COVID-19 coverage from six network and cable news sources in the United States: Representation of misinformation, correction, and portrayals of severity.

The COVID-19 pandemic in the United States is marked by divisions in perceptions of disease severity as well as misperceptions about the virus and vaccine that vary along ideological and political party lines. Perceptual differences may be due to differences in the information about the virus that individuals are exposed to within their own identity-affirming ideological news bubbles. This content analysis of six different national network transcripts highlights differences in coverage of severity, and the prevalence of misinformation and its correction that are consistent with previously established preferred news channels of conservatives/Republicans and liberals/Democrats and their perceptions and misperceptions about the pandemic. Results contribute to the growing body of country-specific COVID-19 media studies that allow for comparisons across nations with different cultures and media systems, as these factors play a pivotal role in national responses and experiences.

Urban Youth Perceptions of Sports and Energy Drinks: Insights for Health Promotion Messaging.

Objective: This study aimed to examine urban adolescents' beliefs about sports and energy drinks to identify factors for health messaging to discourage youth consumption. Design: Focus group study involving thirty-four adolescents in urban areas (12 female, 12 male, and 10 unreported sex; 19 Hispanic, 11 Non-Hispanic Black, 2 Asian, and 1 unknown race or ethnicity). Setting: Four focus groups were conducted with adolescents in urban areas. Method: Each on-time moderated group discussion was structured to generate an inventory of attitudinal, normative and efficacy beliefs associated with sports and energy drink consumption and reduction. Thematic analysis was used to analyse the data. Results: Attitudinal and normative beliefs were more positive towards sports drink consumption and energy drink reduction. Misperceptions about the need for sports drinks to avoid dehydration during physical activity were evident. Product accessibility and advertising pervasiveness were facilitators influencing consumption and barriers to reduction for both products. Conclusion: Results highlight important differences in perceptions about sports and energy drinks that indicate the need for different approaches and messages for interventions designed to curb consumption of these products. Recommendations for message design are provided.

Television News Media Consumption and Misperceptions about COVID-19 among US Populations at High Risk for Severe Health Outcomes Early in the Pandemic.

Research indicates that misperceptions that become part of people's initial mental models about an issue tend to persist and influence their attitudes even after the misperception has been corrected. Recent work on evolving mental models suggests that communication efforts about the ongoing COVID-19 pandemic and its aftermath may be improved by crafting messages that acknowledge biases and misunderstandings about the virus and other infectious diseases that may remain among members of the target audience. This study was designed to provide insight into such biases by: (1) establishing salient categories of COVID-related misperceptions in the earliest months of the pandemic in the United States among (a) the general population, and (b) demographic sub-populations at high risk of severe health outcomes; (2) identifying demographic predictors of misperceptions; and (3) examining the relationship between consumption of different television news outlets and agreement with misperceptions about COVID-19. A national sample of 1,000 adults in the United States (48.1% male; M age = 47.32, SD = 18.01; 72.9% White/Caucasian, 14.3% Black/African American, 15.9% Hispanic/Latinx) completed a survey between March 19 and March 25, 2020. Results identify prevalent classes of salient early COVID-19 misperceptions. Adjusting for numerous covariates, data indicated individuals over the age of 60 held the fewest COVID-related misperceptions among various demographic sub-populations, misperceptions were most prevalent among Black respondents, and increased consumption of television network news was associated with lower levels of misperception. Consumption of some 24-hour news networks (FOX and MSNBC) were significant positive correlates of misperceptions.

An Elicitation Study to Understand Black, Hispanic, and Male Older Adults' Willingness to Participate in Alzheimer's Disease-Focused Research Registries.

BACKGROUND: There is a lack of racial, ethnic, and sex diversity in recruitment research registries and Alzheimer's disease (AD) research studies and trials. Theory-based recruitment messages may provide an opportunity to increase study participant diversity in AD research studies and trials. OBJECTIVE: To identify behavioral, normative, and control beliefs that are associated with joining an AD-focused recruitment registry among historically underrepresented groups. METHOD: Using a Reasoned Action Approach, we conducted 60 semi-structured phone interviews in 2020 among White, Black, and Hispanic adults ages 49-79 years in Philadelphia, PA. Underlying beliefs were elicited for the target behavior of "signing up to be on a registry for brain health research studies in the next month." Percentages based on counts are reported for the overall sample and by race and ethnicity and sex. RESULTS: Participants were most concerned that if they were to sign up for a registry, they would be asked to participate in experimental studies. Advancing science to help others was a commonly reported positive belief about signing up. Participants' children and friends/neighbors were important from a normative perspective. Barriers to enrollment focused on logistical concerns and inconvenient sign-up processes, including using a computer. Results show generally few racial and ethnic or sex group differences. CONCLUSION: The elicited beliefs from underrepresented groups offer a basis for understanding the behavior of signing up for research registries. However, there were few differences between the groups. Implications for outreach and recruitment are discussed.

