bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learner-Controlled Practice Difficulty and Task Exploration in an Active-Learning Gaming Environment
Authors: Westlin Joseph , Day Eric Anthony , Hughes Michael G. 
Published: September 2019

Background. With the use of computer-based simulations and games becoming increasingly common in education and organizational contexts for delivering training and instruction, learners are being granted unprecedented control over their learning. This increase in learner control leaves large differences in how learners challenge themselves and explore their learning environments. Learners can benefit from task difficulty, an aspect of challenge, when they are neither overwhelmed nor underwhelmed. The purpose of the present lab study was to test a model of how encouraging learners to challenge themselves with greater task difficulty when practicing a video game could be a “double-edged sword” in terms of their skill-based learning. Method. Using a first-person shooter computer game as the criterion task, 120 undergraduate males were randomly assigned to one of two groups. Half of the participants were encouraged to practice at a difficulty level that matched their skill level, while the other half were encouraged to practice at a difficulty that greatly exceeded their skill. Exploratory behavior was reflected in the variety of weapons used. Results. Findings supported a model of inconsistent mediation predicting that difficulty encouragement instructions would lead to higher selected practice difficulty, which in turn would have positive direct effects on skill transfer yet negative indirect effects through exploratory behavior. Discussion. The present study demonstrated that encouraging learners to practice at high levels of task difficulty is a “double-edged sword.” Although high levels of task difficulty can help in the preparation for future difficulties, it can also undermine exploratory behavior which is an important aspect of the learning process. This research speaks to the potential of encouraging learners to practice under difficult conditions without undermining their learning.
Novel multi-drugs incorporating hybrid-structured nanofibers enhance alkylating agent activity in malignant gliomas
Authors: Liu Shih-Jung , Yang Shun-Tai , Chen Shu-Mei , Huang Yin-Chen , Lee Wei-Hwa , Ho Jui , Chen Yin-Chun , Tseng Yuan-Yun 
Published: September 2019

Background: Malignant gliomas (MGs) are highly chemotherapy-resistant. Temozolomide (TMZ) and carmustine (BiCNU) are alkylating agents clinically used for treating MGs. However, their effectiveness is restrained by overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in tumors. O6-benzylguanine (O6-BG) is a nonreversible inhibitor of MGMT, it promotes the cytotoxicity of alkylating chemotherapy. The authors have developed a hybrid-structured nanofibrous membrane (HSNM) that sequentially delivers high concentrations of O6-BG, BiCNU, and TMZ in an attempt to provide an alternative to the current therapeutic options for MGs. Methods: The HSNMs were implanted onto the cerebral surface of pathogen-free rats following surgical craniectomy, while the in vivo release behaviors of O6-BG, TMZ, and BiCNU from the HSNMs were explored. Subsequently, the HSNMs were surgically implanted onto the brain surface of two types of tumor-bearing rats. The survival rate, tumor volume, malignancy of tumor, and apoptotic cell death were evaluated and compared with other treatment regimens. Results: The biodegradable HSNMs sequentially and sustainably delivered high concentrations of O6-BG, BiCNU, and TMZ for more than 14 weeks. The tumor-bearing rats treated with HSNMs demonstrated therapeutic advantages in terms of retarded and restricted tumor growth, prolonged survival time, and attenuated malignancy. Conclusion: The results demonstrated that O6-BG potentiates the effects of interstitially transported BiCNU and TMZ. Therefore, O6-BG may be required for alkylating agents to offer maximum therapeutic benefits for the treatment of MGMT-expressing tumors. In addition, the HSNM-supported chemoprotective gene therapy enhanced chemotherapy tolerance and efficacy. It can, therefore, potentially provide an improved therapeutic alternative for MGs.
Metabolomics of exercise pulmonary hypertension are intermediate between controls and patients with pulmonary arterial hypertension
Authors: Sanders Jason L. , Han Yuchi , Urbina Mariana F. , Systrom David M. , Waxman Aaron B. 
Published: September 2019

