Cross-Sectional Analysis of Exome Sequencing Diagnosis in Patients With Neurologic Phenotypes Facing Barriers to Clinical Testing.

Background and Objectives: Exome sequencing (ES) demonstrates a 20-50 percent diagnostic yield for patients with a suspected monogenic neurologic disease. Despite the proven efficacy in achieving a diagnosis for such patients, multiple barriers for obtaining exome sequencing remain. This study set out to assess the efficacy of ES in patients with primary neurologic phenotypes who were appropriate candidates for testing but had been unable to pursue clinical testing. Methods: A total of 297 patients were identified from the UCLA Clinical Neurogenomics Research Center Biobank, and ES was performed, including bioinformatic assessment of copy number variation and repeat expansions. Information regarding demographics, clinical indication for ES, and reason for not pursuing ES clinically were recorded. To assess diagnostic efficacy, variants were interpreted by a multidisciplinary team of clinicians, bioinformaticians, and genetic counselors in accordance with the American College of Medical Genetics and Genomics variant classification guidelines. We next examined the specific barriers to testing for these patients, including how frequently insurance-related barriers such as coverage denials and inadequate coverage of cost were obstacles to pursuing exome sequencing. Results: The cohort primarily consisted of patients with sporadic conditions (n = 126, 42.4%) of adult-onset (n = 239, 80.5%). Cerebellar ataxia (n = 225, 75.8%) was the most common presenting neurologic phenotype. Our study found that in this population of mostly adult patients with primary neurologic phenotypes that were unable to pursue exome sequencing clinically, 47 (15.8%) had diagnostic results while an additional 24 patients (8.1%) had uncertain results. Of the 297 patients, 206 were initially recommended for clinical exome but 88 (42.7%) could not pursue ES because of insurance barriers, of whom 14 (15.9%) had diagnostic findings, representing 29.8% of all patients with diagnostic findings. In addition, the incorporation of bioinformatic repeat expansion testing was valuable, identifying a total of 8 pathogenic repeat expansions (17.0% of all diagnostic findings) including 3 of the common spinocerebellar ataxias and 2 patients with Huntington disease. Discussion: These findings underscore the importance and value of clinical ES as a diagnostic tool for neurogenetic disease and highlight key barriers that prevent patients from receiving important clinical information with potential treatment and psychosocial implications for patients and family members.

Does source matter? Examining the effects of health experts, friends, and social media influencers on young adult perceptions of Instagram e-cigarette education messages.

PURPOSE: Young adults' e-cigarette use is a leading public health concern. Using messages from credible sources can help improve message acceptance, yet little research has examined the role of source credibility on young adults' responses to e-cigarette education messages. METHODS: We examined the impact of source on young adults' perceptions of e-cigarette education messages and e-cigarettes. In July 2022, we conducted an experimental study using an online sample of young adults (N=459, Mage=24.6) who were randomized to one of three source conditions: expert, friend, or influencer, and viewed e-cigarette education messages. We used one-way ANOVA to estimate the association between the conditions and outcomes (perceived source credibility, message trust, curiosity, use interests, perceived message effectiveness, beliefs, harm perceptions, and intentions to refrain). RESULTS: The expert condition was associated with significantly higher perceived source credibility (vs. friend, influencer; p<0.001), message trust (vs. friend, influencer; p<0.001), and curiosity (vs. influencer; p's<0.05). CONCLUSIONS: Public health campaigns may leverage health experts to deliver e-cigarette education messages targeting young adults to improve effectiveness of the messages.

