Perceptions of the Addictiveness of Low-Nicotine Cigarettes Versus Typical Cigarettes and Exposure to Tobacco Industry-Sponsored Corrective Campaign.

BACKGROUND: In 2017, the U.S. Food and Drug Administration (FDA) announced a regulatory plan to reduce the nicotine content of cigarettes. This study examines the association of exposure to industry-sponsored corrective statements on perceptions of the addictiveness of low-nicotine cigarettes relative to typical cigarettes within the general US population. METHODS: The study comprised 4975 US adult respondents of the 2019 Health Information National Trends Survey (HINTS 5, Cycle 3). Multinomial logistic regression models were used to examine associations between exposure to tobacco industry corrective messages and perceptions of the addictiveness of low-nicotine cigarettes relative to typical cigarettes. RESULTS: In the overall population, 4.1% reported that low-nicotine cigarettes were much more addictive than typical cigarettes, 67.5% said they were equally addictive, while 28.4% reported they were slightly/much less addictive. Adults exposed to industry-sponsored corrective messages had higher odds of perceiving low-nicotine cigarettes as equally addictive as typical cigarettes (aOR 1.57; 95% CI, 1.13-2.19) than those who saw no corrective messages. Those exposed to the corrective messages specifically about the addictiveness of smoking and nicotine had higher odds of perceiving low-nicotine cigarettes as equally addictive as typical cigarettes (aOR, 1.73; 95% CI, 1.07-2.81) compared to those who saw no corrective message. CONCLUSIONS: Our findings suggest that exposure to court-ordered tobacco industry corrective statements may have reinforced perceptions on the addictive potential of nicotine. However, study findings indicate a need for campaigns specifically tailored to address misperceptions observed in this study.

67.5% of US adults perceived low-nicotine cigarettes and typical cigarettes as being equally addictiveExposure to court-ordered corrective statements increased the odds of equal addictiveness perceptionExposure to corrective statements specifically tailored to addiction increased the odds of equal addictiveness perception.

Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample.

Despite the large public health toll of smoking, genetic studies of smoking cessation have been limited with few discoveries of risk or protective loci. We investigated common and rare variant associations with success in quitting smoking using a cohort from 8 randomized controlled trials involving 2231 participants and a total of 10,020 common and 24,147 rare variants. We identified 14 novel markers including 6 mapping to genes previously related to psychiatric and substance use disorders, 4 of which were protective (CYP2B6 (rs1175607105), HTR3B (rs1413172952; rs1204720503), rs80210037 on chr15), and 2 of which were associated with reduced cessation (PARP15 (rs2173763), SCL18A2 (rs363222)). The others mapped to areas associated with cancer including FOXP1 (rs1288980) and ZEB1 (rs7349). Network analysis identified significant canonical pathways for the serotonin receptor signaling pathway, nicotine and bupropion metabolism, and several related to tumor suppression. Two novel markers (rs6749438; rs6718083) on chr2 are flanked by genes associated with regulation of bodyweight. The identification of novel loci in this study can provide new targets of pharmacotherapy and inform efforts to develop personalized treatments based on genetic profiles.

HPV vaccination in Africa in the COVID-19 era: a cross-sectional survey of healthcare providers' knowledge, training, and recommendation practices.

Introduction: Although the burden of cervical cancer in Africa is highest, HPV vaccination coverage remains alarmingly low in this region. Providers' knowledge and recommendation are key drivers of HPV vaccination uptake. Yet, evidence about providers' knowledge and recommendation practices about the HPV vaccine against a backdrop of emerging vaccine hesitancy fueled by the COVID-19 pandemic is lacking in Africa. Methods: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior training, the availability of the HPV vaccine in their practice, whether they recommended the HPV vaccine, and, if not, the reasons for not recommending it. Their knowledge about the HPV vaccine was assessed through self-reporting (perceived knowledge) and with three pre-tested knowledge questions (measured knowledge). Results: Of the 153 providers from 23 African countries who responded to the survey (mean age: 38.5 years, SD: 10.1), 75 (54.0%) were female and 97 (63.4%) were based In countries with national HPV immunization programs. Overall, 57 (43.8%) reported having received prior training on HPV vaccine education/counseling, and 40 (37.4%) indicated that the HPV vaccine was available at the facility where they work. Most respondents (109, 83.2%) reported recommending the HPV vaccine in their practice. Vaccine unavailability (57.1%), lack of effective communication tools and informational material (28.6%), and need for adequate training (28.6%) were the most commonly reported reasons for not recommending the HPV vaccine. While 63 providers (52.9%) reported that their knowledge about HPV vaccination was adequate for their practice, only 9.9% responded correctly to the 3 knowledge questions. Conclusion: To increase HPV vaccination coverage and counter misinformation about this vaccine in Africa, adequate training of providers and culturally appropriate educational materials are needed to improve their knowledge of the HPV vaccine and to facilitate effective communication with their patients and the community.

Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis.

The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia-like NSCs contributing to neurogenesis throughout adulthood. However, the underlying regulatory mechanism during the transition from quiescent NSCs to activated NSCs in the postnatal NSC niche is not fully understood. Lipid metabolism and lipid composition play important roles in regulating NSC fate determination. Biological lipid membranes define the individual cellular shape and help maintain cellular organization and are highly heterogeneous in structure and there exist diverse microdomains (also known as lipid rafts), which are enriched with sugar molecules, such as glycosphingolipids. An often overlooked but key aspect is that the functional activities of proteins and genes are highly dependent on their molecular environments. We previously reported that ganglioside GD3 is the predominant species in NSCs and that the reduced postnatal NSC pools are observed in global GD3-synthase knockout (GD3S-KO) mouse brains. The specific roles of GD3 in determining the stage and cell-lineage determination of NSCs remain unclear, since global GD3S-KO mice cannot distinguish if GD3 regulates postnatal neurogenesis or developmental impacts. Here, we show that inducible GD3 deletion in postnatal radial glia-like NSCs promotes NSC activation, resulting in the loss of the long-term maintenance of the adult NSC pools. The reduced neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of GD3S-conditional-knockout mice led to the impaired olfactory and memory functions. Thus, our results provide convincing evidence that postnatal GD3 maintains the quiescent state of radial glia-like NSCs in the adult NSC niche.

Pilot study of a Spanish language measure of financial toxicity in underserved Hispanic cancer patients with low English proficiency.

Background: Financial toxicity (FT) reflects multi-dimensional personal economic hardships borne by cancer patients. It is unknown whether measures of FT-to date derived largely from English-speakers-adequately capture economic experiences and financial hardships of medically underserved low English proficiency US Hispanic cancer patients. We piloted a Spanish language FT instrument in this population. Methods: We piloted a Spanish version of the Economic Strain and Resilience in Cancer (ENRICh) FT measure using qualitative cognitive interviews and surveys in un-/under-insured or medically underserved, low English proficiency, Spanish-speaking Hispanics (UN-Spanish, n = 23) receiving ambulatory oncology care at a public healthcare safety net hospital in the Houston metropolitan area. Exploratory analyses compared ENRICh FT scores amongst the UN-Spanish group to: (1) un-/under-insured English-speaking Hispanics (UN-English, n = 23) from the same public facility and (2) insured English-speaking Hispanics (INS-English, n = 31) from an academic comprehensive cancer center. Multivariable logistic models compared the outcome of severe FT (score > 6). Results: UN-Spanish Hispanic participants reported high acceptability of the instrument (only 0% responded that the instrument was "very difficult to answer" and 4% that it was "very difficult to understand the questions"; 8% responded that it was "very difficult to remember resources used" and 8% that it was "very difficult to remember the burdens experienced"; and 4% responded that it was "very uncomfortable to respond"). Internal consistency of the FT measure was high (Cronbach's α = 0.906). In qualitative responses, UN-Spanish Hispanics frequently identified a total lack of credit, savings, or income and food insecurity as aspects contributing to FT. UN-Spanish and UN-English Hispanic patients were younger, had lower education and income, resided in socioeconomically deprived neighborhoods and had more advanced cancer vs. INS-English Hispanics. There was a higher likelihood of severe FT in UN-Spanish (OR = 2.73, 95% CI 0.77-9.70; p = 0.12) and UN-English (OR = 4.13, 95% CI 1.13-15.12; p = 0.03) vs. INS-English Hispanics. A higher likelihood of severely depleted FT coping resources occurred in UN-Spanish (OR = 4.00, 95% CI 1.07-14.92; p = 0.04) and UN-English (OR = 5.73, 95% CI 1.49-22.1; p = 0.01) vs. INS-English. The likelihood of FT did not differ between UN-Spanish and UN-English in both models (p = 0.59 and p = 0.62 respectively). Conclusion: In medically underserved, uninsured Hispanic patients with cancer, comprehensive Spanish-language FT assessment in low English proficiency participants was feasible, acceptable, and internally consistent. Future studies employing tailored FT assessment and intervention should encompass the key privations and hardships in this population.

Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis.

The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia-like NSCs contributing to neurogenesis throughout adulthood. However, the underlying regulatory mechanism during the transition from quiescent NSCs to activated NSCs in the postnatal NSC niche is not fully understood. Lipid metabolism and lipid composition play important roles in regulating NSC fate determination. Biological lipid membranes define the individual cellular shape and help maintain cellular organization and are highly heterogenous in structure and there exist diverse microdomains (also known as lipid rafts), which are enriched with sugar molecules, such as glycosphingolipids. An often overlooked but key aspect is that the functional activities of proteins and genes are highly dependent upon their molecular environments. We previously reported that ganglioside GD3 is the predominant species in NSCs and that the reduced postnatal NSC pools are observed in global GD3-synthase knockout (GD3S-KO) mouse brains. The specific roles of GD3 in determining the stage and cell-lineage determination of NSCs remain unclear, since global GD3S-KO mice cannot distinguish if GD3 regulates postnatal neurogenesis or developmental impacts. Here we show that inducible GD3 deletion in postnatal radial glia-like NSCs promotes the NSC activation, resulting in the loss of the long-term maintenance of the adult NSC pools. The reduced neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of GD3S-conditional-knockout mice led to impaired olfactory and memory functions. Thus, our results provide convincing evidence that postnatal GD3 maintains the quiescent state of radial glia-like NSCs in the adult NSC niche.

Association between employer-based health promotion programs and adherence to breast cancer screening in Texas.

Breast cancer is the most common cancer diagnosed among women in Texas. Although adherence to recommended screening mammogram guidelines enables early detection and reduces breast cancer risks, screening mammogram adherence is low in Texas. With the rising percentage of women in the workforce, employer-based health promotion programs could be an effective measure in increasing mammogram adherence, thereby reducing breast cancer risk in Texas. Although employer-based health programs are common in the state, little is known about their effectiveness in increasing screening mammogram adherence among age-eligible employed females. The study survey was administered using Qualtrics and the study participants were representative of the Texas population. The study population included 318 females from Texas who were 50-74 years old. Among those who had access to employer-based health promotion programs, 65.4 % were adherent and 34.6 % were non-adherent to the guidelines. Population-weighted survey logistic regression analysis showed no significant association between access to employer-based health promotion programs and mammogram adherence for employed women (AOR: 0.85 [0.15-4.79], p-value = 0.86). However, access to healthcare coverage (AOR: 7.58 [2.89-19.88], p-value < 0.001), those who disagree with the fatalistic belief that everything causes cancer (AOR: 2.99 [1.45-6.19], p-value < 0.001), and those who perceive cancer screening important (AOR: 12.36 [2.26-67.47], p < 0.05) were found as significant determinants of mammogram adherence among females in Texas. The study concluded that access to employer-based health promotion programs alone was insufficient to improve breast cancer screening. The employers and the insurance companies, with support from the government, should develop a comprehensive program that addresses all structural and psychosocial barriers to employee breast cancer screening adherence.

Restoration of Adult Neurogenesis by Intranasal Administration of Gangliosides GD3 and GM1 in The Olfactory Bulb of A53T Alpha-Synuclein-Expressing Parkinson's-Disease Model Mice.

