Identifying beliefs driving COVID-19 vaccination: Lessons for effective messaging.

Increasing vaccination acceptance has been essential during the COVID-19 pandemic and in preparation for future public health emergencies. This study aimed to identify messaging strategies to encourage vaccine uptake by measuring the drivers of COVID-19 vaccination among the general public. A survey to assess COVID-19 vaccination acceptance and hesitancy was advertised on Facebook in February-April 2022. The survey included items asking about COVID-19 vaccination status and participant demographics, and three scales assessing medical mistrust, perceived COVID-19 risk, and COVID-19 vaccine confidence (adapted from the Oxford COVID-19 vaccine confidence and complacency scale). The main outcome was vaccination, predicted by patient demographics and survey scale scores. Of 1,915 survey responses, 1,450 (75.7%) were included, with 1,048 (72.3%) respondents reporting they had been vaccinated. In a multivariable regression model, the COVID-19 vaccine confidence scale was the strongest predictor of vaccination, along with education level and perceived COVID-19 risk. Among the items on this scale, not all were equally important in predicting COVID-19 vaccination. The items that best predicted vaccination, at a given score on the COVID-19 vaccine confidence scale, included confidence that vaccine side effects are minimal, that the vaccine will work, that the vaccine will help the community, and that the vaccine provides freedom to move on with life. This study improved our understanding of perceptions most strongly associated with vaccine acceptance, allowing us to consider how to develop messages that may be particularly effective in encouraging vaccination among the general public for both the COVID-19 pandemic and future public health emergencies.

Understanding Concerns about COVID-19 and Vaccination: Perspectives from Kidney Transplant Recipients.

The COVID-19 pandemic poses a significant risk for immunosuppressed groups such as transplant patients. The purpose of this study was to improve our understanding of the impact of the COVID-19 pandemic on kidney transplant recipients, including their views on COVID-19 vaccination. Semi-structured interviews were conducted from December 2021 to August 2022 with 38 kidney transplant recipients who had an appointment with their transplant care team within the previous 6 months. We used qualitative thematic analysis to characterize the perspectives of interviewees. Regardless of COVID-19 vaccination status, most interviewees reported utilizing public health measures such as masking, hand washing, and avoiding crowds to protect themselves against COVID-19. Vaccinated interviewees (n = 31) noted that they chose to receive a COVID-19 vaccine because of their increased risk due to their immunocompromised state. For unvaccinated interviewees (n = 7), reasons for not receiving a COVID-19 vaccine included concerns about the safety and efficacy of the vaccine. Both vaccinated and unvaccinated interviewees expressed concerns about the lack of adequate testing of the vaccine in transplant patients and questioned if the vaccine might have unknown side effects for transplant recipients. Regardless of the vaccination status, most interviewees noted having trust in their healthcare team. Interviewees also described interpersonal tensions that arose during the pandemic, many of which surrounded vaccination and other preventive measures that were important to participants to protect their health. Together, these data demonstrate differing concerns and experiences related to the COVID-19 pandemic for vaccinated and unvaccinated transplant recipients. These findings highlight the unique needs of transplant recipients and reveal opportunities to support this vulnerable patient population in efforts to protect their health as the COVID-19 pandemic evolves.

Estetrol Is Safe and Well Tolerated during Treatment of Hospitalized Men and Women with Moderate COVID-19 in a Randomized, Double-Blind Study.

Epidemiological data suggest that the severe acute respiratory syndrome coronavirus 2 infection rate is higher in women than in men, but the death rate is lower, while women (>50 years) on menopausal hormone therapy (MHT) have a higher survival rate than those not on MHT. Classical oral estrogen enhances the synthesis of coagulation markers and may increase the risk of thromboembolic events that are common in coronavirus disease 2019 (COVID-19). The favorable hemostatic profile of estetrol (E4) might be suitable for use in women who are receiving estrogen treatment and contract COVID-19. A multicenter, randomized, double-blind, placebo-controlled, phase 2 study (NCT04801836) investigated the efficacy, safety, and tolerability of E4 versus placebo in hospitalized patients with moderate COVID-19. Eligible postmenopausal women and men (aged ≥ 18 years old) were randomized to E4 15 mg or placebo, once daily for 21 days, in addition to the standard of care (SoC). The primary efficacy endpoint of improvement in COVID-19 (percentage of patients recovered at day 28) between the placebo and E4 arms was not met. E4 was well tolerated, with no safety signals or thromboembolic events, suggesting that postmenopausal women can safely continue E4-based therapy in cases of moderate COVID-19 managed with SoC.

