Immunomethylomic profiles of long-term head and neck squamous cell carcinoma survivors on immune checkpoint inhibitors.

Aim: This study addresses the challenge of predicting the response of head and neck squamous cell carcinoma (HNSCC) patients to immunotherapy. Methods: Using DNA methylation cytometry, we analyzed the immune profiles of six HNSCC patients who showed a positive response to immunotherapy over a year without disease progression. Results: There was an initial increase in CD8 T memory cells and natural killer cells during the first four cycles of immunotherapy, which then returned to baseline levels after a year. Baseline CD8 T cell levels were lower in HNSCC immunotherapy responders but became similar to those in healthy subjects after immunotherapy. Conclusion: These findings suggest that monitoring fluctuations in immune profiles could potentially identify biomarkers for immunotherapy response in HNSCC patients.

[Box: see text].

Review of the U.S. Air Force Academy Hepatitis C Virus Screening Program to Ensure High-Value Care.

INTRODUCTION: Hepatitis C virus (HCV) is primarily transmitted through blood-to-blood contact. Leading health agencies have called for the elimination of HCV as a public health threat, with universal screening considered a part of the strategy. Hepatitis C virus screening among incoming cadets and cadet candidates at the United States Air Force Academy (USAFA) was implemented in 2023. The purpose of this quality improvement project was to determine the results of this screening and the associated fiscal costs, benefits, and harms to make a recommendation for future incoming classes. MATERIALS AND METHODS: The prevalence of HCV antibody positivity and confirmed HCV infections were calculated among the incoming cadets and cadet candidates at USAFA in summer 2023. Screening was conducted with a highly sensitive HCV total antibody test, and those who screened positive were further tested with a quantitative HCV polymerase chain reaction. The screening and follow-up care costs were calculated, and the potential harm of receiving a false positive notification was considered. RESULTS: Of the 1,360 persons screened at USAFA in 2023, no confirmed HCV infections were identified. There was one false positive on screening in the cadet population (n = 1,131) and one false positive in the cadet candidate population (n = 229). The fiscal cost of universal HCV screening upon accession of cadets and cadet candidates, including medical follow-up, was at least $5,279. The opportunity cost was minimal because blood was drawn for other mandatory programs, although screening may have caused social and psychological harm to those receiving a false positive notification. CONCLUSIONS: The prevalence of chronic HCV infection among incoming USAFA cadets and cadet candidates was 0%, below the population screening threshold that warrants screening, according to the Centers for Disease Control and Prevention. The harms of screening, including fiscal costs and potential psychological harm to individuals with a false positive screen, likely outweigh the benefits. We recommend against universal HCV screening in 2024 upon accession of USAFA cadets and cadet candidates.

Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.

Background: Idiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF). Methods: Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared to controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles which were then analyzed to predict survival outcomes and investigate associated pathways. Results: Proteomic profiling successfully differentiated IIP from controls. k-means clustering, based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology (GAP) index (C-index 0.794 vs. 0.709). The cluster with the worst prognosis featured decreased inflammatory signaling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B cell-mediated immunity. Conclusions: The unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalized treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.

DNA Methylation-Derived Immune Cell Proportions and Cancer Risk, Including Lung Cancer, in Black Participants.

Prior cohort studies assessing cancer risk based on immune cell subtype profiles have predominantly focused on White populations. This limitation obscures vital insights into how cancer risk varies across race. Immune cell subtype proportions were estimated using deconvolution based on leukocyte DNA methylation markers from blood samples collected at baseline on participants without cancer in the Atherosclerosis Risk in Communities (ARIC) Study. Over a mean of 17.5 years of follow-up, 668 incident cancers were diagnosed in 2,467 Black participants. Cox proportional hazards regression was used to examine immune cell subtype proportions and overall cancer incidence and site-specific incidence (lung, breast, and prostate cancers). Higher T regulatory cell proportions were associated with statistically significantly higher lung cancer risk (hazard ratio = 1.22, 95% confidence interval = 1.06-1.41 per percent increase). Increased memory B cell proportions were associated with significantly higher risk of prostate cancer (1.17, 1.04-1.33) and all cancers (1.13, 1.05-1.22). Increased CD8+ naïve cell proportions were associated with significantly lower risk of all cancers in participants ≥55 years (0.91, 0.83-0.98). Other immune cell subtypes did not display statistically significant associations with cancer risk. These results in Black participants align closely with prior findings in largely White populations. Findings from this study could help identify those at high cancer risk and outline risk stratifying to target patients for cancer screening, prevention, and other interventions. Further studies should assess these relationships in other cancer types, better elucidate the interplay of B cells in cancer risk, and identify biomarkers for personalized risk stratification.