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the body and mind of millions of people in the world. As PD progresses, bradykinesia, rigidity, and tremor worsen. These motor symptoms are associated with the neurodegeneration of dopaminergic neurons in the substantia nigra. PD is also associated with non-motor symptoms, including loss of smell (hyposmia), sleep disturbances, depression, anxiety, and cognitive impairment. This broad spectrum of non-motor symptoms is in part due to olfactory and hippocampal dysfunctions. These non-motor functions are suggested to be linked with adult neurogenesis. We have reported that ganglioside GD3 is required to maintain the neural stem cell (NSC) pool in the subventricular zone (SVZ) of the lateral ventricles and the subgranular layer of the dentate gyrus (DG) in the hippocampus. In this study, we used nasal infusion of GD3 to restore impaired neurogenesis in A53T alpha-synuclein-expressing mice (A53T mice). Intriguingly, intranasal GD3 administration rescued the number of bromodeoxyuridine + (BrdU +)/Sox2 + NSCs in the SVZ. Furthermore, the administration of gangliosides GD3 and GM1 increases doublecortin (DCX)-expressing immature neurons in the olfactory bulb, and nasal ganglioside administration recovered the neuronal populations in the periglomerular layer of A53T mice. Given the relevance of decreased ganglioside on olfactory impairment, we discovered that GD3 has an essential role in olfactory functions. Our results demonstrated that intranasal GD3 infusion restored the self-renewal ability of the NSCs, and intranasal GM1 infusion promoted neurogenesis in the adult brain. Using a combination of GD3 and GM1 has the potential to slow down disease progression and rescue dysfunctional neurons in neurodegenerative brains.

kHz-precision wavemeter based on reconfigurable microsoliton.

The mode-locked microcomb offers a unique and compact solution for photonics applications, ranging from the optical communications, the optical clock, optical ranging, the precision spectroscopy, novel quantum light source, to photonic artificial intelligence. However, the photonic micro-structures are suffering from the perturbations arising from environment thermal noises and also laser-induced nonlinear effects, leading to the frequency instability of the generated comb. Here, a universal mechanism for fully stabilizing the microcomb is proposed and experimentally verified. By incorporating two global tuning approaches and the autonomous thermal locking mechanism, the pump laser frequency and repetition rate of the microcomb can be controlled independently in real-time without interrupting the microcomb generation. The high stability and controllability of the microcomb frequency enables its application in wavelength measurement with a precision of about 1 kHz. The approach for the full control of comb frequency could be applied in various microcomb platforms, and improve their performances in timing, spectroscopy, and sensing.

Immunogenetic Determinants of Susceptibility to Head and Neck Cancer in the Million Veteran Program Cohort.

Increasing rates of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) have largely offset declines in tobacco-associated head and neck squamous cell carcinoma (HNSCC) at non-OPC sites. Host immunity is an important modulator of HPV infection, persistence, and clearance, and also of immune evasion in both virally- and nonvirally-driven cancers. However, the association between collective known cancer-related immune gene variants and HNSCC susceptibility has not been fully characterized. Here, we conducted a genetic association study in the multiethnic Veterans Affairs Million Veteran Program cohort, evaluating 16,050 variants in 1,576 immune genes in 4,012 HNSCC cases (OPC = 1,823; non-OPC = 2,189) and 16,048 matched controls. Significant polymorphisms were further examined in a non-Hispanic white (NHW) validation cohort (OPC = 1,206; non-OPC = 955; controls = 4,507). For overall HNSCC susceptibility in NHWs, we discovered and validated a novel 9q31.1 SMC2 association and replicated the known 6p21.32 HLA-DQ-DR association. Six loci/genes for overall HNSCC susceptibility were selectively enriched in African-Americans (6p21.32 HLA-G, 9q21.33 GAS1, 11q12.2 CD6, 11q23.2 NCAM1/CD56, 17p13.1 CD68, 18q22.2 SOCS6); all 6 genes function in antigen-presenting regulation and T-cell activation. Two additional loci (10q26 DMBT1, 15q22.2 TPM1) were uncovered for non-OPC susceptibility, and three loci (11q24 CRTAM, 16q21 CDH5, 18q12.1 CDH2) were identified for HPV-positive OPC susceptibility. This study underscores the role of immune gene variants in modulating susceptibility for both HPV-driven and non-HPV-driven HNSCC. Additional large studies, particularly in racially diverse populations, are needed to further validate the associations and to help elucidate other potential immune factors and mechanisms that may underlie HNSCC risk. SIGNIFICANCE: Several inherited variations in immune system genes are significantly associated with susceptibility to head and neck cancer, which could help improve personalized cancer risk estimates.

