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With the highest cancer incidence and mortality rates in the country, rural Appalachia has experienced a decades-long health decline, due in part to high smoking rates. Cigarette smoking prevalence exceeds 30% in much of the region. Oral nicotine pouches (ONPs), which contain nicotine but no tobacco, present an unexplored opportunity to reduce cigarette smoking and cancer incidence. We outline the protocol for the Appalachian Research to Impact Smoking's Effects (ARISE) study, a randomized controlled trial to determine whether ONPs affect cigarette smoking patterns short- and long-term, and to evaluate their abuse liability versus nicotine replacement therapy (NRT) in a large sample of Appalachian smokers (clinicaltrials.gov: NCT06763536). Between 2025 and 2029, we will recruit 1,000 adult smokers living in rural Appalachian counties across 11 states. Participants will be identified via media outreach, mobile cancer screening, community events, and respondent-driven sampling, then randomized to ONP or NRT and complete four study phases: Baseline, Sampling, Switch, and Observation. In the Sampling phase, participants will receive varied flavors and nicotine strengths of their assigned product and select preferred options for use. During the Switch Phase, they will attempt to quit smoking and switch completely to their assigned product. The Observation phase will monitor tobacco use after discontinuation of study products. Study procedures will be conducted online and by mail, including surveys, expired carbon monoxide verification, and product delivery. The primary outcome is 7-day biochemically verified cigarette abstinence at the end of the Switch Phase. Secondary outcomes include switching rates, product appeal, craving, withdrawal, dependence, and purchases during the Observation phase. An intention-to-treat log-binomial regression model will estimate the effect of intervention assignment on cigarette abstinence. Results will inform whether and how ONPs should be regulated, approached clinically, and used in public health interventions to reduce the burdens of cigarette smoking in Appalachia.

BackgroundLesbian, gay, bisexual, transgender and queer (LGBTQ+) young adults (YA) experience disparities in nicotine and tobacco use. Mass-reach health communications can prevent nicotine and tobacco initiation and progression, but LGBTQ+adults report low engagement. Although cultural targeting (CT) could reach LGBTQ+YA, we know little about the strategies that resonate with this population. We probed how LGBTQ+YA perceived CT content to inform tobacco public education campaigns on strategies to engage this population.MethodsWe conducted six focus groups with N=20 LGBTQ+YA (18–35) who had ever used vapes, cigarettes or both. We showed participants examples of CT tobacco public education campaigns, probed their opinions and perceptions and coded transcripts using a data-driven inductive approach.ResultsParticipants were more inclined to view an ad as effective when they felt it was authentically created for the LGBTQ+community. Avoiding stereotyping, including diversity, using ‘subtle’ LGBTQ+iconography (ie, rainbows), and including personal experiences all contributed to the authenticity of the ad. Participants discussed the importance of visual appeal; bright colours made ads appear too corporate or like an ad for a tobacco product. Lastly, participants responded well to gain-framed messages rather than traditional risk messaging.ConclusionTobacco public education ads featuring ‘every-day’ LGBTQ+people in candid or unposed shots, personal stories with gain-framed messaging, and subtle Pride iconography and colours may increase acceptability among LGBTQ+YA. Researchers should focus on cultivating authenticity in ads and avoid outdated trends by consulting with the community and moving with speed from development to implementation.

