Awareness and perceived behaviour changes following the New York state vaping flavour ban, 2021-2022.

SIGNIFICANCE: Despite an electronic cigarette (e-cigarette) flavour ban in New York (NY) since May 2020, most youth who vape continue to report vaping restricted flavours. This study aims to examine youth awareness and perceived behaviour change associated with the NY vaping flavour ban. METHODS: NY cross-sectional data from 2021 and 2022 ITC Youth Survey were combined and analysed (N=1014). Weighted analyses were used to describe awareness and understanding of the e-cigarette flavour ban, as well as changes in tobacco use behaviour. RESULTS: Only 0.9% (n=8) of NY youth understood the flavour ban, in that they were both aware of the flavour ban in all stores and accurately reported that all non-tobacco flavours were banned. Awareness and understanding of the flavour ban differed by vaping status (p<0.01): respondents who had vaped in the past 12 months or 30 days were more likely (adjusted OR (aOR)=2.15, 95% CI 1.34, 3.45; aOR=2.07, 95% CI 1.17, 3.64, respectively) to be aware of the flavour ban but misunderstand the stores or flavours included. Of the majority of youth who reported awareness of a flavour ban and vaped (n=122) or smoked (n=78) in the past 12 months reported no changes in behaviour (64.0% and 69.7%, respectively). CONCLUSIONS: Less than one-third of NY youth, regardless of vaping status, reported that an e-cigarette flavour ban was present where they live. Further, most youth who were aware of the ban misunderstood which flavours were restricted and/or that the ban applied to all stores that sold e-cigarettes. Increased enforcement and educational efforts could improve awareness and understanding of the NY e-cigarette flavour ban.

The Cannabis Gray Market: A Case for Cannabis Regulatory Science Research.

The cannabis gray market poses significant public health concerns and remains a major threat to consumer and/or potential consumer uptake of regulated cannabis markets in jurisdictions with legal state-sponsored cannabis programs. In this perspective, we provide an overview of the cannabis gray market, and describe an integrated epidemiological and regulatory science framework to study the gray market. Using tobacco regulatory science as a guide, we introduce example cannabis regulatory science research activities as a means to improve the field's understanding of the cannabis gray market. Cannabis regulatory science is a developing field that can improve our understanding of the cannabis regulatory ecosystem and provide regulatory officials and policymakers alike with much needed data to inform regulatory decision-making and improve the success and uptake of state-sponsored cannabis programs.

Personal characteristics associated with switching from Cigarettes to Non-combustible tobacco and nicotine products among U.S. adults: Findings from PATH Study Wave 1 - Wave 5.

INTRODUCTION: Reducing the disease burden from tobacco smoking may encompass switching to non-combustible (NCs), along with cessation. This study evaluates factors associated with switching to NCs (e-cigarettes, smokeless, snus) versus continued smoking, complete cessation, or dual use. METHODS: Population Assessment of Tobacco and Health adult data were analyzed in three two-year wave pairs across 2013-2019 to assess product transitions among people who exclusively smoked tobacco. Generalized estimating equations examined demographics, smoking characteristics, perceptions, and messaging exposure as predictors of transitions from cigarette smoking. RESULTS: Ages 18-44 years (ref=65+; aORs=3.79-5.92), males (aOR=1.18, 95%CI[1.01,1.37]), and perceiving NCs as less harmful than smoking (ref=not; aOR=1.47, 95%CI[1.28,1.69]) were positively associated with switching to NCs versus continued smoking, while being Black (ref=White; aOR=0.36, 95%CI[0.26,0.48]) or Hispanic (ref=Non-Hispanic; aOR=0.59, 95%CI[0.45,0.78]) were negatively associated. Ages 18-64 years (aORs=2.49-5.89), noticing promotional ads (ref=not; aOR=1.34, 95%CI[1.14,1.58]), daily light or heavy smoking (ref=nondaily; aORs=2.33-3.72), and smoking within 30 mins of waking (ref=>30min; aOR=1.47, 95%CI[1.18,1.85]) were positively associated with switching to NCs versus cessation, while being Black (aOR=0.55, 95%CI[0.38,0.74]) or Hispanic (aOR=0.52, 95%CI[0.38,0.71]) were negatively associated.. Incomes of $10,000->$100,000 (ref=<$10,000; aORs=2.08-3.13) and daily heavy smoking (aOR=1.96, 95%CI[1.11,3.48]) were positively associated with switching to NCs versus dual use, while being male (aOR=0.44, 95%CI[0.29,0.65]) was negatively associated. CONCLUSION: Transitioning to NCs was unequally distributed among sociodemographic groups and smoking characteristics. The mere availability of NCs may not promote health equity. Continued market and regulatory efforts that promote both smoking cessation and transitioning to NCs among various populations may promote public health gains. IMPLICATIONS: This study examines factors associated with transitioning from smoking to non-combustible tobacco product use. We examined three different product use scenarios that may be associated with varied levels of exposure to harm. We observed that younger ages and perceiving NCs as less harmful than cigarettes were more likely to transition to NCs as compared to continued smoking and cessation, while Black or Hispanic individuals were less likely to transition to NCs. This highlights the need for more focused harm reduction efforts for racial and ethnic minority populations as a complementary strategy to cessation to reduce health disparities from smoking.

