutral). ANALYSIS: Mixed-effects linear probability models estimated changes in perceived beverage healthfulness in Philadelphia, relative to Baltimore, following a difference-in-differences approach. Mixed-effects linear probability models estimated pre-post changes in tax awareness and opinions in Philadelphia-only. RESULTS: The probability of perceiving taxed beverages as unhealthy increased 2-years post-tax relative to Baltimore (regular soda: 5.7% [95% confidence interval (CI), 0.9-10.6], P = 0.02; diet soda: 7.7% [95% CI, 1.5-13.8], P < 0.001; sports drinks: 6.4% [95% CI, 0.4-12.4], P = 0.04), with similar changes at 1-year post-tax, whereas perceived healthfulness of untaxed 100% fruit juice did not change. Tax awareness was high at baseline (72%) and increased post-implementation; however, the probability of opposing the tax (22%) also increased over time. CONCLUSIONS AND IMPLICATIONS: Decreases in the perceived healthfulness of taxed beverages suggest the tax had a health-signaling effect. Consumer awareness and health education efforts could complement tax policies to enhance understanding of health risks.

Impact of Privacy Messaging on COVID-19 Exposure Notification App Downloads: Evidence From a Randomized Experiment.

Introduction: Digital contact-tracing smartphone apps have the potential to slow the spread of disease but are not widely used. We tested whether messages describing how a COVID-19 digital contact-tracing app protects users' privacy led to increased or decreased intentions to download the app by either calming privacy concerns or increasing their saliency. Design: Randomized controlled trial. Setting/participants: We recruited adult smartphone owners in the U.S. (oversampled for younger adults aged 18-34 years) in November 2020 through an online panel. Intervention: Survey software randomly assigned 860 participants to 1 of 2 parallel messaging conditions (n=430 privacy assured, n=430 no privacy described). Main outcome measures: 4-point scale of intention to use the app "if public health officials released a COVID Exposure Notification app in their state" that averaged likelihood to (1) download and install the app on their phone; (2) keep the app active on their phone; and (3) keep Bluetooth active on their phone (needed for the app to work). Results: After removing incompletes, those who failed the manipulation checks, or those who had already downloaded a COVID-19 digital contact-tracing app, we analyzed 671 participants (n=330 privacy, n=341 no privacy) in 2021. There was no relationship between privacy condition and download intention (meanprivacy=2.69, meannoprivacy=2.69, b=0.01, 95% CI= -0.13, 0.15, p=0.922) but also no evidence that describing the app's security increased context-dependent privacy concerns (measured 3 ways). Instead, we found increased endorsement of data security in the privacy condition using a scale of beliefs about the app keeping privacy secure (meanprivacy=2.74, meannoprivacy=2.58, b=0.16, 95% CI=0.04, 0.28, p=0.009, small effect ω2=0.009). Conclusions: This study provides some evidence that people developing contact-tracing messaging campaigns do not need to worry that describing a digital contact-tracing app's privacy protections will backfire. Future mixed methods testing of messages about who has access to information-and for how long-may uncover new communication strategies to increase public trust in contact-tracing apps. Trial registration: This study is registered with AsPredicted#51826.

Effects of 4 Interpretive Front-of-Package Labeling Systems on Hypothetical Beverage and Snack Selections: A Randomized Clinical Trial.

Importance: Policymakers and researchers have proposed a variety of interpretative front-of-package food labeling systems, but it remains unclear which is most effective at encouraging people to choose healthier foods and beverages, including among people with less education. Objective: To test the effects of 4 interpretative front-of-package food labeling systems on the healthfulness of beverage and snack selections, overall and by education level. Design, Setting, and Participants: This randomized clinical trial of a national sample of US adults 18 years and older was conducted online from November 16 to December 3, 2022. Intervention: Participants were randomized to view products with 1 of 5 food labeling systems, including control (calorie labels only) or 1 of 4 interpretative labeling systems: green ("choose often") labels added to healthy foods; single traffic light labels added to healthy, moderately healthy, and unhealthy foods; physical activity calorie equivalent labels added to all products; and nutrient warning labels added to products high in calories, sugar, saturated fat, or sodium. All conditions had calorie labels on all products. Main Outcomes and Measures: Participants selected 1 of 16 beverages and 1 of 16 snacks that they wanted to hypothetically purchase. The primary outcomes were calories selected from beverages and from snacks. Secondary outcomes included label reactions and perceptions. Results: A total of 7945 participants completed the experiment and were included in analyses (4078 [51%] female, 3779 [48%] male, and 88 [1%] nonbinary or another gender; mean [SD] age, 47.5 [17.9 years]). Compared with the control arm, exposure to the green (average differential effect [ADE], -34.2; 95% CI, -42.2 to -26.1), traffic light (ADE, -31.5; 95% CI, -39.5 to -23.4), physical activity (ADE, -39.0; 95% CI, -47.0 to -31.1), or nutrient warning labels (ADE, -28.2; 95% CI, -36.2 to -20.2) led participants to select fewer calories from beverages (all P < .001). Similarly, compared with the control label, exposure to the green (ADE, -12.7; 95% CI, -17.3 to -8.2), traffic light (ADE, -13.7; 95% CI, -18.2 to -9.1), physical activity (ADE, -18.5; 95% CI, -23.1 to -13.9), or nutrient warning labels (ADE, -14.2; 95% CI, -18.8 to -9.6) led participants to select fewer calories from snacks (all P < .001). These effects did not differ by education level. The green labels were rated as less stigmatizing than the other interpretative systems but otherwise generally received the least favorable label reactions and perceptions (eg, elicited less attention, were perceived as less trustworthy), while the nutrient warnings and physical activity labels received the most favorable ratings. Conclusions and Relevance: In this randomized clinical trial of front-of-package food labeling systems, all 4 interpretative labeling systems reduced calories selected from beverages and from snacks compared with calorie labels, with no differences by education level. Trial Registration: ClinicalTrials.gov Identifier: NCT05432271.

