Health Messaging Strategies for Vaping Prevention and Cessation Among Youth and Young Adults: A Systematic Review.

This systematic review evaluates health messaging strategies for the prevention and cessation of e-cigarette use among youth and young adults. Health messaging strategies were defined as the strategic process of developing messages with the intent to shape, reinforce, or change recipients' health attitudes and behaviors. McGuire's Communication/Persuasion Model guided the analysis of the messaging strategies, focusing on the model's five communication inputs (i.e. source, message, channel, audience, destination) and 14 persuasive outcomes. Nine databases were searched from January 2007 to September 2023. The inclusion criteria encompassed studies in English that presented quantitative data on messaging strategies aimed at discouraging vaping among youth and young adults. Each study was also coded for study characteristics and the utilization of theory. Out of 6,045 studies, 25 met the inclusion criteria. The reviewed studies exhibit a diverse array of research methods and a consistent integration of theories. The review emphasizes the nuanced main and interaction effects of various communication inputs, such as message features and audience characteristics, while also pointing out a research gap in message sources. In addition, the utilization of social media for effective messaging to engage the audience requires further research. Only one study specifically evaluated messaging strategies for vaping cessation. More research is imperative to develop targeted and tailored messages that effectively prevent and reduce vaping, especially among populations at higher risk of vaping-related harms, while also leveraging effective channels and innovative communication technologies to engage the audience.

A systematic review on the biochemical threshold of mitochondrial genetic variants.

Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measuring oxidative phosphorylation (OXPHOS) complex activities in relation to VAF. We identified 76 eligible publications, describing 69, 12, 16, and 49 cases for complexes I, III, IV, and V, respectively. Few studies evaluated OXPHOS activities in diverse tissue types, likely reflective of clinical access. A number of cases with similar VAFs for the same pathogenic variant had varying degrees of residual activity of the affected complex, alluding to the presence of modifying variants. Tissues and cells with VAFs <60% associated with low complex activities were described, suggesting the possibility of a biochemical threshold of <60%. Using Kendall rank correlation tests, the VAF of the m.8993T > G variant correlated with complex V activity in skeletal muscle (τ = -0.58, P = 0.01, n = 13); however, no correlation was observed in fibroblasts (P = 0.7, n = 9). Our systematic review highlights the need to investigate the biochemical threshold over a wider range of VAFs in disease-relevant cell types to better define the biochemical threshold for specific mtDNA variants.

Social media use, brand engagement, and tobacco product initiation among youth: Evidence from a prospective cohort study.

OBJECTIVE: To evaluate whether frequent social media use and liking/following tobacco brand accounts was associated with increased risk of tobacco and polytobacco initiation over approximately 1-year follow-up among youth with no prior tobacco use. METHODS: Associations between measures of social media engagement (daily social media use and liking/following tobacco brands) and tobacco initiation risk were examined using data from Waves 2 and 3 (2014-2015) of the US Population Assessment for Tobacco and Health study. Separate log-binomial models, accounting for missing data via multiple imputation and using propensity score adjustment to address confounding, estimated the adjusted relative risk (aRR) of any tobacco initiation and poly-use (2 + products) initiation at 1-year follow-up. RESULTS: Among the 8,672 youth with no prior tobacco use (49.3% female, mean [SD] age 14.1 [1.7]), 63.5% used social media at least daily, and 3.3% reported liking/following ≥ 1 tobacco brands on social media. Those reporting daily or more frequent social media use (compared to less) were at increased risk for tobacco (aRR 1.67; 95% CI 1.38-2.02) and polytobacco initiation (aRR 1.32; 95% CI 0.98-1.78). Although results were imprecise, liking/following ≥ 1 tobacco brands on social media (versus none) was associated with tobacco (aRR 1.34; 95% CI 0.95-1.89) or polytobacco initiation (aRR 1.60; 95% CI 0.99-2.60). In sensitivity analyses, liking/following cigarette or cigarillo brands was associated with polytobacco initiation. CONCLUSIONS: This study adds to a growing evidence-base describing the exposure of youth to tobacco-related social media content. Such content-often generated by tobacco companies-may contribute to youth tobacco initiation.

