High-resolution functional mapping of RAD51C by saturation genome editing.

Pathogenic variants in RAD51C confer an elevated risk of breast and ovarian cancer, while individuals homozygous for specific RAD51C alleles may develop Fanconi anemia. Using saturation genome editing (SGE), we functionally assess 9,188 unique variants, including >99.5% of all possible coding sequence single-nucleotide alterations. By computing changes in variant abundance and Gaussian mixture modeling (GMM), we functionally classify 3,094 variants to be disruptive and use clinical truth sets to reveal an accuracy/concordance of variant classification >99.9%. Cell fitness was the primary assay readout allowing us to observe a phenomenon where specific missense variants exhibit distinct depletion kinetics potentially suggesting that they represent hypomorphic alleles. We further explored our exhaustive functional map, revealing critical residues on the RAD51C structure and resolving variants found in cancer-segregating kindred. Furthermore, through interrogation of UK Biobank and a large multi-center ovarian cancer cohort, we find significant associations between SGE-depleted variants and cancer diagnoses.

Variant Library Annotation Tool (VaLiAnT): an oligonucleotide library design and annotation tool for saturation genome editing and other deep mutational scanning experiments.

MOTIVATION: CRISPR/Cas9-based technology allows for the functional analysis of genetic variants at single nucleotide resolution whilst maintaining genomic context. This approach, known as saturation genome editing (SGE), a form of deep mutational scanning, systematically alters each position in a target region to explore its function. SGE experiments require the design and synthesis of oligonucleotide variant libraries which are introduced into the genome. This technology is applicable to diverse fields such as disease variant identification, drug development, structure-function studies, synthetic biology, evolutionary genetics and host-pathogen interactions. Here, we present the Variant Library Annotation Tool (VaLiAnT) which can be used to generate variant libraries from user-defined genomic coordinates and standard input files. The software can accommodate user-specified species, reference sequences and transcript annotations. RESULTS: Coordinates for a genomic range are provided by the user to retrieve a corresponding oligonucleotide reference sequence. A user-specified range within this sequence is then subject to systematic, nucleotide and/or amino acid saturating mutator functions. VaLiAnT provides a novel way to retrieve, mutate and annotate genomic sequences for oligonucleotide library generation. Specific features for SGE library generation can be employed. In addition, VaLiAnT is configurable, allowing for cDNA and prime editing saturation library generation, with other diverse applications possible. AVAILABILITY AND IMPLEMENTATION: VaLiAnT is a command line tool written in Python. Source code, testing data, example input and output files and executables are available (https://github.com/cancerit/VaLiAnT) in addition to a detailed user manual (https://github.com/cancerit/VaLiAnT/wiki). VaLiAnT is licensed under AGPLv3. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association between burnout and insomnia in U.S. Air Force Pararescue personnel: A cross-sectional study.

Studies have examined burnout and its impact on health, to include its influence on sleep. While many studies report a significant relationship between burnout and insomnia in civilian populations, no studies have examined this relationship in a military population. The United States Air Force (USAF) Pararescue personnel are an elite combat force who are specially trained to conduct both first-line combat and full spectrum personnel recovery and may be at high risk of burnout and insomnia. The current study investigated the association between dimensions of burnout and insomnia, and also examined potential moderators of the associations. A cross-sectional survey was administered to 203 Pararescue personnel (Mean Age = 32.1 years; 100% Male; 90.1% Caucasian) recruited from six US bases. The survey included measures of three dimensions of burnout (emotional exhaustion, depersonalization, personal achievement), insomnia, psychological flexibility, and social support. Emotional exhaustion was significantly associated with insomnia with a moderate to large effect size, when controlling for covariates. Depersonalization, but not personal achievement, was also significantly associated with insomnia. There was no evidence that associations between burnout and insomnia were moderated by psychological flexibility or social support. These findings help to identify individuals at risk of insomnia and may ultimately be useful in developing interventions for insomnia in this population.

Use of electronic cigarettes in the United States service member and Veteran populations: A narrative review (2019).

Electronic Nicotine Delivery Systems (ENDS) are an increasingly popular form of a nicotine delivery device, particularly among young adults and adolescents. The health consequences of long-term ENDS use are not known. Two populations that warrant special consideration are members of the United States Military (service members) and US Veterans. In this narrative review of literature before December 2019, research on ENDS use in these two populations is described in relation to four themes relevant to ENDS use: Prevalence of ENDS use; perceptions of ENDS; correlates of ENDS use; and use of ENDS for smoking cessation. This narrative review summarized research findings in each of these four areas and identified areas for future research.

