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IntroductionLocal e-cigarette sales restrictions (ESRs) may impact e-cigarette use. This study examined the associations between living in localities with various ESR policies and changes in e-cigarette use among young adults in Los Angeles (LA) County, California, USA.MethodsData were from a cohort of LA County young adults (18–21 years; n=2100) who completed two waves of surveys (Fall 2018–Summer 2019 and Summer–Fall 2020). Local flavoured (n=9) and comprehensive (n=2) ESRs in LA County implemented between June 2019 and May 2020 were identified, coded and merged with the baseline data. Multivariable logistic regressions were used to examine the associations between living in ESR localities and e-cigarette use at follow-up, controlling for covariates and stratified by cigarette smoking at baseline.ResultsOverall, 20.9% and 14.3% of participants lived in localities with flavoured and comprehensive ESRs, respectively. Participants who were non-Hispanic, had higher socioeconomic statuses and were currently using e-cigarettes were generally more likely to live in ESR localities than their counterparts. The associations between living in ESR localities and e-cigarette use at follow-up were not found among baseline non-e-cigarette users regardless of their cigarette smoking status; a positive relationship was found among baseline e-cigarette users who also smoked cigarettes but not among non-smokers.DiscussionParticipants who lived in localities with various ESR policies were different in their baseline e-cigarette use and socioeconomic backgrounds. Future research examining the potential impact of ESRs on e-cigarette use change should consider the localities’ overall sociodemographic and tobacco-using characteristics and individuals’ cigarette smoking histories.

Younger age of initiating cigar smoking is associated with greater nicotine dependence and current use. Age of initiating cigarette smoking has increased over time, whereas trends in age of initiating cigar smoking remain understudied. These trends were examined by race/ethnicity, by education, and at their intersection.The analytic sample included U.S. Hispanic, Black, and White cigar-ever-smokers aged 24‒25 years (n=29,715) from the 2002‒2019 National Survey on Drug Use and Health. Participants reported their age, race/ethnicity, sex, education (≤high school; some college; ≥bachelor's degree), age of initiating cannabis use, and cigar smoking. Weighted multivariable linear regressions adjusted for sex and age of cannabis use initiation were used to examine trends in age of initiating cigar smoking by race/ethnicity, education, and education Χ year interactions within racial/ethnic groups. Age of initiating cigar smoking comparisons across race/ethnicity and education were examined using the most recent 2019 data.During 2002‒2019, across education, White cigar-ever-smokers started smoking cigars at an older age, whereas it remained unchanged among Hispanic cigar-ever-smokers. Among Black cigar-ever-smokers, age of initiating cigar smoking did not change among those with ≤high school and some college, and was older among those with ≥bachelor's degree. In 2019, age of initiating cigar smoking did not vary by educational level among Hispanic and White cigar-ever-smokers. Black cigar-ever-smokers with ≥bachelor's degree initiated cigar smoking at older ages than their White counterparts.Black individuals experienced widening education-related disparities, and Hispanic individuals had no progress in delaying age of initiating cigar smoking. Regulatory action banning cigar flavors may impact these trends.

This study assessed the hypothetical impact of flavored cigar sales restrictions on cigar smoking among Black young adult cigar smokers (ages 21-29). Forty in-depth interviews were conducted in 2020. Interviews were independently coded and analyzed using thematic analysis. When asked how they would smoke cigars given a flavor sales restriction, half of participants reported they would smoke in the same way, a third would stop or reduce smoking, and a few were unsure of what they would do. Cigar smoking outcome expectancies, preference for flavors, and perceived addictiveness of cigar products may predict cigar smoking change given flavor sales restrictions.

Purpose This study aims to examine the impact of the transformation of an assessment on students’ performance and perspectives in an English for Academic Purposes course in Hong Kong. The assessment was changed from the traditional pen-and-paper mode to an unproctored online mode. Design/methodology/approach Using mixed methods, the research team analysed the differences between the assessment performances of those who took the course before the pandemic (n = 664) and those who took it during the pandemic (n = 702). Furthermore, focus group interviews were conducted with seven students regarding their perspectives on the unproctored assessment. Findings The results revealed that, although there were no major differences in the overall grades of the two groups, students who were assessed online during the pandemic performed significantly better in terms of their English use. Nevertheless, the shift to online assessment had several negative effects on the students. Originality/value Previous studies on unproctored online assessments (UOA) were concerned with potential learning quality issues, such as plagiarism and grade inflation. This study, however, provided empirical evidence that high-quality assessment delivery can be provided via UOA if the question types and assessment arrangements are carefully decided.

