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Abstract Alcohol Use Disorder (AUD) contributes significantly to global mortality. GLP-1 (Glucagon-like peptide-1) and GLP-1/GIP (Glucose-dependent Insulinotropic Polypeptide) agonists, FDA-approved for managing type 2 diabetes and obesity, where the former has shown to effectively reduce the consumption of alcohol in animal models but no reports exist on the latter. In this report, we conducted two studies. In the first study, we conducted an analysis of abundant social media texts. Specifically, a machine-learning based attribution mapping of ~ 68,250 posts related to GLP-1 or GLP-1/GIP agonists on the Reddit platform. Secondly, we recruited participants (n = 153; current alcohol drinkers; BMI ≥ 30) who self-reported either taking Semaglutide (GLP-1 agonist), Tirzepatide (the GLP-1/GIP combination) for ≥ 30 days or, as a control group; no medication to manage diabetes or weight loss for a within and between subject remote study. In the social media study, we report 8 major themes including effects of medications (30%); diabetes (21%); and Weight loss and obesity (19%). Among the alcohol-related posts (n = 1580), 71% were identified as craving reduction, decreased desire to drink, and other negative effects. In the remote study, we observe a significantly lower self-reported intake of alcohol, drinks per drinking episode, binge drinking odds, Alcohol Use Disorders Identification Test (AUDIT) scores, and stimulating, and sedative effects in the Semaglutide or Tirzepatide group when compared to prior to starting medication timepoint (within-subjects) and the control group (between-subjects). In summary, we provide initial real-world evidence of reduced alcohol consumption in people with obesity taking Semaglutide or Tirzepatide medications, suggesting potential efficacy for treatment in AUD comorbid with obesity.

ObjectiveDissociation is a conscious state characterized by alterations in sensation and perception and is thought to arise from traumatic life experiences. Previous research has demonstrated that individuals with high levels of dissociation show impairments in cognitive-emotional processes. Therefore, using the Competing Neurobehavioral Decisions System (CNDS) theory, we used statistical modeling to examine whether dissociative experience and trauma symptoms are independently predicted by impulsivity, risk-seeking, affective state (i.e., anxiety, depression, stress, and negative affect), and trauma history.MethodIn this cross-sectional study design, data were collected via Amazon Mechanical Turk from a total of n = 557 English-speaking participants in the United States. Using Qualtrics, participants answered a series of self-reported questionnaires and completed several neurocognitive tasks. Three independent multiple linear regression models were conducted to assess whether impulsivity, risk seeking, affective state, and trauma history predict depersonalization, trauma symptoms, and PTSD symptoms.ResultsAs hypothesized, we found that depersonalization and other trauma symptoms are associated with heightened impulsivity, increased risk-seeking, impaired affective states, and a history of traumatic experiences.ConclusionWe demonstrate that an imbalanced CNDS (i.e., hyperimpulsive/hypoexecutive), as evidenced by decreased future valuation, increased risk seeking, and impaired affective states, predicts heightened depersonalization and other trauma and PTSD symptomatology. This is the first time that dissociation has been connected to delay discounting (i.e., the tendency to place more value on rewards received immediately compared to farther in the future). Interventions that positively impact areas of the CNDS, such as episodic future thinking or mindfulness meditation, may be a target to help decrease dissociative symptoms.

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 (β = -1.158[-1.213,-1.102]) and Convenience (β = -0.132[-0.185,-0.078]) scores were negatively associated, while Confidence and Risk Calculation (β = 0.283[0.230,0.337]) and Complacency (β = 0.412[0.358,0.466]) scores were positively associated with COVID-19 vaccine hesitancy. Additionally, Collective Responsibility (β = -0.060[-0.101,-0.018]) was negatively associated, and Complacency (β = -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 (β = 0.069[0.022,0.116]) and Complacency (β = 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.

This systematic review aims to characterize the utility of machine learning to identify the predictors of smoking cessation outcomes and identify the machine learning methods applied in this area. In the current study, multiple searches occurred through December 9, 2022 in MEDLINE, Science Citation Index, Social Science Citation Index, EMBASE, CINAHL Plus, APA PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, and the IEEE Xplore were performed. Inclusion criteria included various machine learning techniques, studies reporting cigarette smoking cessation outcomes (smoking status and the number of cigarettes), and various experimental designs (e.g., cross-sectional and longitudinal). Predictors of smoking cessation outcomes were assessed, including behavioral markers, biomarkers, and other predictors. Our systematic review identified 12 papers fitting our inclusion criteria. In this review, we identified gaps in knowledge and innovation opportunities for machine learning research in the field of smoking cessation.