The single-cell opioid responses in the context of HIV (SCORCH) consortium.

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.

A master regulator of opioid reward in the ventral prefrontal cortex.

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express µ-opioid receptors (µORs). Disrupting µOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.

Social intuition: behavioral and neurobiological considerations.

Social intuition is instrumental in bringing about successful human interactions, yet its behavioral and neural underpinnings are still poorly understood. We focus in this article on the automatic, involuntary, nature of social intuition, rather than on higher-level cognitive and explicit Theory-of-Mind processes (which contribute to rendering social intuition meaningful in real-life situations). We argue that social-affective implicit learning plays a crucial role in establishing automatic social intuition. These implicit learning processes involve associations between the perception of other's bodily articulations, concurrent events, and the consequences or outcomes in terms of subsequent actions, affective valences and visceral states. The traditional non-social implicit learning paradigms do not allow one to draw conclusions about the role of implicit learning processes in social intuition, as they lack these vital characteristics typically associated with human actions. We introduce a new implicit learning paradigm, which aims to fill these gaps. It targets agile, rapid, social-affective learning processes, involving cue contingencies with a relatively simple structure, unlike the very complex structures that underpin the traditional tasks. The paradigm features matching social and non-social versions, allowing direct comparison. Preliminary data suggest equal performance of TD (typically-developed) and ASC (autism spectrum conditions) groups on the non-social version, but impaired implicit learning in ASC on the social version. We hypothesize that this reflects an anomalous use of implicitly learned affective information in ASC when judging other people. We further argue that the mirror neuron mechanism (MNM), which is part of the Action Observation Network, forms an integral part of the neural substrate for social intuition. In particular as there are indications that the MNM supports action anticipation, and that implicitly learned information can trigger MNM activation, which both seem vital to a social intuition ability. The insights that can be derived from comparing the performances of TD and ASC individuals on (non)social implicit learning tasks, and the implications for the role of MNM activation, are discussed.

Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are a dominant cell type in the stroma of non-small cell lung cancer (NSCLC). Fibroblast heterogeneity reflects subpopulations of CAFs, which can influence prognosis and treatment efficacy. We describe the subtypes of CAFs in NSCLC. METHODS: Primary human NSCLC resections were assessed by flow cytometry and multiplex immunofluorescence for markers of fibroblast activation which allowed identification of CAF subsets. Survival data were analysed for our NSCLC cohort consisting of 163 patients to understand prognostic significance of CAF subsets. RESULTS: We identified five CAF populations, termed CAF S1-S5. CAF-S5 represents a previously undescribed population, and express FAP and PDPN but lack the myofibroblast marker αSMA, whereas CAF-S1 populations express all three. CAF-S5 are spatially further from tumour regions then CAF-S1 and scRNA data demonstrate an inflammatory phenotype. The presence of CAF-S1 or CAF-S5 is correlated to worse survival outcome in NSCLC, despite curative resection, highlighting the prognostic importance of CAF subtypes in NSCLC. TCGA data suggest the predominance of CAF-S5 has a poor prognosis across several cancer types. CONCLUSION: This study describes the fibroblast heterogeneity in NSCLC and the prognostic importance of the novel CAF-S5 subset where its presence correlates to worse survival outcome.