Enhancing Smoking Risk Communications: The Influence of Health Literacy and Message Content.

Background: Efforts are needed to ensure that smokers with lower health literacy are provided with understandable and impactful information about the health consequences of smoking and benefits of quitting. Purpose: To test the influence of health literacy on smokers' responses to health risk messages manipulated on framing (gain vs. loss) and emotionality (factual vs. emotional). Methods: Participants (N = 402) were randomized to evaluate one of four sets of smoking risk messages (factual gain-framed, factual loss-framed, emotional gain-framed, or emotional loss-framed). Multiple linear regressions examined main effects of health literacy, message emotionality, and message framing on: (a) risk perceptions, (b) behavioral expectations (i.e. cut down, limit, quit), and (c) risk knowledge. Two-way interactions of health literacy with emotionality and framing were examined for these outcomes. Analyses were based on theory-driven, a priori hypotheses. Results: As hypothesized, main effects emerged such that smokers with higher health literacy reported stronger risk perceptions and knowledge retention regardless of message type. Additionally, emotional (vs. factual) and gain- (vs. loss-) framed messages were associated with certain lower risk perceptions regardless of health literacy level. Consistent with hypotheses, two-way crossover interactions emerged between health literacy and emotionality. Among smokers with higher health literacy, factual messages produced higher perceived risk and stronger expectations for quitting. Among smokers with lower health literacy, emotional messages produced higher perceived risk and stronger expectations for quitting. Conclusions: Health literacy plays an important role in influencing how smokers respond to different risk messages. One's health literacy should be considered when determining whether risk communications emphasize factual or emotional content.

HIV Care Initiation: A Teachable Moment for Smoking Cessation?

Introduction: Tobacco use among persons living with HIV represents an important risk factor for poor treatment outcomes, morbidity, and mortality. Thus, efforts designed to inform the development of appropriate smoking cessation programs for this population remains a public health priority. To address this need, a study was conducted to longitudinally assess the relationship between intention to quit smoking and cessation over the 12-month period following initiation of HIV care. Methods: Patients initiating HIV care at a large inner city safety net clinic were enrolled (n = 378) in a 12-month prospective study. Audio computer-assisted self-interviews were conducted at baseline, and at 3, 6, 9, and 12 months post-enrollment, and HIV-related clinical data were collected from participants' electronic medical records. Variables of interest included intention to quit smoking, 7-day point prevalence smoking abstinence (biochemically verified), and stage of HIV. Data were collected in Houston, Texas from 2009 to 2015. Results: The sample was 75% male and 62% Black. Findings indicated that intention to quit smoking increased between baseline and 3 months, and subsequently trended downward from 3 to 12 months. Results from linear and generalized linear mixed models indicated that participants with advanced HIV disease (vs. not advanced) reported significantly (p < .05) higher intention to quit smoking at 3, 6, and 12 months post-study enrollment. A similar though nonsignificant pattern was observed in the smoking abstinence outcome. Conclusions: HIV treatment initiation appears to be associated with increases in intention to quit smoking thus serves as a potential teachable moment for smoking cessation intervention. Implications: This study documents significant increases in intention to quit smoking in the 3-month period following HIV care initiation. Moreover, quit intention trended downward following the 3-month follow-up until the 12-month follow-up. In addition, a marked effect for HIV disease stage was observed, whereby participants with advanced HIV disease (vs. those without) experienced a greater increase in intention to quit. HIV treatment initiation appears to be associated with increases in intention to quit smoking, thus serves as a crucial teachable moment for smoking cessation intervention for people living with HIV.

Effects of galantamine on smoking behavior and cognitive performance in treatment-seeking smokers prior to a quit attempt.