Ganglioside Microdomains on Cellular and Intracellular Membranes Regulate Neuronal Cell Fate Determination.

Gangliosides are sialylated glycosphingolipids (GSLs) with essential but enigmatic functions in brain activities and neural stem cell (NSC) maintenance. Our group has pioneered research on the importance of gangliosides for growth factor receptor signaling and epigenetic regulation of NSC activity and differentiation. The primary localization of gangliosides is on cell-surface microdomains and the drastic dose and composition changes during neural differentiation strongly suggest that they are not only important as biomarkers, but also are involved in modulating NSC fate determination. Ganglioside GD3 is the predominant species in NSCs and GD3-synthase knockout (GD3S-KO) revealed reduction of postnatal NSC pools with severe behavioral deficits. Exogenous administration of GD3 significantly restored the NSC pools and enhanced the stemness of NSCs with multipotency and self-renewal. Since morphological changes during neurogenesis require a huge amount of energy, mitochondrial functions are vital for neurogenesis. We discovered that a mitochondrial fission protein, the dynamin-related protein-1 (Drp1), as a novel GD3-binding protein, and GD3 regulates mitochondrial dynamics. Furthermore, we discovered that GM1 ganglioside promotes neuronal differentiation by an epigenetic regulatory mechanism. Nuclear GM1 binds with acetylated histones on the promoters of N-acetylgalactosaminyltransferase (GalNAcT; GM2 synthase) as well as on the NeuroD1 genes in differentiated neurons. In addition, epigenetic activation of the GalNAcT gene was detected as accompanied by an apparent induction of neuronal differentiation in NSCs responding to an exogenous supplement of GM1. GM1 is indeed localized in the nucleus where it can interact with transcriptionally active histones. Interestingly, GM1 could induce epigenetic activation of the tyrosine hydroxylase (TH) gene, with recruitment of nuclear receptor related 1 (Nurr1, also known as NR4A2), a dopaminergic neuron-associated transcription factor, to the TH promoter region. In this way, GM1 epigenetically regulates dopaminergic neuron specific gene expression. GM1 interacts with active chromatin via acetylated histones to recruit transcription factors at the nuclear periphery, resulting in changes in gene expression for neuronal differentiation. The significance is that multifunctional gangliosides modulate lipid microdomains to regulate functions of important molecules on multiple sites: the plasma membrane, mitochondrial membrane, and nuclear membrane. Versatile gangliosides could regulate functional neurons as well as sustain NSC functions via modulating protein and gene activities on ganglioside microdomains.

Functional Impairment of the Nervous System with Glycolipid Deficiencies.

Patients with nervous system disorders suffer from impaired cognitive, sensory and motor functions that greatly inconvenience their daily life and usually burdens their family and society. It is difficult to achieve functional recovery for the damaged central nervous system (CNS) because of its limited ability to regenerate. Glycosphingolipids (GSLs) are abundant in the CNS and are known to play essential roles in cell-cell recognition, adhesion, signal transduction, and cellular migration, that are crucial in all phases of neurogenesis. Despite intense investigation of CNS regeneration, the roles of GSLs in neural regeneration remain unclear. Here we focus on the respective potentials of glycolipids to promote regeneration and repair of the CNS. Mice lacking glucosylceramide, lactosylceramide or gangliosides show lethal phenotypes. More importantly, patients with ganglioside deficiencies exhibit severe clinical phenotypes. Further, neurodegenerative diseases and mental health disorders are associated with altered GSL expression. Accumulating studies demonstrate that GSLs not only delimit physical regions but also play central roles in the maintenance of the biological functions of neurons and glia. We anticipate that the ability of GSLs to modulate behavior of a variety of molecules will enable them to ameliorate biochemical and neurobiological defects in patients. The use of GSLs to treat such defects in the human CNS will be a paradigm-shift in approach since GSL-replacement therapy has not yet been achieved in this manner clinically.

Development, Implementation, and Evaluation of a Distance Learning and Telementoring Program for Cervical Cancer Prevention in Cameroon.