FABEL: Forecasting Animal Behavioral Events with Deep Learning-Based Computer Vision.

Behavioral neuroscience aims to provide a connection between neural phenomena and emergent organism-level behaviors. This requires perturbing the nervous system and observing behavioral outcomes, and comparing observed post-perturbation behavior with predicted counterfactual behavior and therefore accurate behavioral forecasts. In this study we present FABEL, a deep learning method for forecasting future animal behaviors and locomotion trajectories from historical locomotion alone. We train an offline pose estimation network to predict animal body-part locations in behavioral video; then sequences of pose vectors are input to deep learning time-series forecasting models. Specifically, we train an LSTM network that predicts a future food interaction event in a specified time window, and a Temporal Fusion Transformer that predicts future trajectories of animal body-parts, which are then converted into probabilistic label forecasts. Importantly, accurate prediction of food interaction provides a basis for neurobehavioral intervention in the context of compulsive eating. We show promising results on forecasting tasks between 100 milliseconds and 5 seconds timescales. Because the model takes only behavioral video as input, it can be adapted to any behavioral task and does not require specific physiological readouts. Simultaneously, these deep learning models may serve as extensible modules that can accommodate diverse signals, such as in-vivo fluorescence imaging and electrophysiology, which may improve behavior forecasts and elucidate invervention targets for desired behavioral change.

Amygdala-liver signaling orchestrates rapid glycemic responses to stress and drives stress-induced metabolic dysfunction.

Behavioral adaptations to environmental threats are crucial for survival and necessitate rapid deployment of energy reserves. The amygdala coordinates behavioral adaptations to threats, but little is known about its involvement in underpinning metabolic adaptations. Here, we show that acute stress activates medial amygdala (MeA) neurons that innervate the ventromedial hypothalamus (MeAVMH neurons), which precipitates hyperglycemia and hypophagia. The glycemic actions of MeAVMH neurons occur independent of adrenal or pancreatic glucoregulatory hormones. Instead, using whole-body virus tracing, we identify a polysynaptic connection from MeA to the liver, which promotes the rapid synthesis of glucose by hepatic gluconeogenesis. Repeated stress exposure disrupts MeA control of blood glucose and appetite, resulting in diabetes-like dysregulation of glucose homeostasis and weight gain. Our findings reveal a novel amygdala-liver axis that regulates rapid glycemic adaptations to stress and links recurrent stress to metabolic dysfunction.

Nicotine, Humectants, and Tobacco-Specific Nitrosamines (TSNAs) in IQOS Heated Tobacco Products (HTPs): A Cross-Country Study.