OBJECTIVE: Drugs that enhance cholinergic transmission have demonstrated promise treating addictive disorders. Galantamine, an acetylcholinesterase inhibitor, may reduce cigarette smoking in otherwise healthy treatment-seeking smokers. METHODS: The current study is a double-blind, placebo-controlled, study that randomized daily smokers (n = 60) to receive one of two doses of galantamine extended release (8 or 16 mg/day), or a placebo treatment. Participants completed a smoking choice task as well as study measures and cognitive tasks in the laboratory and daily life using ecological momentary assessment. Analysis focused on smoking behavior and satisfaction, cognitive performance, and decision to smoke prior to a quit attempt. RESULTS: Linear mixed models demonstrated that, compared with placebo, both doses of galantamine reduced smoking in a laboratory choice task (p = 0.006) and decreased urine cotinine levels, but not self-reported cigarettes, during the pre-quit period (p = 0.007). Treatment had minimal effect on smoking satisfaction or cognitive performance. CONCLUSIONS: The results suggest that galantamine reduces nicotine intake but it is unlikely that galantamine improves cognitive performance in otherwise healthy, treatment-seeking smokers. Larger randomized clinical trials can determine if galantamine adjunctive to addiction treatment can improve smoking treatment outcomes.

A systematic review of attentional biases in disorders involving binge eating.

OBJECTIVE: Attentional bias (AB) may be one mechanism contributing to the development and/or maintenance of disordered eating. AB has traditionally been measured using reaction time in response to a stimulus. Novel methods for AB measurement include eye tracking to measure visual fixation on a stimulus, and electroencephalography to measure brain activation in response to a stimulus. This systematic review summarizes, critiques, and integrates data on AB gathered using the above-mentioned methods in those with binge eating behaviors, including binge eating, loss of control eating, and bulimia nervosa. METHOD: Literature searches on PubMed and PsycInfo were conducted using combinations of terms related to binge eating and biobehavioral AB paradigms. Studies using AB paradigms with three categories of stimuli were included: food, weight/shape, and threat. For studies reporting means and standard deviations of group bias scores, Hedges' g effect sizes for group differences in AB were calculated. RESULTS: Fifty articles met inclusion criteria and were reviewed. Individuals who binge eat in the absence of compensatory behaviors show an increased AB to food cues, but few studies have examined such individuals' AB toward weight/shape and threatening stimuli. Individuals with bulimia nervosa consistently show an increased AB to shape/weight cues and socially threatening stimuli, but findings for AB to food cues are mixed. DISCUSSION: While there are important research gaps, preliminary evidence suggests that the combination of AB to disorder-specific cues (i.e., food and weight/shape) and AB toward threat may be a potent contributor to binge eating. This conclusion underscores previous findings on the interaction between negative affect and AB to disorder-specific cues. Recommendations for future research are provided.

Effect of Brief Mindfulness Practice on Self-Reported Affect, Craving, and Smoking: A Pilot Randomized Controlled Trial Using Ecological Momentary Assessment.

INTRODUCTION: Despite efficacious pharmacological and behavioral treatments, most smokers attempt to quit without assistance and fail to quit. Mindfulness practice may be useful in smoking cessation. METHODS: This ecological momentary assessment (EMA) study was a pilot parallel group randomized controlled trial of a brief mindfulness practice (Brief-MP) intervention on self-reported smoking behavior delivered to smokers on a Personal Digital Assistant (PDA) in the field. Adult community smokers (N = 44) were randomly assigned to a Brief-MP (n = 24) or Control (sham meditation; n = 20) group. Participants were instructed to smoke as much or as little as they liked. Participants carried a PDA for 2 weeks and were instructed to initiate 20 minutes of meditation (or control) training on the PDA daily, completing an assessment of cognitive and affective processes immediately afterwards. Additionally, they completed assessments at random times up to four times per day. Primary outcome variables were negative affect, craving, and cigarettes smoked per day, all self-reported. RESULTS: Thirty-seven participants provided EMA data totaling 1874 assessments. Linear Mixed Model analyses on EMA data revealed that Brief-MP (vs. Control) reduced overall negative affect, F(1, 1798) = 13.8, P = .0002; reduced craving immediately post-meditation, (Group × Assessment Type interaction, F(2, 1796) = 12.3, P = .0001); and reduced cigarettes smoked per day over time (Group × Day interaction, F(1, 436) = 5.50, P = .01). CONCLUSIONS: Brief-MP administered in the field reduced negative affect, craving, and cigarette use, suggesting it may be a useful treatment.

Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders.

Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% to 73%, with the most common being mood disorders (13% to 64%) and anxiety disorders (21% to 50%), as well as non-substance-induced psychotic disorders (<10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible transdiagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive control and include cholinesterase inhibitors (e.g., galantamine, rivastigmine) and monoamine transporter inhibitors (e.g., modafinil, methylphenidate). Cognitive behavioral therapy and cognitive rehabilitation also enhance executive control, while cognitive bias modification targets impairments associated with automatic processes. Cognitive enhancement to improve treatment outcomes is a novel and promising strategy, but its clinical value for the treatment of stimulant use disorder, with or without other psychiatric comorbidities, remains to be determined in future studies.