"I feel it in my gut:" Epistemic Motivations, Political Beliefs, and Misperceptions of COVID-19 and the 2020 U.S. Presidential Election.

This project examines the intersection of political constructs and epistemic motivations as they relate to belief in misinformation. How we value the origins of knowledge - through feelings and intuition or evidence and data - has important implications for our susceptibility to misinformation. This project explores how these epistemic motivations correlate with political ideology, party identification, and favorability towards President Trump, and how epistemic and political constructs predict belief in misinformation about COVID and the 2020 election. Results from a US national survey from Nov-Dec 2020 illustrate that Republicans, conservatives, and those favorable towards President Trump held greater misperceptions about COVID and the 2020 election. Additionally, epistemic motivations were associated with political preferences; Republicans and conservatives were more likely to reject evidence, and Trump supporters more likely to value feelings and intuition. Mediation analyses support the proposition that Trump favorability, Republicanism, and conservatism may help account for the relationships between epistemic motivations and misperceptions. Results are discussed in terms of the messaging strategies of right-wing populist movements, and the implications for democracy and public health.

Site-Specific Conjugation of the Indolinobenzodiazepine DGN549 to Antibodies Affords Antibody-Drug Conjugates with an Improved Therapeutic Index as Compared with Lysine Conjugation.

Antibody-drug conjugates have elicited great interest recently as targeted chemotherapies for cancer. Recent preclinical and clinical data have continued to raise questions about optimizing the design of these complex therapeutics. Biochemical methods for site-specific antibody conjugation have been a design feature of recent clinical ADCs, and preclinical reports suggest that site-specifically conjugated ADCs generically offer improved therapeutic indices (i.e., the fold difference between efficacious and maximum tolerated doses). Here we present the results of a systematic preclinical comparison of ADCs embodying the DNA-alkylating linker-payload DGN549 generated with both heterogeneous lysine-directed and site-specific cysteine-directed conjugation chemistries. Importantly, the catabolites generated by each ADC are the same regardless of the conjugation format. In two different model systems evaluated, the site-specific ADC showed a therapeutic index benefit. However, the therapeutic index benefit is different in each case: both show evidence of improved tolerability, though with different magnitudes, and in one case significant efficacy improvement is also observed. These results support our contention that conjugation chemistry of ADCs is best evaluated in the context of a particular antibody, target, and linker-payload, and ideally across multiple disease models.

Synthesis and Evaluation of Camptothecin Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) that incorporate the exatecan derivative DXd in their payload are showing promising clinical results in solid tumor indications. The payload has an F-ring that also contains a second chiral center, both of which complicate its synthesis and derivatization. Here we report on new camptothecin-ADCs that do not have an F-ring in their payloads yet behave similarly to DXd-bearing conjugates in vitro and in vivo. This simplification allows easier derivatization of camptothecin A and B rings for structure-activity relationship studies and payload optimization. ADCs having different degrees of bystander killing and the ability to release hydroxyl or thiol-bearing metabolites following peptide linker cleavage were investigated.

Peptide-Cleavable Self-immolative Maytansinoid Antibody-Drug Conjugates Designed To Provide Improved Bystander Killing.

A new type of antibody-drug conjugate (ADC) has been prepared that contains a sulfur-bearing maytansinoid attached to an antibody via a highly stable tripeptide linker. Once internalized by cells, proteases in catabolic vesicles cleave the peptide of the ADC's linker causing self-immolation that releases a thiol-bearing metabolite, which is then S-methylated. Conjugates were prepared with peptide linkers containing only alanyl residues, which were all l isomers or had a single d residue in one of the three positions. A d-alanyl residue in the linker did not significantly impair a conjugate's cytotoxicity or bystander killing unless it was directly attached to the immolative moiety. Increasing the number of methylene units in the maytansinoid side chain of a conjugate did not typically affect an ADC's cytotoxicity to targeted cells but did increase bystander killing activity. ADCs with the highest in vitro bystander killing were then evaluated in vivo in mice, where they displayed improved efficacy compared to previously described types of maytansinoid conjugates.