Mechanisms underlying pulmonary arterial hypertension (PAH) remain elusive. Pulmonary arterial hypertension and exercise PH share similar physiologic consequences; it is debated whether they share biologic mechanisms and if exercise PH represents an early phase of pulmonary arterial hypertension. We conducted an observational study to test if there is a graded metabolic disturbance along the severity of PH, which may indicate shared or disparate pathophysiology. Individuals referred to an academic medical dyspnea center with unexplained exertional intolerance underwent invasive cardiopulmonary exercise testing. We identified controls with no hemodynamic exercise limitation, individuals with exercise PH (mean pulmonary arterial pressure (mPAP) < 25 mmHg at rest but ≥ 30 mmHg during exercise without pulmonary venous hypertension) and pulmonary arterial hypertension (mPAP > 25 mmHg at rest without pulmonary venous hypertension) (n = 26 in each group). Unbiased metabolomics with chromatography mass spectrometry was performed on pulmonary arterial blood at rest and peak exercise. Random forest analysis and hierarchical clustering were used to quantify metabolite prediction of group membership and rank metabolites which were significantly different between groups. Compared to controls, pulmonary arterial hypertension subjects exhibited perturbations in pathways involving glycolysis, TCA cycle, fatty acid and complex lipid oxidation, collagen deposition and fibrosis, nucleotide metabolism, and others. The metabolic signature of exercise PH was uniquely between that of control and pulmonary arterial hypertension subjects. Accuracy predicting control, exercise PH, and pulmonary arterial hypertension group was 96%, 90%, and 88%, respectively, using paired rest‐exercise metabolic changes. Our data suggest the metabolic profile of exercise PH is between that of controls and patients with pulmonary arterial hypertension.
Breakthrough Therapy, PRIME and Sakigake: A Comparison Between Neuroscience and Oncology in Obtaining Preferred Regulatory Status
Authors: Muensterman Elena Tomaselli , Luo Yijia , Parker Jonathon M. 
Published: September 2019

Background: Because of the increasing demand for drugs addressing life-threatening and rare diseases, regulatory agencies have developed a variety of accelerated regulatory pathways. These programs are aimed at prioritizing the most promising drug candidates for diseases lacking satisfactory treatments. The most prominent accelerated programs introduced have been Breakthrough-Therapy Designation (BTD) in the United States, Priority Medicine (PRIME) in the European Union and Sakigake in Japan. This article reviews these designations and looks at differences in how they are granted across the 3 jurisdictions focusing on neuroscience and oncology. Methods: Our objective was to analyze BTD, PRIME, and Sakigake approvals between 2012 and 2019 with a focus on numerical disparities of designations granted between the 2 therapeutic areas. A search of public sources pertaining to topics of BTD, PRIME, and Sakigake was undertaken. Results: This analysis revealed that 48% of BTD were granted in oncology, while neuroscience received 8% of these designations, for PRIME designations were 27% received by oncology and 15% by neuroscience and in Japan, 50% of Sakigake were granted to oncology and 22% to neuroscience products. Conclusion: Given the global nature of drug development and relative similarity of these regulatory mechanisms, there is an apparent disparity between the US granting special status at 6:1 (oncology: neuroscience) and both the EU and Japan granting at 2:1. This disproportionate ratio is likely impacted by multifactorial issues; however, this difference is worth further investigation.
Association of Adolescent Sport Participation With Cognition and Depressive Symptoms in Early Adulthood
Authors: Bohr Adam D. , Boardman Jason D. , McQueen Matthew B. 
Published: September 2019