Teamwork makes the dream work: functional collaborations between families, scientists, and healthcare providers to drive progress in the treatment of Leigh Syndrome.

BACKGROUND: Leigh syndrome, an inherited neurometabolic disorder, is estimated to be the most common pediatric manifestation of mitochondrial disease. No treatments are currently available for Leigh syndrome due to many hurdles in drug discovery efforts. Leigh syndrome causal variants span over 110 different genes and likely lead to both unique and shared biochemical alterations, often resulting in overlapping phenotypic features. The mechanisms by which pathogenic variants in mitochondrial genes alter cellular phenotype to promote disease remain poorly understood. The rarity of cases of specific causal variants creates barriers to drug discovery and adequately sized clinical trials. BODY: To address the current challenges in drug discovery and facilitate communication between researchers, healthcare providers, patients, and families, the Boston University integrative Cardiovascular Metabolism and Pathophysiology (iCAMP) Lab and Cure Mito Foundation hosted a Leigh Syndrome Symposium. This symposium brought together expert scientists and providers to highlight the current successes in drug discovery and novel models of mitochondrial disease, and to connect patients to providers and scientists to foster community and communication. CONCLUSION: In this symposium review, we describe the research presented, the hurdles ahead, and strategies to better connect the Leigh syndrome community members to advance treatments for Leigh syndrome.

Patterns of use, perceptions, and cardiopulmonary health risks of cigar products: a systematic review.

OBJECTIVE: A systematic review was conducted to evaluate the use patterns, health perceptions, and cardiopulmonary health effects of cigars. DATA SOURCES: PubMed and Google Scholar were searched for peer-reviewed articles published between June 2014 and February 2021. Search keywords included cigars, cigarillos, little cigars, and cardiopulmonary health outcomes. STUDY SELECTION: Of 782 papers identified, we excluded non-English articles, review articles, commentaries, and those without empirical data on cigars. Three coders independently reviewed all articles and compared codes to resolve discrepancies. 93 articles met the inclusion criteria and were included. DATA SYNTHESIS: Cigars have evolved from premium cigars to encompass little cigars and cigarillos (LCCs). LCCs are available in an array of flavors and at a price advantage, and as a result, are used by different groups compared to premium cigars. LCCs are more frequently used by youth, young adults, and those who identify as Black/African American. LCCs are often used in combination with other tobacco products, alcohol, and cannabis. Despite limited regulation, cigars generate smoke of a similar composition as cigarettes. Among the studies identified, evidence suggests that cigar use is associated with cardiovascular and pulmonary toxicity. Higher all-cause and cancer-related mortalities are associated with cigar use, particularly with more frequent and deeper inhalation, compared to non-tobacco users. CONCLUSIONS: LCCs are used more frequently by at-risk groups compared to premium cigars. Recent studies evaluating cigar cardiopulmonary health effects are limited but suggest cigars have similar health risks as conferred by cigarette smoking. With the use of LCCs and targeted marketing on the rise among high-risk groups, there is a critical need for continued research in this area.

Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products: A Scientific Statement From the American Heart Association.

Vaping and electronic cigarette (e-cigarette) use have grown exponentially in the past decade, particularly among youth and young adults. Cigarette smoking is a risk factor for both cardiovascular and pulmonary disease. Because of their more limited ingredients and the absence of combustion, e-cigarettes and vaping products are often touted as safer alternative and potential tobacco-cessation products. The outbreak of e-cigarette or vaping product use-associated lung injury in the United States in 2019, which led to >2800 hospitalizations, highlighted the risks of e-cigarettes and vaping products. Currently, all e-cigarettes are regulated as tobacco products and thus do not undergo the premarket animal and human safety studies required of a drug product or medical device. Because youth prevalence of e-cigarette and vaping product use was as high as 27.5% in high school students in 2019 in the United States, it is critical to assess the short-term and long-term health effects of these products, as well as the development of interventional and public health efforts to reduce youth use. The objectives of this scientific statement are (1) to describe and discuss e-cigarettes and vaping products use patterns among youth and adults; (2) to identify harmful and potentially harmful constituents in vaping aerosols; (3) to critically assess the molecular, animal, and clinical evidence on the acute and chronic cardiovascular and pulmonary risks of e-cigarette and vaping products use; (4) to describe the current evidence of e-cigarettes and vaping products as potential tobacco-cessation products; and (5) to summarize current public health and regulatory efforts of e-cigarettes and vaping products. It is timely, therefore, to review the short-term and especially the long-term implications of e-cigarettes and vaping products on cardiopulmonary health. Early molecular and clinical evidence suggests various acute physiological effects from electronic nicotine delivery systems, particularly those containing nicotine. Additional clinical and animal-exposure model research is critically needed as the use of these products continues to grow.