Importance: Although Africa has the highest burden of cervical cancer in the world, educational resources to achieve the 90-70-90 targets set by the World Health Organization in its strategy to eliminate cervical cancer are lacking in the region. Objectives: To adapt, implement, and evaluate the Project Extension for Community Health Care Outcomes (ECHO), an innovative learning tool, to build capacity of clinicians to better incorporate new evidence-based guidelines into cervical cancer control policies and clinical practices. Design, Setting, and Participants: This cross-sectional study assessed knowledge and practices of clinicians and support staff regarding cervical cancer prevention and control and compared them among respondents who had attended Project ECHO sessions (prior ECHO attendees) with those who had not but were planning on attending in the near future (newcomers) as part of the Cameroon Cervical Cancer Prevention Project ECHO. Satisfaction of prior ECHO attendees was also evaluated. Data were analyzed from January to March 2022. Main Outcomes and Measures: Main outcomes were practices and knowledge regarding cervical cancer education and prevention and preinvasive management procedures compared among prior ECHO attendees and newcomers. Results: Of the 75 participants (mean [SD] age, 36.4 [10.0] years; 65.7% [95% CI, 54.3%-77.1%] women) enrolled in this study, 41 (54.7%; 95% CI, 43.1%-66.2%) were prior ECHO attendees, and most were clinicians (55 respondents [78.6%; 95% CI, 68.7%-88.4%]). Overall, 50% (95% CI, 37.8%-62.2%) of respondents reported performing cervical cancer screening with visual inspection of the cervix after application of acetic acid (VIA) and/or visual inspection of the cervix after application of Lugol's iodine (VILI), 46.3% (95% CI, 34.0%-58.5%) of respondents reported performing human papillomavirus (HPV) testing, and 30.3% (95% CI, 18.9%-41.7%) of respondents reported performing cervical cytological examination in their practices, Approximately one-fourth of respondents reported performing cryotherapy (25.4% [95% CI, 14.7%-36.1%]), thermal ablation (27.3% [95% CI, 16.2%-38.3%]) or loop electrosurgical excisional procedure (LEEP, 25.0% [95% CI, 14.4%-35.6%]) for treatment of preinvasive disease. The clinical use of many of these screening and treatment tools was significantly higher among prior ECHO attendees compared with newcomers (VIA/VILI: 63.2% [95% CI, 47.4%-78.9%] vs 33.3% [95% CI, 16.0%-50.6%]; P = .03; cryotherapy: 40.5% [95% CI, 24.3%-56.8%] vs 6.7% [95% CI, 0.0%-15.8%]; P = .002; thermal ablation: 43.2% [95% CI, 26.9%-59.6%] vs 6.9% [95% CI, 0.0%-16.4%]; P = .002). Knowledge about cervical cancer education, prevention, and management procedures was satisfactory in 36.1% (95% CI, 23.7%-48.5%) of respondents; this proportion was significantly higher among prior ECHO attendees (53.8% [95% CI, 37.7%-69.9%]) compared with newcomers (4.5% [95% CI, 0.0%-13.5%]; P < .001). Approximately two-thirds of participants (68.8% [95% CI, 51.8%-85.8%]) reported that they had applied knowledge learned in our ECHO sessions to patient care in their practice or adopted best-practice care through their participation in this ECHO program. Conclusions and Relevance: These findings suggest that the Project ECHO e-learning and telementoring program was associated with improved skills for clinicians and support staff and enhanced quality of care for patients. In the COVID-19 era and beyond, reinforced efforts to strengthen cervical cancer knowledge and best practices through distance learning and collaboration are needed.

HPV Vaccination Uptake, Hesitancy, and Refusal: Observations of Health-Care Professionals During the COVID-19 Pandemic.