With the outbreak of COVID-19 in 2020, many universities shifted to online teaching. However, some online instruction had already been implemented well before the pandemic. This study investigates (1) how engagement in blended CALL activities differed during the pandemic, and (2) in what ways the assessment outcomes were associated with student engagement during the pandemic. The study was conducted in an English for academic purposes (EAP) course at a Hong Kong university that had already implemented blended learning for several years. Adopting an analytics-based approach, 469,286 data logs in a learning management system were analyzed to measure students’ engagement and their respective self-directed behavior. The retrieved student data covered the time both before and during the pandemic. Our findings reveal that students were primarily engaged for assessment purposes; however, those in the pandemic cohort demonstrated better self-directed behavior, such as early and regular engagement. Although the results indicated a relatively strong association between student engagement and course outcomes, the students during the pandemic seem to have managed their learning more effectively.

Little is known about awareness, beliefs, and use of nicotine pouches (NPs). Data from 1583 U.S. adult (age ≥ 21 years) current tobacco users were collected in 2021. Respondents self-reported NP awareness, beliefs, use, and susceptibility as well as current tobacco product use and socio-demographics. We used weighted logistic and multinomial regression models to explore the associations between these variables. Overall, 46.6% of U.S. adult current tobacco users were aware of, 16.4% had ever used, and 3.0% currently used NPs. Younger individuals (vs. 61+ years) were more likely to have ever heard of NPs, while Black individuals (vs. White) were less likely to have ever heard of NPs. Individuals younger than 45 years (vs. 61+ years) and those using smokeless tobacco products (vs. non-users) were more likely to have ever used NPs. Additionally, younger than 45 years (vs. 61+ years) and current use of certain tobacco products (e.g., smokeless) were associated with current NP use. Holding favorable beliefs about NPs was associated with susceptibility to and more advanced NP use statuses (p < 0.05). Continuous surveillance of NP use and beliefs is important.

Introduction 18 F-Fludeoxyglucose PET-CT (FDG) is increasingly used to stage breast cancer. Most breast cancers express the Oestrogen Receptor (ER) and Progesterone Receptor (PR), and this subtype demonstrates lower activity on FDG imaging. Somatostatin receptors (SSTR) offer a potentially improved radiotracer target for ER+ /PR+ breast cancer. We present the first in␣vivo clinical study comparing 68 Ga-DOTATATE PET-CT (DOTA) to FDG and conventional imaging (bone scan and diagnostic CT), in metastatic ER+ /PR+ human epidermal growth factor receptor 2 (HER2) negative breast cancer. Methods Patients with clinically progressive metastatic ER+ /PR+ HER2- breast cancer underwent restaging with DOTA, FDG and conventional imaging. Scans were analysed visually, and semi-quantitatively. Wilcoxon-Rank Scoring was used to assess significance. Results Ten women (mean age 57 years) underwent imaging. 8/10 demonstrated disease on both DOTA and FDG. 2/10 positive on conventional imaging, but DOTA- /FDG- , and had no disease progression at 1-year follow-up. Heterogeneity of uptake was seen between DOTA and FDG with 5 bone lesions DOTA+ /FDG- and 1 bone lesion FDG+ /DOTA- . Twenty-one visceral lesions were FDG+ /DOTA- (2 patients), with 10/21 identified on conventional imaging. Maximum standard uptake values (SUV max) of DOTA were greater than FDG (10.9 vs. 6.6, P = ns). Four sites were biopsied (3 patients). 3/4 had high ER/PR expression (mean DOTA SUV max 9.4) and 1/4 low ER/PR expression (DOTA SUV max 3.1). Conclusion Whilst we have not demonstrated DOTA to be superior to FDG in staging of ER+ /PR+ breast cancers, DOTA may have a role in assessing HR status and treatment decisions; further evaluation of this is warranted.

Advances in human epidermal growth factor receptor 2 (HER2)-directed therapies have revolutionised the care of patients with HER2-positive breast cancer. While adjuvant trastuzumab in combination with chemotherapy has dramatically improved the prognosis for patients with early-stage disease, up to a quarter of patients will develop recurrent disease. The standard-of-care treatment paradigm has evolved with the introduction of newer HER2-directed therapies and increasing use of neoadjuvant systemic therapy, the latter providing us with important functional data to HER2-directed therapies and impacting subsequent adjuvant therapy decisions. However, these new strategies come at a cost of increased toxicity and economic burden, and only a subset of patients benefit from such approaches. Thus, ongoing work is required to identify predictive biomarkers of response, to de-escalate treatment in patients who may do just as well with less therapy, and new therapeutic approaches for patients who do not respond to currently used therapies. In this review, we will examine the current therapeutic landscape, summarise the latest evidence, and list the current treatment algorithms for early stage HER2-positive breast cancer.

