Risk factors associated with oral Human Papillomavirus (HPV) prevalence within a young adult population.

BACKGROUND: The prevalence of, and risk factors for, genital Human Papillomavirus (HPV) infections within the young adult population are well-established; the same is not known for oral HPV. This observational study aimed to determine oral HPV prevalence and abundance within a UK young adult population, and examine if sexual practices and established risk factors of oropharyngeal squamous cell carcinomas (OPSCCs) (such as smoking and alcohol consumption) influenced HPV prevalence. METHODS: Convenience sampling was used to recruit a small sample of 452 UK-based young adults studying at a higher education (HE) institution to the study; the study was not powered. A highly sensitive real-time PCR HPV screening method was developed for the detection of multiple HPV subtypes from oral swabs. HPV-positive samples were subsequently screened by qPCR for viral subtypes HPV-6, HPV-11, HPV-16, HPV-18. Results were analysed by univariate and multivariate methods and stratified for gender, with lifestyle behaviour data collected via questionnaire. Socio-economic status was not captured within the questionnaire. RESULTS: We found a high oral HPV prevalence of 22.79%, with a dominance of high-risk viral type HPV-16 (prevalence 19.12%; abundance average 1.08 × 105 copies/million cells) detected within healthy young adults. Frequent smoking (p = .05), masturbation (p = .029), and engagement in multiple sexual activities (p = .057), were found to be associated with oral HPV prevalence, and HPV-16 prevalence, whilst behaviours traditionally associated with genital HPV were not. CONCLUSIONS: Our results strengthen the link between sexual practices and oral HPV transmission. We suggest that young adults should be considered high-risk for the contraction of oral HPV, although acknowledge that this sample of HE students may not be representative of the wider population. We show that high-risk HPV-16 is prevalent in the healthy population, as well as dominating within OPSCC; this study is one of the first to determine the dominance of oral HPV-16 prevalence and abundance within this population, presenting a clear need for greater awareness of oral HPV infections, and the risk factors for HPV-positive OPSCC within young adults.

Risk factors for persistent fatal opioid-involved overdose clusters in Massachusetts 2011-2021: a spatial statistical analysis with socio-economic, accessibility, and prescription factors.

BACKGROUND: Fatal opioid-involved overdose rates increased precipitously from 5.0 per 100,000 population to 33.5 in Massachusetts between 1999 and 2022. METHODS: We used spatial rate smoothing techniques to identify persistent opioid overdose-involved fatality clusters at the ZIP Code Tabulation Area (ZCTA) level. Rate smoothing techniques were employed to identify locations of high fatal opioid overdose rates where population counts were low. In Massachusetts, this included areas with both sparse data and low population density. We used Local Indicators of Spatial Association (LISA) cluster analyses with the raw incidence rates, and the Empirical Bayes smoothed rates to identify clusters from 2011 to 2021. We also estimated Empirical Bayes LISA cluster estimates to identify clusters during the same period. We constructed measures of the socio-built environment and potentially inappropriate prescribing using principal components analysis. The resulting measures were used as covariates in Conditional Autoregressive Bayesian models that acknowledge spatial autocorrelation to predict both, if a ZCTA was part of an opioid-involved cluster for fatal overdose rates, as well as the number of times that it was part of a cluster of high incidence rates. RESULTS: LISA clusters for smoothed data were able to identify whether a ZCTA was part of a opioid involved fatality incidence cluster earlier in the study period, when compared to LISA clusters based on raw rates. PCA helped in identifying unique socio-environmental factors, such as minoritized populations and poverty, potentially inappropriate prescribing, access to amenities, and rurality by combining socioeconomic, built environment and prescription variables that were highly correlated with each other. In all models except for those that used raw rates to estimate whether a ZCTA was part of a high fatality cluster, opioid overdose fatality clusters in Massachusetts had high percentages of Black and Hispanic residents, and households experiencing poverty. The models that were fitted on Empirical Bayes LISA identified this phenomenon earlier in the study period than the raw rate LISA. However, all the models identified minoritized populations and poverty as significant factors in predicting the persistence of a ZCTA being part of a high opioid overdose cluster during this time period. CONCLUSION: Conducting spatially robust analyses may help inform policies to identify community-level risks for opioid-involved overdose deaths sooner than depending on raw incidence rates alone. The results can help inform policy makers and planners about locations of persistent risk.

Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set.

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.

Exploring the Collateral Damage of the COVID-19 Pandemic on Stroke Care: A Statewide Analysis.

[Figure: see text].