Selective Reduction of Socioeconomic Disparities in the Experimental Tobacco Marketplace: Effects of Cigarette and E-cigarette Flavor Restrictions.

INTRODUCTION: Cigarette smoking accounts for >30% of the socioeconomic gap in life expectancy. Flavored restrictions claim to promote equity; however, no previous studies have compared the effect of cigarette and e-cigarette flavor restrictions among individuals who smoke with lower and higher socioeconomic status (SES). AIMS AND METHODS: In a between-group within-subject design, individuals with lower (n = 155) and higher (n = 125) SES completed hypothetical purchasing trials in the experimental tobacco marketplace (ETM). Conditions were presented in a 2 × 2 factorial design (cigarette flavors restricted or unrestricted and e-cigarette flavors restricted or unrestricted) with increasing cigarette prices across trials. RESULTS: Results show (1) SES differences in cigarette, e-cigarette, and NRT purchases under unrestricted policies, with lower SES showing higher cigarette demand and lower e-cigarette and NRT substitution than higher SES, (2) cigarette restrictions decreased cigarette and increased NRT purchases among lower SES, but no significant changes among higher SES, (3) decreased SES differences in cigarette demand under cigarette restrictions, but persistence under e-cigarette restrictions or their combination, (4) persistence of SES differences in e-cigarette purchases when all restrictions were enforced, and (5) waning of SES differences in NRT purchasing under all restrictions. CONCLUSIONS: Flavor restrictions differentially affected individuals based on SES. Within-group comparisons demonstrated restrictions significantly impacted lower SES, but not higher SES. Between-group comparisons showed SES differences in cigarette purchasing decreased under cigarette restrictions, but persisted under e-cigarette-restrictions or their combination. Additionally, SES differences in NRT substitution decreased under flavor restrictions. These findings highlight the utility of the ETM to investigate SES disparities. IMPLICATIONS: With increasing trends of socioeconomic differences in smoking prevalence and cessation rates, smoking-related health disparities are expected to continue to widen. Restricting menthol flavor in cigarettes while enhancing the availability and affordability of NRT have the potential to alleviate SES disparities in tobacco use, therefore, positively impacting health equity. However, this effect may depend on flavor availability in other tobacco products.

The influence of biopsy site and pregnancy on stable isotope ratios in humpback whale skin.

RATIONALE: Stable isotope analysis (SIA) of free-swimming mysticetes using biopsies is often limited in sample size and uses only one sample per individual, failing to capture both intra-individual variability and the influence of demographic and physiological factors on isotope ratios. METHODS: We applied SIA of δ13C and δ15N to humpback whale (Megaptera novaeangliae) biopsies taken during the foraging season along the western Antarctic Peninsula to quantify intra-individual variation from repeatedly sampled individuals, as well as to determine the effect of biopsy collection site, sex, and pregnancy on isotope ratios. RESULTS: There was substantial variability in δ13C from multiple biopsies taken from the same individuals, though δ15N was much more consistent. Side of the body (left versus right) and biopsy location (dorsal, anterior, ventral, and posterior) did marginally affect the isotopic composition of δ15N but not δ13C. Pregnancy had a significant effect on both δ13C and δ15N, where pregnant females were depleted in both when compared to non-pregnant females and males. CONCLUSIONS: These results indicate that isotopic signatures are influenced by multiple endogenous and exogenous factors and emphasize value in accounting for intra-individual variability and pregnancy status within a sampled population. Placed within an ecological context, the endogenous variability in δ13C observed here may be informative for future isotopic analyses.

Summer Cancer Research Experience for High School Students from Historically Marginalized Populations in Kansas City.

The Accelerate Cancer Education (ACE) summer research program at The University of Kansas Cancer Center (KUCC) is a six-week, cancer-focused, summer research experience for high school students from historically marginalized populations in the Kansas City metropolitan area. Cancer affects all populations and continues to be the second leading cause of death in the United States, and a large number of disparities impact racial and ethnic minorities, including increased cancer incidence and mortality. Critically, strategies to bolster diversity, equity, inclusion, and accessibility are needed to address persistent cancer disparities. The ACE program offers an educational opportunity for a population of students who otherwise would not have easy access onto a medical center campus to make connections with cancer physicians and researchers and provides a vital response to the need for a more diverse and expansive oncology workforce. Students grow their technical, social, and professional skills and develop self-efficacy and long-lasting connections that help them matriculate and persist through post-secondary education. Developed in 2018, the ACE program has trained 37 high school junior and senior students. This article describes the need for and how we successfully developed and implemented the ACE program.