Plasma from patients with vaccine-induced immune thrombotic thrombocytopenia displays increased fibrinolytic potential and enhances tissue-type plasminogen activator but not urokinase-mediated plasminogen activation.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus vector-based COVID-19 vaccines. VITT is associated with markedly raised levels of D-dimer; yet, how VITT modulates the fibrinolytic system is unknown. OBJECTIVES: We aimed to compare changes in fibrinolytic activity in plasma from patients with VITT, patients diagnosed with venous thromboembolism (VTE) after vaccination but without VITT (VTE-no VITT), and healthy vaccinated controls. METHODS: Plasma levels of plasmin-antiplasmin (PAP) complexes, plasminogen, and alpha-2-antiplasmin (α2AP) from 10 patients with VITT, 10 patients with VTE-no VITT, and 14 healthy vaccinated controls were evaluated by enzyme-linked immunosorbent assay and/or Western blotting. Fibrinolytic capacity was evaluated by quantitating PAP levels at baseline and after ex vivo plasma stimulation with 50-nM tissue-type plasminogen activator (tPA) or urokinase for 5 minutes. RESULTS: Baseline PAP complex levels in control and VTE-no VITT individuals were similar but were ∼7-fold higher in plasma from patients with VITT (P < .0001). VITT samples also revealed consumption of α2AP and fibrinogenolysis consistent with a hyperfibrinolytic state. Of interest, VITT plasma produced significantly higher PAP levels after ex vivo treatment with tPA, but not urokinase, compared to the other groups, indicative of increased fibrinolytic potential. This was not due to D-dimer as addition of D-dimer to VTE-no VITT plasma failed to potentiate tPA-induced PAP levels. CONCLUSION: A marked hyperfibrinolytic state occurs in patients with VITT, evidenced by marked elevations in PAP, α2AP consumption, and fibrinogenolysis. An unidentified plasma cofactor that selectively potentiates tPA-mediated plasminogen activation also appears to exist in the plasma of patients with VITT.

Incivility in COVID-19 Vaccine Mandate Discourse and Moral Foundations: Natural Language Processing Approach.

BACKGROUND: Vaccine hesitancy poses a substantial threat to efforts to mitigate the harmful effects of the COVID-19 pandemic. To combat vaccine hesitancy, officials in the United States issued vaccine mandates, which were met with strong antivaccine discourse on social media platforms such as Reddit. The politicized and polarized nature of COVID-19 on social media has fueled uncivil discourse related to vaccine mandates, which is known to decrease confidence in COVID-19 vaccines. OBJECTIVE: This study examines the moral foundations underlying uncivil COVID-19 vaccine discourse. Moral foundations theory poses that individuals make decisions to express approval or disapproval (ie, uncivil discourse) based on innate moral values. We examine whether moral foundations are associated with dimensions of incivility. Further, we explore whether there are any differences in the presence of incivility between the r/coronaviruscirclejerk and r/lockdownskepticism subreddits. METHODS: Natural language processing methodologies were leveraged to analyze the moral foundations underlying uncivil discourse in 2 prominent antivaccine subreddits, r/coronaviruscirclejerk and r/lockdownskepticism. All posts and comments from both of the subreddits were collected since their inception in March 2022. This was followed by filtering the data set for key terms associated with the COVID-19 vaccine (eg, "vaccinate" and "Pfizer") and mandates (eg, "forced" and "mandating"). These key terms were selected based on a review of existing literature and because of their salience in both of the subreddits. A 10% sample of the filtered key terms was used for the final analysis. RESULTS: Findings suggested that moral foundations play a role in the psychological processes underlying uncivil vaccine mandate discourse. Specifically, we found substantial associations between all moral foundations (ie, care and harm, fairness and cheating, loyalty and betrayal, authority and subversion, and sanctity and degradation) and dimensions of incivility (ie, toxicity, insults, profanity, threat, and identity attack) except for the authority foundation. We also found statistically significant differences between r/coronaviruscirclejerk and r/lockdownskepticism for the presence of the dimensions of incivility. Specifically, the mean of identity attack, insult, toxicity, profanity, and threat in the r/lockdownskepticism subreddit was significantly lower than that in the r/coronaviruscirclejerk subreddit (P<.001). CONCLUSIONS: This study shows that moral foundations may play a substantial role in the presence of incivility in vaccine discourse. On the basis of the findings of the study, public health practitioners should tailor messaging by addressing the moral values underlying the concerns people may have about vaccines, which could manifest as uncivil discourse. Another way to tailor public health messaging could be to direct it to parts of social media platforms with increased uncivil discourse. By integrating moral foundations, public health messaging may increase compliance and promote civil discourse surrounding COVID-19.

Extubation to High-Flow Nasal Cannula in Infants Following Cardiac Surgery: A Retrospective Cohort Study.

