HPV Vaccine Awareness, Past Behaviors, and Future Intentions Among a Diverse Sample of Fathers Aged 27 to 45 Years: A National Survey.

Men aged 27 to 45 are eligible for human papillomavirus (HPV) vaccination as of 2019, yet relatively little is known about whether they have received or intend to receive it. We conducted a cross-sectional, online survey among fathers aged 27 to 45 between March and April 2022, to assess associations between HPV vaccination awareness, behaviors, intentions, and psychosocial constructs from the Health Belief Model. We examined the characteristics of those who had (a) heard of the HPV vaccine, (b) already received ≥ 1 dose, and (c) intentions for future vaccination among those who had never been vaccinated. Among 400 men who completed the survey, 32% were not aware of the HPV vaccine. Among those who were aware, 41% had received ≥ 1 dose. Sixty-three percent of unvaccinated men reported that they intended to get vaccinated in the future. Multivariable logistic regression analyses revealed that age and race/ethnicity were associated with having been vaccinated previously. Among the unvaccinated, multivariable logistic regression analyses revealed that those with a higher perceived risk of HPV-associated cancer had 3.73 greater odds of reporting they would seek vaccination compared to those with lower perceived risk (95% confidence interval [CI] = [1.28, 12.3]). We did not find perceived benefits, barriers, or decision self-efficacy to be related to future vaccine intentions. Since recommendations for this group include shared clinical decision-making, public health efforts should focus on raising awareness of vaccine eligibility, emphasizing risk factors for HPV-associated cancers so that individuals have an accurate perception of risk, and encouraging conversation between men and their providers.

Impact of the COVID-19 pandemic on social media utilization, influences related to parental vaccine decision making, and opinions on trustworthy social media vaccination campaigns: A qualitative analysis.

There is a continued need for research to better understand the influence social media has on parental vaccination attitudes and behaviors, especially research capturing the effects of the COVID-19 pandemic. The goal of this study was to explore parents' perspectives related to the impact the pandemic had on 1) social media engagement, 2) vaccine messaging on social media, and 3) factors to guide future intervention development. Between February and March 2022, 6 online, synchronous, text-based focus groups were conducted with parents of adolescents aged 11 to 17 years. Participants who all utilized social media were recruited from across the United States. Qualitative data were analyzed using content analysis. A total of 64 parents participated. Average age was 47 years, and participants were predominantly White (71.9%), female (84.3%), and engaged with social media multiple times per day (51.6%). Participants (95.3%) viewed obtaining all recommended vaccines as important or very important; however, overall vaccination rates for their adolescents were varied (50% ≥1 dose HPV; 59.4% MenACWY; 78.1% Tdap; 65.6% Flu; 81.3% COVID-19). Three themes emerged highlighting the pandemic's impact on parent's (1) general patterns of social media use, (2) engagement about vaccines on social media and off-line behaviors related to vaccination, and (3) perspectives for developing a credible and trustworthy social media intervention about vaccination. Participants reported fatigue from contentious vaccine-related content on social media and desired future messaging to be from recognizable health institutions/associations with links to reputable resources. Plus, providers should continue to provide strong vaccine recommendations in clinic.

High expression of NFX1-123 in HPV positive head and neck squamous cell carcinomas.

BACKGROUND: High-risk human papillomaviruses (HR HPV) cause nearly all cervical cancers and, in the United States, the majority of head and neck cancers (HNSCCs). NFX1-123 is overexpressed in cervical cancers, and NFX1-123 partners with the HR HPV type 16 E6 oncoprotein to affect multiple growth, differentiation, and immune response genes. However, neither the expression of NFX1-123 nor the levels of these genes have been investigated in HPV positive (HPV+) or negative (HPV-) HNSCCs. METHODS: The Cancer Genome Atlas Splicing Variants Database and HNSCC cell lines were used to quantify expression of NFX1-123 and cellular genes increased in cervical cancers. RESULTS: NFX1-123 was increased in HPV+ HNSCCs compared to HPV- HNSCCs. LCE1B, KRT16, SPRR2G, and FBN2 were highly expressed in HNSCCs compared to normal tissues. Notch1 and CCNB1IP1 had greater expression in HPV+ HNSCCs compared to HPV- HNSCCs. CONCLUSION: NFX1-123 and a subset of its known targets were increased in HPV+ HNSCCs.