Judging Truth.

Deceptive claims surround us, embedded in fake news, advertisements, political propaganda, and rumors. How do people know what to believe? Truth judgments reflect inferences drawn from three types of information: base rates, feelings, and consistency with information retrieved from memory. First, people exhibit a bias to accept incoming information, because most claims in our environments are true. Second, people interpret feelings, like ease of processing, as evidence of truth. And third, people can (but do not always) consider whether assertions match facts and source information stored in memory. This three-part framework predicts specific illusions (e.g., truthiness, illusory truth), offers ways to correct stubborn misconceptions, and suggests the importance of converging cues in a post-truth world, where falsehoods travel further and faster than the truth.

DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1ß Signaling.

Rhinoviral infection is a common trigger of the excessive inflammation observed during exacerbations of asthma and chronic obstructive pulmonary disease. Rhinovirus (RV) recognition by pattern recognition receptors activates the mitogen-activated protein kinase (MAPK) pathways, which are common inducers of inflammatory gene production. A family of dual-specificity phosphatases (DUSPs) can regulate MAPK function, but their roles in rhinoviral infection are not known. We hypothesized that DUSPs would negatively regulate the inflammatory response to RV infection. Our results revealed that the p38 and c-Jun N-terminal kinase (JNK) MAPKs play key roles in the inflammatory response of epithelial cells to RV infection. Three DUSPs previously shown to have roles in innate immunity (DUSPs 1, 4, and 10) were expressed in primary bronchial epithelial cells, and one of them, DUSP10, was downregulated by RV infection. Small interfering RNA-mediated knockdown of DUSP10 identified a role for the protein in negatively regulating inflammatory cytokine production in response to interleukin-1ß (IL-1ß), alone and in combination with RV, without any effect on RV replication. This study identifies DUSP10 as an important regulator of airway inflammation in respiratory viral infection.IMPORTANCE Rhinoviruses are one of the causes of the common cold. In patients with asthma or chronic obstructive pulmonary disease, viral infections, including those with rhinovirus, are the commonest cause of exacerbations. Novel therapeutics to limit viral inflammation are clearly required. The work presented here identifies DUSP10 as an important protein involved in limiting the inflammatory response in the airway without affecting immune control of the virus.

Neural basis of goal-driven changes in knowledge activation.

Depending on a person's goals, different aspects of stored knowledge are accessed. Decades of behavioral work document the flexible use of knowledge, but little neuroimaging work speaks to these questions. We used representational similarity analysis to investigate whether the relationship between brain activity and semantic structure of statements varied in two tasks hypothesized to differ in the degree to which knowledge is accessed: judging truth (semantic task) and judging oldness (episodic task). During truth judgments, but not old/new recognition judgments, a left-lateralized network previously associated with semantic memory exhibited correlations with semantic structure. At a neural level, people activate knowledge representations in different ways when focused on different goals. The present results demonstrate the potential of multivariate approaches in characterizing knowledge storage and retrieval, as well as the ways that it shapes our understanding and long-term memory.

Targeted transgene integration overcomes variability of position effects in zebrafish.

Zebrafish transgenesis is increasingly popular owing to the optical transparency and external development of embryos, which provide a scalable vertebrate model for in vivo experimentation. The ability to express transgenes in a tightly controlled spatio-temporal pattern is an important prerequisite for exploitation of zebrafish in a wide range of biomedical applications. However, conventional transgenesis methods are plagued by position effects: the regulatory environment of genomic integration sites leads to variation of expression patterns of transgenes driven by engineered cis-regulatory modules. This limitation represents a bottleneck when studying the precise function of cis-regulatory modules and their subtle variants or when various effector proteins are to be expressed for labelling and manipulation of defined sets of cells. Here, we provide evidence for the efficient elimination of variability of position effects by developing a PhiC31 integrase-based targeting method. To detect targeted integration events, a simple phenotype scoring of colour change in the lens of larvae is used. We compared PhiC31-based integration and Tol2 transgenesis in the analysis of the activity of a novel conserved enhancer from the developmentally regulated neural-specific esrrga gene. Reporter expression was highly variable among independent lines generated with Tol2, whereas all lines generated with PhiC31 into a single integration site displayed nearly identical, enhancer-specific reporter expression in brain nuclei. Moreover, we demonstrate that a modified integrase system can also be used for the detection of enhancer activity in transient transgenesis. These results demonstrate the power of the PhiC31-based transgene integration for the annotation and fine analysis of transcriptional regulatory elements and it promises to be a generally desirable tool for a range of applications, which rely on highly reproducible patterns of transgene activity in zebrafish.