Metabolomic Profiles, Ideal Cardiovascular Health, and Risk of Heart Failure and Atrial Fibrillation: Insights From the Framingham Heart Study.

Background The American Heart Association's framework "ideal cardiovascular health" (CVH) focuses on modifiable risk factors to reduce cardiovascular disease (CVD). Metabolomics provides important pathobiological insights into risk factors and CVD development. We hypothesized that metabolomic signatures associate with CVH status, and that metabolites, at least partially, mediate the association of CVH score with atrial fibrillation (AF) and heart failure (HF). Methods and Results We studied 3056 adults in the FHS (Framingham Heart Study) cohort to evaluate CVH score and incident outcomes of AF and HF. Metabolomics data were available in 2059 participants; mediation analysis was performed to evaluate the mediation of metabolites in the association of CVH score and incident AF and HF. In the smaller cohort (mean age, 54 years; 53% women), CVH score was associated with 144 metabolites, with 64 metabolites shared across key cardiometabolic components (body mass index, blood pressure, and fasting blood glucose) of the CVH score. In mediation analyses, 3 metabolites (glycerol, cholesterol ester 16:1, and phosphatidylcholine 32:1) mediated the association of CVH score with incident AF. Seven metabolites (glycerol, isocitrate, asparagine, glutamine, indole-3-proprionate, phosphatidylcholine C36:4, and lysophosphatidylcholine 18:2), partly mediated the association between CVH score and incident HF in multivariable-adjusted models. Conclusions Most metabolites that associated with CVH score were shared the most among 3 cardiometabolic components. Three main pathways: (1) alanine, glutamine, and glutamate metabolism; (2) citric acid cycle metabolism; and (3) glycerolipid metabolism mediated CVH score with HF. Metabolomics provides insights into how ideal CVH status contributes to the development of AF and HF.

Association Between Electrocardiographic Age and Cardiovascular Events in Community Settings: The Framingham Heart Study.

BACKGROUND: Deep neural networks have been used to estimate age from ECGs, the electrocardiographic age (ECG-age), which predicts adverse outcomes. However, this prediction ability has been restricted to clinical settings or relatively short periods. We hypothesized that ECG-age is associated with death and cardiovascular outcomes in the long-standing community-based FHS (Framingham Heart Study). METHODS: We tested the association of ECG-age with chronological age in the FHS cohorts in ECGs from 1986 to 2021. We calculated the gap between chronological and ECG-age (Δage) and classified individuals as having normal, accelerated, or decelerated aging, if Δage was within, higher, or lower than the mean absolute error of the model, respectively. We assessed the associations of Δage, accelerated and decelerated aging with death or cardiovascular outcomes (atrial fibrillation, myocardial infarction, and heart failure) using Cox proportional hazards models adjusted for age, sex, and clinical factors. RESULTS: The study population included 9877 FHS participants (mean age, 55±13 years; 54.9% women) with 34 948 ECGs. ECG-age was correlated to chronological age (r=0.81; mean absolute error, 9±7 years). After 17±8 years of follow-up, every 10-year increase of Δage was associated with 18% increase in all-cause mortality (hazard ratio [HR], 1.18 [95% CI, 1.12-1.23]), 23% increase in atrial fibrillation risk (HR, 1.23 [95% CI, 1.17-1.29]), 14% increase in myocardial infarction risk (HR, 1.14 [95% CI, 1.05-1.23]), and 40% increase in heart failure risk (HR, 1.40 [95% CI, 1.30-1.52]), in multivariable models. In addition, accelerated aging was associated with a 28% increase in all-cause mortality (HR, 1.28 [95% CI, 1.14-1.45]), whereas decelerated aging was associated with a 16% decrease (HR, 0.84 [95% CI, 0.74-0.95]). CONCLUSIONS: ECG-age was highly correlated with chronological age in FHS. The difference between ECG-age and chronological age was associated with death, myocardial infarction, atrial fibrillation, and heart failure. Given the wide availability and low cost of ECG, ECG-age could be a scalable biomarker of cardiovascular risk.