Black Cigarette Smokers Report More Attention to Smoking Cues Than White Smokers: Implications for Smoking Cessation.

INTRODUCTION: Black cigarette smokers have lower rates of smoking cessation compared with Whites. However, the mechanisms underlying these differences are not clear. Many Blacks live in communities saturated by tobacco advertisements. These cue-rich environments may undermine cessation attempts by provoking smoking. Moreover, attentional bias to smoking cues (attention capture by smoking cues) has been linked to lower cessation outcomes. Cessation attempts among Blacks may be compromised by attentional bias to smoking cues and a cue-rich environment. METHOD: Attention to smoking cues in Black and White smokers was examined in 2 studies. In both studies, assessments were completed during 2 laboratory visits: a nonabstinent session and an abstinent session. In study 1, nontreatment-seeking smokers (99 Whites, 104 Blacks) completed the Subjective Attentional Bias Questionnaire (SABQ; a self-report measure of attention to cues) and the Smoking Stroop task (a reaction time measure of attentional bias to smoking cues). In study 2, 110 White and 74 Black treatment-seeking smokers completed these assessments and attempted to quit. RESULTS: In study 1, Blacks reported higher ratings than Whites on the SABQ (p = .005). In study 2, Blacks also reported higher ratings than Whites on the SABQ (p = .003). In study 2, Blacks had lower biochemical-verified point prevalence abstinence than Whites, and the between-race difference in outcome was partially mediated by SABQ ratings. CONCLUSION: Blacks reported greater attention to smoking cues than Whites, possibly due to between-race differences in environments. Greater attention to smoking cues may undermine cessation attempts.

Cognition and craving during smoking cessation: an ecological momentary assessment study.

INTRODUCTION: Some studies using ecological momentary assessment (EMA) have revealed an association between craving for cigarettes and relapse. It is therefore important to understand the correlates of craving during smoking cessation. Attentional bias to smoking cues is a potential correlate of craving, but it has not previously been assessed using EMA during smoking cessation. METHODS: Smokers enrolled in a research smoking cessation study were offered the opportunity to take part in an EMA study. Volunteers carried around a personal digital assistant (PDA) for the first week of their quit attempt. They completed up to 4 random assessments (RAs) per day as well as assessments when they experienced a temptation to smoke and when they relapsed. Craving for cigarettes was assessed with a single item (1-7 scale). Attentional bias was assessed with a smoking Stroop task (a reaction time task) at every other assessment, as was self-reported attention to cigarettes. RESULTS: Data were available from 119 participants. Across 882 assessments, participants exhibited a significant smoking Stroop effect. Linear mixed models revealed a significant between-subject association between craving and the smoking Stroop effect. Individuals with higher levels of craving exhibited greater attentional bias. The within-subject association was not significant. Similar results were obtained for the relationship between self-reported attention to cigarettes and attentional bias. CONCLUSIONS: Attentional bias can be assessed in the natural environment using EMA during smoking cessation, and attentional bias is a correlate of craving during the early stages of a quit attempt.

Cortisol levels decrease after acute tobacco abstinence in regular smokers.

OBJECTIVE: The aim of this study was to examine the effect of acute tobacco abstinence on cortisol levels in regular smokers, and whether abstinence-induced changes in cortisol levels are correlated with various signs and symptoms of the tobacco withdrawal syndrome. METHODS: Smokers (N = 77, ≥15 cigarettes/day) attended two counterbalanced sessions (avg = 1 h), one following 12-20 h of abstinence and the other following ad lib smoking. At both sessions, salivary cortisol levels were measured at three time points. Additionally, a battery of self-report questionnaires, physiological assessments, and cognitive performance tasks were administered to measure signs and symptoms of tobacco withdrawal. RESULTS: Salivary cortisol levels were significantly lower during the abstinent session versus the non-abstinent session. No significant associations were found between abstinence-induced changes in cortisol and other tobacco withdrawal measures, although there was suggestive evidence that abstinence-induced changes in cortisol levels and hunger were inversely associated to a modest degree. CONCLUSION: Acute tobacco abstinence was associated with decreased cortisol levels. Cortisol dampening during acute tobacco abstinence may reflect nicotine-mediated modulation of hypothalamic-pituitary-adrenal axis activity, which may be relevant to the maintenance of tobacco dependence. Tobacco-withdrawal cortisol changes do not appear to be a cause or consequence of many manifestations of acute tobacco withdrawal with the possible exception of hunger.