BackgroundTranslating repetitive transcranial magnetic stimulation (rTMS) into evidence-based clinical applications relies on research volunteers with different perspectives on the burden of study participation. Additionally, clinical applications of rTMS require multiple visits over weeks or months, the impact of research burden is an important component for these studies and translation of these findings to clinical practice. High frequency rTMS has significant potential to be developed as an evidence-based treatment for smoking cessation, however, the optimal rTMS dosing strategies have yet to be determined. Participant burden is an important component of determining optimal dosing strategy for rTMS as a treatment for long-term smoking cessation.MethodsIn this double-blinded, sham-controlled, randomized design, the effects of treatment duration, intensity, and active/sham assignment of rTMS on research burden were examined.ResultsOverall level of perceived research burden was low. Experienced burden (M = 26.50) was significantly lower than anticipated burden (M = 34.12). Research burden did not vary by race or income.ConclusionsOverall research burden was relatively low. Contrary to our hypotheses, we found little evidence of added significant burden for increasing the duration or intensity of rTMS, and we found little evidence for differences in research burden by race or income.Clinical Trial Registrationidentifier NCT03865472.

Episodic Future Thinking (EFT) reduces delay discounting and may have the potential as a clinical tool to increase the likelihood of health-promoting behaviors. However, evaluations of EFT in clinical settings require control conditions that match the effort and frequency of cue generation, as well as participants' expectations of improvement. The Health Information Thinking (HIT) control addresses these issues, but how this control affects delay discounting in individuals with diabetes and obesity when utilizing diabetes-management specific health-information vignettes is unknown. Moreover, little research has explored whether EFT reduces delay discounting in individuals with type 2 diabetes. To this end, we examined the impact of EFT, HIT, and a secondary no-cue control condition (NCC; assessments as usual) on delay discounting in 434 adults with self-reported type 2 diabetes and obesity recruited using Amazon Mechanical Turk. After completing an initial screening questionnaire, eligible participants reported demographics, then were randomized to EFT, HIT, or NCC conditions. Following the generation of seven EFT or HIT cues, participants assigned to EFT or HIT conditions completed a delay discounting task while imagining EFT or HIT cues; no-cue participants completed the task without cues. EFT participants demonstrated significantly lower delay discounting levels than HIT or NCC participants; no differences in delay discounting between HIT and NCC participants were observed. These results suggest that engaging in EFT, but not diabetes-specific HIT, results in lower delay discounting in adults with type 2 diabetes and obesity. This provides further evidence for the appropriateness of the HIT control for clinical trials examining the effect of EFT on delay discounting in adults with self-reported type 2 diabetes.

The Monetary Choice Questionnaire (MCQ) is a widely used behavioral task that measures the rate of delay discounting (i.e., k), the degree to which a delayed reward loses its present value as a function of the time to its receipt. Both 21- and 27-item MCQs have been extensively validated and proven valuable in research. Different methods have been developed to streamline MCQ scoring. However, existing scoring methods have yet to tackle the issue of missing responses or provide clear guidance on imputing such data. Due to this lack of knowledge, the present study developed and compared three imputation approaches that leverage the MCQ's structure and prioritize ease of implementation. Additionally, their performance was compared with mode imputation. A Monte Carlo simulation was conducted to evaluate the performance of these approaches in handling various missing responses in each observation across two datasets from prior studies that employed the 21- and 27-item MCQs. One of the three approaches consistently outperformed mode imputation across all performance measures. This approach involves imputing missing values using congruent non-missing responses to the items corresponding to the same k value or introducing random responses when congruent answers are unavailable. This investigation unveils a straightforward method for imputing missing data in the MCQ while ensuring unbiased estimates. Along with the investigation, an R tool was developed for researchers to implement this strategy while streamlining the MCQ scoring process.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a novel treatment for smoking cessation and delay discounting rate is novel therapeutic target. Research to determine optimal therapeutic targets and dosing parameters for long-term smoking cessation is needed. Due to potential biases and confounds introduced by the COVID-19 pandemic, we report preliminary results from an ongoing study among participants who reached study end prior to the pandemic.MethodsIn a 3 × 2 randomized factorial design, participants (n = 23) received 900 pulses of 20 Hz rTMS to the left dorsolateral prefrontal cortex (PFC) in one of three Durations (8, 12, or 16 days of stimulation) and two Intensities (1 or 2 sessions per day). We examined direction and magnitude of the effect sizes on latency to relapse, 6-month point-prevalence abstinence rates, research burden, and delay discounting rates.ResultsA large effect size was found for Duration and a medium for Intensity for latency to relapse. Increasing Duration increased the odds of abstinence 7–8-fold while increasing Intensity doubled the odds of abstinence. A large effect size was found for Duration, a small for Intensity for delay discounting rate. Increasing Duration and Intensity had a small effect on participant burden.ConclusionFindings provide preliminary support for delay discounting as a therapeutic target and for increasing Duration and Intensity to achieve larger effect sizes for long-term smoking cessation and will provide a pre-pandemic comparison for data collected during the pandemic.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT03865472].