HPV vaccination is highly effective at preventing several types of cancer; however, vaccine uptake is suboptimal. The COVID-19 pandemic has affected participation in cancer prevention measures such as HPV vaccination. To assess changes and barriers to HPV vaccination during the COVID-19 pandemic, we conducted a statewide cross-sectional survey of health-care professionals (HCPs) in Texas. Specifically, we evaluated changes observed by HCPs regarding HPV vaccination during the COVID-19 pandemic: 1) hesitancy, 2) refusal, and 3) uptake. Decreased HPV vaccination uptake were reported by 19.3% of HCPs, whereas increased HPV vaccination hesitancy and refusal were reported by 17.1% and 14.8% of HCPs in Texas, respectively. The COVID-19 pandemic had a negative impact on HPV vaccination. Our study identified barriers to HPV vaccination that are unique to the COVID-19 pandemic.

Genetic susceptibility to patient-reported xerostomia among long-term oropharyngeal cancer survivors.

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions (2p13.3, rs6546481, Minor Allele (MA) = A, ANTXR1, P = 4.3 × 10-7; 5p13.2-p13.1, rs16903936, MA = G, EGFLAM, P = 5.1 × 10-6; 4q21.1, rs10518156, MA = G, SHROOM3, P = 7.1 × 10-6; 19q13.42, rs11882068, MA = G, NLRP9, P = 1.7 × 10-5; 12q24.33, rs4760542, MA = G, GLT1D1, P = 1.8 × 10-5; and 3q27.3, rs11714564, MA = G, RTP1, P = 2.9 × 10-5. Seven SNPs were associated with lower risk of moderate to severe xerostomia, of which only one mapped to specific genomic region (15q21.3, rs4776140, MA = G, LOC105370826, a ncRNA class RNA gene, P = 1.5 × 10-5). Although our small exploratory study did not reach genome-wide statistical significance, our study provides, for the first time, preliminary evidence of genetic susceptibility to xerostomia. Further studies are needed to elucidate the role of genetic susceptibility to xerostomia.

Are beliefs about the importance of genetics for cancer prevention and early detection associated with high risk cancer genetic testing in the U.S. Population?

Public attitudes towards germline genetic testing for inherited cancers have been found to be generally positive. Past research demonstrated that diverse causal beliefs and contextual factors are associated with uptake of genetic testing. However, it is unclear how beliefs about genetically informed cancer prevention and early detection ultimately shape testing behaviors. We used data from the National Health Information National Trends Survey (HINTS 5 Cycle 4) to evaluate these beliefs and the relationship between beliefs related to cancer genetics and participation in cancer genetic testing. Overall, 5.24% of the total weighted sample underwent cancer genetic testing, of whom 70.5% (n = 141) had no personal history of cancer, whereas others had a personal diagnosis of breast, ovarian, or colorectal cancer (23.0%), or other cancers (6.5%). In adjusted multivariable analysis, testing was positively associated with personal history of breast, ovarian, or colorectal cancer (OR = 28.37, 95% CI: 10.19-79.04), female sex (OR = 2.97, 95% CI: 1.41-6.26), having high cancer worry (OR = 4.78, 95%: 2.19-10.45), and negatively associated with being Hispanic (OR = 0.37, 95%: 0.16-0.86) or non-Hispanic Asian (OR = 0.12, 95% CI: 0.04-0.33). Belief in the importance of genetics for early detection of cancer was associated with testing (OR = 18.03, 95% CI: 4.07-79.79), whereas belief in the importance of genetics for cancer prevention was not. The association between testing and belief about the importance of genetics for early detection of cancer, but not cancer prevention, is a surprising finding that warrants further research. Better understanding of these beliefs and their potential impact on test uptake may inform population genetic testing efforts.

Clinical Cancer and Direct-to-Consumer Genetic Test Result-Sharing Behavior: Findings from HINTS 2020.

INTRODUCTION: Sharing genetic test results with different stakeholders such as family members, healthcare providers and genetic counselors (HCP/GCs), spouses/partners, and friends is a health behavior of clinical importance in genomic medicine. METHODS: Using nationally representative population-based data collected from the Health Information National Trends Survey (HINTS 5, cycle 4), we identified the prevalence and factors associated with genetic test result-sharing behavior for high-risk cancer tests, genetic health risk tests, and ancestry tests within four groups: HCP/GCs, first-degree relatives (FDRs), spouse/partner, and friend/other. RESULTS: Overall, 68.4% of those who underwent high-risk cancer genetic testing shared their results with FDRs, whereas 89.9% shared with HCP/GCs. In adjusted multivariable analyses, women were nine times more likely than men to share (p = 0.006), and those with a personal history of cancer were less likely to share with HCP/GCs (OR = 0.025, p ≤ 0.001). Of those tested for genetic health risk, 66.5% shared with HCP/GCs, 38.7% with FDRs, 66.6% with a spouse/partner, 12.8% with a friend, and 14.1% did not share results with anyone. Of those who underwent ancestry testing, very few shared results with HCP/GCs (2.6%), whereas modest sharing was reported with FDRs, spouses/partners, and friends. DISCUSSION: These data add empirical evidence about the population prevalence of genetic information sharing and serve as a metric for public engagement with genetic testing.