The Mighty NUMT: Mitochondrial DNA Flexing Its Code in the Nuclear Genome.

Nuclear-mitochondrial DNA segments (NUMTs) are mitochondrial DNA (mtDNA) fragments that have been inserted into the nuclear genome. Some NUMTs are common within the human population but most NUMTs are rare and specific to individuals. NUMTs range in size from 24 base pairs to encompassing nearly the entire mtDNA and are found throughout the nuclear genome. Emerging evidence suggests that the formation of NUMTs is an ongoing process in humans. NUMTs contaminate sequencing results of the mtDNA by introducing false positive variants, particularly heteroplasmic variants present at a low variant allele frequency (VAF). In our review, we discuss the prevalence of NUMTs in the human population, the potential mechanisms of de novo NUMT insertion via DNA repair mechanisms, and provide an overview of the existing approaches for minimizing NUMT contamination. Apart from filtering known NUMTs, both wet lab-based and computational methods can be used to minimize the contamination of NUMTs in analyses of human mtDNA. Current approaches include: (1) isolating mitochondria to enrich for mtDNA; (2) applying basic local alignment to identify NUMTs for subsequent filtering; (3) bioinformatic pipelines for NUMT detection; (4) k-mer-based NUMT detection; and (5) filtering candidate false positive variants by mtDNA copy number, VAF, or sequence quality score. Multiple approaches must be applied in order to effectively identify NUMTs in samples. Although next-generation sequencing is revolutionizing our understanding of heteroplasmic mtDNA, it also raises new challenges with the high prevalence and individual-specific NUMTs that need to be handled with care in studies of mitochondrial genetics.

A Longitudinal Study of Perceptions of the Massachusetts Menthol Ban and Its Impact on Smoking Behaviors among Marginalized Individuals.

Menthol cigarettes have had a profound adverse effect on public health. On 1 June 2020, Massachusetts became the first state to ban the sale of menthol cigarettes. We explored how perceptions of the ban and smoking behaviors changed over time among a group of 27 individuals who smoked menthol cigarettes at our safety-net hospital. In a convergent mixed methods study, we administered questionnaires and interviews simultaneously at two timepoints: 1 month pre-ban and 6 months post-ban. Pre-ban, we assessed perceptions of the ban and anticipated smoking behaviors after the ban. Post-ban, we assessed participants' actual smoking behaviors and elicited suggestions to avoid unintended consequences that might undermine intended policy effects. Several respondents perceived the Massachusetts ban as positive because it could promote smoking cessation, prevent youth initiation, and mitigate unfair targeting of socioeconomically disadvantaged populations. Others perceived the ban as an overreach of government policy, financially motivated, and unfairly targeting the Black community. Many continued to smoke menthol cigarettes obtained outside Massachusetts. Individuals suggested promoting tobacco treatment for people affected by the ban and a national ban to circumvent out-of-state purchasing of menthol cigarettes. Our findings suggest that in order to be most effective, healthcare systems must promote tobacco treatment and ensure that treatment is accessible to all individuals affected by the ban.

Compliance With the US Food and Drug Administration's Guidelines for Health Warning Labels and Engagement in Little Cigar and Cigarillo Content: Computer Vision Analysis of Instagram Posts.