High-flow nasal cannula (HFNC) therapy is commonly used in the pediatric intensive care unit (PICU) for postextubation respiratory support. This hypothesis-generating retrospective cohort study aimed to compare postextubation PICU length of stay in infants extubated to HFNC and low flow oxygen (LF) in PICU following cardiac surgery. Of 136 infants (newborn to 1 year) who were intubated and mechanically ventilated in PICU following cardiac surgery, 72 (53%) were extubated to HFNC and 64 (47%) to LF. Compared with patients extubated to LF, those extubated to HFNC had significantly longer durations of cardiopulmonary bypass (152 vs. 109 minutes; p = 0.002), aortic cross-clamp (90 vs. 63 minutes; p = 0.003), and invasive mechanical ventilation (3.2 vs. 1.6 days; p < 0.001), although demographic and preoperative clinical variables were similar. No significant difference was observed in postextubation PICU length of stay between HFNC and LF groups in unadjusted analysis (3.3 vs. 2.6 days, respectively; p = 0.19) and after controlling for potential confounding variables (F [1,125] = 0.17, p = 0.68, R 2 = 0.16). Escalation of therapy was similar between HFNC and LF groups (8.3 vs. 14.1%; p = 0.41). HFNC was effective as rescue therapy for six patients in the LF group requiring escalation of therapy. Need for reintubation was similar between HFNC and LF groups (8.3 vs. 4.7%; p = 0.5). Although extubation to HFNC was associated with a trend toward longer postextubation PICU length of stay and was successfully used as rescue therapy for several infants extubated to LF, our results must be interpreted with caution given the limitations of our study.

A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA and adenovirus vectored vaccines.

Identifying the molecular mechanisms that promote optimal immune responses to coronavirus disease 2019 (COVID-19) vaccination is critical for future rational vaccine design. Here, we longitudinally profile innate and adaptive immune responses in 102 adults after the first, second, and third doses of mRNA or adenovirus-vectored COVID-19 vaccines. Using a multi-omics approach, we identify key differences in the immune responses induced by ChAdOx1-S and BNT162b2 that correlate with antigen-specific antibody and T cell responses or vaccine reactogenicity. Unexpectedly, we observe that vaccination with ChAdOx1-S, but not BNT162b2, induces an adenoviral vector-specific memory response after the first dose, which correlates with the expression of proteins with roles in thrombosis with potential implications for thrombosis with thrombocytopenia syndrome (TTS), a rare but serious adverse event linked to adenovirus-vectored vaccines. The COVID-19 Vaccine Immune Responses Study thus represents a major resource that can be used to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.

Improving the rate of inferior vena cava filter retrieval through multidisciplinary engagement.

Background: The placement of retrievable inferior vena cava (IVC) filters occurs commonly, but retrieval rates remain low. Consequently, there is an unmet clinical need to ensure appropriate follow-up and retrieval of these devices. Objectives: To determine the association between an IVC filter surveillance team with filter retrievals or a documented filter plan, time to retrieval, and incidence of filter complications or recurrent venous thromboembolism. Methods: Ambidirectional cohort study evaluating consecutive IVC filter insertions before and after the implementation of a multidisciplinary surveillance team (MDST). We report an odds ratio (OR) with 95% CIs, adjusted by age, sex, weight, and malignancy status. Results: Overall, 453 patients were included, with 272 individuals in the pre-MDST cohort and 181 individuals in the post-MDST cohort. The MDST was associated with a higher composite primary outcome of IVC filter retrieval or a documented filter plan from 79.4% in the pre-MDST cohort to 96.1% in the post-MDST cohort (OR, 6.44; 95% CI, 3.06-15.84). Compared with the pre-MDST cohort, IVC filter retrieval rates were higher in the post-MDST cohort (52.6%-73.5%, respectively; (OR, 2.50; 95% CI, 1.67-3.78). The MDST was associated with a shorter median time-to-filter retrieval (187-150 days, hazard ratio, 1.78; 95% CI, 1.39-2.29), but there was no significant difference when comparing symptomatic or clinically significant IVC filter complications, recurrent venous thromboembolism, or mortality. Conclusion: Our study demonstrates the importance of a structured program to ensure timely IVC filter retrieval and ultimately improve patient care.

Emotions and Incivility in Vaccine Mandate Discourse: Natural Language Processing Insights.