"You're Someone Different Now": An Autoethnography on Identity and Occupational Identity Disruption After Traumatic Brain Injury.

IMPORTANCE: Identity disruption and occupational identity disruption are common after traumatic brain injury (TBI), but the relationship between these two phenomena is underexplored. Occupational therapy practitioners should be knowledgeable about identity challenges after TBI and ways to reconstruct a sense of self. OBJECTIVE: To sensitize readers to the experience of identity disruption and occupational identity disruption and describe how those two experiences are interrelated and transactional in nature. DESIGN: We completed an autoethnography, because this method privileges the insider perspective of participants as members of the research team. We interviewed Andi's family and friends, with textual and nontextual data being reviewed during team meetings that occurred 3 times per month over 3 yr. Data were analyzed by hand-coding transcripts to organize findings until we identified themes and salient text for constructing a narrative.  Setting: Community. PARTICIPANTS: TBI survivor. RESULTS: Identity disruption after TBI occurs because of physiological difficulties, psychological changes, and cognitive deficits. Additionally, survivors face interruptions in occupational participation that affect their identity as doers. Andi experienced identity disruption that was exacerbated by being unable to engage in written expression. When he was able to resume writing and regain his occupational identity, Andi was able to reconstruct his sense of self. CONCLUSIONS AND RELEVANCE: Identity is created by occupational engagement. Occupational therapy practitioners can better serve their clients by exploring identity disruption and occupational identity disruption after TBI. Plain-Language Summary: This article describes the lived experience of identity disruption and occupational identity disruption with an emphasis on the transformative nature of occupation. Occupational therapists should work collaboratively with clients to identify key occupations that support their sense of identity.

SWOG S1820: A pilot randomized trial of the Altering Intake, Managing Bowel Symptoms Intervention in Survivors of Rectal Cancer.

BACKGROUND: Survivors of rectal cancer experience persistent bowel dysfunction after treatments. Dietary interventions may be an effective approach for symptom management and posttreatment diet quality. SWOG S1820 was a pilot randomized trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention for bowel dysfunction in survivors of rectal cancer. METHODS: Ninety-three posttreatment survivors were randomized to the AIMS-RC group (N = 47) or the Healthy Living Education attention control group (N = 46) after informed consent and completion of a prerandomization run-in. Outcome measures were completed at baseline and at 18 and 26 weeks postrandomization. The primary end point was total bowel function score, and exploratory end points included low anterior resection syndrome (LARS) score, quality of life, dietary quality, motivation, self-efficacy, and positive/negative affect. RESULTS: Most participants were White and college educated, with a mean age of 55.2 years and median time since surgery of 13.1 months. There were no statistically significant differences in total bowel function score by group, with the AIMS-RC group demonstrating statistically significant improvements in the exploratory end points of LARS (p = .01) and the frequency subscale of the bowel function index (p = .03). The AIMS-RC group reported significantly higher acceptability of the study. CONCLUSIONS: SWOG S1820 did not provide evidence of benefit from the AIMS-RC intervention relative to the attention control. Select secondary end points did demonstrate improvements. The study was highly feasible and acceptable for participants in the National Cancer Institute Community Oncology Research Program. Findings provide strong support for further refinement and effectiveness testing of the AIMS-RC intervention.

Matched analysis of detailed peripheral blood and tumor immune microenvironment profiles in bladder cancer.

Background: Bladder cancer and therapy responses hinge on immune profiles in the tumor microenvironment (TME) and blood, yet studies linking tumor-infiltrating immune cells to peripheral immune profiles are limited. Methods: DNA methylation cytometry quantified TME and matched peripheral blood immune cell proportions. With tumor immune profile data as the input, subjects were grouped by immune infiltration status and consensus clustering. Results: Immune hot and cold groups had different immune compositions in the TME but not in circulating blood. Two clusters of patients identified with consensus clustering had different immune compositions not only in the TME but also in blood. Conclusion: Detailed immune profiling via methylation cytometry reveals the significance of understanding tumor and systemic immune relationships in cancer patients.