Background: Health warnings in tobacco advertisements provide health information while also increasing the perceived risks of tobacco use. However, existing federal laws requiring warnings on advertisements for tobacco products do not specify whether the rules apply to social media promotions. Objective: This study aims to examine the current state of influencer promotions of little cigars and cigarillos (LCCs) on Instagram and the use of health warnings in influencer promotions. Methods: Instagram influencers were identified as those who were tagged by any of the 3 leading LCC brand Instagram pages between 2018 and 2021. Posts from identified influencers, which mentioned one of the three brands were considered LCC influencer promotions. A novel Warning Label Multi-Layer Image Identification computer vision algorithm was developed to measure the presence and properties of health warnings in a sample of 889 influencer posts. Negative binomial regressions were performed to examine the associations of health warning properties with post engagement (number of likes and comments). Results: The Warning Label Multi-Layer Image Identification algorithm was 99.3% accurate in detecting the presence of health warnings. Only 8.2% (n=73) of LCC influencer posts included a health warning. Influencer posts that contained health warnings received fewer likes (incidence rate ratio 0.59, P<.001, 95% CI 0.48-0.71) and fewer comments (incidence rate ratio 0.46, P<.001, 95% CI 0.31-0.67). Conclusions: Health warnings are rarely used by influencers tagged by LCC brands' Instagram accounts. Very few influencer posts met the US Food and Drug Administration's health warning requirement of size and placement for tobacco advertising. The presence of a health warning was associated with lower social media engagement. Our study provides support for the implementation of comparable health warning requirements to social media tobacco promotions. Using an innovative computer vision approach to detect health warning labels in influencer promotions on social media is a novel strategy for monitoring health warning compliance in social media tobacco promotions.

Pod-based e-liquids impair human vascular endothelial cell function.

Pod-based electronic (e-) cigarettes more efficiently deliver nicotine using a protonated formulation. The cardiovascular effects associated with these devices are poorly understood. We evaluated whether pod-based e-liquids and their individual components impair endothelial cell function. We isolated endothelial cells from people who are pod users (n = 10), tobacco never users (n = 7), and combustible cigarette users (n = 6). After a structured use, pod users had lower acetylcholine-mediated endothelial nitric oxide synthase (eNOS) activation compared with never users and was similar to levels from combustible cigarette users (overall P = 0.008, P = 0.01 pod vs never; P = 0.96 pod vs combustible cigarette). The effects of pod-based e-cigarettes and their constituents on vascular cell function were further studied in commercially available human aortic endothelial cells (HAECs) incubated with flavored JUUL e-liquids or propylene glycol (PG):vegetable glycerol (VG) at 30:70 ratio with or without 60 mg/mL nicotine salt for 90 min. A progressive increase in cell death with JUUL e-liquid exposure was observed across 0.0001-1% dilutions; PG:VG vehicle with and without nicotine salt induced cell death. A23187-stimulated nitric oxide production was decreased with all JUUL e-liquid flavors, PG:VG and nicotine salt exposures. Aerosols generated by JUUL e-liquid heating similarly decreased stimulated nitric oxide production. Only mint flavored e-liquids increased inflammation and menthol flavored e-liquids enhanced oxidative stress in HAECs. In conclusion, pod e-liquids and their individual components appear to impair endothelial cell function. These findings indicate the potential harm of pod-based devices on endothelial cell function and thus may be relevant to cardiovascular injury in pod type e-cigarette users.

Association of electronic cigarette use with circulating angiogenic cell levels in healthy young adults: Evidence for chronic systemic injury.