Hedonic dysregulation is evident in addiction and substance use disorders, but it is not clearly understood how hedonic processes may interact with brain development related to cognitive control to influence risky decision making and substance use during adolescence. The present study used prospective longitudinal data to clarify the role of cognitive control in the link between hedonic experiences and the development of substance use during adolescence. Participants included 167 adolescents (53% male) assessed at four time points, annually. Adolescents participated in a functional magnetic resonance imaging (fMRI) session where blood-oxygen level dependent (BOLD) response was monitored during the Multi-Source- Interference Task to assess cognitive control. Substance use and hedonia were assessed using self-report. A two-group growth curve model of substance use with hedonia as a time-varying covariate indicated that higher levels of hedonia predicted higher substance use, but only in adolescents with higher activation in the frontoparietal regions and in the rostral anterior cingulate cortex during cognitive control. Results elucidate the moderating effects of neural cognitive control on associations between hedonia and adolescent substance use, suggesting that lower cognitive control functioning in the brain may exacerbate risk for substance use promoted by hedonia.

Background: SARS-CoV-2 infection is believed to adversely affect the brain, but the degree of impact on socially relevant cognitive functioning and decision-making is not well-studied, particularly among those less vulnerable to age-related mortality. The current study sought to determine whether infection status and COVID-19 symptom severity are associated with cognitive dysfunction among young and middled-aged adults in the general population, using self-reported lapses in executive control and a standardized decision-making task. Method: The survey sample comprised 1958 adults with a mean age of 37 years (SD ​= ​10.4); 60.8% were female. Participants reported SARS-CoV-2 infection history and, among those reporting a prior infection, COVID-19 symptom severity. Primary outcomes were self-reported symptoms of cognitive dysfunction assessed via an abbreviated form of the Barkley Deficits in Executive Functioning Scale (BDEFS) and performance on a validated delay-discounting task. Results: Young and middle-aged adults with a positive SARS-CoV-2 infection history reported a significantly higher number of cognitive dysfunction symptoms (Madj ​= ​1.89, SE ​= ​0.08, CI: 1.74, 2.04; n ​= ​175) than their non-infected counterparts (Madj ​= ​1.63, SE ​= ​0.08, CI: 1.47,1.80; n ​= ​1599; β ​= ​0.26, p ​= ​.001). Among those infected, there was a dose-response relationship between COVID-19 symptom severity and level of cognitive dysfunction reported, with moderate (β ​= ​0.23, CI: 0.003–0.46) and very/extremely severe (β ​= ​0.69, CI: 0.22–1.16) COVID-19 symptoms being associated with significantly greater cognitive dysfunction. These effects remained reliable and of similar magnitude after controlling for demographics, vaccination status, mitigation behavior frequency, and geographic region, and after removal of those who had been intubated during hospitalization. Very similar—and comparatively larger—effects were found for the delay-discounting task, and when using only PCR confirmed SARS-CoV-2 cases. Conclusions: Positive SARS-CoV-2 infection history and moderate or higher COVID-19 symptom severity are associated with significant symptoms of cognitive dysfunction and amplified delay discounting among young and middle-aged adults with no history of medically induced coma.