Heated Tobacco Products (HTPs) purport to reduce exposure to tobacco-related toxicants compared to combustible cigarettes. This cross-sectional study examined the content of nicotine, two humectants (propylene glycol (PG) and vegetable glycerin (VG)), and four tobacco-specific nitrosamines (TSNAs: NNN, NNK, NAT, and NAB) in the tobacco filler of a popular HTP brand (IQOS). Non-menthol and menthol IQOS sticks were purchased from nine countries between 2017 and 2020 and were classified into two versions ("Bold" and "Light") using Philip Morris's flavor descriptors. The average nicotine concentration was 4.7 ± 0.5 mg/stick, and the highest nicotine concentration was found in products from Japan (5.1 ± 0.2 mg/stick). VG was the dominant humectant found in all sticks, with an average concentration of (31.5 ± 2.3 mg/stick). NNN, NNK, and NAT were substantially higher in the "Bold" sticks than the "Light" sticks. Significant differences between countries for TSNAs were also observed: the NAT and NAB contents were the highest in the "Light" products from Canada (192.5 ± 24.1 and 22.9 ± 1.0 ng/stick, respectively); the NNK concentration was the highest in the "Bold" products from Poland (64.8 ± 7.9 ng/stick); and the highest NNN concentrations were observed in the "Bold" products from South Africa (488.9 ± 26.7 ng/stick). As NNN and NNK are known human carcinogens, and as humectants like PG and VG can degrade into toxic carbonyl compounds upon heating, monitoring the concentration of these chemicals in HTPs is important for protecting users' health and ensuring compliance with regulations.

How to Identify e-Cigarette Brands Available in the United States During 2020-2022: Development and Usability Study.

BACKGROUND: Prior studies have demonstrated that the e-cigarette market contains a large number of brands. Identifying these existing e-cigarette brands is a key element of market surveillance, which will further assist in policy making and compliance checks. OBJECTIVE: To facilitate the surveillance of the diverse product landscape in the e-cigarette market, we constructed a semantic database of e-cigarette brands that have appeared in the US market as of 2020-2022. METHODS: In order to build the brand database, we searched and compiled e-cigarette brands from a comprehensive list of retail channels and sources, including (1) e-liquid and disposable brands sold in web-based stores, (2) e-cigarette brands sold in brick-and-mortar stores and collected by the Nielsen Retail Scanner Data, (3) e-cigarette brands compiled by Wikipedia, (4) self-reported e-cigarette brands from the 2020 International Tobacco Control Four-Country Smoking and Vaping (ITC 4CV) US survey, and (5) e-cigarette brands on Twitter. We also estimated the top 5 e-cigarette brands by sales volume in brick-and-mortar stores, by the frequency and variety of offerings in web-based shops, and by the frequency of self-reported brands from the 2020 ITC 4CV US survey. RESULTS: As of 2020-2022, a total of 912 e-cigarette brands have been sold by various retail channels. During 2020-2022, the top 5 brands are JUUL, vuse, njoy, blu, and logic in brick-and-mortar stores; blu, king, monster, twist, and air factory for e-liquids in web-based stores; hyde, pod mesh, suorin, vaporlax, and xtra for disposables sold in web-based stores; and smok, aspire, vaporesso, innokin, and eleaf based on self-reported survey data. CONCLUSIONS: As the US Food and Drug Administration enforces the premarket tobacco market authorization, many e-cigarette brands may become illegal in the US market. In this context, how e-cigarette brands evolve and consolidate in different retail channels will be critical for understanding the regulatory impacts on product availability. Our semantic database of e-cigarette brands can serve as a useful tool to monitor product and marketplace development, conduct compliance checks, assess manufacturers' marketing behaviors, and identify regulatory impacts.

Acute effects of charcoal filters and package color on cigarette perceptions and use behaviors: Results from a randomized pilot study examining Natural American Spirit "Sky".

INTRODUCTION: Charcoal-filtered cigarettes have been available for decades but have never held a major share of the U.S. cigarette market. This pilot study gathered initial behavioral data characterizing how "Sky"-a recently introduced charcoal-filtered cigarette variety that uses potentially misleading marketing features-is used and what impact its packaging color has on consumer perceptions. METHODS: Forty adult daily non-menthol cigarettes users (52.5% male, 75.0% White, mean age = 46.1, 14.3 mean cigarettes/day) completed a single-session deception study utilizing a 2 ×2 mixed factorial design to manipulate cigarette filter condition (charcoal vs. non-charcoal) and pack color (light vs. dark). Participants smoked two cigarettes identical in appearance and packaging but differing in filter type (blinded and order counterbalanced) and completed pre- and post-cigarette CO samples and post-cigarette questionnaires. RESULTS: Participants endorsed more favorable subjective ratings, puffed less of, held more correct beliefs about risks, and expressed greater intentions to use the charcoal (vs. non-charcoal)-filtered cigarette (p's <0.05). Pack color had few effects on outcomes; however, cigarettes in light vs. dark colored packs were rated as cleaner tasting (p <0.01). Neither filter condition nor pack color affected CO boost. There were no interaction effects on any outcomes. CONCLUSIONS: Under blinded conditions, Sky charcoal-filtered cigarettes are initially appealing independent of their packaging color. Findings warrant further study of these effects on perceptions, behavior, and harm exposure after longer, open-label use periods. Findings may inform regulatory decisions regarding cigarette packaging and filter composition.