Correcting misperceptions of gun policy support can foster intergroup cooperation between gun owners and non-gun owners.

Past research finds that a majority of gun and non-gun owners support key gun safety policies, yet gun owners tend to underestimate other gun owners' support for these policies. We predicted that these misperceptions of support might lead gun owners to view non-gun owners as being less similar to themselves, which might undermine intergroup cooperation to promote gun safety policies and fuel intergroup animosity. Importantly, we also predicted that correcting these misperceptions would be an effective way to reduce intergroup division and enhance intergroup cooperation. We tested these predictions across two studies in which participants were randomly assigned to read information designed to correct misperceptions of gun owner support or to read other, control information. Across both studies, we find that correcting gun owners' misperceptions of gun owner support for gun safety policies leads to greater perceptions of identity overlap between gun and non-gun owners, greater willingness to work with each other to promote gun safety policies, and less negative affect towards each other. This suggests that correcting gun owner misperceptions of gun owners' support for gun safety policies might be an effective intervention to facilitate intergroup cooperation to promote these policies. Therefore, efforts to promote gun safety policies might benefit from educating gun owners about the degree of support for these policies that already exists among gun owners. Doing so might present a simple and cost-effective way to mobilize gun owners in support of these policies.

Changes in COVID-19 Vaccine Hesitancy Among Black and White Individuals in the US.

Importance: COVID-19 has disproportionately affected Black individuals in the US; however, vaccination rates among Black individuals trail those among other racial groups. This disparity is often attributed to a high level of vaccine hesitancy among Black individuals, but few studies have examined changes in vaccine hesitancy over time. Objectives: To compare changes in vaccine hesitancy between Black and White individuals in the US and to examine mechanisms that might help explain the observed differences. Design, Setting, and Participants: This survey study used 7 waves of data collected using a panel design. A total of 1200 English-speaking adults in the US were recruited from a nonprobability online panel to construct a census-matched sample. Participants were contacted monthly between December 9, 2020, and June 16, 2021. Main Outcomes and Measures: The main outcome of interest was self-reported vaccination intention, measured on a 6-point scale (where 1 indicates extremely unlikely and 6 indicates extremely likely). Beliefs about the safety, effectiveness, and necessity of COVID-19 vaccines were measured on a 5-point Likert scale, with higher scores denoting greater agreement. Results: The baseline data included 1200 participants (693 women [52.0%; weighted]; 921 White individuals [64.0%; weighted], 107 Black individuals [12.2%; weighted]; weighted mean [SD] age, 49.5 [17.6] years). The survey participation rate was 57.0% (1264 of 2218). Black and White individuals had comparable vaccination intentions in December 2020, but Black individuals experienced larger increases in vaccination intention than White individuals relative to baseline in March 2021 (b = 0.666; P < .001), April 2021 (b = 0.890; P < .001), May 2021 (b = 0.695; P < .001), and June 2021 (b = 0.709; P < .001). The belief that the vaccines are necessary for protection also increased more among Black than White individuals in March 2021 (b = 0.221; P = .01) and April 2021 (b = 0.187; P = .04). Beliefs that the vaccines are safe and effective (b = 0.125; P < .001) and necessary (b = 0.405; P < .001) were positively associated with vaccination intention. There was no evidence that these associations varied by race. Conclusions and Relevance: This survey study suggests that the intention of Black individuals to be vaccinated was initially comparable to that of White individuals but increased more rapidly. There is some evidence that this increase is associated with changes in beliefs about the vaccine. Vaccination rates continue to be lower among Black individuals than White individuals, but these results suggest that this might be less likely the result of vaccine hesitancy than other factors.