BackgroundAdherence to COVID-19 protective measures is lowest for young people and males. The current study investigated characteristics associated with adherence to COVID-19 protective measures among male youth during the early months of the pandemic.MethodThe study used data from a prospective cohort study among male youth with baseline assessment in 2015/2016 and follow-up measurements in 2019 and summer 2020. Attrition-weighted multivariable ordinal logistic and log-binomial regression models were used to assess factors associated with adherence to overall and specific adherence measures, respectively.ResultsAmong 571 male youth (mean age 18.5), overall adherence was higher for those who were older (OR: 1.15; 95% CI: 1.03–1.30), non-White (OR: 1.96; 95% CI: 1.20–3.32), and residing in an urban area (OR: 2.06; 95% CI: 1.46–3.01). Overall adherence was lower for those who had a history of being drunk (OR: 0.65; 95% CI: 0.42–0.99). For outdoor mask-wearing, adherence was higher for youth with attention-deficit disorder or attention-deficit/hyperactivity disorder (RR: 1.58; 95% CI: 1.16–1.97) and lower for youth who currently used tobacco products (RR: 0.42; 95% CI: 0.21–0.70). Before a statewide mask mandate was issued, non-White youth were more likely to report wearing masks in outdoor spaces than their non-Hispanic White peers (RR: 2.34; 95% CI: 1.75–3.23).ConclusionThe study identified demographic, psychosocial, and behavioral factors associated with adherence to COVID-19 protective behaviors among male youth. The findings illustrate characteristics that could be leveraged for targeted preventive efforts during the ongoing pandemic and future outbreaks in a low-compliance group.

Background People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continue to struggle to have their condition recognised as disabling in the face of public and professional prejudice and discrimination. Objective The aim of this study was to compare the functional status and well-being of people with well-characterised ME/CFS with people with multiple sclerosis (PWMS), as well as healthy controls (HCs). Methods In this cross-sectional study, we used data collected as part of the UK ME/CFS Biobank to compare actual participant scores from the Medical Outcomes Survey Short Form-36 v2™ (SF-36v2™) between groups, as a proxy for impact of disability, and from a bespoke questionnaire seeking data on employment and income. Results People with ME/CFS scored significantly lower than PWMS or HCs in almost all SF-36v2™ areas. Prominent were lower scores for people with ME/CFS in the Physical Component Summary and Role Physical and Social Function domains, while the smallest differences were seen in the Mental Health domain. Responses to the bespoke questionnaire indicated that people with ME/CFS in this study work fewer hours and have lower incomes compared with people in the other two groups. Conclusions Using SF-36v2™ scores as a proxy, people with ME/CFS were measurably more disabled than PWMS or HCs in this study population. Furthermore, employment and income data are consistent with loss of functional status. These findings should encourage the health community to recognise the disabling effects of ME/CFS, to advocate for the needs of people with ME/CFS, and to investigate strategies to address the cost of the disease to both individuals and society.

Exposure to tobacco advertisements is associated with initiation of tobacco use among youth. The mechanisms underlying this association are less clear. We estimated longitudinal associations between youths’ cognitive and affective responses to advertisements for cigarettes, e-cigarettes, and smokeless tobacco (SLT) and initiation of these products. N = 1220 Ohio-residing boys of ages 11–16 were recruited into a cohort in 2015 and 2016. Participants completed surveys every six months for four years. Surveys assessed cognitive and affective responses to tobacco advertisements (which included health warnings) and tobacco use after an advertisement viewing activity. We used mixed-effects Poisson regression models with robust standard errors to estimate risk of initiating use of each tobacco product according to participants’ cognitive (i.e., memorability of health risks) and affective (i.e., likability of advertisement) responses to advertisements for that product. No associations between affective responses to advertisements and tobacco use outcomes were detected in adjusted models. However, finding health risks memorable was associated with reduced risk of ever smoking initiation (aRR = 0.57; 95% CI: 0.34, 0.95) and a reduced risk of ever SLT initiation that approached statistical significance (aRR = 0.61; 95% CI: 0.36, 1.05). Measures to increase saliency of health risks on cigarette and SLT advertisements might reduce use among youth.