Rethinking egocentric bias: A computer mouse-tracking study of adult belief processing.

Several theories of belief processing assume that processing another's false belief requires overcoming an egocentric bias toward one's current knowledge. The current evidence in support of this claim, however, is limited. In order to investigate the presence of egocentric bias in adult belief processing, computer mouse tracking was used across three experiments to measure attraction toward response options reflecting one's current knowledge while reporting a false belief. Participants viewed scenarios in which an agent either had a true belief or a false belief about the location of a set of keys. Participants used a mouse to answer reality questions "where are the keys currently hidden?" and belief questions "where does she think the keys are?" Mouse-tracking measures indexing attraction toward response options during decision making were measured, along with time taken to make a response and accuracy. Experiment 1 found no evidence, in any measures, that participants showed a bias toward their own knowledge when reporting another's false belief. Experiment 2 investigated whether differences in event timings between true belief and false belief scenarios in Experiment 1 masked an egocentric bias. Experiment 3 investigated whether the lack of egocentric bias could be explained by participants prioritizing encoding the other's beliefs. Neither follow-up experiment found evidence supporting the presence of an egocentric bias. Overall, contrary to many theories of belief processing, our results suggest that adults are readily able to process other people's beliefs without having to overcome a default bias toward their own knowledge. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Chemicals in cigarette flavor capsules from Guatemala and Mexico.

BACKGROUND: The global market share for cigarettes with flavor capsules has grown exponentially over the last decade, particularly in Latin America. When smoking, consumers crush a liquid capsule in the filter that flavors the smoke. Little is known about the chemical constituents of the liquids in capsules or their potential health risks. METHODS: Based on consumer data and availability in Mexico and Guatemala, 31 flavor capsule brands were purchased (19 and 12, respectively) in 2020. Since some cigarettes included multiple capsules in a stick (up to 2) or pack (up to 4), the final analytic sample included 50 capsules. We conducted qualitative and quantitative analysis using gas chromatography with mass spectrometry (GC-MS, Agilent Technologies, Inc.). RESULTS: The qualitative analysis detected 296 compounds (range=9 to 67 per capsule), and all capsules contained menthol. Among the compounds detected in more than half the sample were limonene, menthone, benzaldehyde, eucalyptol and triacetin. Traces of nicotine were found in 22% of the capsules. In the quantitative analysis, menthol concentrations were 33 times greater than the next most common compound (limonene). Benzyl alcohol and vanillin were also found in high concentrations. Comparing same brand varieties across countries showed substantial variability in the concentration of menthol and other compounds. CONCLUSION: Menthol is an omnipresent constituent in capsule cigarettes, perhaps because of its anesthetizing and reinforcing addictive properties. Other compounds found are toxic, potentially carcinogenic, and may enhance addictiveness. Variance in the presence and concentrations of such compounds highlights the importance of product standards to regulate capsule content. IMPLICATIONS: This study evaluated the chemical content of capsule cigarettes from two Latin American countries that have two of the highest market shares for capsule cigarettes worldwide. Compared to other studies, our assessment included brand varieties from two countries to compare the differences in chemical content by country. Our results yield that menthol is found in all capsules, and that other chemicals found may prolong nicotine exposure and therefore reinforce the addictive properties of cigarettes.