Expertise effects in the Moses illusion: detecting contradictions with stored knowledge.

People frequently miss contradictions with stored knowledge; for example, readers often fail to notice any problem with a reference to the Atlantic as the largest ocean. Critically, such effects occur even though participants later demonstrate knowing the Pacific is the largest ocean (the Moses Illusion) [Erickson, T. D., & Mattson, M. E. (1981). From words to meaning: A semantic illusion. Journal of Verbal Learning & Verbal Behavior, 20, 540-551]. We investigated whether such oversights disappear when erroneous references contradict information in one's expert domain, material which likely has been encountered many times and is particularly well-known. Biology and history graduate students monitored for errors while answering biology and history questions containing erroneous presuppositions ("In what US state were the forty-niners searching for oil?"). Expertise helped: participants were less susceptible to the illusion and less likely to later reproduce errors in their expert domain. However, expertise did not eliminate the illusion, even when errors were bolded and underlined, meaning that it was unlikely that people simply skipped over errors. The results support claims that people often use heuristics to judge truth, as opposed to directly retrieving information from memory, likely because such heuristics are adaptive and often lead to the correct answer. Even experts sometimes use such shortcuts, suggesting that overlearned and accessible knowledge does not guarantee retrieval of that information.

On Known Unknowns: Fluency and the Neural Mechanisms of Illusory Truth.

The "illusory truth" effect refers to the phenomenon whereby repetition of a statement increases its likelihood of being judged true. This phenomenon has important implications for how we come to believe oft-repeated information that may be misleading or unknown. Behavioral evidence indicates that fluency, the subjective ease experienced while processing information, underlies this effect. This suggests that illusory truth should be mediated by brain regions previously linked to fluency, such as the perirhinal cortex (PRC). To investigate this possibility, we scanned participants with fMRI while they rated the truth of unknown statements, half of which were presented earlier (i.e., repeated). The only brain region that showed an interaction between repetition and ratings of perceived truth was PRC, where activity increased with truth ratings for repeated, but not for new, statements. This finding supports the hypothesis that illusory truth is mediated by a fluency mechanism and further strengthens the link between PRC and fluency.

Correcting false memories: Errors must be noticed and replaced.

Memory can be unreliable. For example, after reading The new baby stayed awake all night, people often misremember that the new baby cried all night (Brewer, 1977); similarly, after hearing bed, rest, and tired, people often falsely remember that sleep was on the list (Roediger & McDermott, 1995). In general, such false memories are difficult to correct, persisting despite warnings and additional study opportunities. We argue that errors must first be detected to be corrected; consistent with this argument, two experiments showed that false memories were nearly eliminated when conditions facilitated comparisons between participants' errors and corrective feedback (e.g., immediate trial-by-trial feedback that allowed direct comparisons between their responses and the correct information). However, knowledge that they had made an error was insufficient; unless the feedback message also contained the correct answer, the rate of false memories remained relatively constant. On the one hand, there is nothing special about correcting false memories: simply labeling an error as "wrong" is also insufficient for correcting other memory errors, including misremembered facts or mistranslations. However, unlike these other types of errors--which often benefit from the spacing afforded by delayed feedback--false memories require a special consideration: Learners may fail to notice their errors unless the correction conditions specifically highlight them.

Multiple-choice tests stabilize access to marginal knowledge.

Marginal knowledge refers to knowledge that is stored in memory, but is not accessible at a given moment. For example, one might struggle to remember who wrote The Call of the Wild, even if that knowledge is stored in memory. Knowing how best to stabilize access to marginal knowledge is important, given that new learning often requires accessing and building on prior knowledge. While even a single opportunity to restudy marginal knowledge boosts its later accessibility (Berger, Hall, & Bahrick, 1999), in many situations explicit relearning opportunities are not available. Our question is whether multiple-choice tests (which by definition expose the learner to the correct answers) can also serve this function and, if so, how testing compares to restudying given that tests can be particularly powerful learning devices (Roediger & Karpicke, 2006). In four experiments, we found that multiple-choice testing had the power to stabilize access to marginal knowledge, and to do so for at least up to a week. Importantly, such tests did not need to be paired with feedback, although testing was no more powerful than studying. Overall, the results support the idea that one's knowledge base is unstable, with individual pieces of information coming in and out of reach. The present findings have implications for a key educational challenge: ensuring that students have continuing access to information they have learned.