Optimizing Lysosomal Activation of Antibody-Drug Conjugates (ADCs) by Incorporation of Novel Cleavable Dipeptide Linkers.

Although peptide linkers are used in multiple clinical-stage ADCs, there are only few reports on optimizing peptide linkers for efficient lysosomal proteolysis and for stability in circulation. We screened multiple dipeptide linkers for efficiency of proteolysis and compared them to the dipeptide linkers currently being evaluated in the clinic: Val-Cit, Val-Ala, and Ala-Ala. Lead dipeptide linkers selected from the initial screen were incorporated into ADCs with indolinobenzodiazepine dimer (IGN) payloads to evaluate cellular processing, in vitro cytotoxic activity, plasma stability, and in vivo efficacy. ADCs with several dipeptide linkers bearing l-amino acids showed faster lysosomal processing in target cancer cells compared to the l-Ala-l-Ala linked ADC. These variances in linker processing rates did not result in different in vitro and in vivo activities among peptide linker ADCs, presumably due to accumulation of threshold cytotoxic catabolite levels for ADCs of several peptide linkers in the cell lines and xenografts tested. ADCs with l-amino acid dipeptide linkers exhibited superior in vitro cytotoxic potencies in multiple cell lines compared to an ADC with a d-Ala-d-Ala dipeptide linker and an ADC with a noncleavable linker. This work adds to the toolbox of stable, lysosomally cleavable peptide linkers for ADCs.

Attitudinal Spillover from Misleading Natural Cigarette Marketing: An Experiment Examining Current and Former Smokers' Support for Tobacco Industry Regulation.

This research examined the influence of natural cigarette advertising on tobacco control policy support, and the potential for misbeliefs arising from exposure to cigarette marketing to affect such support. Ample research indicates that natural cigarettes such as Natural American Spirit (NAS) are widely and erroneously perceived as safer than their traditional counterparts because of their marketed "natural" composition. Yet regulatory action regarding natural cigarette marketing has been limited in scope, and little research has examined whether misleading product advertising affects support for related policy, an important component of the policy process. Here, we administered a large-scale randomized experiment (n = 1128), assigning current and former smokers in the United States to an NAS advertising condition or a control group and assessing their support for tobacco industry regulation. Results show that exposure to NAS advertising reduces support for policies to ban potentially misleading terminology from cigarette advertising, and these effects are stronger for daily smokers. Further, misinformed beliefs about the healthy composition of NAS partially mediate effects on policy support. Yet interestingly, exposure to NAS marketing does not reduce support for policies to establish standards for when certain terms are permissible in cigarette advertising. The results of this analysis indicate potential spillover effects from exposure to NAS advertising in the realm of support for regulatory action pertaining to tobacco industry marketing.

The Effects of Graphic Warning Labels' Vividness on Message Engagement and Intentions to Quit Smoking.

The current study examined the effects of manipulating the level of vividness through the presence of various textual and visual components in the context of tobacco warning labels. An online experiment was conducted (N=2165) to examine whether increasing the vividness of warning labels, using narrative and non-narrative components, increased engagement with the messages, and the subsequent effects of vividness and engagement on intentions to quit smoking. Results showed that more vivid warning labels led to increased engagement, which in turn was linked to increased intentions to quit smoking. Specifically, the indirect effect of vividness on intentions to quit smoking was largely driven by the emotional component of engagement. Indirect effects of cognitive engagement were only apparent at higher levels of vividness.

Effect of Linker Stereochemistry on the Activity of Indolinobenzodiazepine Containing Antibody-Drug Conjugates (ADCs).

Antibody-drug conjugates (ADCs) that incorporate potent indolinobenzodiazepine DNA alkylators as the payload component are currently undergoing clinical evaluation. In one ADC design, the payload molecules are linked to the antibody through a peptidase-labile l-Ala-l-Ala linker. In order to determine the role of amino acid stereochemistry on antitumor activity and tolerability, we incorporated l- and d-alanyl groups in the dipeptide, synthesized all four diastereomers, and prepared and tested the corresponding ADCs. Results of our preclinical evaluation showed that the l-Ala-l-Ala configuration provided the ADC with the highest therapeutic index (antitumor activity vs toxicity).

Synthesis of Highly Potent N-10 Amino-Linked DNA-Alkylating Indolinobenzodiazepine Antibody-Drug Conjugates (ADCs).