Background: Recent studies have associated sport-related concussion with depression and impaired cognitive ability later in life in former professional football players. However, population studies with two 1950s-era cohorts did not find an association between high school football participation and impaired cognition or depressive symptoms in late adulthood. Purpose/Hypothesis: This study assessed whether actual/intended participation in contact sports during adolescence had an adverse effect on participants’ cognition or depressive symptoms in early adulthood. We hypothesized that there would not be an association. Study Design: Cohort study; Level of evidence, 2. Methods: This study used a subsample (n = 10,951) from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally (United States) representative prospective cohort study following participants through 4 waves of data collection from 1994 through 2008. Participants were categorized as actual/intended participation in no sports, noncontact sports only, and contact sports. We constructed 6 multivariate and logistic regression models predicting word recall, number recall, modified Center for Epidemiologic Studies Depression Scale, depression diagnosis, suicide ideation, and suicide attempts at wave IV as a function of sport participation during wave I. Sport participation was treated as a factor with the referent category noncontact sports. This analysis was repeated on a males-only sample (n = 5008). In the males-only analysis, participants were classified as actual/intended participation in no sports, noncontact sports, contact sports other than American football, and American football. The referent category remained noncontact sports. Results: Intention to participate in contact sports was not significantly associated with any of the outcomes in the full-sample analysis. Intention to participate in football was significantly associated with a reduced odds of depression diagnosis in adulthood (odds ratio, 0.70; P = .02) when compared with noncontact sports participation in the males-only sample. Football was not significantly associated with impaired cognitive ability, increased depressive symptoms, or increased suicide ideation. Conclusion: Actual/intended participation in contact sports during adolescence did not adversely affect Add Health participants’ cognition or depressive symptoms in young adulthood.
Return to Sports and Recreational Activity After Single-Stage Bilateral Short-Stem Total Hip Arthroplasty: 5-Year Results of a Prospective Observational Study
Authors: Donner Stefanie , Rehbein Philipp , Schneider Michael , Pfeil Joachim , Drees Philipp , Kutzner Karl Philipp 
Published: September 2019

Background: Single-stage bilateral total hip arthroplasty (THA) is an alternative to staged unilateral THA in patients suffering from bilateral hip arthritis; however, there is still broad concern regarding the safety and reliability of this procedure. Short-stem THA has emerged in recent years. To date, no data are available on sports and recreational activity levels after single-stage bilateral short-stem THA in the general patient population. Hypothesis: Patients who have undergone single-stage bilateral short-stem THA return to a satisfying level of sports and recreational activity at midterm follow-up. Study Design: Case series; Level of evidence, 4. Methods: A total of 54 consecutive patients (108 hips) were prospectively included. Midterm follow-up was performed in 51 patients (94.4%). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and the Harris Hip Score (HHS) were assessed clinically after a mean of 5.2 years. After a mean of 4.9 years, activity levels were assessed using the University of California, Los Angeles (UCLA) activity scale via a questionnaire. Additionally, a detailed evaluation of sports behavior was conducted using an additional questionnaire. Pain and satisfaction with sporting ability were assessed using a visual analog scale (VAS). Complications and revisions were documented. Results: Patients had a mean WOMAC score of 98.0 (range, 60.0-100.0) and HHS score of 97.8 (range, 65.0-100.0) at final follow-up. The mean UCLA activity score was 4.7 (range, 2.0-10.0). An increasing number of patients were active in sports at follow-up compared with before surgery (76.5% vs 60.8%, respectively); 2 patients (3.9%) stopped participating in sports on a regular basis, and 10 (19.6%) commenced with sports after surgery. The most popular activities before surgery were cycling (31.4%), hiking (29.4%), swimming (21.6%), and fitness/weight training (15.7%). At follow-up, most patients were engaged in cycling (35.3%) and fitness/weight training (33.3%), followed by swimming (25.5%) and hiking (19.6%). The duration (hours per week) and frequency (times per week) of sporting activities remained stable. The mean VAS pain level during sports was 1.3 (range, 0.0-7.0). No revision surgery had to be performed. Conclusion: After single-stage bilateral short-stem THA, the study patients returned to satisfying levels of activity at midterm follow-up. Postoperatively, few patients were engaged in high-impact sports; however, more patients commenced with lower impact activities. Satisfaction with sporting abilities was high, and the complication rate in total was low.
Medical and Dental Electronic Health Record Reporting Discrepancies in Integrated Patient Care
Authors: Adibi S. , Li M. , Salazar N. , Seferovic D. , Kookal K. , Holland J.N. , Walji M. , Farach-Carson M.C. 
Published: September 2019