Bladder cancer and treatment outcomes depend on the immune profiles in the tumor and blood. Our study, using DNA methylation cytometry, measured immune cell proportions in both areas. Patients were grouped based on immune status and consensus clustering. Results showed distinct immune compositions in the tumor, but not in blood, for hot and cold groups. Consensus clustering revealed two patient clusters with differing immune compositions in both tumor and blood. This detailed immune profiling highlights the importance of understanding the complex interplay between tumor and systemic immunity in bladder cancer patients.

Latent profiles of regulatory flexibility in alcohol use disorder: Associations with delay discounting and symptoms of depression, anxiety, and stress.

BACKGROUND: Regulatory flexibility (RF) involves three distinct components of self-regulation: context sensitivity, repertoire, and feedback responsiveness. Subgroups based on differences in RF have been identified in a general sample and are differentially associated with symptoms of anxiety and depression. However, potential RF profiles have not been examined in individuals with substance use disorders. This study examined RF subtypes in individuals with alcohol use disorder (AUD) and their associations with psychosocial outcomes (i.e., depression, anxiety, and stress) and delay discounting (a core feature of addiction). METHODS: Individuals (n = 200) with an Alcohol Use Disorders Identification Test score of >16 (mean = 24.12 (±6.92)) were recruited from Amazon Mechanical Turk (mean = 37.26 years old (±11.41); 94 (47%) women). Participants completed the Context Sensitivity Index, the Flexible Regulation of Emotional Expression Scale, and the Coping Flexibility Scale to assess RF. Participants also completed an Adjusting Amount Delay Discounting Task and the Depression, Anxiety, and Stress Scale (DASS-21). Latent profile analyses (LPA) were used to identify patterns in RF deficits. Kruskal-Wallis and Dunn's tests were performed to examine differences in discounting rates and symptoms of depression, anxiety, and stress across RF profiles. RESULTS: The LPA revealed a 2-profile characterization, including (1) context sensitive regulators (CSR; n = 39) and (2) moderate flexibility regulators (MFR; n = 161). CSR demonstrated significantly lower symptoms of depression (p = 0.004), anxiety (p < 0.001), and stress (p < 0.001) than MFR. CSR also displayed significantly lower AUDIT scores (p = 0.031). CONCLUSIONS: Findings illustrate that among individuals with moderate-severe AUD, those high in context sensitivity coupled with moderate abilities in repertoire and feedback responsiveness have fewer symptoms of depression, anxiety, and stress. Together, context sensitivity may be an important and protective component of RF among individuals with AUD.

Illegal product purchasing in the experimental tobacco marketplace: Effects of menthol cigarette and cigarette ventilation ban.

BACKGROUND: Tobacco regulations may increase demand for illegal cigarettes. We use the Experimental Tobacco Marketplace to estimate the impact of banning menthol cigarettes (Experiment 1) and decreasing allowable cigarette filter ventilation levels (Experiment 2). METHODS: Crowdsourced participants were randomized into one of four groups (2×2 factorial design). Experiment 1 included menthol availability (yes/no) by purchasing option (legal only vs illegal available). Experiment 2 included filter-vented cigarettes availability (yes/no) by purchasing option (legal only vs illegal available). Participants were given an individualized budget to purchase tobacco. Percent budget spent was the outcome measure. RESULTS: Experiment 1, with a legal marketplace only, non-menthol cigarette purchasing was lower (p=0.010) and electronic-cigarette purchasing was higher (p=0.016), when cigarettes were banned compared to when they were available. With an illegal marketplace, switching to legal non-menthol cigarettes was less likely (p<0.001) and purchasing illegal menthol cigarettes was higher (p<0.001), when cigarettes were banned compared to when they were available. Experiment 2, with a legal marketplace only, cigarette purchasing was lower (p=0.010), when the participant's filtered vented cigarettes were banned compared to when they were available. With an illegal marketplace, purchasing the legal low-ventilated cigarette option was lower (p<0.001) and significant differences in illegal filter-vented cigarette purchasing were not observed, when their filter-vented cigarettes were banned compared to when they were available legally. CONCLUSIONS: Without an illegal option, both restrictions decreased cigarette purchasing, but the menthol ban increased e-cigarette purchasing. With an illegal option, a menthol ban increased illegal cigarette purchasing, but decreasing filter ventilation did not.

optima: an open-source R package for the Tapestri platform for integrative single cell multiomics data analysis.