Public Opinion Perceptions, Private Support, and Public Actions of US Adults Regarding Gun Safety Policy.

Importance: Despite broad public support for gun safety policies, minimal policy implementation has occurred. Objective: To investigate factors that encourage greater private support for and public action on gun safety policy. Design, Setting, and Participants: Three studies were conducted: a public opinion survey (Study 1) was conducted from January 8 to 22, 2019, and 2 experiments (Studies 2 and 3) were conducted from August 27 to October 17, 2019, and April 15 to 21, 2020, respectively. Adults living in the US were eligible to participate in Studies 1 and 3. Students 18 years and older participating in a research experience program were eligible to participate in Study 2. Study 1 was administered online by Ipsos, a market research company. A nationally representative sample of 1000 US adults was obtained from Ipsos' online KnowledgePanel, of whom 508 completed the public opinion survey. For Study 2, which was conducted in a university laboratory, 354 participants were recruited from a university research pool, all of whom completed the study. Study 3 was administered online by the market research company YouGov, which identified 727 US gun owners from its opt-in panel, from which it constructed a census-matched sample of 400 participants. Exposures: Participants read a statement about the 2018 Marjory Stoneman Douglas High School shooting. Content was manipulated as a 2 (corrective information vs no corrective information) × 2 (system changeable vs system not changeable) between-subjects factorial design with random assignment. The corrective information included polling data highlighting widespread support among gun owners for several gun safety policies. System changeable described gun safety policies passed by Florida's legislature. Main Outcomes and Measures: Main outcomes were support for gun safety policies and public disclosure of support. Results: The 3 studies included a total of 1262 participants (Study 1: 508 participants; weighted mean [SD] age, 47.7 [17.5] years; 261.9 women [51.6%]; 82.5 Hispanic [16.2%] and 60.3 Black [11.9%]; Study 2: 354 participants; mean [SD] age, 20.0 [2.3] years; 232 women [65.9%]; 100 Asian [28.3%] and 37 Black [10.5%]; Study 3: 400 participants; weighted mean [SD] age, 52.1 [16.4] years; 187.3 women [46.8%]; 295.5 White [73.9%], 44.5 Hispanic [11.1%], and 32.4 Black [8.1%]). Study 1 found that 63% to 91% of gun owners and 83% to 93% of non-gun owners supported key gun safety policies, yet both groups significantly underestimated gun owners' support for these policies by between 12% and 31%. Studies 2 and 3 found that exposure to corrective information was associated with a small increase in support for 2 gun safety policies of between 4% and 15%, both in terms of participants' privately held beliefs and the beliefs they would be willing to share publicly. Conclusions and Relevance: This survey study found that many US adults failed to recognize that most gun owners support key gun safety policies. Correcting this misperception was associated with greater private and public support for gun safety policy.

Undermining Credibility: The Limited Influence of Online Comments to Vaccine-related News Stories.

State-sponsored disinformation campaigns increasingly use anti-vaccine comments to not only undermine public health but to also reduce confidence and participation in a democratic society. Despite these dangers, research has not fully explored whether anti-vaccine comments can achieve these effects. To address this gap, an online survey experiment was conducted using a national sample of 1010 U.S. adults. Participants read a mainstream news article discussing the flu vaccine that included random variations of user comments adapted from a documented state-sponsored disinformation campaign. While exposure to anti-vaccine comments did not affect participants' views of vaccines or their willingness to discuss vaccines, participants holding pro-vaccine views reported lower confidence in news organizations and viewed the journalist who authored their article as less credible. These results suggest that anti-vaccine comments may produce effects that align with the goals of state-sponsored disinformation campaigns.

Jargon as a barrier to effective science communication: Evidence from metacognition.