Lower health literacy predicts smoking relapse among racially/ethnically diverse smokers with low socioeconomic status.

BACKGROUND: Nearly half of U.S. adults have difficulties with health literacy (HL), which is defined as the ability to adequately obtain, process, and understand basic health information. Lower HL is associated with negative health behaviors and poor health outcomes. Racial/ethnic minorities and those with low socioeconomic status (SES) are disproportionately affected by poor HL. They also have higher smoking prevalence and more difficulty quitting smoking. Thus, lower HL may be uniquely associated with poorer cessation outcomes in this population. METHODS: This study investigated the association between HL and smoking cessation outcomes among 200, low-SES, racially/ethnically diverse smokers enrolled in smoking cessation treatment. Logistic regression analyses adjusted for demographics (i.e., age, gender, race/ethnicity, relationship status), SES-related characteristics (i.e., education, income), and nicotine dependence were conducted to investigate associations between HL and smoking relapse at the end of treatment (3 weeks post quit day). RESULTS: Results indicated that smokers with lower HL (score of < 64.5 on the Rapid Estimate of Adult Literacy in Medicine [REALM]) were significantly more likely than those with higher HL (score of ≥ 64.5 on the REALM) to relapse by the end of treatment, even after controlling for established predictors of cessation including demographics, SES, and nicotine dependence (OR = 3.26; 95% CI = 1.14, 9.26). CONCLUSIONS: Findings suggest that lower HL may serve as an independent risk factor for smoking relapse among low-SES, racially/ethnically diverse smokers enrolled in treatment. Future research is needed to investigate longitudinal relations between HL and cessation outcomes and potential mechanisms of this relationship.

Social support mediates the association of health literacy and depression among racially/ethnically diverse smokers with low socioeconomic status.

Nearly half of U.S. adults have health literacy (HL) difficulties, and lack the ability to effectively obtain, process, and understand health information. Poor HL is associated with depression, yet mechanisms of this relation are unclear. This study examined whether social support mediated the relation between HL and depressive symptoms in 200 low-socioeconomic status (SES), racially/ethnically diverse smokers enrolled in cessation treatment. Mediation analyses were conducted using bootstrapping and controlling for SES and nicotine dependence. In simple mediation models, social support [Interpersonal Support Evaluation List (ISEL) total, subscales (Appraisal, Belonging, Tangible)] mediated the effect of HL on depression, such that lower HL was associated with lower perceived support, which predicted higher depressive symptoms (ps < .05). A multiple mediation model, with ISEL subscales entered simultaneously as mediators, was significant (p < .05) but only the Belonging subscale demonstrating independent significance (p < .05). Thus, social support may be a critical factor underlying the HL-depression relationship in low-SES, racially/ethnically diverse smokers.

Analyzing the functional effects of DNA variants with gene editing.

Continual advancements in genomics have led to an ever-widening disparity between the rate of discovery of genetic variants and our current understanding of their functions and potential roles in disease. Systematic methods for phenotyping DNA variants are required to effectively translate genomics data into improved outcomes for patients with genetic diseases. To make the biggest impact, these approaches must be scalable and accurate, faithfully reflect disease biology, and define complex disease mechanisms. We compare current methods to analyze the function of variants in their endogenous DNA context using genome editing strategies, such as saturation genome editing, base editing and prime editing. We discuss how these technologies can be linked to high-content readouts to gain deep mechanistic insights into variant effects. Finally, we highlight key challenges that need to be addressed to bridge the genotype to phenotype gap, and ultimately improve the diagnosis and treatment of genetic diseases.

Evaluating the Acceptability and Feasibility of Collecting Passive Smartphone Data to Estimate Psychological Functioning in U.S. Service Members and Veterans: A Pilot Study.