SUMMARY: The Tapestri platform offers DNA and protein analysis at the single-cell level. Integrating both types of data is beneficial for studying multiple cell populations in heterogeneous microenvironments, such as tumor tissues. Here, we present optima, an R package for the processing and analysis of data generated from the Tapestri platform. This package provides streamlined functionality for raw data filtering, integration, normalization, transformation, and visualization. Insights gained from the optima package help users to identify unique cell populations and uncover surface protein expression patterns. The results generated by optima help researchers elucidate dynamic changes at the single-cell level in heterogeneous microenvironments. AVAILABILITY AND IMPLEMENTATION: This package is available in Github: https://github.com/rachelgriffard/optima.

Genome-Scale Methylation Analysis Identifies Immune Profiles and Age Acceleration Associations with Bladder Cancer Outcomes.

BACKGROUND: Immune profiles have been associated with bladder cancer outcomes and may have clinical applications for prognosis. However, associations of detailed immune cell subtypes with patient outcomes remain underexplored and may contribute crucial prognostic information for better managing bladder cancer recurrence and survival. METHODS: Bladder cancer case peripheral blood DNA methylation was measured using the Illumina HumanMethylationEPIC array. Extended cell-type deconvolution quantified 12 immune cell-type proportions, including memory, naïve T and B cells, and granulocyte subtypes. DNA methylation clocks determined biological age. Cox proportional hazards models tested associations of immune cell profiles and age acceleration with bladder cancer outcomes. The partDSA algorithm discriminated 10-year overall survival groups from clinical variables and immune cell profiles, and a semi-supervised recursively partitioned mixture model (SS-RPMM) with DNA methylation data was applied to identify a classifier for 10-year overall survival. RESULTS: Higher CD8T memory cell proportions were associated with better overall survival [HR = 0.95, 95% confidence interval (CI) = 0.93-0.98], while higher neutrophil-to-lymphocyte ratio (HR = 1.36, 95% CI = 1.23-1.50), CD8T naïve (HR = 1.21, 95% CI = 1.04-1.41), neutrophil (HR = 1.04, 95% CI = 1.03-1.06) proportions, and age acceleration (HR = 1.06, 95% CI = 1.03-1.08) were associated with worse overall survival in patient with bladder cancer. partDSA and SS-RPMM classified five groups of subjects with significant differences in overall survival. CONCLUSIONS: We identified associations between immune cell subtypes and age acceleration with bladder cancer outcomes. IMPACT: The findings of this study suggest that bladder cancer outcomes are associated with specific methylation-derived immune cell-type proportions and age acceleration, and these factors could be potential prognostic biomarkers.

Congenital Retinal Macrovessel and Cavernous Hemangioma in Cowden Syndrome - A Case Report and Review of Literature.

PURPOSE: To describe a case of unilateral congenital retinal macrovessel with a retinal cavernous hemangioma in a patient with Cowden syndrome (CS). In addition, we summarize previously reported cases of ocular findings in CS in the literature. METHODS: Observational case report and literature review. RESULTS: A 45-year-old white female with Cowden syndrome presented for routine ocular examination. She had a history of thyroid carcinoma, fallopian para-tubal cyst, chromophobe type renal cell carcinoma, multiple benign skin lesions, and macrocephaly. At presentation, she was asymptomatic with good vision. On dilated fundus examination, the right eye revealed a congenital retinal macrovessel and retinal cavernous hemangioma. Previously performed genetic testing revealed a pathogenic c.46dupT mutation in the PTEN gene which was consistent with CS. CONCLUSION: Our patient had a history of multiple malignancies and hamartomas consistent with her genetic diagnosis of CS. We incidentally discovered a congenital retinal macrovessel with a retinal cavernous hemangioma. Patients with CS should be referred for interdisciplinary evaluation including routine ocular examinations.

Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Can delay discounting predict vaccine hesitancy 4-years later? A study among US young adults.

