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Abstract Background Papillomaviruses undergo a complex life cycle requiring regulated DNA replication. The papillomavirus E1 helicase is essential for viral DNA replication and plays a key role in controlling viral genome copy number. The E1 helicase is regulated at least in part by protein phosphorylation, however no systematic approach to phosphate site mapping has been attempted. We have utilized mass spectrometry of purified bovine papillomavirus E1 protein to identify and characterize new sites of phosphorylation. Results Mass spectrometry and in silico sequence analysis were used to identify phosphate sites on the BPV E1 protein and kinases that may recognize these sites. Five new and two previously known phosphorylation sites were identified. A phosphate site map was created and used to develop a general model for the role of phosphorylation in E1 function. Conclusion Mass spectrometric analysis identified seven phosphorylated amino acids on the BPV E1 protein. Taken with three previously identified sites, there are at least ten phosphoamino acids on BPV E1. A number of kinases were identified by sequence analysis that could potentially phosphorylate E1 at the identified positions. Several of these kinases have known roles in regulating cell cycle progression. A BPV E1 phosphate map and a discussion of the possible role of phosphorylation in E1 function are presented.

Objectives: To assess the prevalence of lung cancer in Lung-RADS category 4 patients, and to elucidate if clinical or imaging features help differentiate benign lesions from lung cancer., Materials/methods: A retrospective review of lung cancer screening (LCS) studies at a single university screening program between January 2018 and December 2021 identified all patients with Lung-RADS category 4 lesions. Patient demographics, symptoms within the prior 6 months, and imaging features were recorded., Results: During the defined period, 4819 baseline and annual LCS exams were performed; 7.6 % (n = 368) of exams had category 4 nodules and 59 (1.2 %) patients had biopsy-proven lung cancer. Distribution of Lung-RADS category 4 lesions and lung cancer diagnosis were as follows: 4A - 223 nodules, 6.3 % malignant; 4B - 114 nodules, 20.2 % malignant; and 4X - 31 nodules, 71.0 % malignant. Symptoms were reported in 9.0 % (n = 20) of category 4A (2 were malignant), 15.8 % (n = 18) category 4B (1 was malignant) and 22.6 % (n = 7) category 4X (5 were malignant). Imaging features associated with malignancy included endobronchial obstruction with distal atelectasis, pleural tethering, irregular shape, cavitation, and heterogeneous cystic appearance. Twenty-four nodules increased in size, however, only 7 were biopsy proven. Relative to the risk seen with 4A disease, multivariable logistic analyses showed that the odds of a malignancy increased significantly by 3.8 fold (95 % CI: 1.9, 7.9) and 39.2 fold (95 % CI: 14.9, 103.0) with 4B and 4X disease, respectively (p < 0.0001). A separate analysis involving only category 4A and 4B patients jointly showed that disease category (OR = 3.0; 95 % CI: 1.5, 6.4) and additional imaging features (OR = 3.2; 95 % CI: 1.4, 7.0) were significant predictors of malignancy. The presence of clinical symptoms was not statistically associated with lung cancer., Conclusions: Lung-RADS 4 nodules were found in 7.6% of LCS examinations and 16% of these nodules were lung cancer. The probability of lung cancer increases from category 4A to 4X, and imaging features may help differentiate benign from malignant nodules in this LCS category., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Science is among humanity's greatest achievements, yet scientific censorship is rarely studied empirically. We explore the social, psychological, and institutional causes and consequences of scientific censorship (defined as actions aimed at obstructing particular scientific ideas from reaching an audience for reasons other than low scientific quality). Popular narratives suggest that scientific censorship is driven by authoritarian officials with dark motives, such as dogmatism and intolerance. Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups. This perspective helps explain both recent findings on scientific censorship and recent changes to scientific institutions, such as the use of harm-based criteria to evaluate research. We discuss unknowns surrounding the consequences of censorship and provide recommendations for improving transparency and accountability in scientific decision-making to enable the exploration of these unknowns. The benefits of censorship may sometimes outweigh costs. However, until costs and benefits are examined empirically, scholars on opposing sides of ongoing debates are left to quarrel based on competing values, assumptions, and intuitions., Competing Interests: Competing interests statement:The authors declare no competing interest.