INTRODUCTION: This study investigated the acceptability and feasibility of digital phenotyping in a military sample with a history of traumatic brain injury and co-occurring psychological and cognitive symptoms. The first aim was to evaluate the acceptability of digital phenotyping by (1a) quantifying the proportion of participants willing to download the app and rates of dropout and app discontinuation and (1b) reviewing the stated reasons for both refusing and discontinuing use of the app. The second aim was to investigate technical feasibility by (2a) characterizing the amount and frequency of transferred data and (2b) documenting technical challenges. Exploratory aim 3 sought to leverage data on phone and keyboard interactions to predict if a participant (a) is depressed and (b) has depression that improves over the course of the study. MATERIALS AND METHODS: A passive digital phenotyping app (Mindstrong Discovery) functioned in the background of the participants' smartphones and passively collected phone usage and typing kinematics data. RESULTS: Fifteen out of 16 participants (93.8%) consented to install the app on their personal smartphone devices. Four participants (26.7%) discontinued the use of the app partway through the study, primarily because of keyboard usability and technical issues. Fourteen out of 15 participants (93.3%) had at least one data transfer, and the median number of days with data was 40 out of a possible 57 days. The exploratory machine learning models predicting depression status and improvement in depression performed better than chance. CONCLUSIONS: The findings of this pilot study suggest that digital phenotyping is acceptable and feasible in a military sample and provides support for future larger investigations of this technology.

A Pilot Randomized Control Trial Testing a Smartphone-Delivered Food Attention Retraining Program in Adolescent Girls with Overweight or Obesity.

BACKGROUND/OBJECTIVES: Attention bias (AB) toward food is associated with obesity, but it is unclear if programs designed to reduce AB can impact adolescents' eating behavior. We investigated whether a two-week, smartphone-delivered attention retraining (AR) program (vs a control program) altered food AB in adolescent girls with overweight. METHODS: Participants completed three food-cue visual-probe trainings/day. The AR and control programs directed attention away from food stimuli during 100% and 50% of trainings, respectively. Before and after completion of the programs, girls completed a food-cue visual-probe task while undergoing magnetoencephalography (MEG), and then a laboratory test meal. RESULTS: Sixty-eight adolescents were randomized; 58 completed post-program visits. There was minimal effect of condition on AB scores (ß [95%CI] = -1.9 [-20.8, 16.9]; d = -0.06). There was a small effect of condition on energy intake (EMMcontrol = 1017 kcal, EMMAR = 1088 kcal, d = 0.29). Within the AR group, there was slightly blunted initial engagement in brain areas associated with reward response and subsequent increased goal-directed attention and action control. CONCLUSIONS: We found preliminary support for efficacy of an intensive smartphone-delivered AR program to alter neural correlates of attention processing in adolescent girls with overweight or obesity. Studies with larger sample sizes are needed to elucidate if AR trainings disrupt the link between food AB and eating behavior.

Saturation genome editing of BAP1 functionally classifies somatic and germline variants.

Many variants that we inherit from our parents or acquire de novo or somatically are rare, limiting the precision with which we can associate them with disease. We performed exhaustive saturation genome editing (SGE) of BAP1, the disruption of which is linked to tumorigenesis and altered neurodevelopment. We experimentally characterized 18,108 unique variants, of which 6,196 were found to have abnormal functions, and then used these data to evaluate phenotypic associations in the UK Biobank. We also characterized variants in a large population-ascertained tumor collection, in cancer pedigrees and ClinVar, and explored the behavior of cancer-associated variants compared to that of variants linked to neurodevelopmental phenotypes. Our analyses demonstrated that disruptive germline BAP1 variants were significantly associated with higher circulating levels of the mitogen IGF-1, suggesting a possible pathological mechanism and therapeutic target. Furthermore, we built a variant classifier with >98% sensitivity and specificity and quantify evidence strengths to aid precision variant interpretation.

Associations between health literacy and established predictors of smoking cessation.

OBJECTIVES: We examined associations between health literacy and predictors of smoking cessation among 402 low-socioeconomic status (SES), racially/ethnically diverse smokers. METHODS: Data were collected as part of a larger study evaluating smoking health risk messages. We conducted multiple linear regression analyses to examine relations between health literacy and predictors of smoking cessation (i.e., nicotine dependence, smoking outcome expectancies, smoking risk perceptions and knowledge, self-efficacy, intentions to quit or reduce smoking). RESULTS: Lower health literacy was associated with higher nicotine dependence, more positive and less negative smoking outcome expectancies, less knowledge about smoking health risks, and lower risk perceptions. Associations remained significant (P < .05) after controlling for demographics and SES-related factors. CONCLUSIONS: These results provide the first evidence that low health literacy may serve as a critical and independent risk factor for poor cessation outcomes among low-socioeconomic status, racially/ethnically diverse smokers. Research is needed to investigate potential mechanisms underlying this relationship.