Tobacco-Free Oral Nicotine Product Use Among Youth in the U.S., 2019-2021.

Introduction: Novel tobacco-free oral nicotine products are not combusted, easy to conceal, available in flavors, and do not contain tobacco leaf. Since 2016, oral nicotine product sales have increased and may be gaining popularity among youth. This study aims to examine the trends in the prevalence and correlates of oral nicotine product use among U.S. youth. Methods: Data from participants aged 16-19 years in the U.S. International Tobacco Control Policy Evaluation Project Youth Tobacco and Vaping Survey were analyzed cross-sectionally from August 2019, February 2020, August 2020, February 2021, and August 2021. Weighted descriptive statistics and logistic regressions were used to describe the use and correlates of oral nicotine products. Results: Oral nicotine product use significantly increased from 3.5% in August 2019 to 4.1% in August 2021. Oral nicotine product use was most prevalent among those aged 18 years, male, and non-Hispanic White. Those who used cigarettes (AOR=2.18, 95% CI=19.37, 40.88), nicotine vaping products (AOR=4.27, 95% CI=3.02, 6.04), and smokeless tobacco (AOR=28.14, 95% CI=19.37, 40.88) in the past 30 days were more likely to report recent use of oral nicotine products. Conclusions: Although oral nicotine products are less popular among U.S. youth than cigarettes, nicotine vaping products, and smokeless tobacco, their prevalence of use significantly increased. Oral nicotine product users are more likely to use other nicotine products, but the availability of flavors and easy-to-conceal design may be appealing to those who may not use nicotine products. Researchers should continue to observe the behaviors associated with oral nicotine product use to inform the need for future regulatory efforts.

Perceived Truthfulness of Reduced Lung Cancer Risk Advertising Claims Influences Consumers' Intention to try and to Purchase Snus.

The objective of the current study was to evaluate the impact of a reduced risk claim about lung cancer, presented in various formats, on smokers' and non-smokers' interest in trying Camel Snus and intention to purchase Camel Snus. We varied claim formats by varying advertising messages for Camel Snus in 4 ways (1) text only; (2) bar chart; (3) text/testimonial; and (4) bar chart/testimonial. 3001 participants were recruited from a web-based consumer specialty panel via an email invitation. In 2015, a second study was conducted, using similar methods, where 3001 additional participants were recruited. Overall, controlling for other factors, the presence of an MRTP claim was not significantly related to interest in trying snus [X2 (4) = 8.567, P = .073], or purchase intentions [X2 (4) = 1.148, P = .887]. Relative to a control ad where no explicit health risk claim was made, the Graphic + testimonial [OR = 1.29] or Text only [OR = 1.41] claims did significantly increase interest in trying Camel Snus. However, the adverting format did not impact interest in purchasing Camel Snus. While current smokeless tobacco users (95%) and smokers (59%) expressed interest in trying Camel Snus, non-tobacco users (7%) showed low interest in trying or purchasing Camel Snus (P < .001). Interest in trying Camel Snus was stronger in younger smokers compared to older smokers. Among current smokers, worry about lung cancer (the key focus of the reduced risk claim) was not associated with interest in trying Camel Snus or with purchase intention [OR = .91, 95% CI: .72, 1.14] or intention to purchase snus [OR = 1.07, 95% CI: .86, 1.32]. Future research should evaluate how claim and messaging formats influence perceived truthfulness and whether this effect differs among sub-groups of consumers, such as adolescents, those with tobacco-related disease, and former smokers. It will also be helpful to understand whether perceptions of ad truthfulness result in changes in product use patterns over time. In sum, giving people truthful, credible information about relative product risks, such as through authorized MRTP claims, is important, but such information is likely insufficient to get smokers to switch.

Associations between smokers' knowledge of causes of smoking harm and related beliefs and behaviors: Findings from the International Tobacco Control (ITC) Four Country Smoking and Vaping Survey.