We examined the prevalence and correlates of anticipated responses to hypothetical cigar price increases. Data are from a 2021 representative sample of U.S. adults who reported past-30-day cigar use ( n = 454; mean age = 39.8 years). Weighted multivariable logistic regressions assessed the correlates of behavior change responses. If cigar price increased, 77.2% intend to pay more, 44.7% intend to reduce use, and 39.9%, 37.7%, and 17.1% intend to use other tobacco, cannabis, and cheaper cigars, respectively. Those who smoked cigarillos (vs. other cigars) had higher odds of intending to pay more (adjusted odds ratio [AOR] = 2.73; 95% confidence interval [CI] = [1.41, 5.29]) and use other tobacco (AOR = 2.35; 95%CI = [1.26, 4.36]). Those who smoked within 5 min of waking (vs. >60 min) had higher odds of intending to use cheaper cigars (AOR = 5.19, 95%CI = [1.38, 19.46]). Almost half of U.S. adults who report past-30-day cigar use may reduce cigar smoking in response to price increases, though behavioral response may depend on cigar type smoked and tobacco dependence.

Many countries have responded to the current global biodiversity crisis by committing to protect 30% of the Earth by 2030, a goal known as “30 x 30”. However, an excessive emphasis on megafauna to the exclusion of other species weakens our current protected area (PA) network. This limited perspective overvalues large, connected PAs, while disregarding the potential impacts of small PAs in preserving biodiversity. Using public databases of 31,828 terrestrial vertebrate species we demonstrate that range sizes for the most vulnerable class of vertebrates, the amphibians, are smaller than those of reptiles, birds, and mammals and suggest that small PAs are overlooked as conservation tools for this group. We found that, though each of many endangered amphibians could have their entire distribution protected by a single microreserve (< 10 km2), the current PA network fails at adequately protecting most threatened amphibian species. Furthermore, we show that many current microreserves have amphibian species richnesses rivaling those of the largest PAs (10,000–100,00 km2), and that PA networks accumulate new amphibian species more rapidly through the addition of smaller rather than larger PAs. Unfortunately, the global rate of new PA establishment has slowed since 2010, so we illustrate global regions where the addition of microreserves could be most beneficial to amphibian conservation. We conclude that incorporating the needs of overlooked taxa into PA design will require us to complement networks of large, connected PAs with many strategically-placed, biodiversity-motivated microreserves.

BACKGROUND Eye tracking provides an objective way to measure attention, which can advance researchers’ and policy makers’ understanding of tobacco marketing influences. The development of remote webcam-based eye-tracking technology, integrated with web-based crowdsourcing studies, may be a cost-effective and time-efficient alternative to laboratory-based eye-tracking methods. However, research is needed to evaluate the utility of remote eye-tracking methods. OBJECTIVE This study aimed to detail the process of designing a remote webcam-based eye-tracking experiment and provide data on associations between participant characteristics and the outcomes of experiment completion. METHODS A total of 2023 young adult (aged 18-34 years) cigarette smokers in the United States were recruited to complete a web-based survey that included a 90-second remote eye-tracking experiment that examined attention to e-cigarette marketing materials. Primary outcome measures assessed the completion of the remote eye-tracking experiment—specifically, experiment initiated versus not initiated, experiment completed versus not completed, and usable versus nonusable eye-tracking data generated. Multivariable logistic regressions examined the associations between outcome measures and participants’ sociodemographic backgrounds, tobacco use history, and electronic devices (mobile vs desktop) used during the experiment. RESULTS Study recruitment began on April 14, 2022, and ended on May 3, 2022. Of the 2023 survey participants, 1887 (93.28%) initiated the experiment, and 777 (38.41%) completed the experiment. Of the 777 participants who completed the experiment, 381 (49%) generated usable data. Results from the full regression models show that non-Hispanic Black participants (adjusted odds ratio [AOR] 0.64, 95% CI 0.45-0.91) were less likely to complete the eye-tracking experiment than non-Hispanic White participants. In addition, female (vs male) participants (AOR 1.46, 95% CI 1.01-2.11), those currently using (vs not using) e-cigarettes (AOR 2.08, 95% CI 1.13-3.82), and those who used mobile (vs desktop) devices (AOR 5.10, 95% CI 3.05-8.52) were more likely to generate usable eye-tracking data. CONCLUSIONS Young adult participants were willing to try remote eye-tracking technology, and nearly half of those who completed the experiment generated usable eye-tracking data (381/777, 49%). Thus, we believe that the use of remote eye-tracking tools, integrated with crowdsourcing recruitment, can be a useful approach for the tobacco regulatory science research community to collect high-quality, large-scale eye-tracking data in a timely fashion and thereby address research questions related to the ever-evolving tobacco marketing landscape. It would be useful to investigate techniques to enhance completion rates and data usability. INTERNATIONAL REGISTERED REPORT RR1-10.2196/43512

