Spatially resolved multiomics of human cardiac niches.

The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system1. The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated FOXP2 in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom CellPhoneDB.org module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interactions to provide mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG+ and IgA+ plasma cells forming immune niches that may contribute to infection defence. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be applied to other tissues and organs.

Cells of the human intestinal tract mapped across space and time.

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.

Single-cell mutation analysis of clonal evolution in myeloid malignancies.

Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk molecular profiling has suggested that mutations are acquired in a stepwise fashion: mutant genes with high variant allele frequencies appear early in leukaemogenesis, and mutations with lower variant allele frequencies are thought to be acquired later1-3. Although bulk sequencing can provide information about leukaemia biology and prognosis, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity, or definitively elucidate the order of mutations. To delineate the clonal framework of myeloid malignancies, we performed single-cell mutational profiling on 146 samples from 123 patients. Here we show that AML is dominated by a small number of clones, which frequently harbour co-occurring mutations in epigenetic regulators. Conversely, mutations in signalling genes often occur more than once in distinct subclones, consistent with increasing clonal diversity. We mapped clonal trajectories for each sample and uncovered combinations of mutations that synergized to promote clonal expansion and dominance. Finally, we combined protein expression with mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our findings provide insights into the pathogenesis of myeloid transformation and how clonal complexity evolves with disease progression.

ArCH: improving the performance of clonal hematopoiesis variant calling and interpretation.

MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. The lack of well-validated bioinformatic pipelines for CH calling may contribute to lack of reproducibility in studies of CH. RESULTS: Here, we developed ArCH, an Artifact filtering Clonal Hematopoiesis variant calling pipeline for detecting single nucleotide variants and short insertions/deletions by combining the output of four variant calling tools and filtering based on variant characteristics and sequencing error rate estimation. ArCH is an end-to-end cloud-based pipeline optimized to accept a variety of inputs with customizable parameters adaptable to multiple sequencing technologies, research questions, and datasets. Using deep targeted sequencing data generated from six acute myeloid leukemia patient tumor: normal dilutions, 31 blood samples with orthogonal validation, and 26 blood samples with technical replicates, we show that ArCH improves the sensitivity and positive predictive value of CH variant detection at low allele frequencies compared to standard application of commonly used variant calling approaches. AVAILABILITY AND IMPLEMENTATION: The code for this workflow is available at: https://github.com/kbolton-lab/ArCH.

A Randomized Controlled Trial to Improve Unmet Social Needs and Clinical Outcomes Among Adults with Diabetes.

BACKGROUND: Adults with type 1 or type 2 diabetes often face financial challenges and other unmet social needs to effective diabetes self-management. OBJECTIVE: Whether a digital intervention focused on addressing socioeconomic determinants of health improves diabetes clinical outcomes more than usual care. DESIGN: Randomized trial from 2019 to 2023. PARTICIPANTS: A total of 600 adults with diabetes, HbA1c ≥ 7.5%, and self-reported unmet social needs or financial burden from a health system and randomized to the intervention or standard care. INTERVENTION: CareAvenue is an automated, e-health intervention with eight videos that address unmet social needs contributing to poor outcomes. MEASURES: Primary outcome was HbA1c, measured at baseline, and 6 and 12 months after randomization. Secondary outcomes included systolic blood pressure and reported met social needs, cost-related non-adherence (CRN), and financial burden. We examined main effects and variation in effects across predefined subgroups. RESULTS: Seventy-eight percent of CareAvenue participants completed one or more modules of the website. At 12-month follow-up, there were no significant differences in HbA1c changes between CareAvenue and control group (p = 0.24). There were also no significant between-group differences in systolic blood pressure (p = 0.29), met social needs (p = 0.25), CRN (p = 0.18), and perceived financial burden (p = 0.31). In subgroup analyses, participants with household incomes 100-400% FPL (1.93 (SE = 0.76), p < 0.01), 201-400% FPL (1.30 (SE = 0.62), p < 0.04), and > 400% FPL (1.27 (SE = 0.64), p < 0.05) had significantly less A1c decreases compared to the control group. CONCLUSIONS: On average, CareAvenue participants did not achieve better A1c lowering, met needs, CRN, or perceived financial burden compared to control participants. CareAvenue participants with higher incomes achieved significantly less A1c reductions than control. Further research is needed on social needs interventions that consider tailored approaches to population subgroups. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov ID NCT03950973, May 2019.

Examining the relationship of flavored tobacco product policy restrictions and flavored tobacco product use, among adolescents and young adults in the U.S.