Cervical Cancer Development: Implications of HPV16 E6E7-NFX1-123 Regulated Genes.

High-risk human papillomavirus (HR HPV) causes nearly all cervical cancers, half of which are due to HPV type 16 (HPV16). HPV16 oncoprotein E6 (16E6) binds to NFX1-123, and dysregulates gene expression, but their clinical implications are unknown. Additionally, HPV16 E7's role has not been studied in concert with NFX1-123 and 16E6. HR HPVs express both oncogenes, and transformation requires their expression, so we sought to investigate the effect of E7 on gene expression. This study's goal was to define gene expression profiles across cervical precancer and cancer stages, identify genes correlating with disease progression, assess patient survival, and validate findings in cell models. We analyzed NCBI GEO datasets containing transcriptomic data linked with cervical cancer stage and utilized LASSO analysis to identify cancer-driving genes. Keratinocytes expressing 16E6 and 16E7 (16E6E7) and exogenous NFX1-123 were tested for LASSO-identified gene expression. Ten out of nineteen genes correlated with disease progression, including CEBPD, NOTCH1, and KRT16, and affected survival. 16E6E7 in keratinocytes increased CEBPD, KRT16, and SLPI, and decreased NOTCH1. Exogenous NFX1-123 in 16E6E7 keratinocytes resulted in significantly increased CEBPD and NOTCH1, and reduced SLPI. This work demonstrates the clinical relevance of CEBPD, NOTCH1, KRT16, and SLPI, and shows the regulatory effects of 16E6E7 and NFX1-123.

Short-duration splice promoting compound enables a tunable mouse model of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality. SMA results from insufficient survival motor neuron (SMN) protein due to alternative splicing. Antisense oligonucleotides, gene therapy and splicing modifiers recently received FDA approval. Although severe SMA transgenic mouse models have been beneficial for testing therapeutic efficacy, models mimicking milder cases that manifest post-infancy have proven challenging to develop. We established a titratable model of mild and moderate SMA using the splicing compound NVS-SM2. Administration for 30 d prevented development of the SMA phenotype in severe SMA mice, which typically show rapid weakness and succumb by postnatal day 11. Furthermore, administration at day eight resulted in phenotypic recovery. Remarkably, acute dosing limited to the first 3 d of life significantly enhanced survival in two severe SMA mice models, easing the burden on neonates and demonstrating the compound as suitable for evaluation of follow-on therapies without potential drug-drug interactions. This pharmacologically tunable SMA model represents a useful tool to investigate cellular and molecular pathogenesis at different stages of disease.

Optimization of a series of heterocycles as survival motor neuron gene transcription enhancers.

Spinal muscular atrophy (SMA) is a neurodegenerative disorder that results from mutations in the SMN1 gene, leading to survival motor neuron (SMN) protein deficiency. One therapeutic strategy for SMA is to identify compounds that enhance the expression of the SMN2 gene, which normally only is a minor contributor to functional SMN protein production, but which is unaffected in SMA. A recent high-throughput screening campaign identified a 3,4-dihydro-4-phenyl-2(1H)-quinolinone derivative (2) that increases the expression of SMN2 by 2-fold with an EC50 = 8.3 µM. A structure-activity relationship (SAR) study revealed that the array of tolerated substituents, on either the benzo portion of the quinolinone or the 4-phenyl, was very narrow. However, the lactam ring of the quinolinone was more amenable to modifications. For example, the quinazolinone (9a) and the benzoxazepin-2(3H)-one (19) demonstrated improved potency and efficacy for increase in SMN2 expression as compared to 2.

Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. We previously developed a high-throughput assay that employs an SMN2-luciferase reporter allowing identification of compounds that act transcriptionally, enhance exon recognition, or stabilize the SMN protein. We describe optimization and characterization of an analog suitable for in vivo testing. Initially, we identified analog 4m that had good in vitro properties but low plasma and brain exposure in a mouse PK experiment due to short plasma stability; this was overcome by reversing the amide bond and changing the heterocycle. Thiazole 27 showed excellent in vitro properties and a promising mouse PK profile, making it suitable for in vivo testing. This series post-translationally stabilizes the SMN protein, unrelated to global proteasome or autophagy inhibition, revealing a novel therapeutic mechanism that should complement other modalities for treatment of SMA.