Abstract Background Despite the considerable success of comprehensive tobacco control efforts, tobacco use remains one of the greatest preventable causes of death and disease today. Over half of all smokers in the US make quit attempts every year, but over 90% relapse within 12 months, choosing the immediate reinforcement of smoking over the long-term benefits of quitting. Conceptual and empirical evidence supports continued investigation of high frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex in reducing relapse and decreasing cigarette consumption. While this evidence is compelling, an optimal dosing strategy must be determined before a long-term efficacy trial can be conducted. The goal of this study is to determine a dosing strategy for 20 Hz rTMS that will produce the best long-term abstinence outcomes with the fewest undesirable effects. Methods This is a fully crossed, double-blinded, sham-controlled, 3x2x2 randomized factorial study. The three factors are duration (stimulation days: 8, 12, and 16); intensity (900 or 1800 pulses per day); and sham control. Participants (n = 258) will consist of adults (18–65) who are motivated to quit smoking cigarettes and who will be followed for 6 months post-quit. Outcomes include latency to relapse, point prevalence abstinence rates, delay discounting rates, cognitive-behavioral skills acquisition, and multiple measures of potential undesirable effects that impact participant compliance. Discussion This study integrates existing theoretical concepts and methodologies from neuropsychology, behavioral economics, brain stimulation, clinical psychology, and the evidence-based treatment of tobacco dependence in the development of a promising and innovative approach to treat tobacco dependence. This study will establish an optimal dosing regimen for efficacy testing. Findings are expected to have a significant influence on advancing this approach as well as informing future research on clinical approaches that combine rTMS with other evidence-based treatments for tobacco dependence and perhaps other addictions. Trial registration Clinical Trials NCT03865472 (retrospectively registered). The first participant was fully enrolled on November 26, 2018. Registration was posted on March 7, 2019.

Choice bundling, in which a single choice produces a series of repeating consequences over time, increases valuation of delayed monetary and non-monetary gains. Interventions derived from this manipulation may be an effective method for mitigating the elevated delay discounting rates observed in cigarette smokers. No prior work, however, has investigated whether the effects of choice bundling generalize to reward losses. In the present study, an online panel of cigarette smokers (N = 302), recruited using survey firms Ipsos and InnovateMR, completed assessments for either monetary gains or losses (randomly assigned). In Step 1, participants completed a delay-discounting task to establish Effective Delay 50 (ED50), or the delay required for an outcome to lose half of its value. In Step 2, participants completed three conditions of an adjusting-amount task, choosing between a smaller, sooner (SS) adjusting amount and a larger, later (LL) fixed amount. The bundle size (i.e., number of consequences) was manipulated across conditions, where a single choice produced either 1 (control), 3, or 9 consequences over time (ascending/descending order counterbalanced). The delay to the first LL amount in each condition, as well as the intervals between all additional SS and LL amounts (where applicable), were set to individual participants’ ED50 values from Step 1 to control for differences in discounting of gains and losses. Results from Step 1 showed significantly higher ED50 values (i.e., less discounting) for losses compared to gains (p < 0.001). Results from Step 2 showed that choice bundling significantly increased valuation of both LL gains and losses (p < 0.001), although effects were significantly greater for losses (p < 0.01). Sensitivity analyses replicated these conclusions. Future research should examine the potential clinical utility of choice bundling, such as development of motivational interventions that emphasize both the bundled health gains associated with smoking cessation and the health losses associated with continued smoking.

Background Sacubitril/Valsartan has been highly efficacious in randomized trials of heart failure with reduced ejection fraction (HFrEF). However, the effectiveness of sacubitril/valsartan in older patients hospitalized for HFrEF in real‐world US practice is unclear. Methods and Results This study included Medicare beneficiaries age ≥65 years who were hospitalized for HFrEF ≤40% in the Get With The Guidelines–Heart Failure registry between October 2015 and December 2018, and eligible for sacubitril/valsartan. Associations between discharge prescription of sacubitril/valsartan and clinical outcomes were assessed after inverse probability of treatment weighting and adjustment for other HFrEF medications. Overall, 1551 (10.9%) patients were discharged on sacubitril/valsartan. Of those not prescribed sacubitril/valsartan, 7857 (62.0%) were prescribed an angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker. Over 12‐month follow‐up, compared with a discharge prescription of angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker, sacubitril/valsartan was independently associated with lower all‐cause mortality (adjusted hazard ratio [HR], 0.82; 95% CI, 0.72–0.94; P=0.004) but not all‐cause hospitalization (adjusted HR, 0.97; 95% CI, 0.89–1.07; P=0.55) or heart failure hospitalization (adjusted HR, 1.04; 95% CI, 0.91–1.18; P=0.59). Patients prescribed sacubitril/valsartan versus those without a prescription had lower risk of all‐cause mortality (adjusted HR, 0.69; 95% CI, 0.60–0.79; P