Background: Despite vaccine availability, vaccine hesitancy has inhibited public health officials' efforts to mitigate the COVID-19 pandemic in the United States. Although some US elected officials have responded by issuing vaccine mandates, others have amplified vaccine hesitancy by broadcasting messages that minimize vaccine efficacy. The politically polarized nature of COVID-19 information on social media has given rise to incivility, wherein health attitudes often hinge more on political ideology than science. Objective: To the best of our knowledge, incivility has not been studied in the context of discourse regarding COVID-19 vaccines and mandates. Specifically, there is little focus on the psychological processes that elicit uncivil vaccine discourse and behaviors. Thus, we investigated 3 psychological processes theorized to predict discourse incivility-namely, anxiety, anger, and sadness. Methods: We used 2 different natural language processing approaches: (1) the Linguistic Inquiry and Word Count computational tool and (2) the Google Perspective application programming interface (API) to analyze a data set of 8014 tweets containing terms related to COVID-19 vaccine mandates from September 14, 2021, to October 1, 2021. To collect the tweets, we used the Twitter API Tweet Downloader Tool (version 2). Subsequently, we filtered through a data set of 375,000 vaccine-related tweets using keywords to extract tweets explicitly focused on vaccine mandates. We relied on the Linguistic Inquiry and Word Count computational tool to measure the valence of linguistic anger, sadness, and anxiety in the tweets. To measure dimensions of post incivility, we used the Google Perspective API. Results: This study resolved discrepant operationalizations of incivility by introducing incivility as a multifaceted construct and explored the distinct emotional processes underlying 5 dimensions of discourse incivility. The findings revealed that 3 types of emotions-anxiety, anger, and sadness-were uniquely associated with dimensions of incivility (eg, toxicity, severe toxicity, insult, profanity, threat, and identity attacks). Specifically, the results showed that anger was significantly positively associated with all dimensions of incivility (all P<.001), whereas sadness was significantly positively related to threat (P=.04). Conversely, anxiety was significantly negatively associated with identity attack (P=.03) and profanity (P=.02). Conclusions: The results suggest that our multidimensional approach to incivility is a promising alternative to understanding and intervening in the psychological processes underlying uncivil vaccine discourse. Understanding specific emotions that can increase or decrease incivility such as anxiety, anger, and sadness can enable researchers and public health professionals to develop effective interventions against uncivil vaccine discourse. Given the need for real-time monitoring and automated responses to the spread of health information and misinformation on the web, social media platforms can harness the Google Perspective API to offer users immediate, automated feedback when it detects that a comment is uncivil.

U.S. adolescents' attitudes toward school, social connection, media use, and mental health during the COVID-19 pandemic: Differences as a function of gender identity and school context.

The COVID-19 pandemic changed school contexts and social opportunities dramatically for adolescents around the world. Thus, certain adolescents may have been more susceptible to the stress of the pandemic as a function of differences in schooling. We present data from 1256 United States adolescents (ages 14-16) to examine how the 2020-2021 school context (in-person, hybrid, or virtual) related to feelings of school satisfaction and success, social connection, mental health, and media use. We also examine differences as a function of gender identity. Results demonstrate that school context, particularly in-person compared to virtual schooling, was related to higher school satisfaction and academic success, stronger feelings of social connection and inclusion, lower levels of anxiety and depression, and less problematic media use. Interestingly, adolescents did seem to use media as a tool to support social connection when in hybrid or virtual school contexts, but they also reported higher rates of problematic media use, thus suggesting that media use needs to be examined more carefully to understand its role as a potential protective mechanism for adolescents' social connection and mental health. These findings provide baseline information about how schools' responses to the COVID-19 pandemic may have created disparities among youth. These findings have implications for current school interventions.

C-reactive protein, immunothrombosis and venous thromboembolism.