Moral foundations theory has been a generative framework in moral psychology in the last 2 decades. Here, we revisit the theory and develop a new measurement tool, the Moral Foundations Questionnaire-2 (MFQ-2), based on data from 25 populations. We demonstrate empirically that equality and proportionality are distinct moral foundations while retaining the other four existing foundations of care, loyalty, authority, and purity. Three studies were conducted to develop the MFQ-2 and to examine how the nomological network of moral foundations varies across 25 populations. Study 1 ( N = 3,360, five populations) specified a refined top-down approach for measurement of moral foundations. Study 2 ( N = 3,902, 19 populations) used a variety of methods (e.g., factor analysis, exploratory structural equations model, network psychometrics, alignment measurement equivalence) to provide evidence that the MFQ-2 fares well in terms of reliability and validity across cultural contexts. We also examined population-level, religious, ideological, and gender differences using the new measure. Study 3 ( N = 1,410, three populations) provided evidence for convergent validity of the MFQ-2 scores, expanded the nomological network of the six moral foundations, and demonstrated the improved predictive power of the measure compared with the original MFQ. Importantly, our results showed how the nomological network of moral foundations varied across cultural contexts: consistent with a pluralistic view of morality, different foundations were influential in the network of moral foundations depending on cultural context. These studies sharpen the theoretical and methodological resolution of moral foundations theory and provide the field of moral psychology a more accurate instrument for investigating the many ways that moral conflicts and divisions are shaping the modern world. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Authoritarianism has been the subject of scientific inquiry for nearly a century, yet the vast majority of authoritarianism research has focused on right-wing authoritarianism. In the present studies, we investigate the nature, structure, and nomological network of left-wing authoritarianism (LWA), a construct famously known as "the Loch Ness Monster" of political psychology. We iteratively construct a measure and data-driven conceptualization of LWA across six samples (N = 7,258) and conduct quantitative tests of LWA's relations with more than 60 authoritarianism-related variables. We find that LWA, right-wing authoritarianism, and social dominance orientation reflect a shared constellation of personality traits, cognitive features, beliefs, and motivational values that might be considered the "heart" of authoritarianism. Relative to right-wing authoritarians, left-wing authoritarians were lower in dogmatism and cognitive rigidity, higher in negative emotionality, and expressed stronger support for a political system with substantial centralized state control. Our results also indicate that LWA powerfully predicts behavioral aggression and is strongly correlated with participation in political violence. We conclude that a movement away from exclusively right-wing conceptualizations of authoritarianism may be required to illuminate authoritarianism's central features, conceptual breadth, and psychological appeal. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Developing novel therapeutic agents to treat amyotrophic lateral sclerosis (ALS) has been difficult due to multifactorial pathophysiologic processes at work. Intrathecal drug administration shows promise due to close proximity of cerebrospinal fluid (CSF) to affected tissues. Development of effective intrathecal pharmaceuticals will rely on accurate models of how drugs are dispersed in the CSF. Therefore, a method to quantify these dynamics and a characterization of differences across disease states is needed., Methods: Complete intrathecal 3D CSF geometry and CSF flow velocities at six axial locations in the spinal canal were collected by T2-weighted and phase-contrast MRI, respectively. Scans were completed for eight people with ALS and ten healthy controls. Manual segmentation of the spinal subarachnoid space was performed and coupled with an interpolated model of CSF flow within the spinal canal. Geometric and hydrodynamic parameters were then generated at 1 mm slice intervals along the entire spine. Temporal analysis of the waveform spectral content and feature points was also completed., Results: Comparison of ALS and control groups revealed a reduction in CSF flow magnitude and increased flow propagation velocities in the ALS cohort. Other differences in spectral harmonic content and geometric comparisons may support an overall decrease in intrathecal compliance in the ALS group. Notably, there was a high degree of variability between cases, with one ALS patient displaying nearly zero CSF flow along the entire spinal canal., Conclusion: While our sample size limits statistical confidence about the differences observed in this study, it was possible to measure and quantify inter-individual and cohort variability in a non-invasive manner. Our study also shows the potential for MRI based measurements of CSF geometry and flow to provide information about  the hydrodynamic environment of the spinal subarachnoid space. These dynamics may be studied further to understand the behavior of CSF solute transport in healthy and diseased states.