Indolinobenzodiazepine DNA alkylators (IGNs) are the cytotoxic payloads in antibody-drug conjugates (ADCs) currently undergoing Phase I clinical evaluation (IMGN779, IMGN632, and TAK164). These ADCs possess linkers that have been incorporated into a central substituted phenyl spacer. Here, we present an alternative strategy for the IGNs, linking through a carbamate at the readily available N-10 amine present in the monoimine containing dimer. As a result, we have designed a series of N-10 linked IGN ADCs with a wide range of in vitro potency and tolerability, which may allow us to better match an IGN with a particular target based on the potential dosing needs.

A Case Study Comparing Heterogeneous Lysine- and Site-Specific Cysteine-Conjugated Maytansinoid Antibody-Drug Conjugates (ADCs) Illustrates the Benefits of Lysine Conjugation.

Antibody-drug conjugates are an emerging class of cancer therapeutics constructed from monoclonal antibodies conjugated with small molecule effectors. First-generation molecules of this class often employed heterogeneous conjugation chemistry, but many site-specifically conjugated ADCs have been described recently. Here, we undertake a systematic comparison of ADCs made with the same antibody and the same macrocyclic maytansinoid effector but conjugated either heterogeneously at lysine residues or site-specifically at cysteine residues. Characterization of these ADCs in vitro reveals generally similar properties, including a similar catabolite profile, a key element in making a meaningful comparison of conjugation chemistries. In a mouse model of cervical cancer, the lysine-conjugated ADC affords greater efficacy on a molar payload basis. Rather than making general conclusions about ADCs conjugated by a particular chemistry, we interpret these results as highlighting the complexity of ADCs and the interplay between payload class, linker chemistry, target antigen, and other variables that determine efficacy in a given setting.

Design, synthesis and evaluation of novel, potent DNA alkylating agents and their antibody-drug conjugates (ADCs).

Antibody-drug conjugates (ADCs) incorporating potent indolinobenzodiazepine (IGN) DNA alkylators as the cytotoxic payload are currently undergoing clinical evaluation. The optimized design of these payloads consists of an unsymmetrical dimer possessing both an imine and an amine effectively eliminating DNA crosslinking and demonstrating improved tolerability in mice. Here we present an alternate approach to generating DNA alkylating ADCs by linking the IGN monomer with a biaryl system which has a high DNA binding affinity to potentially enhance tolerability. These BIA ADCs were found to be highly cytotoxic in vitro and demonstrated potent antitumor activity in vivo.

Regulating language, not inference: an examination of the potential effectiveness of Natural American Spirit advertising restrictions.

OBJECTIVE: In 2017, the United States Food and Drug Administration (FDA) reached an agreement with Santa Fe Natural Tobacco Company (SFNTC) stipulating that SFNTC will remove 'natural' and 'additive-free' from Natural American Spirit (NAS) marketing to combat misperceptions that NAS is a healthier cigarette. The purpose of this study was to assess experimentally the potential effectiveness of the agreement in addressing NAS misperceptions. METHODS: In an online experiment, 820 current and former smokers were assigned randomly to advertising conditions with existing claims from NAS advertisements, modified claims or a no-exposure control. Advertising conditions included (1) 'original' NAS advertising text before the agreement; (2) '2017 agreement' language permissible under the FDA-SFNTC agreement (removing 'natural', 'additive-free'); (3) more restrictive ('stricter') language representing additional regulation (removing 'natural' from the brand name and the phrases 'tobacco+water', 'no chemicals'). Participants completed outcome measures assessing misinformed beliefs and intentions towards NAS. RESULTS: One-way ANOVA showed that relative to the 'original' language, the '2017 agreement' language reduced misconceptions about NAS addictiveness, but not about health or constituent composition. Yet 'stricter' language significantly reduced all categories of misinformed beliefs, which in turn mediated effects on (lower) intentions to use NAS. CONCLUSION: The 2017 agreement helps dispel some misconceptions about NAS addictiveness, but does not sufficiently rectify misinformation about health or composition. Since 'stricter' language more effectively corrects misinformed beliefs, our results suggest the need for further regulations in addressing misinformation that drives intentions towards NAS.

Does Interest in Smoking Affect Youth Selection of Pro-smoking Videos? A Selective Exposure Experiment.