C-reactive protein (CRP) is a member of the highly conserved pentraxin superfamily of proteins and is often used in clinical practice as a marker of infection and inflammation. There is now increasing evidence that CRP is not only a marker of inflammation, but also that destabilized isoforms of CRP possess pro-inflammatory and pro-thrombotic properties. CRP circulates as a functionally inert pentameric form (pCRP), which relaxes its conformation to pCRP* after binding to phosphocholine-enriched membranes and then dissociates to monomeric CRP (mCRP). with the latter two being destabilized isoforms possessing highly pro-inflammatory features. pCRP* and mCRP have significant biological effects in regulating many of the aspects central to pathogenesis of atherothrombosis and venous thromboembolism (VTE), by directly activating platelets and triggering the classical complement pathway. Importantly, it is now well appreciated that VTE is a consequence of thromboinflammation. Accordingly, acute VTE is known to be associated with classical inflammatory responses and elevations of CRP, and indeed VTE risk is elevated in conditions associated with inflammation, such as inflammatory bowel disease, COVID-19 and sepsis. Although the clinical data regarding the utility of CRP as a biomarker in predicting VTE remains modest, and in some cases conflicting, the clinical utility of CRP appears to be improved in subsets of the population such as in predicting VTE recurrence, in cancer-associated thrombosis and in those with COVID-19. Therefore, given the known biological function of CRP in amplifying inflammation and tissue damage, this raises the prospect that CRP may play a role in promoting VTE formation in the context of concurrent inflammation. However, further investigation is required to unravel whether CRP plays a direct role in the pathogenesis of VTE, the utility of which will be in developing novel prophylactic or therapeutic strategies to target thromboinflammation.

COVID-19 Vaccine Fact-Checking Posts on Facebook: Observational Study.

BACKGROUND: Effective interventions aimed at correcting COVID-19 vaccine misinformation, known as fact-checking messages, are needed to combat the mounting antivaccine infodemic and alleviate vaccine hesitancy. OBJECTIVE: This work investigates (1) the changes in the public's attitude toward COVID-19 vaccines over time, (2) the effectiveness of COVID-19 vaccine fact-checking information on social media engagement and attitude change, and (3) the emotional and linguistic features of the COVID-19 vaccine fact-checking information ecosystem. METHODS: We collected a data set of 12,553 COVID-19 vaccine fact-checking Facebook posts and their associated comments (N=122,362) from January 2020 to March 2022 and conducted a series of natural language processing and statistical analyses to investigate trends in public attitude toward the vaccine in COVID-19 vaccine fact-checking posts and comments, and emotional and linguistic features of the COVID-19 fact-checking information ecosystem. RESULTS: The percentage of fact-checking posts relative to all COVID-19 vaccine posts peaked in May 2020 and then steadily decreased as the pandemic progressed (r=-0.92, df=21, t=-10.94, 95% CI -0.97 to -0.82, P<.001). The salience of COVID-19 vaccine entities was significantly lower in comments (mean 0.03, SD 0.03, t=39.28, P<.001) than in posts (mean 0.09, SD 0.11). Third-party fact checkers have been playing a more important role in more fact-checking over time (r=0.63, df=25, t=4.06, 95% CI 0.33-0.82, P<.001). COVID-19 vaccine fact-checking posts continued to be more analytical (r=0.81, df=25, t=6.88, 95% CI 0.62-0.91, P<.001) and more confident (r=0.59, df=25, t=3.68, 95% CI 0.27-0.79, P=.001) over time. Although comments did not exhibit a significant increase in confidence over time, tentativeness in comments significantly decreased (r=-0.62, df=25, t=-3.94, 95% CI -0.81 to -0.31, P=.001). In addition, although hospitals receive less engagement than other information sources, the comments expressed more positive attitudinal valence in comments compared to other information sources (b=0.06, 95% CI 0.00-0.12, t=2.03, P=.04). CONCLUSIONS: The percentage of fact-checking posts relative to all posts about the vaccine steadily decreased after May 2020. As the pandemic progressed, third-party fact checkers played a larger role in posting fact-checking COVID-19 vaccine posts. COVID-19 vaccine fact-checking posts continued to be more analytical and more confident over time, reflecting increased confidence in posts. Similarly, tentativeness in comments decreased; this likewise suggests that public uncertainty diminished over time. COVID-19 fact-checking vaccine posts from hospitals yielded more positive attitudes toward vaccination than other information sources. At the same time, hospitals received less engagement than other information sources. This suggests that hospitals should invest more in generating engaging public health campaigns on social media.

Constituents' Inferences of Local Governments' Goals and the Relationship Between Political Party and Belief in COVID-19 Misinformation: Cross-sectional Survey of Twitter Followers of State Public Health Departments.