BACKGROUND: Circulating angiogenic cells (CACs) are indicative of vascular health and repair capacity; however, their relationship with chronic e-cigarette use is unclear. This study aims to assess the association between e-cigarette use and CAC levels. METHODS: We analyzed CAC levels in 324 healthy participants aged 21-45 years from the cross-sectional Cardiovascular Injury due to Tobacco Use study in four groups: never tobacco users (n = 65), sole e-cigarette users (n = 19), sole combustible cigarette users (n = 212), and dual users (n = 28). A total of 15 CAC subpopulations with four cell surface markers were measured using flow cytometry: CD146 (endothelial), CD34 (stem), CD45 (leukocyte), and AC133 (early progenitor/stem). Generalized linear models with gamma distribution and log-link were generated to assess association between CACs and smoking status. Benjamini-Hochberg were used to adjust p-values for multiple comparisons. RESULTS: The cohort was 47% female, 51% Black/African American, with a mean (± SD) age of 31 ± 7 years. Sole cigarette use was significantly associated with higher levels of two endothelial marker CACs (Q ⩽ 0.05). Dual users had higher levels of four endothelial marker CACs and one early progenitor/stem marker CAC (Q ⩽ 0.05). Sole e-cigarette users had higher levels of one endothelial and one leukocyte marker CAC (Q ⩽ 0.05). CONCLUSION: Dual use of e-cigarettes and combustible cigarettes was associated with higher levels of endothelial origin CACs, indicative of vascular injury. Sole use of e-cigarettes was associated with higher endothelial and inflammatory CACs, suggesting ongoing systemic injury. Distinct patterns of changes in CAC subpopulations suggest that CACs may be informative biomarkers of changes in vascular health due to tobacco product use.

Systematic dissection, preservation, and multiomics in whole human and bovine hearts.

OBJECTIVES: We sought to develop a rigorous, systematic protocol for the dissection and preservation of human hearts for biobanking that expands previous success in postmortem transcriptomics to multiomics from paired tissue. BACKGROUND: Existing cardiac biobanks consist largely of biopsy tissue or explanted hearts in select diseases and are insufficient for correlating whole organ phenotype with clinical data. METHODS: We demonstrate optimal conditions for multiomics interrogation (ribonucleic acid (RNA) sequencing, untargeted metabolomics) in hearts by evaluating the effect of technical variables (storage solution, temperature) and simulated postmortem interval (PMI) on RNA and metabolite stability. We used bovine (n=3) and human (n=2) hearts fixed in PAXgene or snap-frozen with liquid nitrogen. RESULTS: Using a paired Wald test, only two of the genes assessed were differentially expressed between left ventricular samples from bovine hearts stored in PAXgene at 0 and 12 hours PMI (FDR q<0.05). We obtained similar findings in human left ventricular samples, suggesting stability of RNA transcripts at PMIs up to 12 hours. Different library preparation methods (mRNA poly-A capture vs. rRNA depletion) resulted in similar quality metrics with both library preparations achieving >95% of reads properly aligning to the reference genomes across all PMIs for bovine and human hearts. PMI had no effect on RNA Integrity Number or quantity of RNA recovered at the time points evaluated. Of the metabolites identified (855 total) using untargeted metabolomics of human left ventricular tissue, 503 metabolites remained stable across PMIs (0, 4, 8, 12 hours). Most metabolic pathways retained several stable metabolites. CONCLUSIONS: Our data demonstrate a technically rigorous, reproducible protocol that will enhance cardiac biobanking practices and facilitate novel insights into human CVD. CONDENSED ABSTRACT: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Current biobanking practices insufficiently capture both the diverse array of phenotypes present in CVDs and the spatial heterogeneity across cardiac tissue sites. We have developed a rigorous and systematic protocol for the dissection and preservation of human cardiac biospecimens to enhance the availability of whole organ tissue for multiple applications. When combined with longitudinal clinical phenotyping, our protocol will enable multiomics in hearts to deepen our understanding of CVDs.

Moralization of E-cigarette Use and Regulation: A Mixed-Method Computational Analysis of Opinion Polarization.