BACKGROUND: Many pro-smoking videos on YouTube reach view counts in the hundreds of thousands and more. Yet, there is limited information on who is viewing these potentially misleading videos. This study attempts to understand the viewership of online pro-smoking videos to examine if youth at high risk for smoking are more likely to watch these videos. METHODS: We conducted a selective exposure experiment with a national sample of youths (ages 15-21 years; n = 614) to identify characteristics that make individuals more likely to select pro-smoking videos. During a 10-min browsing session, participants were given a set of 16 videos (eight smoking and eight nonsmoking) and were asked to view video(s) of their choice. Exposure to videos was unobtrusively logged. View count was manipulated such that smoking videos had either high or low views. RESULTS: Behavioral data revealed that youth with higher interest in smoking were more likely to select and spend more time watching pro-smoking videos than youth with lower interest in smoking. The view count manipulation did not affect selection patterns. However, exposure to high view count smoking videos was associated with more positive attitudes toward smoking. CONCLUSIONS: The findings of this study call into question the existence and prominence of pro-smoking videos on YouTube and bring to attention the need for regulatory or monitoring efforts of such content. IMPLICATIONS: Given the presence and prevalence of misleading pro-smoking videos online, this is the first study to ask the practical and important question of who is viewing these videos. Using behavioral data, we are able to demonstrate that youth who are high at risk for smoking are more susceptible to select and spend more time viewing pro-smoking videos than youth who are low at risk for smoking. Findings also show that when pro-smoking videos appear to be "popular," they affect attitudes toward smoking. Our findings provide policy implications regarding regulation of smoking promotion videos online.

When Visual Cues Activate Moral Foundations: Unintended Effects of Visual Portrayals of Vaping within Electronic Cigarette Video Advertisements.

Within multimodal persuasive messages, the roles of visual cues in producing unintended effects have been understudied. In an experiment on a sample of former and current smokers (N = 991), we manipulated the presence of visual vaping cues within electronic cigarette video advertisements (N = 25) to evaluate opinions towards vape-free policies. Such cues diminished the effects of pro-vaping arguments to increase support for vape-free policies, inadvertently benefiting public health. Consistent with the moral foundations theory (MFT), endorsement of the care/harm moral foundation strengthened message effects. Furthermore, cognitions and emotions related to moral intuitions mediated the effects of visual vaping cues. These findings suggest that MFT can help explain unintended effects of visual cues when outcomes are related to morality.

A DNA-Interacting Payload Designed to Eliminate Cross-Linking Improves the Therapeutic Index of Antibody-Drug Conjugates (ADCs).

Tumor-selective delivery of cytotoxic agents in the form of antibody-drug conjugates (ADCs) is now a clinically validated approach for cancer treatment. In an attempt to improve the clinical success rate of ADCs, emphasis has been recently placed on the use of DNA-cross-linking pyrrolobenzodiazepine compounds as the payload. Despite promising early clinical results with this class of ADCs, doses achievable have been low due to systemic toxicity. Here, we describe the development of a new class of potent DNA-interacting agents wherein changing the mechanism of action from a cross-linker to a DNA alkylator improves the tolerability of the ADC. ADCs containing the DNA alkylator displayed similar in vitro potency, but improved bystander killing and in vivo efficacy, compared with those of the cross-linker. Thus, the improved in vivo tolerability and antitumor activity achieved in rodent models with ADCs of the novel DNA alkylator could provide an efficacious, yet safer option for cancer treatment. Mol Cancer Ther; 17(3); 650-60. ©2018 AACR.

Treatment decision making in early-stage papillary thyroid cancer.

OBJECTIVE: The purpose of this study was to develop an in-depth understanding of papillary microcarcinoma (PMC) patients' decision-making process when offered options of surgery and active surveillance. METHODS: Fifteen PMC patients and 6 caregivers participated in either a focus group or individual interview. Focus groups were segmented by patients' treatment choice. Primary themes were identified in transcripts using thematic text analysis. RESULTS: Four themes emerged from the surgery subsample: (1) Decision to undergo thyroidectomy quickly and with a sense of urgency; (2) Perception of PMC as a potentially life-threatening disease; (3) Fear of disease progression and unremitting uncertainty with active surveillance; and (4) Surgery as a means of control and potential cure. Three themes emerged from the active surveillance subsample: (1) View of PMC as a common, indolent, and low-risk disease; (2) Concerns about adjusting to life without a thyroid and becoming reliant on hormone replacement medication; and (3) Openness to reconsidering surgery over the long run. Two themes were identified that were shared by participants from both subsamples: (1) Deep level of trust and confidence in physician and cancer center; and (2) Use of physician and internet as primary sources of disease and treatment-related information. CONCLUSIONS: Several factors influenced participants' treatment choice, with similarities and differences noted between surgery and active surveillance subsamples. Many of the emergent themes are consistent with research on decision making among localized prostate cancer patients. Findings suggest that participants from both PMC treatment subsamples are motivated to reduce illness and treatment-related uncertainty.