OBJECTIVE: This work examines the relationship between local flavor policy exposure and any tobacco product use and flavored tobacco product use among U.S. youth and young adults, as well as the equity potential of these policies by race/ethnicity. METHODS: Participants were aged 15-36 (n = 10,893) surveyed from September-December 2019 using national, address- and probability-based sampling. Local flavor policies enacted before survey completion were linked to participant home address. Weighted cross-sectional multivariable logistic regression examined individual coverage by flavor policy vs. no flavor policy, with current any tobacco or flavored tobacco use, controlling for individual and county-level demographics, psychosocial variables, and other tobacco control policies. Interactions between race/ethnicity and any tobacco use and flavored tobacco use were assessed. RESULTS: Those covered by a flavor policy vs. no policy had lower odds of any tobacco use (aOR = 0.74, 95% CI = 0.55-1.00) and current flavored tobacco use (aOR = 0.67, 95% CI = 0.48-0.93). Compared with Non-Hispanic (NH)-White individuals, NH-Black individuals (aOR = 1.08, CI = 1.04-1.12) had higher odds of any tobacco use, and non-Hispanic Asian individuals had lower odds of any tobacco use (aOR = 0.67, CI = 0.53-0.85). Hispanic individuals exposed to policy had lower odds of flavored tobacco use compared to NH-White peers. CONCLUSIONS: Exposure to flavor restriction policies is associated with lower odds of any tobacco and flavored use among youth and young adults. Flavor restrictions may be beneficial in reducing tobacco use in youth from diverse racial/ethnic backgrounds. However, passing policies covering NH-Black individuals is needed to mitigate disparities in tobacco use by flavor policy coverage over time.

Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes.

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn -/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.

Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations.

Somatic mutations in the isocitrate dehydrogenase 2 gene (IDH2) contribute to the pathogenesis of acute myeloid leukaemia (AML) through the production of the oncometabolite 2-hydroxyglutarate (2HG)1-8. Enasidenib (AG-221) is an allosteric inhibitor that binds to the IDH2 dimer interface and blocks the production of 2HG by IDH2 mutants9,10. In a phase I/II clinical trial, enasidenib inhibited the production of 2HG and induced clinical responses in relapsed or refractory IDH2-mutant AML11. Here we describe two patients with IDH2-mutant AML who had a clinical response to enasidenib followed by clinical resistance, disease progression, and a recurrent increase in circulating levels of 2HG. We show that therapeutic resistance is associated with the emergence of second-site IDH2 mutations in trans, such that the resistance mutations occurred in the IDH2 allele without the neomorphic R140Q mutation. The in trans mutations occurred at glutamine 316 (Q316E) and isoleucine 319 (I319M), which are at the interface where enasidenib binds to the IDH2 dimer. The expression of either of these mutant disease alleles alone did not induce the production of 2HG; however, the expression of the Q316E or I319M mutation together with the R140Q mutation in trans allowed 2HG production that was resistant to inhibition by enasidenib. Biochemical studies predicted that resistance to allosteric IDH inhibitors could also occur via IDH dimer-interface mutations in cis, which was confirmed in a patient with acquired resistance to the IDH1 inhibitor ivosidenib (AG-120). Our observations uncover a mechanism of acquired resistance to a targeted therapy and underscore the importance of 2HG production in the pathogenesis of IDH-mutant malignancies.

Racial and Ethnic Differences in Elective Versus Emergency Surgery for Colorectal Cancer.

OBJECTIVE: To evaluate differences in presentation and outcomes of surgery for colorectal cancer. BACKGROUND: Although racial and socioeconomic disparities in colorectal cancer outcomes are well documented, disparities in access affecting disease presentation are less clear. METHODS: We conducted a statewide retrospective study of patients who underwent resection for colorectal cancer between January 1, 2015, and April 30, 2021. The primary outcome was undergoing emergency surgery. Secondary outcomes included preoperative evaluation and postoperative outcomes. Covariates of interest included race/ethnicity, social deprivation index, and insurance type. RESULTS: A total of 4869 patients underwent surgery for colorectal cancer, of whom 1122 (23.0%) underwent emergency surgery. Overall, 28.1% of Black non-Hispanic patients and 22.5% of White non-Hispanic patients underwent emergency surgery. On multivariable logistic regression, Black non-Hispanic race was independently associated with a 5.8 (95% CI, 0.3-11.3) percentage point increased risk of emergency surgery compared with White non-Hispanic race. Patients who underwent emergency surgery were significantly less likely to have preoperative carcinoembryonic antigen measurement, staging for rectal cancer, and wound/ostomy consultation. Patients who underwent emergency surgery had a higher incidence of 30-day mortality (5.5% vs 1.0%, P <0.001), positive surgical margins (11.1% vs 4.9%, P <0.001), complications (29.2% vs 16.0%, P <0.001), readmissions (12.5% vs 9.6%, P =0.005), and reoperations (12.2% vs 8.2%, P <0.001). CONCLUSIONS: Among patients with colorectal cancer, Black non-Hispanic patients were more likely to undergo emergency surgery than White non-Hispanic patients, suggesting they may face barriers to timely screening and evaluation. Undergoing emergency surgery was associated with incomplete oncologic evaluation, increased incidence of postoperative complications including mortality, and increased surgical margin positivity. These results suggest that racial and ethnic differences in the diagnosis and treatment of colorectal cancer impact near-term and long-term outcomes.

Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression.

BACKGROUND: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. METHODS: This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1-6 months after full vaccination. FINDINGS: Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer-BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9-29·8) among people of all ages and 20·7 percentage points (10·2-36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4-41·6) in people of all ages and 32·0 percentage points (11·0-69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1-15·4) in people of all ages and 9·5 percentage points (5·7-14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. INTERPRETATION: COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20-30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. FUNDING: Coalition for Epidemic Preparedness Innovations.

Plasmacytoid dendritic cell expansion defines a distinct subset of RUNX1-mutated acute myeloid leukemia.

Plasmacytoid dendritic cells (pDCs) are the principal natural type I interferon-producing dendritic cells. Neoplastic expansion of pDCs and pDC precursors leads to blastic plasmacytoid dendritic cell neoplasm (BPDCN), and clonal expansion of mature pDCs has been described in chronic myelomonocytic leukemia. The role of pDC expansion in acute myeloid leukemia (AML) is poorly studied. Here, we characterize patients with AML with pDC expansion (pDC-AML), which we observe in ∼5% of AML cases. pDC-AMLs often possess cross-lineage antigen expression and have adverse risk stratification with poor outcome. RUNX1 mutations are the most common somatic alterations in pDC-AML (>70%) and are much more common than in AML without pDC expansion and BPDCN. We demonstrate that pDCs are clonally related to, as well as originate from, leukemic blasts in pDC-AML. We further demonstrate that leukemic blasts from RUNX1-mutated AML upregulate a pDC transcriptional program, poising the cells toward pDC differentiation and expansion. Finally, tagraxofusp, a targeted therapy directed to CD123, reduces leukemic burden and eliminates pDCs in a patient-derived xenograft model. In conclusion, pDC-AML is characterized by a high frequency of RUNX1 mutations and increased expression of a pDC transcriptional program. CD123 targeting represents a potential treatment approach for pDC-AML.

Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia.

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and NPM1 predicted high rates of MRD- remission, while mutations in TP53, SF3B1, ASXL1, and RUNX1 and karyotypic abnormalities including inv (3), monosomy 5 or 7 predicted low rates of MRD- remission. Patients with fewer individual clones were more likely to achieve MRD- remission. Among 132 patients who underwent allo-SCT, outcomes were favorable whether patients achieved early MRD- after induction or later MRD- after subsequent therapy prior to allo-SCT. As MRD conversion with chemotherapy prior to allo-SCT is rarely achieved in patients with specific baseline mutational patterns and high clone numbers, upfront inclusion of these patients into clinical trials should be considered.

Measuring the impact of state and local Tobacco 21 policies in the United States: A longitudinal study of youth and young adults ages 15-21.

INTRODUCTION: Tobacco 21 (T21) policies, which prohibit tobacco sales to individuals under 21, aim to reduce youth tobacco use by limiting youth access to these products. Little, however, is known about the longitudinal effect of T21 policies on youth tobacco use behaviors at the national level. METHODS: Participants aged 15-21 years from a longitudinal study conducted between May 2014 and May 2019 (n = 13,990) were matched to geocoded T21 policies. Generalized linear mixed models examined the association of direct and bordering T21 policy exposure and cigarette and e-cigarette use and intention to use, accounting for individual characteristics. RESULTS: Controlling for sociodemographic and psychosocial covariates, there were statistically significant positive associations between T21 exposure and e-cigarette use (OR = 1.45 [1.03,2.06], p < .003) and intention to use e-cigarettes (OR = 1.54 [1.05,2.26], p < .027). We found no association between T21 policy exposure and cigarette use or intention to use cigarettes. Furthermore, exposure to T21 policies did not significantly modify the relationship between age and either cigarette outcome. CONCLUSIONS: This is the first longitudinal study to evaluate state and local T21 policies at the national level. Our analyses demonstrate that existing T21 policies are not sufficient to reduce youth tobacco use and intentions to use, and suggest that T21 policies need to be a part of a comprehensive tobacco policy landscape. Our findings suggest further research is warranted on state and local T21 policy enforcement and implementation, including how T21 may differentially impact cigarette and e-cigarette use, and may have implications for the federal T21 policy. IMPLICATIONS: This research evaluates state and local T21 policies in the United States longitudinally, finding that T21 policies are not sufficient to stem e-cigarette use among adolescents and young adults. These findings support further policy action and suggest that local and state T21 policies are not sufficient to reduce tobacco use and rather, need to be part of a broader, more comprehensive set of tobacco control policies. Further research on enforcement and implementation challenges of T21 policies and the impacts of the new federal T21 policy is warranted.