Background: Amid the COVID-19 pandemic, social media have influenced the circulation of health information. Public health agencies often use Twitter to disseminate and amplify the propagation of such information. Still, exposure to local government-endorsed COVID-19 public health information does not make one immune to believing misinformation. Moreover, not all health information on Twitter is accurate, and some users may believe misinformation and disinformation just as much as those who endorse more accurate information. This situation is complicated, given that elected officials may pursue a political agenda of re-election by downplaying the need for COVID-19 restrictions. The politically polarized nature of information and misinformation on social media in the United States has fueled a COVID-19 infodemic. Because pre-existing political beliefs can both facilitate and hinder persuasion, Twitter users' belief in COVID-19 misinformation is likely a function of their goal inferences about their local government agencies' motives for addressing the COVID-19 pandemic. Objective: We shed light on the cognitive processes of goal understanding that underlie the relationship between partisanship and belief in health misinformation. We investigate how the valence of Twitter users' goal inferences of local governments' COVID-19 efforts predicts their belief in COVID-19 misinformation as a function of their political party affiliation. Methods: We conducted a web-based cross-sectional survey of US Twitter users who followed their state's official Department of Public Health Twitter account (n=258) between August 10 and December 23, 2020. Inferences about local governments' goals, demographics, and belief in COVID-19 misinformation were measured. State political affiliation was controlled. Results: Participants from all 50 states were included in the sample. An interaction emerged between political party affiliation and goal inference valence for belief in COVID-19 misinformation (∆R 2=0.04; F 8,249=4.78; P<.001); positive goal inference valence predicted increased belief in COVID-19 misinformation among Republicans (ß=.47; t 249=2.59; P=.01) but not among Democrats (ß=.07; t 249=0.84; P=.40). Conclusions: Our results reveal that favorable inferences about local governments' COVID-19 efforts can accelerate belief in misinformation among Republican-identifying constituents. In other words, accurate COVID-19 transmission knowledge is a function of constituents' sentiment toward politicians rather than science, which has significant implications on public health efforts for minimizing the spread of the disease, as convincing misinformed constituents to practice safety measures might be a political issue just as much as it is a health one. Our work suggests that goal understanding processes matter for misinformation about COVID-19 among Republicans. Those responsible for future COVID-19 public health messaging aimed at increasing belief in valid information about COVID-19 should recognize the need to test persuasive appeals that address partisans' pre-existing political views in order to prevent individuals' goal inferences from interfering with public health messaging.

Uncivil Reactions to Sexual Assault Online: Linguistic Features of News Reports Predict Discourse Incivility.

Reports of sexual assault have been found to elicit online discourse incivility. The present study employs a computerized coding tool to examine linguistic characteristics of news media that are likely to influence discourse incivility-specifically, negative emotion, disagreement, and discussion about power relations. Additionally, machine learning was harnessed to measure the levels of comment toxicity, insult, profanity, threat, and identity attack in Reddit and Twitter posts sharing news reports of sexual assault. Findings reveal that linguistic features of news articles interact with platform community norms to predict rape culture as expressed within online responses to reports of sexual assault.

Desensitization to Fear-Inducing COVID-19 Health News on Twitter: Observational Study.

BACKGROUND: As of May 9, 2021, the United States had 32.7 million confirmed cases of COVID-19 (20.7% of confirmed cases worldwide) and 580,000 deaths (17.7% of deaths worldwide). Early on in the pandemic, widespread social, financial, and mental insecurities led to extreme and irrational coping behaviors, such as panic buying. However, despite the consistent spread of COVID-19 transmission, the public began to violate public safety measures as the pandemic got worse. OBJECTIVE: In this work, we examine the effect of fear-inducing news articles on people's expression of anxiety on Twitter. Additionally, we investigate desensitization to fear-inducing health news over time, despite the steadily rising COVID-19 death toll. METHODS: This study examined the anxiety levels in news articles (n=1465) and corresponding user tweets containing "COVID," "COVID-19," "pandemic," and "coronavirus" over 11 months, then correlated that information with the death toll of COVID-19 in the United States. RESULTS: Overall, tweets that shared links to anxious articles were more likely to be anxious (odds ratio [OR] 2.65, 95% CI 1.58-4.43, P<.001). These odds decreased (OR 0.41, 95% CI 0.2-0.83, P=.01) when the death toll reached the third quartile and fourth quartile (OR 0.42, 95% CI 0.21-0.85, P=.01). However, user tweet anxiety rose rapidly with articles when the death toll was low and then decreased in the third quartile of deaths (OR 0.61, 95% CI 0.37-1.01, P=.06). As predicted, in addition to the increasing death toll being matched by a lower level of article anxiety, the extent to which article anxiety elicited user tweet anxiety decreased when the death count reached the second quartile. CONCLUSIONS: The level of anxiety in users' tweets increased sharply in response to article anxiety early on in the COVID-19 pandemic, but as the casualty count climbed, news articles seemingly lost their ability to elicit anxiety among readers. Desensitization offers an explanation for why the increased threat is not eliciting widespread behavioral compliance with guidance from public health officials. This work investigated how individuals' emotional reactions to news of the COVID-19 pandemic manifest as the death toll increases. Findings suggest individuals became desensitized to the increased COVID-19 threat and their emotional responses were blunted over time.