Ganglioside GD3 is up-regulated in microglia and regulates phagocytosis following global cerebral ischemia.

Gangliosides, the major sialic-acid containing glycosphingolipids in the mammalian brain, play important roles in brain development and neural functions. Here, we show that the b-series ganglioside GD3 and its biosynthetic enzyme, GD3-synthase (GD3S), were up-regulated predominantly in the microglia of mouse hippocampus from 2 to 7 days following global cerebral ischemia (GCI). Interestingly, GD3S knockout (GD3S-KO) mice exhibited decreased hippocampal neuronal loss following GCI, as compared to wild-type (WT) mice. While comparable levels of astrogliosis and microglial proliferation were observed between WT and GD3S-KO mice, the phagocytic capacity of the GD3S-KO microglia was significantly compromised after GCI. At 2 and 4 days following GCI, the GD3S-KO microglia demonstrated decreased amoebic morphology, reduced neuronal material engulfment, and lower expression of the phagolysosome marker CD68, as compared to the WT microglia. Finally, by using a microglia-primary neuron co-culture model, we demonstrated that the GD3S-KO microglia isolated from mouse brains at 2 days after GCI are less neurotoxic to co-cultured hippocampal neurons than the WT-GCI microglia. Moreover, the percentage of microglia with engulfed neuronal elements in the co-cultured wells was also significantly decreased in the GD3S-KO mice after GCI. Interestingly, the impaired phagocytic capacity of GD3S-KO microglia could be partially restored by pre-treatment with exogenous ganglioside GD3. Altogether, this study provides functional evidence that ganglioside GD3 regulates phagocytosis by microglia in an ischemic stroke model. Our data also suggest that the GD3-linked microglial phagocytosis may contribute to the mechanism of delayed neuronal death following ischemic brain injury.

Trends in the rates of health-care providers' recommendation for HPV vaccine from 2012 to 2018: a multi-round cross-sectional analysis of the health information national trends survey.

The 2012 report of the President's Cancer Panel highlighted the overriding contribution of missed clinical opportunities to suboptimal HPV vaccination coverage. Since then, it remains unknown whether the rates of provider recommendations for the HPV vaccine in the US population have increased. We conducted an analysis of four rounds of the Health Information National Trends Survey (HINTS), a household survey of civilian US residents aged 18 y or older. A total of 1,415 (2012), 1,476 (2014), 1,208 (2017), and 1,344 (2018) respondents to the HINTS survey who were either HPV vaccine-eligible or living with HPV vaccine-eligible individuals were included. Overall, the rates of providers' recommendations remained stagnated from 2012 to 2018 in all categories of the study population, except for non-Hispanic Blacks (NHBs), where this prevalence increased during the study period (AAPC = 16.4%, p < .001). In vaccine-eligible individuals (18-27 y), declining trends were noted overall (AAPC = -21.6%, p < .001), among NHWs (AAPC = -30.2%, p < .001) and urban dwellers (AAPC = -21.4%, p < .001). Among vaccine-ineligible respondents (˃27 y) living with vaccine-eligible individuals, trends in the prevalence of provider recommendations for HPV vaccine were stagnating overall (AAPC = 0.5%, p = .90), and increasing only among NHBs (AAPC = 13.9%, p < .001). Despite recent progress, our findings indicate variations of trends in provider recommendations for the HPV vaccine in the US adult population according to age, sex, race/ethnicity, and residence. To accelerate HPV vaccination uptake, immediate actions to enhance provider recommendation for HPV vaccine are needed.