Common genetic variation drives molecular heterogeneity in human iPSCs.

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs.

This corrects the article DOI: 10.1038/nature22403.

Association between cigarette sales in the USA and FDA's announcement of its intention to prohibit menthol as a characterising flavour in cigarettes.

INTRODUCTION: On 29 April 2021, the US Food and Drug Administration (FDA) announced its intention to prohibit menthol as a characterising flavour in cigarettes. METHODS: We assessed the changes in cigarette sales associated with the FDA's announcement using interrupted time series analysis based on monthly retail point-of-sale data on cigarettes from the NielsenIQ Local Trade Area (LTA) data from September 2019 to April 2022. Main outcome variables included LTA-level monthly menthol and non-menthol cigarette sales per 1000-persons. RESULTS: Monthly cigarette sales were declining before the FDA's announcement (menthol vs non-menthol: -1.68 (95% CI -1.92, -1.45) vs -3.14 (95% CI -3.33, -2.96) packs per 1000-persons). Monthly menthol cigarette sales increased immediately in May 2021 after the FDA's announcement by 6.44 packs per 1000-persons (95% CI 3.83, 9.05). Analysis stratified by LTA-level racial/ethnic compositions showed that LTAs with a relatively higher proportion of non-Hispanic Black population (>8.94%) experienced higher spike in menthol cigarette sales in May 2021 immediately after the announcement and higher post-announcement 12-month menthol cigarette sales than expected. CONCLUSIONS: Areas with a relatively higher proportion of non-Hispanic Black population are potentially at risk of experiencing increased burden of menthol cigarette consumption. Targeted community level cessation support in non-Hispanic Black majority areas may help mitigate the growing burden of menthol cigarette smoking and improve health equity. The findings of this study also suggest that FDA's prompt finalisation and enforcement of such ban may help avoid extending the increased burden of menthol cigarette consumptions in non-Hispanic Black majority areas.

Support for cigarette filter waste policies among US adults.

INTRODUCTION: Little is known on whether cigarette filter-related knowledge or beliefs are associated with support for policies to reduce their environmental impact. METHODS: A cross-sectional, population-based sample of US adults aged 18-64 years (n=2979) was used to evaluate filter-related knowledge and beliefs by smoking status using data collected between 24 October 2018 and 17 December 2018. Multivariate logistic regression models explored whether these knowledge and belief items were associated with support for two policies, a US$0.75 litter fee and a ban on sales of filtered cigarettes, controlling for demographic characteristics and smoking status. RESULTS: Regardless of smoking status, 71% did not know plastic was a cigarette filter component and 20% believed filters were biodegradable. Overall, 23% believed filters reduce health harms and 60% believed filters make it easier to smoke; 90% believed cigarette butts are harmful to the environment. Individuals believing cigarette butts harmed the environment were more likely to support a litter fee (adjusted OR (aOR)=2.33, 95% CI: 1.71 to 3.17). Individuals believing that filters are not biodegradable had higher odds of supporting a litter fee (OR=1.47, 95% CI: 1.15 to 1.88). Respondents believing that filters do not make cigarettes less harmful were more likely to support a litter fee (aOR=1.50, 95% CI: 1.20 to 1.88) and filter ban (aOR=2.03, 95% CI: 1.64 to 2.50). Belief that filters make it easier to smoke was associated with decreased support for a filter ban (aOR=0.69, 95% CI: 0.58 to 0.83). CONCLUSIONS: Comprehensive efforts are needed to educate the public about the impact of cigarette filters in order to build support for effective tobacco product waste policy.

Comparative predictors for cervical cancer screening in Southeast Michigan for Middle Eastern-North African (MENA), White and African American/black women.