In this experiment (N = 650), we examine the negative consequences of jargon on individuals' perceptions of emerging scientific technology and aim to explain these effects. We find that the presence of jargon impairs people's ability to process scientific information, and that this impairment leads to greater motivated resistance to persuasion, increased risk perceptions, and lower support for technology adoption. These findings suggest that the use of jargon undermines efforts to inform and persuade the public through the cognitive mechanism of metacognition.

Enhanced anti-tumor efficacy of checkpoint inhibitors in combination with the histone deacetylase inhibitor Belinostat in a murine hepatocellular carcinoma model.

Immune checkpoint inhibitors are currently tested in different combinations in patients with advanced hepatocellular carcinoma (HCC). Nivolumab, an anti-PD-1 agent, has gained approval in the second-line setting in the USA. Epigenetic drugs have immune-mediated antitumor effects that may improve the activity of immunotherapy agents. Our aim was to study the therapeutic efficacy of checkpoint inhibitors (anti-CTLA-4 and anti-PD-1 antibodies) in combination with the histone deacetylase inhibitor (HDACi) Belinostat. In a subcutaneous Hepa129 murine HCC model, we demonstrated that Belinostat improves the antitumor activity of anti-CTLA-4 but not of anti-PD-1 therapy. This effect correlated with enhanced IFN-γ production by antitumor T-cells and a decrease in regulatory T-cells. Moreover, the combination induced early upregulation of PD-L1 on tumor antigen-presenting cells and late expression of PD-1 on tumor-infiltrating effector T-cells, suggesting the suitability of PD-1 blockade. Indeed, Belinostat combined with the simultaneous blockade of CTLA-4 and PD-1 led to complete tumor rejection. These results provide a rationale for testing Belinostat in combination with checkpoint inhibitors to enhance their therapeutic activity in patients with HCC.

Making Vaccine Messaging Stick: Perceived Causal Instability as a Barrier to Effective Vaccine Messaging.

Health officials often face challenges in communicating the risks associated with not vaccinating, where persuasive messages can fail to elicit desired responses. However, the mechanisms behind these failures have not been fully ascertained. To address this gap, an experiment (N = 163) tested the differences between loss-framed messages-one emphasizing the consequence of not receiving a flu vaccine; the other emphasizing the consequence of receiving the flu vaccine. Despite an identical consequence (i.e., Guillain-Barre syndrome), the message highlighting the consequence of not receiving the flu vaccine produced lower negative affect scores as compared to the message highlighting the consequence of receiving the flu vaccine. Mediation analyses suggest that one reason for this difference is due to non-vaccination being perceived as temporary and reversible, whereas vaccination is perceived as being permanent. Implications on health communication and future research are discussed.

Social media as a platform for science and health engagement: challenges and opportunities.

Social media has become a major platform for debates on science and health. This commentary argues that while social media can present challenges to communicating important health matters, it can also provide health experts a unique opportunity to engage with and build trust among members of the public.

Disruption and eradication of P. aeruginosa biofilms using nitric oxide-releasing chitosan oligosaccharides.

Biofilm disruption and eradication were investigated as a function of nitric oxide- (NO) releasing chitosan oligosaccharide dose and the results compared with control (i.e., non-NO-releasing) chitosan oligosaccharides and tobramycin. Quantification of biofilm expansion/contraction and multiple-particle tracking microrheology were used to assess the structural integrity of the biofilm before and after antibacterial treatment. While tobramycin had no effect on the physical properties of the biofilm, NO-releasing chitosan oligosaccharides exhibited dose-dependent behavior with biofilm degradation. Control chitosan oligosaccharides increased biofilm elasticity, indicating that the scaffold may mitigate the biofilm disrupting power of nitric oxide somewhat. The results from this study indicate that nitric oxide-releasing chitosan oligosaccharides act as dual-action therapeutics capable of eradicating and physically disrupting P. aeruginosa biofilms.

The Influence of Weight-of-Evidence Messages on (Vaccine) Attitudes: A Sequential Mediation Model.