Cigar consumption has increased in the U.S. over the past decade, yet gaps remain in research on cigar promotion in print magazines. This study examines ad placement, volume, ad characteristics, and associated expenditures for cigars from 2018–2021, and readership data for magazines containing cigar ads. We merged content analysis data with Kantar Media data on magazine placement and expenditures and used magazine readership data from MRI-Simmons. The only brand in print magazines was Black & Mild (B & M), a top cigar brand in the U.S. There were 30 unique B & M magazine ads and 284 occurrences (i.e., appearances in magazines), translating to $46,504,578 in expenditures. All ads featured the word “enjoy/enjoyment” and a warning label. Filtered cigars were the most featured cigar type (75%) and sweets was the most featured flavor (78%). Nearly half of the publications in which B & M were advertised in have substantial Black/African American readership and were featured in publications with disproportionate young adult and Hispanic/Latino readership. This study identified tactics used in print advertising for a top cigar brand. Future research should examine how these tactics impact consumer perceptions. Findings of cigar ads reaching vulnerable populations may inform the FDA’s efforts to reduce health disparities through regulations and public education.

OBJECTIVES: To investigate functional outcomes and state of consciousness at 1 year and ≥2 years postinjury in children who sustained a traumatic brain injury and were in a disorder of consciousness (DOC), either vegetative state (VS) or minimally conscious state (MCS), upon admission to inpatient rehabilitation. DESIGN: Retrospective chart review. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: Children aged 2–18 years (N=37) who were admitted to inpatient rehabilitation with admission scores

E-cigarette price promotions (EPPs; i.e., marketed reductions in cost) may influence young adult cigarette smokers to try, dual use with, or completely transition to e-cigarettes. We assessed whether receiving EPPs was associated with subsequent e-cigarette use among this group.Data were from Waves 4 (2016-2018) and 5 (2018-2019) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study survey. Analysis was restricted to participants who were young adult (18-34 years) established, current cigarette smokers who did not use e-cigarettes at Wave 4 (baseline; n = 2,664; Sample 1), and a subsample of those who tried to quit smoking completely in the past year at Wave 5 (follow-up; n = 948; Sample 2). Multivariable logistic regressions were used to examine associations between receiving EPPs at baseline and past year use of e-cigarettes in general (Sample 1) and to help quit smoking (Sample 2) at follow-up, controlling for covariates.Overall, 4.1% and 4.9% of Sample 1 and 2 participants received EPPs, respectively; At follow-up, 33.4% of Sample 1 participants used e-cigarettes, and 12.0% of Sample 2 participants used e-cigarettes to quit smoking. Receiving EPPs was associated with subsequent past-year e-cigarette use in general (AOR = 2.07; 95% CI = 1.31 to 3.27), and past-year e-cigarette use to help with quitting smoking (AOR = 3.20; 95% CI = 1.48 to 6.90).EPPs may increase e-cigarette use among established, current smokers and may be used to quit smoking. Research is needed to understand how EPPs may be differentially associated with complete product transition versus dual/poly use among young adult smokers.

Electronic consultations (eConsultations) are increasingly used to obtain specialist guidance, avoiding unnecessary face-to-face patient visits for certain clinical questions. During the COVID-19 pandemic, when in-person care was limited, eConsultations may have helped clinicians obtain specialist input to guide patient care.To understand how the use of eConsultations changed during the COVID-19 pandemic and whether trends in eConsultation utilization differed based on patient's payer and primary language.This retrospective cohort study was conducted at 6 academic medical centers in the United States, all participating in the Association of American Colleges Coordinating Optimal Referral Experiences program. Participants included adult patients who had an outpatient visit, referral, or eConsultation during the study period. Data were analyzed from June 4, 2019, to July 28, 2020.The primary outcome was the eConsultation proportion of specialty contact, defined as the number of completed eConsultations divided by the sum of the number of completed eConsultations and specialty referrals, expressed as a percentage. eConsultation percentages of specialty contact were further stratified by payer type and language. Payers included commercial, Medicare, Medicaid, self-pay or uninsured, and other. Primary language included English and non-English languages.A total of 14 545 completed eConsultations and 189 776 referrals were included. More eConsultations were completed for English-speaking patients (11 363 eConsultations [95.0%]) than non-English-speaking patients (597 eConsultations [5.0%]). Patients with commercial insurance represented the highest number of completed eConsultations (8848 eConsultations [60.8%]) followed by Medicare (3891 eConsultations [26.8%]), Medicaid (930 eConsultations [6.4%]), other insurance (745 eConsultations [5.1%]), and self-pay or no insurance (131 eConsultations [0.9%]). At the start of the pandemic, across all academic medical centers, the percentage of specialty contact conducted via eConsultation significantly increased by 6.21% (95% CI, 4.97%-7.44%; P .001). When stratified by payer and language, the percentage of specialty contact conducted via eConsultation significantly increased at the beginning of the pandemic for both English-speaking patients (change, 6.09% (95% CI, 4.82% to 7.37%; P .001) and non-English-speaking patients (change, 8.48% [95% CI, 5.79% to 11.16%]; P .001) and for all payers, except self-pay and uninsured patients (change, -0.21% [95% CI, [-1.35% to 0.92%]; P = .70).This retrospective cohort study found that eConsultations provided an accessible mechanism for clinicians to receive specialist input when in-person care was limited.