The cervical cancer screening behaviors of Arab American women are not adequately understood, in part because Middle Eastern North African (MENA) descent is not a US Census category. Others have shown decreased cervical cancer screening in this race of women. Our primary aim is to evaluate the predictors of cervical cancer screening among MENA, White and Black women of southeast Michigan. A community-wide health survey reached MENA, White and Black populations asking self-report questions about health behaviors, attitudes, and medical history. Cervical cancer screening was considered up-to-date if it was reported to have occurred within the past three years. Survey responses were limited to women 30-65 years old and were analyzed with inferential and logistic regression models to determine risk factors for cervical cancer screening. Overall, 78% reported cervical cancer screening within the past three years. MENA women screened less often if time in the US was less than ten years (aOR 0.24 (0.05, 0.76)) compared to more than ten years and if single (aOR 0.27 (0.07, 0.97)) compared to married. Religion was not associated with screening in any study population. Those of all races without insurance screened significantly less often than those with insurance. The barriers to cervical cancer screening among MENA women are not associated with religion but instead with lack of insurance and length of time residing in the US.

Centering equity in flavored tobacco ban policies: Implications for tobacco control researchers.

To achieve equity in protection from poor health outcomes due to tobacco use, tobacco control policies and interventions need to affect socially disadvantaged groups more strongly than advantaged groups. Flavored tobacco bans have been seen as a policy with this potential. However, tobacco control researchers, in close concert with policy advocates, need to consider how to center equity throughout the policy process to achieve equitable outcomes from banning flavored tobacco. In this commentary, we outline the rationale for how and why tobacco control researchers should consider equity throughout the policy process to help fully achieve the potential of flavored tobacco ban policies. These recommendations emerged from a presentation at the Vermont Center on Behavior and Health 2021 Conference. Specifically, we focus on recommendations for tobacco control researchers to center equity including partnering with communities in agenda setting, examining how various policy formulations or exemptions may increase or decrease disparities, determining where flavor policies need to reach and whether policies are equitably reaching all populations disproportionately burdened by flavored tobacco, assessing whether policy implementation/enforcement is carried out equitably to maximize policy benefits, and evaluating policy impact with as much granularity as possible. Considering the entire policy process is central to enhancing equitable outcomes from banning flavored tobacco. Tobacco control researchers can play a key role in ensuring that these policies are viewed through an equity lens to, not just improve population health, but also to reduce harms to those disproportionately burdened by use of flavored products.

Individual Health Determinants That Predict Low Risk of Transitioning to Tobacco Use During Young Adulthood: An In-Depth Examination of Race and Ethnicity.

INTRODUCTION: The present study examines the contributions of individual-level health determinants on young adult tobacco use initiation to improve understanding of racial and ethnic distinctions and to inform effective tobacco prevention strategies. METHODS: Using time-to-event analyses, the 10-wave (2011-2016) Truth Initiative Young Adult Cohort, a probability-based, nationally representative sample of the US young adults aged 18-34 years (N = 7 665), provides data to examine differences in variables that influence tobacco uptake, by race and ethnicity. RESULTS: Among Non-Hispanic White young adults, having fewer peers who smoke cigarettes is protective against any tobacco initiation, whereas hazard of tobacco initiation increases for males, having low confidence to resist smoking, and having higher proclivity for sensation seeking. Depressive and anxiety symptoms increase uptake hazard most in the Non-Hispanic All Other Races group and least among Non-Hispanic Black individuals. Among Hispanic young adults, being female and perceiving tobacco as harmful are notably protective while being male is a notable uptake hazard. Unlike other groups, higher income levels do not lower hazards among Hispanic individuals. Cannabis use and overestimating the smoking rate among peers increase hazard least among Hispanic individuals. In the Non-Hispanic All Other Races group, aging is least protective; hazard increases notably if individuals engage in regular alcohol or cannabis use. CONCLUSIONS: Tobacco prevention efforts are critical during young adulthood. Specific tobacco uptake hazard and protective factors exist by race and ethnicity and should be considered when developing selective young adult prevention, particularly among groups with the highest risk for tobacco initiation during this life stage. IMPLICATIONS: Rising rates of tobacco initiation among the US young adults necessitate expanded efforts to prevent tobacco use initiation and progression beyond youth. Results highlight nuanced and differential tobacco uptake hazards by race and ethnicity for late initiation and sustained non-tobacco use among young adults. The study confirms existing evidence on tobacco use patterns and contributes to new knowledge on risk and protective factors. Tobacco prevention and control interventions, including policies, tailored in more meaningful ways could reduce tobacco use disparities among those most disproportionately affected.