E-cigarette use, or vaping, is undergoing a process of moralization in which issues about vaping evolve from being morally neutral to having discernible moral implications. Using Moral Foundations Theory, this study compared the moral narratives underlying polarized views about e-cigarette use and regulation. We integrated computational and human strategies by conducting the Chow test on the time series data and classification, topic modeling, and Chi-square tests on posts (N = 2,669) from 26 pro-vaping and 19 anti-vaping Facebook Pages. The observation period (August 1, 2019 to March 5, 2020) encompassed the outbreak of "e-cigarette or vaping product use associated lung injury" (EVALI), deaths and subsequent legislation. Results revealed that pro-vaping posts were more likely than anti-vaping posts to mention Fairness/cheating and Authority/subversion, involving a conspiracy belief in an "e-cigarettes vs. Big Tobacco" rivalry, while anti-vaping posts were more likely to mention Sanctity/degradation. There were no significant differences between pro-vaping and anti-vaping posts in the likelihood of mentioning Care/harm or Loyalty/betrayal. Nevertheless, according to the topic modeling results, the use of moral foundations varied between pro-vaping and anti-vaping narratives, with the meanings of Care/harm and Loyalty/betrayal dependent on the post author's group affiliation. Health interventions can tailor persuasive messages to different moral values and debunk misinformation about public health policies to mitigate the vaping epidemic. Theoretical implications are also discussed.

The Impact of Influencers on Cigar Promotions: A Content Analysis of Large Cigar and Swisher Sweets Videos on TikTok.

Little is known about the content, promotions, and individuals in cigar-related videos on TikTok. TikTok videos with large cigar and Swisher Sweets-related hashtags between July 2016 and September 2020 were analyzed. Follower count was used to identify influencers. We compared content characteristics and demographics of featured individuals between cigar types, and by influencer status. We also examined the association between content characteristics and video engagement. Compared to large cigar videos, Swisher Sweets videos were more likely to feature arts and crafts with cigar packages, cannabis use, and flavored products. In addition, Swisher Sweets videos were also more likely to feature females, Black individuals, and younger individuals. Both Swisher Sweets and large cigar influencers posted more videos of cigar purchasing behaviors than non-influencers, which was associated with more video views. None of the videos disclosed sponsorship with #ad or #sponsored. Videos containing the use of cigar packages for arts and crafts, and flavored products highlight the importance of colorful packaging and flavors in the appeal of Swisher Sweets cigars, lending support for plain packaging requirements and the prohibition of flavors in cigar products to decrease the appeal of cigars. The presence and broad reach of cigar promotions on TikTok requires stricter enforcement of anti-tobacco promotion policies.

A bioinformatics pipeline for estimating mitochondrial DNA copy number and heteroplasmy levels from whole genome sequencing data.

Mitochondrial diseases are a heterogeneous group of disorders that can be caused by mutations in the nuclear or mitochondrial genome. Mitochondrial DNA (mtDNA) variants may exist in a state of heteroplasmy, where a percentage of DNA molecules harbor a variant, or homoplasmy, where all DNA molecules have the same variant. The relative quantity of mtDNA in a cell, or copy number (mtDNA-CN), is associated with mitochondrial function, human disease, and mortality. To facilitate accurate identification of heteroplasmy and quantify mtDNA-CN, we built a bioinformatics pipeline that takes whole genome sequencing data and outputs mitochondrial variants, and mtDNA-CN. We incorporate variant annotations to facilitate determination of variant significance. Our pipeline yields uniform coverage by remapping to a circularized chrM and by recovering reads falsely mapped to nuclear-encoded mitochondrial sequences. Notably, we construct a consensus chrM sequence for each sample and recall heteroplasmy against the sample's unique mitochondrial genome. We observe an approximately 3-fold increased association with age for heteroplasmic variants in non-homopolymer regions and, are better able to capture genetic variation in the D-loop of chrM compared to existing software. Our bioinformatics pipeline more accurately captures features of mitochondrial genetics than existing pipelines that are important in understanding how mitochondrial dysfunction contributes to disease.

Fostering Tobacco Regulatory Team Science through a multisite, virtual fellowship program for early-career researchers.