An eVisit is a form of asynchronous telehealth whereby the patient submits an online request for medical advice and receives a written response from a health care provider. While thought to be an efficient way to resolve low-acuity medical issues, there is limited information on whether eVisits lead the avoidance of in-person care. We reviewed 8627 eVisits that occurred at our institution from July 2017 to March 2020 and found that 23.1% of eVisits required follow-up medical care within 14 days (22.6% with primary care physician, 0.3% with emergency department, 0.2% both). Our results indicate that eVisits are a feasible alternative to in-person care for low-complexity medical issues.

We have recently encountered p53 immunohistochemical (IHC) patterns in human papillomavirus (HPV)-associated carcinomas of the gynecologic tract, which were confused with absent (null) or overexpression TP53 mutational staining. We therefore evaluated p53 and p16 IHC in 25 squamous cell carcinomas (SCC) (16 vulva, 4 Bartholin's gland, and 5 cervix), 20 endocervical adenocarcinomas (EDAC), 14 high-grade squamous intraepithelial lesions (HSIL), 2 adenocarcinoma in situ (AIS), all of which exhibited morphologic features of HPV. Only cases showing diffuse/strong block-like p16 staining were included for further study. All EDACs underwent TP53 sequencing and HPV in situ hybridization (ISH) was performed in selected cases. p53 IHC staining fell into two main patterns. The most common was designated as "markedly reduced (null-like)" (absence or significantly attenuated staining in >70% of cells), which could be confused with true null mutational pattern. This was present in 14/25 (56%) SCCs, 7/14 (50%) HSILs, and 18/20 (90%) EDACs. The second notable pattern was "mid-epithelial (basal sparing)" (distinct absence of staining in basal cells juxtaposed with strong staining in parabasal cells), seen in 10/25 (40%) SCC, 7/14 (50%) HSIL, and none of the EDACs. There was scattered weak to moderate p53 staining (conventional wild type) in 1/25 (4%) SCC and 2/20 (10%) EDAC. No cases showed strong/diffuse overexpression. One EDAC had a TP53 missense mutation and exhibited "markedly reduced (null-like)" staining. HPV ISH revealed an inverse relationship with p53, cells positive for HPV mRNA were negative for p53. Knowledge of these patterns can help pathologists avoid misinterpreting p53 status in the setting of HPVA cancers.

We report a genomics‐guided exploration of the metabolic potential of the brasilicardin producer strain Nocardia terpenica IFM 0406. Bioinformatics analysis of the whole genome sequence revealed the presence of a biosynthetic gene cluster presumably responsible for the generation of formerly unknown nocobactin derivatives. Mass spectrometry‐assisted isolation led to the identification of three new siderophores, terpenibactins A (1), B (2) and C (3), which belong to the class of nocobactins. Their structures were elucidated by employing spectroscopic techniques. Compounds 1–3 demonstrated inhibitory activity towards the muscarinic M3 receptor, while exhibiting only a low cytotoxicity., Nature's combinatorial biosynthesis produces new bioactive nocobactin derivatives. Genome mining led to the discovery and characterization of terpenibactins A−C, three new nocobactins from the bacterium Nocardia terpenica IFM 0406 that exhibit unprecedented combinations of asteroidic acid, lipid and modified lysine residues. They demonstrate low cytotoxicity but potent inhibitory activity towards the muscarinic M3 receptor.