BackgroundWith the highest cancer incidence and mortality rates in the country, rural Appalachia has experienced a decades-long health decline, due in part to high smoking rates. Cigarette smoking prevalence exceeds 30% in much of the region. Oral nicotine pouches (ONPs), which contain nicotine but no tobacco, present an unexplored opportunity to reduce cigarette smoking and cancer incidence.ObjectivesWe outline the protocol for the Appalachian Research to Impact Smoking's Effects (ARISE) study, a randomized controlled trial to determine whether ONPs affect cigarette smoking patterns short- and long-term, and to evaluate their abuse liability versus nicotine replacement therapy (NRT) in a large sample of Appalachian smokers (clinicaltrials.gov: NCT06763536).MethodsBetween 2025 and 2029, we will recruit 1,000 adult smokers living in rural Appalachian counties across 11 states. Participants will be identified via media outreach, mobile cancer screening, community events, and respondent-driven sampling, then randomized to ONP or NRT and complete four study phases: Baseline, Sampling, Switch, and Observation. In the Sampling phase, participants will receive varied flavors and nicotine strengths of their assigned product and select preferred options for use. During the Switch Phase, they will attempt to quit smoking and switch completely to their assigned product. The Observation phase will monitor tobacco use after discontinuation of study products. Study procedures will be conducted online and by mail, including surveys, expired carbon monoxide verification, and product delivery. The primary outcome is 7-day biochemically verified cigarette abstinence at the end of the Switch Phase. Secondary outcomes include switching rates, product appeal, craving, withdrawal, dependence, and purchases during the Observation phase. An intention-to-treat log-binomial regression model will estimate the effect of intervention assignment on cigarette abstinence.ConclusionsResults will inform whether and how ONPs should be regulated, approached clinically, and used in public health interventions to reduce the burdens of cigarette smoking in Appalachia.

ObjectivesAn interferon (IFN) gene signature (IGS) is present in approximately 50% of early, treatment naive rheumatoid arthritis (eRA) patients where it has been shown to negatively impact initial response to treatment. We wished to validate this effect and explore potential mechanisms of action.MethodsIn a multicentre inception cohort of eRA patients (n=191), we examined the whole blood IGS (MxA, IFI44L, OAS1, IFI6, ISG15) with reference to circulating IFN proteins, clinical outcomes and epigenetic influences on circulating CD19+ B and CD4+ T lymphocytes.ResultsWe reproduced our previous findings demonstrating a raised baseline IGS. We additionally showed, for the first time, that the IGS in eRA reflects circulating IFN-α protein. Paired longitudinal analysis demonstrated a significant reduction between baseline and 6-month IGS and IFN-α levels (p<0.0001 for both). Despite this fall, a raised baseline IGS predicted worse 6-month clinical outcomes such as increased disease activity score (DAS-28, p=0.025) and lower likelihood of a good EULAR clinical response (p=0.034), which was independent of other conventional predictors of disease activity and clinical response. Molecular analysis of CD4+ T cells and CD19+ B cells demonstrated differentially methylated CPG sites and dysregulated expression of disease relevant genes, including PARP9, STAT1, and EPSTI1, associated with baseline IGS/IFNα levels. Differentially methylated CPG sites implicated altered transcription factor binding in B cells (GATA3, ETSI, NFATC2, EZH2) and T cells (p300, HIF1α).ConclusionsOur data suggest that, in eRA, IFN-α can cause a sustained, epigenetically mediated, pathogenic increase in lymphocyte activation and proliferation, and that the IGS is, therefore, a robust prognostic biomarker. Its persistent harmful effects provide a rationale for the initial therapeutic targeting of IFN-α in selected patients with eRA.

The Australian Square Kilometre Array Pathfinder (ASKAP) will give us an unprecedented opportunity to investigate the transient sky at radio wavelengths. In this paper we present VAST, an ASKAP survey for Variables and Slow Transients. VAST will exploit the wide-field survey capabilities of ASKAP to enable the discovery and investigation of variable and transient phenomena from the local to the cosmological, including flare stars, intermittent pulsars, X-ray binaries, magnetars, extreme scattering events, interstellar scintillation, radio supernovae and orphan afterglows of gamma ray bursts. In addition, it will allow us to probe unexplored regions of parameter space where new classes of transient sources may be detected. In this paper we review the known radio transient and variable populations and the current results from blind radio surveys. We outline a comprehensive program based on a multi-tiered survey strategy to characterise the radio transient sky through detection and monitoring of transient and variable sources on the ASKAP imaging timescales of five seconds and greater. We also present an analysis of the expected source populations that we will be able to detect with VAST.