Learning misinformation from fictional sources: understanding the contributions of transportation and item-specific processing.

People often pick up incorrect information about the world from movies, novels and other fictional sources. The question asked here is whether such sources are a particularly potent source of misinformation. On the one hand, story-reading involves transportation into a fictional world, with a possible reduction in access to one's prior knowledge (likely reducing the chances that the reader will notice errors). On the other hand, stories encourage relational processing as readers create mental models, decreasing the likelihood that they will encode and remember more peripheral details like erroneous facts. To test these ideas, we examined suggestibility after readers were exposed to misleading references embedded in stories and lists that were matched on a number of dimensions. In two experiments, suggestibility was greater following exposure to misinformation in a list of sentences rather than a coherent story, even though the story was rated as more engaging than the list. Furthermore, processing the story with an item-specific processing task (inserting missing letters) increased later suggestibility, whereas this task had no impact on suggestibility when misinformation was presented within a list. The type of processing used when reading a text affects suggestibility more than engagement with the text.

The role of protein kinase A regulation of the E6 PDZ-binding domain during the differentiation-dependent life cycle of human papillomavirus type 18.

Human papillomavirus (HPV) E6 proteins of high-risk alpha types target a select group of PSD95/DLG1/ZO1 (PDZ) domain-containing proteins by using a C-terminal PDZ-binding motif (PBM), an interaction that can be negatively regulated by phosphorylation of the E6 PBM by protein kinase A (PKA). Here, we have mutated the canonical PKA recognition motif that partially overlaps with the E6 PBM in the HPV18 genome (E6153PKA) and compared the effect of this mutation on the HPVl8 life cycle in primary keratinocytes with the wild-type genome and with a second mutant genome that lacks the E6 PBM (E6ΔPDZ). Loss of PKA recognition of E6 was associated with increased growth of the genome-containing cells relative to cells carrying the wild-type genome, and upon stratification, a more hyperplastic phenotype, with an increase in the number of S-phase competent cells in the upper suprabasal layers, while the opposite was seen with the E6ΔPDZ genome. Moreover, the growth of wild-type genome-containing cells was sensitive to changes in PKA activity, and these changes were associated with increased phosphorylation of the E6 PBM. In marked contrast to E6ΔPDZ genomes, the E6153PKA mutation exhibited no deleterious effects on viral genome amplification or expression of late proteins. Our data suggest that the E6 PBM function is differentially regulated by phosphorylation in the HPV18 life cycle. We speculate that perturbation of protein kinase signaling pathways could lead to changes in E6 PBM function, which in turn could have a bearing on tumor promotion and progression.

Recent study, but not retrieval, of knowledge protects against learning errors.

Surprisingly, people incorporate errors into their knowledge bases even when they have the correct knowledge stored in memory (e.g., Fazio, Barber, Rajaram, Ornstein, & Marsh, 2013). We examined whether heightening the accessibility of correct knowledge would protect people from later reproducing misleading information that they encountered in fictional stories. In Experiment 1, participants studied a series of target general knowledge questions and their correct answers either a few minutes (high accessibility of knowledge) or 1 week (low accessibility of knowledge) before exposure to misleading story references. In Experiments 2a and 2b, participants instead retrieved the answers to the target general knowledge questions either a few minutes or 1 week before the rest of the experiment. Reading the relevant knowledge directly before the story-reading phase protected against reproduction of the misleading story answers on a later general knowledge test, but retrieving that same correct information did not. Retrieving stored knowledge from memory might actually enhance the encoding of relevant misinformation.

Ageing and the Moses illusion: older adults fall for Moses but if asked directly, stick with Noah.

Many people respond "two" to the question "How many animals of each kind did Moses take on the ark?", even though they know the reference should be to Noah. The Moses Illusion demonstrates a failure to apply stored knowledge (Erickson & Mattson, 1981). Of interest was whether older adults' robust knowledge bases would protect them from vulnerability to this illusion. Of secondary interest were any age differences in the memorial consequences of the illusion, and whether older adults' prior knowledge would protect them from later reproducing information from distorted questions (e.g., later saying that Moses took two animals of each kind on the ark). Surprisingly, older adults fell for the Moses Illusion more often than did younger adults. However, falling for the illusion did not affect older adults' later memory; they were less suggestible than young adults. Most importantly, older adults were more likely to recover from exposure to distorted questions and respond correctly. Explanations of these findings, drawing on theories of cognitive ageing, are discussed.

Mindfully and confidently digital: A mixed methods study on personal resources to mitigate the dark side of digital working.