The 2021 National Youth Tobacco Survey (NYTS) was completed by youth online during class time, either in school or at home due to the COVID-19 pandemic. Given the role of NYTS data in tobacco regulatory science, it is vital to understand the effect of survey settings (home, school) on tobacco-use estimates. We used a series of multivariable logistic regressions to examine whether survey settings (home vs. school) predicted current e-cigarette use among high school students, controlling for other known predictors of e-cigarette use as well as the pandemic learning model that was dominant in students’ counties (e.g., nearly all at-home, majority in school). We observed a significant survey setting effect. Those who completed the survey in school had higher odds of current e-cigarette use than those who completed the same survey at home (AOR = 1.74); this effect was attenuated when we controlled for the pandemic learning model (AOR = 1.38). Moreover, e-cigarette use was independently associated with students’ learning model; students whose schools were nearly entirely in-person had the highest odds of e-cigarette use compared to students whose learning model was nearly all at-home (AOR = 1.65). Survey setting is a methodological artifact in the 2021 NYTS. Perceived privacy and peer effects can potentially explain this artifact.

Black young adults have the highest prevalence of cigar smoking in the U.S. Little is known about how this population perceives addiction to cigar smoking, which may influence long-term smoking and cessation outcomes. This study used semi-structured in-depth interviews to understand cravings, triggers, and perceived addiction from cigar smoking among a purposive sample of Black young adult cigar smokers (N = 40; 21–29 years). An iterative process was used to develop the codebook, and thematic analysis was used to capture findings based on the products predominantly used: cigarillos, large cigars, or blunts. Results suggest that while participants may share similar types of cravings and triggers (e.g., stress) across the use of these products, predominant blunt smokers reported more unique triggers related to relieving physical discomforts. While most participants reported cigars could be addictive to people in general, only a few perceived that they themselves were addicted. Participants who predominantly smoked cigarillos reported high perceived addiction to cigars, while those who predominantly smoked blunts reported low addiction. Education messages are needed to inform young Black adult cigar smokers about the risks and health symptoms of cigar addiction. These efforts may help increase cigar cessation seeking and reduce cigar addiction-related health consequences and disparities among Black populations.

Anti-Asian discrimination incidents in the USA have resurged during the COVID-19 pandemic. It is unclear how concern about being discriminatorily treated due to the COVID-19 pandemic varies between Asian and Asian American (AAsA) and White adults. We examined AAsA vs. White differences in concern about COVID-19 discrimination and associations of this concern with changes in cigarette smoking behaviors before and during the pandemic. Data were from a US representative sample of AAsA and White adults (≥ 21 years) who currently and formerly used commercial tobacco (n = 1052), collected through an online panel oversampling AAsA adults in January-February 2021. Participants reported their concern, worry, and stress about COVID-19 discrimination and past-30-day cigarette consumption before and during the pandemic. We examined the association between race and overall concern about COVID-19 discrimination, and this concern's associations with changes in past-30-day cigarette smoking consumption, smoking continuation, and return to smoking using weighted multivariable logistic and linear regression models. Overall concern about COVID-19 discrimination was higher (adjusted mean = 1.7, standard error = 0.16) among AAsA adults who currently and formerly used commercial tobacco than their White counterparts (adjusted mean = 0.60, standard error = 0.04; p 0.01). Overall concern about COVID-19 discrimination was associated with increased past-30-day cigarette consumption by 26.5 cigarettes (95% confidence interval [CI] = 1.2-51.9) and 4.4 times (95% CI = 2.3-8.5) greater odds of return to smoking among adults who smoke cigarettes. AAsA adults who currently and formerly used commercial tobacco disproportionately bore higher concern about COVID-19 discrimination, and in turn could lead to increased smoking behavior and related morbidity and mortality among AAsA adults.

Black young adults experience disparately high rates of cigar use and its health consequences. Little research has explored community-level influences on cigar smoking in this population, especially concerning product-specific influences and cigar smokers’ perceptions. We conducted in-depth interviews with 40 Black young adult (ages 21–29) cigar smokers in the Washington, D.C. area and analyzed themes regarding physical and sociocultural community-level factors perceived to influence cigar use. Themes were further analyzed based on participants’ predominant cigar products (cigarillos, large cigars, blunts). Participants reported easy access to affordable cigarillos, widespread cigarillo sales and targeted marketing, norms of cigar and blunt smoking for stress relief, socialization, and cultural participation, and ubiquitous cigar and blunt smoking cues, all of which promoted cigar use in their communities. Future research should further explore how community-level influences contribute to disproportionate cigar use among Black young adults. Our findings suggest that programs and policies addressing physical and sociocultural community-level pro-smoking influences may help mitigate cigar smoking disparities.