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Objective: Understanding individuals who are successful in recovery from substance use disorders will help to inform treatments and preventative measures. Stress has been shown to be associated with both substance use and relapse. Delay discounting is associated with risk of substance use; it is predictive of treatment outcomes and maintained abstinence. Associations between perceived stress, beliefs about locus of control, and delay discounting have yet to be assessed in individuals in recovery from substance use disorder. Methods: Data from 93 individuals in recovery from substance use recruited from the International Quit and Recovery Registry (IQRR) were analyzed. Individuals completed the adjusting amount delay discounting procedure to obtain delay discounting rates. Level of perceived stress was assessed by the Perceived Stress Scale (PSS). An individual’s belief about locus of control was assessed using the Internality, Powerful Others and Chance Scale (IPCS). Results: Delay discounting was a significant predictor of perceived stress and scores associated with beliefs about a Chance locus of control (i.e., belief that events that occur in an individual’s life are because of chance or luck), even after controlling for demographic characteristics. Time in recovery was also predictive of levels of perceived stress; this relationship was mediated by delay discounting. Conclusion: The present study indicates that delay discounting can predict perception of stress and beliefs about a chance locus of control in individuals in recovery. This information may help understand, identify, and assist individuals whomay need different, new, or more intensive interventions for their substance use disorder.

Many active pharmaceutical ingredients (APIs) in the pharmaceutical pipeline require bioavailability enhancing formulations due to very low aqueous solubility. Although spray dried dispersions (SDDs) have demonstrated broad utility in enhancing the bioavailability of such APIs by trapping them in a high-energy amorphous form, many new chemical entities (NCEs) are poorly soluble not just in water, but in preferred organic spray drying solvents, e.g., methanol (MeOH) and acetone. Spraying poorly solvent soluble APIs from dilute solutions leads to low process throughput and small particles that challenge downstream processing. For APIs with basic pKa values, spray solvent solubility can be dramatically increased by using an acid to ionize the API. Specifically, we show that acetic acid can increase API solubility in MeOH:H2O by 10-fold for a weakly basic drug, gefitinib (GEF, pKa 7.2), by ionizing GEF to form the transient acetate salt. The acetic acid is removed during drying, resulting in a SDD of the original GEF free base having performance similar to SDDs sprayed from solvents without acetic acid. The increase in solvent solubility enables large scale manufacturing for these challenging APIs by significantly increasing the throughput and reducing the amount of solvent required.

Abstract Background The objective of the study was to determine whether levels of biochemical and haematological parameters in patients with eating disorders (EDs) varied from the general population. Whilst dietary restrictions can lead to nutritional deficiencies, specific abnormalities may be relevant to the diagnosis, pathogenesis and treatment of EDs. Methods With ethics approval and informed consent, a retrospective chart audit was conducted of 113 patients with EDs at a general practice in Brisbane, Australia. This was analysed first as a total group (TG) and then in 4 ED subgroups: Anorexia nervosa (AN), Bulimia nervosa (BN), ED Not Otherwise Specified (EDNOS), and AN/BN. Eighteen parameters were assessed at or near first presentation: cholesterol, folate, vitamin B12, magnesium, manganese, zinc, calcium, potassium, urate, sodium, albumin, phosphate, ferritin, vitamin D, white cell count, neutrophils, red cell count and platelets. Results were analysed using IBM SPSS 21 and Microsoft Excel 2013 by two-tailed, one-sample t-tests (TG and 4 subgroups) and chi-square tests (TG only) and compared to the population mean standards. Results for the TG and each subgroup individually were then compared with the known reference interval (RI). Results For the total sample, t-tests showed significant differences for all parameters (p