Changes in Dental Outcomes After Implementation of the Philadelphia Beverage Tax.

INTRODUCTION: Beverage taxes are associated with declines in sugar-sweetened beverage sales and consumption, but few studies have evaluated the associations of these taxes with health outcomes. This study analyzed changes in dental decay after the implementation of the Philadelphia sweetened beverage tax. METHODS: Electronic dental record data were obtained on 83,260 patients living in Philadelphia and control areas from 2014 to 2019. Difference-in-differences analyses compared the number of new Decayed, Missing, and Filled Teeth with that of new Decayed, Missing, and Filled Surfaces before (January 2014-December 2016) and after (January 2019-December 2019) tax implementation in Philadelphia and control patients. Analyses were conducted in older children/adults (aged ≥15 years) and younger children (aged <15 years). Subgroup analyses stratified by Medicaid status. Analyses were conducted in 2022. RESULTS: The number of new Decayed, Missing, and Filled Teeth did not change after tax implementation in Philadelphia in panel analyses of older children/adults (difference-in-differences= -0.02, 95% CI= -0.08, 0.03) or younger children (difference-in-differences=0.07, 95% CI= -0.08, 0.23). There were similarly no post-tax changes in the number of new Decayed, Missing, and Filled Surfaces. However, in cross-sectional samples of patients on Medicaid, the number of new Decayed, Missing, and Filled Teeth was lower after tax implementation in older children/adults (difference-in-differences= -0.18, 95% CI= -0.34, -0.03; -22% decline) and younger children (difference-in-differences= -0.22, 95% CI= -0.46, 0.01; -30% decline), with similar results for number of new Decayed, Missing, and Filled Surfaces. CONCLUSIONS: The Philadelphia beverage tax was not associated with reduced tooth decay in the general population, but it was associated with reduced tooth decay in adults and children on Medicaid, suggesting potential health benefits for low-income populations.

Effects of Sugary Beverage Text and Pictorial Warnings: A Randomized Trial.

INTRODUCTION: Multiple U.S. localities have introduced legislation requiring sugar-sweetened beverage (SSB) warnings. This study effects of different warning designs on beverage selections and perceptions. STUDY DESIGN: The study was an RCT. SETTING/PARTICIPANTS: An online virtual convenience store and survey were used with a nationally representative sample of primary caregivers of 6-11-year-olds (n=961). Data were collected in January 2020 and analyzed in May-July 2020. INTERVENTION: Participants were randomized to view SSBs with 1 of 4 front-of-package label designs: (1) no-warning control, (2) health-related text warning, (3) sugar pictorial warning (image of beverage sugar content in cubes/teaspoons/packets with health-related warning text), or (4) health pictorial warning (image of possible health consequences of overconsuming SSBs with health-related warning text). MAIN OUTCOME MEASURES: Outcomes included participants' beverage choice for their child and perceptions of beverages, their assigned labels, and warning policies. RESULTS: Proportionally fewer participants chose a SSB in the sugar pictorial warning condition (-13.4 percentage points; 95% CI= -21.6 to -0.1 percentage points; p=0.007) and in the health pictorial warning condition (-14.7 percentage points; 95% CI= -22.8 to -0.1 percentage points; p=0.004) compared to the control. Sugar pictorial warnings led to more accurate added-sugar content estimates than all conditions and greater label trust and support for sugar-sweetened beverage warning policies than health pictorial warnings. CONCLUSIONS: SSB warning policies may be most effective if they mandate images of beverages' added sugar content accompanied by warning text. TRIAL REGISTRATION: This study is registered at www. CLINICALTRIALS: gov NCT03648138.