Introduction E-cigarette advertising exposure is linked to e-cigarette initiation and use. Thus, monitoring trends in e-cigarette advertising practices is important to understand e-cigarette use patterns observed over recent years. Aims and Methods E-cigarette advertising expenditures (January 2016–July 2021; Numerator Ad Intel) for 154 U.S. market areas were harmonized with U.S. Census sociodemographic data through Nielsen zip code designations by market area. Descriptive statistics and multivariable linear regressions were used to examine trends in e-cigarette advertising expenditures across media outlets and associations between sociodemographic characteristics and e-cigarette advertising over time. Results E-cigarette advertising expenditures peaked in 2018/2019, followed by a sharp decline in 2020. Expenditures were concentrated primarily on print (58.9%), TV (20.6%), and radio (14.4%). Major print outlets were Sports Illustrated, Rolling Stone, and Star magazines. Top TV channels were AMC, Investigation Discovery, and TBS. TV advertisements were purchased commonly during popular movies and TV series (eg King of Queens, Everybody Loves Raymond, The Walking Dead). Higher expenditures were associated with U.S. market areas that had (1) a larger percentage of non-rural zip codes (radio), (2) smaller male populations (radio), and (3) larger White or Caucasian, Black or African American, American Indian or Alaska Native, Asian, and Other or Multiracial populations (radio, print, online display, and online video). Conclusions E-cigarette companies advertised in print magazines geared toward males and youth and young adults, radio commercials focused in urban areas with smaller male populations, and nationwide TV commercials. Declines in e-cigarette advertising expenditures in 2020 demonstrate the potential impact that federal policies may have on protecting populations who are at higher risk for tobacco use from predatory advertising practices. Implications E-cigarette advertising exposure is associated with the initiation and use of e-cigarettes. This study shows how e-cigarette marketing expenditures in the United States may have targeted specific consumers (eg youth and young adults) between 2016 and 2021. The precipitous drop in advertising expenditures across all outlets during early 2020 corresponds with the implementation of the Tobacco 21 federal policy, the federal enforcement policy to remove most unauthorized flavored e-cigarette cartridges from the U.S. market, preparations for FDA’s premarket review of e-cigarette products, and the decision by several TV broadcast companies to stop showing e-cigarette ads. The potential impact of federal policies may have far-reaching implications for protecting populations who are at high risk for tobacco use and its health consequences.

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with poor prognosis and limited treatment options. One of the mechanisms contributing to this is the ability of TNBC tumors to evade anti-tumour response, limiting the success of immune-checkpoint therapy. In recent studies of the tumor microenvironment, stromal cells have emerged as potential important mediators of lymphocyte function in TNBC. Multi-omics studies from our group and others have elucidated the heterogeneity of stromal cells and their interactions with immune cells in TNBC. However, the clinical relevance and functional characteristics of these relationships remain poorly explored. Our previous work revealed functionally distinct subpopulations of stromal cells in breast cancer: endothelial cells, myofibroblast-like cancer-associated fibroblasts (myCAFs), inflammatory-CAFs (iCAFs), and perivascular-like cells which resemble pericyte and smooth muscle cells in immature and differentiated states (imPVLs; dPVLs), respectively. Here we directly explored the clinical relevance of these stromal subpopulations and their association with immune evasion in a large independent TNBC cohort with long-term survival data. Using markers derived from our single-cell multi-omics studies, we performed multiplex immunofluorescence using the OPAL9 platform on tumor microarrays from 222 TNBC patients to mark myCAFs, iCAFs, dPVLs, endothelial cells, CD8 and/or PD1 positive T-cells. Digital imaging analysis (QuPath) revealed a significant negative correlation between the abundance of stromal cells and CD8 T cells. This cytotoxic T-cell exclusion is primarily driven by smooth muscle dPVLs. Parallel to this T-cell exclusion, our functional studies demonstrate that stromal cells suppress T-cell proliferation. Using multiple ex vivo co-culture models of primary TNBC CAFs and peripheral blood mononuclear cells (PBMCs) from healthy and matched donors, we show that CAFs suppress the proliferative capability of CD4 and CD8 T-cells. ScRNA-seq of these co-culture models demonstrate that CAF educated T cells are driven into a LAG3+ exhausted state enriched for canonical pathways of immunosuppressive cytokine signaling. Our findings suggest that manipulation of these stromal subpopulations could elicit a more effective immune response in a subset of patients through inhibiting T-cell dysfunction and exclusion. Citation Format: Julia Chen, Sunny Wu, Travis Ruan, Iveta Slapetova, Ewan Millar, Elgene Lim, Alex Swarbrick. Stromal mediators of lymphocyte exclusion and dysfunction in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD9-01.