Submassive Pulmonary Embolism: Current Perspectives and Future Directions.

Submassive pulmonary embolism (PE) lies on a spectrum of disease severity between standard and high-risk disease. By definition, patients with submassive PE have a worse outcome than the majority of those with standard-risk PE, who are hemodynamically stable and lack imaging or laboratory features of cardiac dysfunction. Systemic thrombolytic therapy has been proven to reduce mortality in patients with high-risk disease; however, its use in submassive PE has not demonstrated a clear benefit, with haemodynamic improvements being offset by excess bleeding. Furthermore, meta-analyses have been confusing, with conflicting results on overall survival and net gain. As such, significant interest remains in optimising thrombolysis, with recent efforts in catheter-based delivery as well as upcoming studies on reduced systemic dosing. Recently, long-term cardiorespiratory limitations following submassive PE have been described, termed post-PE syndrome. Studies on the ability of thrombolytic therapy to prevent this condition also present conflicting evidence. In this review, we aim to clarify the current evidence with respect to submassive PE management, and also to highlight shortcomings in current definitions and prognostic factors. Additionally, we discuss novel therapies currently in preclinical and early clinical trials that may improve outcomes in patients with submassive PE.

Natural Language Processing Insight into LGBTQ+ Youth Mental Health During the COVID-19 Pandemic: Longitudinal Content Analysis of Anxiety-Provoking Topics and Trends in Emotion in LGBTeens Microcommunity Subreddit.

BACKGROUND: Widespread fear surrounding COVID-19, coupled with physical and social distancing orders, has caused severe adverse mental health outcomes. Little is known, however, about how the COVID-19 crisis has impacted LGBTQ+ youth, who disproportionately experienced a high rate of adverse mental health outcomes before the COVID-19 pandemic. OBJECTIVE: We aimed to address this knowledge gap by harnessing natural language processing methodologies to investigate the evolution of conversation topics in the most popular subreddit for LGBTQ+ youth. METHODS: We generated a data set of all r/LGBTeens subreddit posts (n=39,389) between January 1, 2020 and February 1, 2021 and analyzed meaningful trends in anxiety, anger, and sadness in the posts. Because the distribution of anxiety before widespread social distancing orders was meaningfully different from the distribution after (P<.001), we employed latent Dirichlet allocation to examine topics that provoked this shift in anxiety. RESULTS: We did not find any differences in LGBTQ+ youth anger and sadness before and after government-mandated social distancing; however, anxiety increased significantly (P<.001). Further analysis revealed a list of 10 anxiety-provoking topics discussed during the pandemic: attraction to a friend, coming out, coming out to family, discrimination, education, exploring sexuality, gender pronouns, love and relationship advice, starting a new relationship, and struggling with mental health. CONCLUSIONS: During the COVID-19 pandemic, LGBTQ+ teens increased their reliance on anonymous discussion forums when discussing anxiety-provoking topics. LGBTQ+ teens likely perceived anonymous forums as safe spaces for discussing lifestyle stressors during COVID-19 disruptions (eg, school closures). The list of prevalent anxiety-provoking topics in LGBTQ+ teens' anonymous discussions can inform future mental health interventions in LGBTQ+ youth.

Erratum: Metadata Correction: "Desensitization to Fear-Inducing COVID-19 Health News on Twitter: Observational Study".

[This corrects the article DOI: 10.2196/26876.].