INTRODUCTION: In an era of complex, multi-institutional, team-based science, there is little guidance for the successful creation of effective, collaborative, multisite training programs. OBJECTIVE: We designed, implemented, and evaluated a multi-institutional Tobacco Regulatory Science (TRS) fellowship representing a scalable program that may be customized for other research areas. METHODS: Using a mixed-methods approach, we analyzed program evaluations from trainees enrolled in the first 7 years of the American Heart Association (AHA) Tobacco Regulation and Addiction Center (A-TRAC) fellowship (2014-2021). We also reported the program outcomes, including published TRS manuscripts, independent grant funding, Food and Drug Administration (FDA) Docket comments submitted on TRS topics, TRS oral and poster presentations, research awards, and promotions in the TRS field. RESULTS: Thirty-five unique trainees (49% [n = 17] female, 29% [n = 10] Black) from eight institutions within the A-TRAC network participated in the fellowship since its inception. The trainees reported 74 TRS publications, 78 TRS oral or poster presentations, 25 FDA Docket comment submissions, and 13 funded grant awards. Participant evaluations indicated six areas of programmatic strength: 1) blended instruction medium with webinars and in-person meetings, 2) curricular emphasis on theories of experiential learning, 3) focus on career and professional development, 4) integrated mentorship model, 5) culture of feedback and feedforward to foster successful learning, and 6) focus on recruiting diverse participants. The A-TRAC model stresses experiential education, feedback and feedforward, and peer learning. CONCLUSIONS: Our resource-effective, needs-driven program is a reproducible model for institutions interested in developing multisite, virtual research education programs in the era of team science.

Comparison of mitochondrial DNA sequences from whole blood and lymphoblastoid cell lines.

Lymphoblastoid cell lines (LCLs) provide an unlimited source of genomic DNA for genetic studies. Here, we compared mtDNA sequence variants, heteroplasmic or homplasmic, between LCL (sequenced by mitoRCA-seq method) and whole blood samples (sequenced through whole genome sequencing approach) of the same 130 participants in the Framingham Heart Study. We applied harmonization of sequence coverages and consistent quality control to mtDNA sequences. We identified 866 variation sites in the 130 LCL samples and 666 sites in the 130 blood samples. More than 94% of the identified homoplasmies were present in both LCL and blood samples while more than 70% of heteroplasmic sites were uniquely present either in LCL or in blood samples. The LCL and whole blood samples carried a similar number of homoplasmic variants (p = 0.45) per sample while the LCL carried a greater number of heteroplasmic variants than whole blood per sample (p < 2.2e-16). Furthermore, the LCL samples tended to accumulate low level heteroplasmies (heteroplasmy level in 3-25%) than their paired blood samples (p = 0.001). These results suggest that cautions should be taken in the interpretation and comparison of findings when different tissues/cell types or different sequencing technologies are applied to obtain mtDNA sequences.

Association of Electronic Cigarette Use with Respiratory Symptom Development among U.S. Young Adults.

Rationale: Electronic cigarette (e-cigarette) use is highly prevalent among young adults. However, longitudinal data assessing the association between e-cigarette use and respiratory symptoms are lacking. Objectives: To determine whether e-cigarette use is associated with the development of respiratory symptoms in young adults. Methods: Data are derived from the PATH (Population Assessment of Tobacco and Health) study waves 2 (2014-2015), 3 (2015-2016), 4 (2016-2018), and 5 (2018-2019). Young adults aged 18-24 years at baseline with no prevalent respiratory disease or symptoms were included in the analyses. Binary logistic regression models with a generalized estimating equation were used to estimate time-varying and time-lagged associations of e-cigarette use during waves 2-4, with respiratory symptom development approximately 12 months later at waves 3-5. Measurements and Main Results: The per-wave prevalence of former and current e-cigarette use was 15.2% and 5.6%, respectively. Former e-cigarette use was associated with higher odds of developing any respiratory symptom (adjusted odds ratio [aOR], 1.20; 95% confidence interval [CI], 1.04-1.39) and wheezing in the chest (aOR, 1.41; 95% CI, 1.08-1.83) in multivariable adjusted models. Current e-cigarette use was associated with higher odds for any respiratory symptom (aOR, 1.32; 95% CI, 1.06-1.65) and wheezing in the chest (aOR, 1.51; 95% CI, 1.06-2.14). Associations persisted among participants who never smoked combustible cigarettes. Conclusions: In this nationally representative cohort of young adults, former and current e-cigarette use was associated with higher odds of developing wheezing-related respiratory symptoms, after accounting for cigarette smoking and other combustible tobacco product use.