Media coverage of contentious risk issues often features competing claims about whether a risk exists and what scientific evidence shows, and journalists often cover these issues by presenting both sides. However, for topics defined by scientific agreement, balanced coverage erroneously heightens uncertainty about scientific information and the issue itself. In this article, we extend research on combating so-called information and issue uncertainty using weight of evidence, drawing on the discredited autism-vaccine link as a case study. We examine whether people's perceptions of issue uncertainty (about whether a link exists) change before and after they encounter a news message with weight-of-evidence information. We also explore whether message exposure is associated with broader issue judgments, specifically vaccine attitudes. Participants (n = 181) read news articles that included or omitted weight-of-evidence content stating that scientific studies have found no link and that scientists agree that none exists. Postexposure issue uncertainty decreased-in other words, issue certainty increased-from preexposure levels across all conditions. Moreover, weight-of-evidence messages were associated with positive vaccine attitudes indirectly via reduced information uncertainty (i.e., one's belief that scientific opinion and evidence concerning a potential link is unclear) as well as issue uncertainty. We discuss implications for risk communication.

Including "evidentiary balance" in news media coverage of vaccine risk.

Journalists communicating risk-related uncertainty must accurately convey scientific evidence supporting particular conclusions. Scholars have explored how "balanced" coverage of opposing risk claims shapes uncertainty judgments. In situations where a preponderance of evidence points to a particular conclusion, balanced coverage reduces confidence in such a consensus and heightens uncertainty about whether a risk exists. Using the autism-vaccine controversy as a case study, we describe how journalists can cover multiple sides of an issue and provide insight into where the strength of evidence lies by focusing on "evidentiary balance." Our results suggest that evidentiary balance shapes perceived certainty that vaccines are safe, effective, and not linked to autism through the mediating role of a perception that scientists are divided about whether a link exists. Deference toward science, moreover, moderates these relationships under certain conditions. We discuss implications for journalism practice and risk communication.

The effect of falsely balanced reporting of the autism-vaccine controversy on vaccine safety perceptions and behavioral intentions.

Controversy surrounding an autism-vaccine link has elicited considerable news media attention. Despite being widely discredited, research suggests that journalists report this controversy by presenting claims both for and against a link in a relatively 'balanced' fashion. To investigate how this reporting style influences judgments of vaccine risk, we randomly assigned 320 undergraduate participants to read a news article presenting either claims both for/against an autism-vaccine link, link claims only, no-link claims only or non-health-related information. Participants who read the balanced article were less certain that vaccines are safe, more likely to believe experts were less certain that vaccines are safe and less likely to have their future children vaccinated. Results suggest that balancing conflicting views of the autism-vaccine controversy may lead readers to erroneously infer the state of expert knowledge regarding vaccine safety and negatively impact vaccine intentions.

Discovery of a series of imidazopyrazine small molecule inhibitors of the kinase MAPKAPK5, that show activity using in vitro and in vivo models of rheumatoid arthritis.

MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds.

Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate.

Aspergillus fumigatus is the most frequent causative agent of invasive aspergillosis. Itraconazole became available in 1990 to treat invasive aspergillosis, but instances of resistance have now been described. Drug efflux was a proposed mechanism in one itraconazole resistant clinical isolate (AF72) which accumulates low levels of the drug. Drug efflux in fungi can be mediated by ATP-binding cassette transporter (ABCT) genes, such as CDR1 in Candida albicans. Using a probe derived from CDR1, a gene, atrF, was cloned from A. fumigatus. The atrF gene product (AtrF) is 1547 amino acids long and has characteristic multidrug resistance motifs. Dot blot analysis revealed that AF72 has approximately 5-fold higher levels of atrF mRNA than susceptible isolates AF10 and H06-03 in cultures with sub-minimum inhibitory concentration (sub-MIC) levels of itraconazole. atrF is the first ABCT gene cloned from A. fumigatus, whose overexpression is correlated with itraconazole resistance.