A growing body of research demonstrates the potential of mindfulness to reduce employee stress. However, with work increasingly migrating from the physical to the digital workplace, evidence is lacking on how mindfulness might help employees live healthy digital working lives. In addition, employees' confidence when using the digital workplace is seen as important for productivity but may also play a role in reducing well-being impacts from digital working. Using the Job-Demands Resources model as a theoretical foundation, 142 workers were surveyed regarding their levels of trait mindfulness and digital workplace confidence, along with their experiences of the dark side effects (stress, overload, anxiety, Fear of Missing Out and addiction) and well-being outcomes (burnout and health). 14 workers were also interviewed to provide qualitative insights on these constructs. Results from regression analyses indicated that more digitally confident workers were less likely to experience digital workplace anxiety, while those with higher mindfulness were better protected against all of the dark side of digital working effects. Interview data indicated ways in which digital mindfulness helps protect well-being, as well as how digital workplace confidence enables healthier digital habits.

Comparison of semantic and phonological false memories in short- and long-term tests.

The Deese-Roediger-McDermott (DRM) paradigm has been at the centre of false memory research. Whereas most work with this paradigm has examined memory at the long term and with semantically associated lists, the present study examines phonological and semantic false memories at both short- and long-term delays. In two experiments, participants studied short lists containing six (Experiment 1) or four (Experiment 2) items, either semantically or phonologically related to the same non-studied critical items (CI). Following each list, participants completed 36 trials of an immediate recognition task (short-term memory [STM]-only condition) only or they also completed a surprise recognition test after a 1-min delay after all 36 STM trials (STM + long-term memory [LTM] condition). In STM, false alarms were higher in phonological lists, whereas after the delay, false alarms were higher in semantic lists, reflecting differential sensitivity to the type of association as a function of delay. A third experiment examined LTM performance after controlling for prior testing and yielded highly similar results. Both the activation-monitoring framework (AMF) and fuzzy-trace theory (FTT) can explain the majority of the findings, with some remaining issues. These results confirm that information from the knowledge base (LTM) does influence accuracy in an STM task, albeit less so than perceptual level similarity.

The effects of white matter hyperintensities on MEG power spectra in cognitively healthy aging.

Objective: This study sought to identify magnetoencephalography (MEG) power spectra patterns associated with cerebrovascular damage (white matter hyperintensities - WMH) and their relationship with cognitive performance and brain structure integrity in aging individuals without cognitive impairment. Methods: We hypothesized a "slowness" pattern characterized by increased power in δ and θ bands and decreased power in the ß band associated with the severity of vascular damage. MEG signals were analyzed in cognitively healthy older adults to investigate these associations. Results: Contrary to expectations, we did not observe an increase in δ and θ power. However, we found a significant negative correlation between ß band power and WMH volume. This ß power reduction was linked to structural brain changes, such as larger lateral ventricles, reduced white matter volume, and decreased fractional anisotropy in critical white matter tracts, but not to cognitive performance. This suggests that ß band power reduction may serve as an early marker of vascular damage before the onset of cognitive symptoms. Conclusion: Our findings partially confirm our initial hypothesis by demonstrating a decrease in ß band power with increased vascular damage but not the anticipated increase in slow band power. The lack of correlation between the ßpow marker and cognitive performance suggests its potential utility in early identification of at-risk individuals for future cognitive impairment due to vascular origins. These results contribute to understanding the electrophysiological signatures of preclinical vascular damage and highlight the importance of MEG in detecting subtle brain changes associated with aging.

Heuristic decision-making across adulthood.

In general, research on aging and decision-making has grown in recent years. Yet, little work has investigated how reliance on classic heuristics may differ across adulthood. For example, younger adults rely on the availability of information from memory when judging the relative frequency of plane crashes versus car accidents, but it is unclear if older adults are similarly reliant on this heuristic. In the present study, participants aged 20-90 years old made judgments that could be answered by relying on five different heuristics: anchoring, availability, recognition, representativeness, and sunk-cost bias. We found no evidence of age-related differences in the use of the classic heuristics-younger and older adults employed anchoring, availability, recognition, and representativeness to equal degrees in order to make decisions. However, replicating past work, we found age-related differences in the sunk-cost bias-older adults were more likely to avoid this fallacy compared to younger adults. We explain these different patterns by drawing on the distinctive roles that stored knowledge and personal experience likely play across heuristics. (PsycInfo Database Record (c) 2023 APA, all rights reserved).