BACKGROUND: Most smokers know that smoking is harmful to health, but less is known about their understanding of what causes the harms. The primary aim was to examine smokers' perceptions of the relative contributions to smoking-related morbidity from combustion products, nicotine, other substances present in unburned tobacco, and additives. A secondary aim was to evaluate the association of these perceptions with nicotine vaping product use intentions, and quitting motivation/intentions. METHODS: Participants were current smokers and recent ex-smokers from Australia, Canada, England and the United States (N = 12,904, including 8511 daily smokers), surveyed in the 2018 International Tobacco Control Four Country Smoking and Vaping Survey. Respondents reported on how much they thought combustion products, nicotine, chemicals in the tobacco and additives in cigarettes contribute to smoking-related morbidity (none/very little; some but less than half; around half; more than half; all or nearly all of it; don't know). RESULTS: Overall, 4% of participants provided estimates for all four component causes that fell within the ranges classified correct, with younger respondents and those from England most likely to be correct. Respondents who rated combustion as clearly more important than nicotine in causing harm (25%) were the least likely to be smoking daily and more likely to have quit and/or to be vaping. Among daily smokers, all four cause estimates were independently related to overall health worry and extent of wanting to quit, but the relative rating of combustion compared to nicotine did not add to prediction. Those who answered 'don't know' to the sources of harm questions and those suggesting very little harm were consistently least interested in quitting. CONCLUSIONS: Most smokers' knowledge of specific causes of harm is currently inadequate and could impact their informed decision-making ability.

Location of CD39+ T cell subpopulations within tumors predict differential outcomes in non-small cell lung cancer.

PURPOSE: An improved mechanistic understanding of immunosuppressive pathways in non-small cell lung cancer (NSCLC) is important to develop novel diagnostic and therapeutic approaches. Here, we investigate the prognostic significance of the ectonucleotidases CD39 and CD73 in NSCLC. EXPERIMENTAL DESIGN: The expression and localization of CD39, CD73 and CD103 was digitally quantified in a cohort of 162 early treatment naïve NSCLC patients using multiplex-immunofluorescence and related to patient outcome. Expression among different cell-populations was assessed via flow cytometry. Targeted RNA-Seq was performed on CD4+ and CD8+ T cells from digested NSCLC tumor tissue and single-cell RNA-Seq data was analyzed to investigate the functional significance of CD39+ T cell populations. RESULTS: We demonstrate that flow cytometry of early untreated NSCLC patients shows an upregulation of CD39 expression in the tumor tissue among natural killer (NK) cells, fibroblasts and T cells. CD73 expression is mainly found among fibroblasts and Epcam+cells in the tumor tissue. Multiplex Immunofluorescence in a cohort of 162 early untreated NSCLC patients demonstrates that CD39 expression is mainly localized in the tumor stroma while CD73 expression is equally distributed between tumor nest and stroma, and high expression of CD39 and CD73 in the tumor stroma is associated with poor recurrence-free survival (RFS) at 5 years. Additionally, we find that CD8+T cells located in the tumor nest express CD103 and the density of CD39+CD103+CD8+ T cells in the tumor nest predicts improved RFS at 5 years. Targeted RNA-Seq shows that the tumor microenvironment of NSCLC upregulates regulatory pathways in CD4+ T cells and exhaustion in CD8+ T cells, and analysis of a single cell RNA sequencing dataset shows that CD39+CD4+ cells are enriched in Treg signature gene-sets, and CD39+CD103+ cytotoxic T lymphocyte show gene signatures indicative of an exhausted cytotoxic phenotype with upregulated expression of CXCL13. CONCLUSIONS: Knowledge of patterns of distribution and location are required to understand the prognostic impact of CD39+ T cell populations in NSCLC. This study provides an improved understanding of spatial and functional characteristics of CD39+ T cells and their significance to patient outcome.

Patterns of Premium and Nonpremium Cigar Use in the United States: Findings from Wave 6 (2021) of the Population Assessment of Tobacco and Health Study.