Background The angiotensin‐receptor/neprilysin inhibitor (ARNI) sacubitril/valsartan reduces hospitalization and mortality for patients with heart failure with reduced ejection fraction. However, adoption of ARNI into clinical practice has been slow. Factors influencing use of ARNI have not been fully elucidated. Using data from the Get With The Guidelines‐Heart Failure registry, Hospital Compare, Dartmouth Atlas, and the American Hospital Association Survey, we sought to identify hospital characteristics associated with patient‐level receipt of an ARNI prescription. Methods and Results We analyzed patients with heart failure with reduced ejection fraction who were eligible for ARNI prescription (ejection fraction≤40%, no contraindications) and hospitalized from October 1, 2015 through December 31, 2016. We used logistic regression to estimate the associations between hospital characteristics and patient ARNI prescription at hospital discharge, accounting for clustering of patients within hospitals using generalized estimating equation methods and adjusting for patient‐level covariates. Of 16 674 eligible hospitalizations from 210 hospitals, 1020 patients (6.1%) were prescribed ARNI at discharge. The median hospital‐level proportion of patients prescribed ARNI was 3.3% (Q1, Q3: 0%, 12.6%). After adjustment for patient‐level covariates, for‐profit hospitals had significantly higher odds of ARNI prescription compared with not‐for‐profit hospitals (odds ratio, 2.53; 95% CI, 1.05–6.10; P=0.04), and hospitals located in the Western United States had lower odds of ARNI prescription compared with those in the Northeast (odds ratio, 0.33; 95% CI, 0.13–0.84; P=0.02). Conclusions Relatively few hospital characteristics were associated with ARNI prescription at hospital discharge, in contrast to what has been observed in early adoption in other disease areas. Additional evaluation of barriers to implementing new evidence into heart failure practice is needed.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin—a de novo designed synthetic small molecule that captures the biological properties of HDPs—on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is likely to be a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 against different strains of the virus in cell culture.

BackgroundThymosin beta‐4 (TB4) is an X‐linked gene product with cardioprotective properties. Little is known about plasma concentration of TB4 in heart failure (HF), and its relationship with other cardiovascular biomarkers. We sought to evaluate circulating TB4 in HF patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction compared to non‐HF controls. Methods and ResultsTB4 was measured using a liquid chromatography and mass spectrometry assay in age‐ and sex‐matched HFpEF (n=219), HFrEF (n=219) patients, and controls (n=219) from a prospective nationwide study. Additionally, a 92‐marker multiplex proximity extension assay was measured to identify biomarker covariates. Compared with controls, plasma TB4 was elevated in HFpEF (985 [421–1723] ng/mL versus 1401 [720–2379] ng/mL, P

Insufficient resources are associated with negative consequences including decreased valuation of future reinforcers. To determine if these effects result from scarcity, we examined the consequences of acute, abrupt changes in resource availability on delay discounting-the subjective devaluation of rewards as delay to receipt increases. In the current study, 599 individuals recruited from Amazon Mechanical Turk read a narrative of a sudden change (positive, neutral, or negative) to one's hypothetical future income and completed a delay discounting task examining future and past monetary gains and losses. The effects of the explicit zero procedure, a framing manipulation, was also examined. Negative income shock significantly increased discounting rates for gains and loses occurring both in the future and the past. Positive income windfalls significantly decreased discounting to a lesser extent. The framing procedure significantly reduced discounting under all conditions. Negative income shocks may result in short-term choices.

Modification and prevention of risky sexual behavior is important to individuals' health and public health policy. This study employed a novel sexual discounting task to elucidate the effects of social learning and regret expression on delay to sexual gratification in a behavioral task.Amazon Mechanical Turk Workers were assigned to hear one of three scenarios about a friend who engages in similar sexual behavior. The scenarios included a positive health consequence, a negative health consequence or a negative health consequence with the expression of regret. After reading one scenario, participants were asked to select from 60 images, those with whom they would have casual sex. Of the selected images, participants chose one image each for the person they most and least want to have sex with and person most and least likely to have a sexually transmitted infection. They then answered questions about engaging in unprotected sex now or waiting some delay for condom-protected sex in each partner condition.Results indicate that the negative health outcome scenario with regret expression resulted in delayed sexual gratification in the most attractive and least STI partner conditions, whereas in the least attractive and most STI partner conditions the negative health outcome with and without regret resulted in delayed sexual gratification.Results suggest that the sexual discounting task is a relevant laboratory measure and the framing of information to include regret expression may be relevant for prevention of risky sexual behavior.