Commercial tobacco (CT) users employ tobacco expenditure minimizing strategies (TEMS) to manage their CT expenditures. We examined how financial challenges and hardships during the COVID-19 pandemic relate to increases in TEMS use.Data from a nationally representative sample of 1,700 U.S. adult recent former and current CT users were collected from an online panel during January-February 2021. Participants reported if they had increased use of eight TEMS to save money on CT since the pandemic, and experienced financial challenges (e.g., losing a job) and hardships (e.g., not having enough money to pay for food). The number of financial hardships experienced was counted (range: 0-6). Weighted multivariable logistic regression models were used to examine the associations between financial challenges and hardships and increased TEMS use, adjusting for demographics.Since the COVID-19 pandemic, three TEMS showed the largest increase in use by U.S. adult current and recent former CT users: cutting back (22.4%), finding less expensive places to purchase (15.6%), and buying by bulk (15.5%). Many financial challenges and hardships were consistently associated with increased uses of TEMS. Furthermore, every additional count of financial hardships was associated with higher odds of increasing use of each TEMS (AORs ranging between 1.12 and 1.23).Many CT users increased TEMS use to manage their CT expenditures when facing financial challenges and hardships during the pandemic. This could hinder CT cessation and promote relapse. Prohibiting certain TEMS (e.g., discount coupon and price promotions) may promote CT cessation among this financially vulnerable group.

WinPro: A window of opportunity study of endocrine therapy with and without prometrium in postmenopausal women with early-stage hormone receptor-positive breast cancer Authors Teesha Downton1,2,3, Davendra Segara3, Andrew Ong4, Janne Bingham5, Emma-Kate Carson4, Julia Chen1,2,3, Kate Middleton3, Geoffrey Lindeman6, Andrew Parker3, Elgene Lim1,2,3. Affiliations 1Garvan Institute of Medical Research, Darlinghurst NSW, Australia; 2School of Clinical Medicine, St Vincent’s Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales Sydney, Australia; 3St Vincent’s Hospital Sydney, Darlinghurst NSW, Australia; 4Campbelltown Hospital, Campbelltown NSW, Australia; 5Royal Adelaide Hospital, Adelaide SA, Australia; 6Walter & Eliza Hall Institute of Medical Research, Parkville VIC, Australia Disclosures T. Downton: None. D. Segara: None. A. Ong: None. J. Bingham: None. E. Carson: None. J. Chen: None. K. Middleton: None. G. Lindeman: None. A. Parker: None. E. Lim: Advisory Board for Pfizer, Astra Zeneca, Lilly, Roche, Novartis, Gilead Australia. Research Funding from Pfizer, Novartis, Bayer. Abstract Background: Preclinical studies have observed that progesterone has inhibitory effects on the estrogen-stimulated growth of estrogen receptor (ER)-positive, progesterone receptor (PR)-positive breast cancer. Mohammed H et al. (Nature 2015) identified that activated PR associates with the ER and modulates the interactions of the ER with chromatin, with a shift towards the transcription of genes associated with apoptosis and differentiation, and away from genes associated with proliferation. We hypothesize that the addition of prometrium, a microionized progesterone, may enhance the anti-proliferative effects of standard endocrine therapy in women with ER-positive PR-positive breast cancer. Trial Design: WinPro (NCT03906669) is an ongoing multicenter, phase II, randomized, open-label, window of opportunity study comparing the effect on standard endocrine therapy with or without prometrium on breast cancer cell proliferation. The study population is postmenopausal women with early-stage operable breast cancer where the tumor is ≥5mm on imaging, ER ≥10%, PR≥10%, and HER2-negative. Patients currently on hormone replacement therapy or the oral contraceptive pill, or who have a history of endometrial cancer or venous thromboembolism are not eligible. Patients are randomized 1:1:1 to letrozole 2.5mg daily, letrozole 2.5mg + prometrium 300mg daily, or tamoxifen 20mg + prometrium 300mg daily. Allocated treatment is taken for 14 days prior to surgery. Primary surgery and adjuvant treatment is as per standard of care. Objectives: The primary objective is to compare the geometric mean suppression of centrally assessed Ki67 between the diagnostic biopsy sample (pre-treatment) and the surgical sample (post-treatment). The secondary objective is to evaluate safety and tolerability. Tertiary objectives include defining genes predictive of a reduction in Ki67, and evaluating the changes in ER, PR, AR, FoxA1, Cyclin D1, and apoptotic markers in breast tumors post-intervention. Accrual: This study opened in February 2018 and as of 13 July 2022, 164 patients have been enrolled. Target accrual is 200 patients. Contact information: This study is led at St Vincent’s Hospital Sydney, Australia, and funded by the Cancer Council of NSW and the NHMRC Translational Breast Cancer Project grant. Contact: Elgene Lim MBBS FRACP PhD at e.lim@garvan.org.au. Citation Format: Teesha Downton, Davendra Segara, Andrew Ong, Janne Bingham, Emma-Kate Carson, Julia Chen, Kate Middleton, Geoffrey Lindeman, Andrew Parker, Elgene Lim. WinPro: A window of opportunity study of endocrine therapy with and without prometrium in postmenopausal women with early-stage hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-10.