INTRODUCTION: Understanding the characteristics of premium cigar use patterns is essential for minimizing public health harms. Typically, premium cigars are handmade, larger, more expensive, and without the characterizing flavors that are present in other cigar types: Nonpremium traditional cigars, cigarillos, and filtered cigars. AIMS AND METHODS: Self-reported brand and price data were used from Wave 6 of the Population Assessment of Tobacco and Health (PATH) Study to define and estimate premium versus nonpremium cigar use among U.S. adults, as well as to explore cigar smoking patterns, purchasing behavior, and reasons for use by cigar type. RESULTS: In 2021, 0.9% (95% CI = 0.7-1.0) of adults were premium cigar users, compared to 0.4% of nonpremium traditional cigar users (95% CI = 0.3-0.5), 1.1% of cigarillo users (95% CI = 1.0-1.2), and 0.6% filtered cigar users (95% CI = 0.5-0.7). Premium cigar users were overwhelmingly male (97.7%), and 35.8% were aged ≥55 years. The average premium cigar price/stick was $8.67, $5.50-7.00 more than other cigar types. Compared to other cigar types, significantly fewer premium cigar users had a regular brand with a flavor other than tobacco (~15% vs. 38%-53%). Though flavors remained the top reason for premium cigar use, they were less likely to endorse flavors as a reason for use than other cigar users (~40% vs. 68-74%). Premium cigar users had a lower prevalence (aRR: 0.37, 95% CI = 0.25-0.55) of dual use of cigars and cigarettes. CONCLUSIONS: Although <1% of U.S. adults use premium cigars, their use and purchasing characteristics continue to differ from other cigar types, highlighting the importance of capturing data specific to premium cigar use. IMPLICATIONS: This manuscript extends previous research from the National Academies of Science, Engineering, and Medicine report, "Premium cigars: Patterns of use, marketing, and health effects" by utilizing the most recent PATH Study data (Wave 6) to examine patterns of cigar use, including purchasing behavior and reasons for use, by cigar type (eg, premium traditional cigars, nonpremium traditional cigars, cigarillos, and filtered cigars). The findings support continued research on patterns of premium cigar use, which differ from use patterns of other cigar types.

Cancer-associated fibroblasts drive CXCL13 production in activated T cells via TGF-beta.

Introduction: Tumour-reactive T cells producing the B-cell attractant chemokine CXCL13, in solid tumours, promote development of tertiary lymphoid structures (TLS) and are associated with improved prognosis and responsiveness to checkpoint immunotherapy. Cancer associated fibroblasts are the dominant stromal cell type in non-small cell lung cancer (NSCLC) where they co-localise with T cells and can influence T cell activation and exhaustion. We questioned whether CAF directly promote CXCL13-production during T cell activation. Methods: We characterised surface markers, cytokine production and transcription factor expression in CXCL13-producing T cells in NSCLC tumours and paired non-cancerous lung samples using flow cytometry. We then assessed the influence of human NSCLC-derived primary CAF lines on T cells from healthy donors and NSCLC patients during activation in vitro measuring CXCL13 production and expression of cell-surface markers and transcription factors by flow cytometry. Results: CAFs significantly increased the production of CXCL13 by both CD4+ and CD8+ T cells. CAF-induced CXCL13-producing cells lacked expression of CXCR5 and BCL6 and displayed a T peripheral helper cell phenotype. Furthermore, we demonstrate CXCL13 production by T cells is induced by TGF-ß and limited by IL-2. CAF provide TGF-ß during T cell activation and reduce availability of IL-2 both directly (by reducing the capacity for IL-2 production) and indirectly, by expanding a population of activated Treg. Inhibition of TGF-ß signalling prevented both CAF-driven upregulation of CXCL13 and Treg expansion. Discussion: Promoting CXCL13 production represents a newly described immune-regulatory function of CAF with the potential to shape the immune infiltrate of the tumour microenvironment both by altering the effector-function of tumour infiltrating T-cells and their capacity to attract B cells and promote TLS formation.