A crescendo of incidents have raised concerns about whether scientific practices in psychology may be suboptimal, sometimes leading to the publication, dissemination, and application of unreliable or misinterpreted findings. Psychology has been a leader in identifying possibly suboptimal practices and proposing reforms that might enhance the efficiency of the scientific process and the publication of robust evidence and interpretations. To help shape future efforts, this paper offers a model of the psychological and socio-structural forces and processes that may influence scientists' practices. The model identifies practices targeted by interventions and reforms, and which practices remain unaddressed. The model also suggests directions for empirical research to assess how best to enhance the effectiveness of psychological inquiry., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2019 The Author(s).)

Over the past 16 years, several scientific organizations have proposed systems that incorporate imaging for surveillance, diagnosis, staging, treatment, and monitoring of treatment response of hepatocellular carcinoma (HCC). These systems are needed to standardize the acquisition, interpretation, and reporting of liver imaging examinations; help differentiate benign from malignant observations; improve consistency between radiologists; and provide guidance for management of HCC. This review article discusses the historical evolution of HCC imaging systems. We indicate the features differentiating these systems, including target population, screening and surveillance algorithm, diagnostic imaging modalities, diagnostic scope, expertise and technical requirements, terminology, major and ancillary imaging features, staging and transplant eligibility, and assessment of treatment response. We highlight the potential benefits of unifying the systems, which we anticipate will enable sharing, pooling, and meta-analysis of data; facilitate multi-center trials; and accelerate dissemination of knowledge.

Hypophosphatasia (HPP) is a rare metabolic disease with the hallmark finding of deficient serum tissue nonspecific alkaline phosphatase (TNSALP) activity. TNSALP is primarily known for its role in mineralization; hence, HPP is characterized by defective mineralization of bone and/or teeth. TNSALP is also necessary for proper vitamin B6 metabolism and its participation as a cofactor for neurotransmitters in the central nervous system. Defective TNSALP activity in the brain can result in intractable seizures responsive to pyridoxine. The pathophysiology of pyridoxine-responsive seizures (PRS) in severe HPP remains to be clearly defined. We review the case of a 2-month-old Caucasian boy presenting with seizures refractory to conventional antiepileptic medications. Empiric treatment with favorable response to pyridoxine in conjunction with severe metabolic bone disease, extremely low serum alkaline phosphatase, elevated phosphoethanolamine, hypercalcemia, hypercalciuria, and nephrocalcinosis led to a clinical diagnosis of infantile HPP. Sequence analysis revealed compound heterozygosity of the TNSALP gene with a novel mutation in exon 9 and a previously reported mutation in exon 12. This case reminds the physician that severe infantile HPP can present with PRS as its major initial manifestation and should alert clinicians to consider HPP in their differential of PRS. In addition, despite this severe genotype, the clinical diagnosis of our patient was delayed because of minimal phenotypic features initially. This highlights that the phenotype-genotype correlation could be variable even in severe disease. This case also demonstrates that HPP should be classified as PRS and not a form of pyridoxine-dependent epilepsy (PDE) as our patient was able to stop the pyridoxine supplementation without seizure recurrence once enzyme replacement was initiated. With the advent of enzyme replacement therapy, this once fatal disease may have improved morbidity and mortality.

Aim: To determine if anesthesiologist-monitored use of propofol results in improved detection of adenomas when compared with routine conscious sedation., Methods: This retrospective study was conducted at two separate hospital-based endoscopy units where approximately 12,000 endoscopic procedures are performed annually, with one endoscopy unit exclusively using anesthesiologist-monitored propofol. Three thousand two hundred and fifty-two patients underwent initial screening or surveillance colonoscopies. Our primary end point was the adenoma detection rate, defined as the number of patients in whom at least one adenoma was found, associated with the type of sedation., Results: Three thousand two hundred and fifty-two outpatient colonoscopies were performed by five selected endoscopists. At least one adenoma was detected in 27.6% of patients (95% CI = 26.0-29.1) with no difference in the detection rate between the anesthesiologist-propofol and group and the gastroenterologist-midazolam/fentanyl group (28.1% vs 27.1%, P = 0.53)., Conclusion: The type of sedation used during colonoscopy does not affect the number of patients in whom adenomatous polyps are detected.