Despite being a major threat to health, vaccine hesitancy (i.e., refusal or reluctance to vaccinate despite vaccine availability) is on the rise. Using a longitudinal cohort of young adults (N = 1260) from Los Angeles County, California we investigated the neurobehavioral mechanisms underlying COVID-19 vaccine hesitancy. Data were collected at two time points: during adolescence (12th grade; fall 2016; average age = 16.96 (±0.42)) and during young adulthood (spring 2021; average age = 21.33 (±0.49)). Main outcomes and measures were delay discounting (DD; fall 2016) and tendency to act rashly when experiencing positive and negative emotions (UPPS-P; fall 2016); self-reported vaccine hesitancy and vaccine beliefs/knowledge (spring 2021). A principal components analysis determined four COVID-19 vaccine beliefs/knowledge themes: Collective Responsibility, Confidence and Risk Calculation, Complacency, and Convenience. Significant relationships were found between themes, COVID-19 vaccine hesitancy, and DD. Collective Responsibility (ß = -1.158[-1.213,-1.102]) and Convenience (ß = -0.132[-0.185,-0.078]) scores were negatively associated, while Confidence and Risk Calculation (ß = 0.283[0.230,0.337]) and Complacency (ß = 0.412[0.358,0.466]) scores were positively associated with COVID-19 vaccine hesitancy. Additionally, Collective Responsibility (ß = -0.060[-0.101,-0.018]) was negatively associated, and Complacency (ß = -0.063[0.021,0.105]) was positively associated with DD from fall 2016. Mediation analysis revealed immediacy bias during adolescence, measured by DD, predicted vaccine hesitancy 4 years later while being mediated by two types of vaccine beliefs/knowledge: Collective Responsibility (ß = 0.069[0.022,0.116]) and Complacency (ß = 0.026[0.008,0.044]). These findings provide a further understanding of individual vaccine-related decision-making among young adults and inform public health messaging to increase vaccination acceptance.

Epigenome-wide association study using peripheral blood leukocytes identifies genomic regions associated with periodontal disease and edentulism in the Atherosclerosis Risk in Communities study.

AIM: To investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood. MATERIALS AND METHODS: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs. RESULTS: Our discovery analysis replicated findings from a previous study reporting a region in gene ZFP57 (6p22.1) that was significantly hypomethylated in severe periodontal disease compared with no/mild periodontal disease in European American participants. Higher methylation levels in a separate region in an unknown gene (located in Chr10: 743,992-744,958) was associated with significantly higher odds of edentulism compared with no/mild periodontal disease in African American participants. In subsequent CpG testing, four CpGs in a region previously associated with periodontitis located within HOXA4 were significantly hypermethylated in severe periodontal disease compared with no/mild periodontal disease in African American participants (odds ratio per 1 SD increase in methylation level: cg11015251: 1.28 (1.02, 1.61); cg14359292: 1.24 (1.01, 1.54); cg07317062: 1.30 (1.05, 1.61); cg08657492: 1.25 (1.01, 1.55)). CONCLUSIONS: Our study highlights epigenetic variations in ZPF57 and HOXA4 that are significantly and reproducibly associated with periodontitis. Future studies should evaluate gene regulatory mechanisms in the candidate regions of these loci.

The Phenotype of Recovery X: Associations between delay discounting, regulatory flexibility, and remission from substance use disorder.

INTRODUCTION: Delay discounting (DD) and self-regulation are important predictors of substance use disorder (SUD) outcomes. Further, regulatory flexibility (RF; i.e., selecting, monitoring, and adapting coping techniques based on contextual demands) is related to psychological resilience. However, studies have yet to examine associations among DD, RF, and remission from SUDs among individuals in recovery. METHODS: Individuals (N = 148) in SUD recovery completed the Context Sensitivity Index (CSI), the Flexible Regulation of Emotional Expression (FREE) Scale, and the Perceived Ability to Cope with Trauma (PACT) Scale to assess RF and, an $1000 hypothetical reward Adjusting Amount Delay Discounting Task. The study considered individuals to be in remission from SUD if they did not endorse any SUD DSM-5 symptom other than craving (except tobacco use disorder) in the past three months. The study team used t-tests to examine differences in RF and DD by remission status. Univariate linear regressions were used to examine the relationship between RF and DD. Finally, mediation models examined the dynamic relationship among DD, RF, and remission status. RESULTS: Remitted individuals (n = 82) had significantly lower DD (i.e., greater preference for larger, later rewards) rates (p < .001) and higher context sensitivity (p < .001) and coping flexibility (p < .001). The study found significant negative associations between DD and context sensitivity (p = .008), coping flexibility (p = .002), and emotion regulation flexibility (p < .001). Finally, context sensitivity (p = .023) and coping flexibility (p = .009) mediated the relationship between DD and SUD remission. CONCLUSIONS: Results suggest that individuals in recovery with broader temporal windows can better identify contextual demands and flexibly cope, contributing to improved SUD recovery outcomes.