Amazon Mechanical Turk (MTurk) is one of the most popular crowdsourcing platforms for online research. Although the recent MTurk data quality crisis has raised serious concerns regarding its utility, this issue can be mitigated by including quality control methods. To date, only a few studies have compared the effectiveness of the methods in preserving an experimental effect. To provide empirical guidance on which quality control methods to use for MTurk research, this study compared different methods on their effectiveness in preserving the magnitude effect in delay discounting, a robust finding in the behavioral economics literature. Two groups of MTurkers, whose HIT approval rate (%) was between 95 and 98 and 99 and 100, were recruited in October 2021. They completed a delay discounting task evaluating the magnitude effect and questions from different quality control methods. The results showed that the group with higher HIT approval rates (i.e., 99%--100%) showed a greater magnitude effect and were more likely to pass the quality control methods than those with lower rates. In addition, the majority of the quality control methods were able to preserve the magnitude effect at the expense of sample sizes. The best combinations of quality control methods that optimally maintained the effect were explored with a discussion of their implications. Although improving data quality is imperative, caution should be exercised as the quality control methods may potentially bias the sample in an undesirable manner (e.g., excluding individuals who show steep delay discounting). Keywords MTurk * Data quality * Online research * Delay discounting * Magnitude effect, Introduction The use of online crowdsourcing platforms to collect behavioral data has become popular in social science research in recent decades. These platforms provide evident scientific benefits, including efficiency and [...]

Background Sacubitril/Valsartan has been highly efficacious in randomized trials of heart failure with reduced ejection fraction (HFrEF). However, the effectiveness of sacubitril/valsartan in older patients hospitalized for HFrEF in real-world US practice is unclear. Methods and Results This study included Medicare beneficiaries age ≥65 years who were hospitalized for HFrEF ≤40% in the Get With The Guidelines-Heart Failure registry between October 2015 and December 2018, and eligible for sacubitril/valsartan. Associations between discharge prescription of sacubitril/valsartan and clinical outcomes were assessed after inverse probability of treatment weighting and adjustment for other HFrEF medications. Overall, 1551 (10.9%) patients were discharged on sacubitril/valsartan. Of those not prescribed sacubitril/valsartan, 7857 (62.0%) were prescribed an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. Over 12-month follow-up, compared with a discharge prescription of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, sacubitril/valsartan was independently associated with lower all-cause mortality (adjusted hazard ratio [HR], 0.82; 95% CI, 0.72-0.94; P=0.004) but not all-cause hospitalization (adjusted HR, 0.97; 95% CI, 0.89-1.07; P=0.55) or heart failure hospitalization (adjusted HR, 1.04; 95% CI, 0.91-1.18; P=0.59). Patients prescribed sacubitril/valsartan versus those without a prescription had lower risk of all-cause mortality (adjusted HR, 0.69; 95% CI, 0.60-0.79; P

IntroductionWe describe the development and pilot testing of the experimental tobacco and nicotine product marketplace (ETM)-a method for studying tobacco and nicotine product (TNP) choices and use behavior in a standardized way.Aims and methodsThe ETM resembles an online store populated with TNPs. Surveillance activities and data from a US representative survey and consumer reports were used to determine the most popular TNPs for inclusion in the ETM. Standardized information and videos demonstrating how to use the TNPs were provided. To test the feasibility of using the ETM, smokers (n = 119) underwent monitoring of usual brand cigarette smoking and other TNP use (Baseline Phase) followed by access to the ETM (ETM Phase) that included their usual brand cigarettes, e-cigarettes, moist snuff, snus, and nicotine replacement therapy. During the ETM Phase, participants were provided points based on their baseline TNP consumption to exchange for TNPs in the ETM. Participants were advised to exchange points for enough TNPs to last until their next visit and to refrain from using TNPs not obtained in the ETM. A subset of the participants (n = 62) completed a survey on their experience with the ETM.ResultsThe majority of the participants stated they were comfortable with navigating the ETM (97%), it was easy to determine product characteristics (89%), and they were satisfied with the products included in the marketplace (85%).ConclusionsThe ETM was well received by the vast majority of the participants and can be utilized by researchers to investigate a variety of TNP policy and regulatory science research questions.ImplicationsPatterns of TNP use are complex due to greater availability, marketing, and promotion of a diverse array of TNPs. Innovative methods are needed to experimentally study TNP choices and patterns. Through describing the development of the ETM, we provide researchers with a tool that can be readily adapted to studying a variety of phenomena challenging public health.