This article introduces the political person perception model, which identifies conditions under which perceivers rely on stereotypes (party membership), individuating information (issue position), or both in political person perception. Three studies supported the model's predictions. Study 1 showed that perceivers gave primacy to target information that was narrowly relevant to a judgment, whether that information was stereotypic or individuating. Study 2 found that perceivers relied exclusively on individuating information when it was narrowly relevant to the judgment and relied on both stereotype and individuating information when individuating information was not narrowly relevant to the judgment but did imply a political ideology. Study 3 replicated these findings in a more ecologically valid context and showed that people relied on party information in the absence of narrowly relevant policy positions and when individuating information did not imply a political ideology. Implications for political person perception and theories of stereotyping are discussed.

The number of concussions and other head injuries are increasing in the National Hockey League (NHL). The factors that may influence concussion risk in hockey remain largely unknown. In the current study, data on 787 NHL players from the 2001-2002 season were examined. It was found that a player's average ice time per game was a significant predictor of concussion. A player's total ice time for the season was not a significant predictor, however, and there was no significant difference found in the number of games played in the season between those who suffered a concussion and those who did not. These data suggest that in-game fatigue is an important factor when considering concussions.

We investigated the time course of feature-based attention and compared it to the time course of spatial attention in an experiment with identical stimuli and task. Observers detected a speed increment in a compound motion stimulus preceded by cues that indicated either the target location or direction. The cue-target stimulus-onset-asynchrony (SOA) was varied to assess the time course of the attentional effect. We found that spatial attention was deployed earlier than feature-based attention and that both types of attention improved performance to a similar extent at a longer SOA. Results indicate that attention is a flexible mechanism allowing us to efficiently select task-relevant information based on either spatial or feature dimensions, but that spatial attention exert its effects faster.

There has been an increase in the number of concussions sustained by players in the National Hockey League (NHL). While wearing a helmet is now required by the NHL, the face visor remains optional. It is unknown to what degree face visors influence concussion, other head injury and eye-injury rates at the professional level. Data from the 2001-2002 NHL season were examined. It was found that wearing a face visor did not significantly influence the prevalence of concussion. Visor protection did, however, minimise eye-injuries and other, non-concussion head injuries. These data suggest that, while a visor may prevent some head and eye-injuries, other measures may be necessary to reduce the number of concussions.

Background: Diabetes is one of the most common diseases in the nation. Students with diabetes face the daily task of balancing food, physical activity, and medication to survive. Teachers and school personnel often lack the knowledge needed to assist them., Context: An estimated 2647 schoolchildren in Wisconsin have diabetes. The Wisconsin Diabetes Prevention and Control Program frequently receives anecdotal reports from parents and diabetes educators on the care of children with diabetes in the schools; the program also manages requests for information on new diabetes-related equipment from school personnel., Methods: A statewide workgroup convened to develop Children with Diabetes: A Resource Guide for Wisconsin Schools and Families, aimed at improving the school staff's knowledge of diabetes and its management and their awareness of the benefits of maintaining glucose control. Training sessions for school professionals were developed and conducted around the state. All attendees were asked to complete an evaluation of the training. In addition, the workgroup included an evaluation form with each guide distributed and conducted a follow-up survey on the impact of the guide and changes to school policies., Consequences: Of the 762 people who attended training sessions, 631 (83%) completed the evaluation form. On questions about the training session's content, quality, organization, and appropriateness, responses averaged 4.42 points on a scale of 1 (poor) to 5 (excellent). More than 9713 resource guides were distributed to more than 1359 individuals; 58 recipients responded to the evaluation form included with the resource guide, with 57 (98%) of these indicating that they would recommend the guide to others. Preliminary results of the follow-up impact survey show that many positive changes have been implemented to improve the school environment for children with diabetes since the resource guide was implemented., Interpretation: This model of working with school professionals, health care practitioners, parents, and community organizations to create a resource guide with accompanying training sessions can be used in other states to accomplish similar goals of increasing knowledge about diabetes and improving social and policy environments.

This technique is a controlled process in which the thickness of the obturator can be easily modified by adding to or shaving off the dimensionally stable silicone putty. All phases of the obturator fabrication are heat-cured and not autopolymerized, thus negating the disadvantages of other techniques. The technique provides more predictable results in obturator fabrication as it uses silicone putty as the obturating material as opposed to sugar, asbestos, or other silicone rubber foams that can be messy, dangerous, and unstable. This technique can also be used for patients with atrophic maxillae where the hollow denture can significantly reduce the weight of the restoration.