Introduction: Oral health mirrors systemic health; yet, few clinics worldwide provide dental care as part of primary medical care, nor are dental records commonly integrated with medical records. Objectives: To determine the degree to which misreporting of underlying health conditions poses problems for dental clinicians, we assessed misreporting of 2 common medical health conditions—hypertension and diabetes—at the time of dental examination and assessment. Methods: Using comparative chart analysis, we analyzed medical records of a diverse group of patients previously seen at the University of Texas Physician outpatient practice and then treated at the University of Texas Health Science Center at Houston School of Dentistry. Electronic health records of patients aged ≥18 y were extracted from 2 databases: Allscripts (University of Texas Physician) and axiUm (University of Texas Health Science Center at Houston). We identified 1,013 patients with the commonly occurring conditions of diabetes, hypertension, or both, with nonintegrated records contained in Allscripts and axiUm. We identified the percentage of those patients previously diagnosed with diabetes and/or hypertension by their physicians who failed to report these conditions to their dental clinicians. Results: Of those patients with diabetes, 15.1% misreported their diabetes condition to their dental clinicians, while 29.0% of patients with hypertension also misreported. There was no relationship between sex and misreporting of hypertension or diabetes, but age significantly affected reporting of hypertension, with misreporting decreasing with age. Conclusions: Because these conditions affect treatment planning in the dental clinic, misreporting of underlying medical conditions can have negative outcomes for dental patients. We conclude that policies that support the integration of medical and dental records would meaningfully increase the quality of health care delivered to patients, particularly those dental patients with underlying medical conditions. Knowledge Transfer Statement: Our study illustrates an urgent need for policy innovation within a currently fragmented health care delivery system. Dental clinicians rely on the accuracy of health information provided by patients, which we found was misreported in ~15% to 30% of dental patient records. An integrated health care system can close these misreporting gaps. Policies that support the integration of medical and dental records can improve the quality of health care delivered, particularly for dental patients with underlying medical conditions.
Methylation and transcriptome analysis reveal lung adenocarcinoma-specific diagnostic biomarkers
Authors: Li Rui , Yang Yi-E , Yin Yun-Hong , Zhang Meng-Yu , Li Hao , Qu Yi-Qing 
Published: September 2019

Abstract

Background
DNA methylation can regulate the role of long noncoding RNAs (lncRNAs) in the development of lung adenocarcinoma (LUAD). The present study aimed to identify methylation-driven lncRNAs and mRNAs as biomarkers in the prognosis of LUAD using bioinformatics analysis.

Methods
Differentially expressed RNAs were obtained using the edge R package from 535 LUAD tissues and 59 adjacent non-LUAD tissues. Differentially methylated genes were obtained using the limma R package from 475 LUAD tissues and 32 adjacent non-LUAD tissues. Methylation-driven mRNA and lncRNA were obtained using the MethylMix R package from 465 LUAD tissues with matched DNA methylation and RNA expression and 32 non-LUAD tissues with DNA methylation. Gene ontology and ConsensusPathDB pathway analysis were performed to identify functional enrichment of methylation-driven mRNAs. Univariate and multivariate Cox regression analyses were performed to identify the independent effect of each variable for predicting the prognosis of LUAD. Kaplan–Meier curve analysis of DNA methylation and gene expression might provide potential prognostic biomarkers for LUAD patients.

Results
A total of 99 methylation-driven mRNAs and 17 methylation-driven lncRNAs were obtained. Univariate and multivariate Cox regression analysis showed that 6 lncRNAs (FOXE1, HOXB13-AS1_2, VMO1, HIST1H3F, AJ003147.8, ASXL3) were retrieved to construct a predictive model associated with overall survival in LUAD patients. Combined DNA methylation and gene expression survival analysis revealed that 4 lncRNAs (AC023824.1, AF186192.1, LINC01354 and WASIR2) and 8 mRNAs (S1PR1, CCDC181, F2RL1, EFS, KLHDC9, MPV17L, GKN2, ITPRIPL1) might act as independent biomarkers for the prognosis of LUAD.

Conclusions
Methylation-driven lncRNA and mRNA contribute to the survival of LUAD, and 4 lncRNAs and 8 mRNAs might be potential biomarkers for the prognosis of LUAD.
Development and characterization of a CRISPR/Cas9n-based multiplex genome editing system for Bacillus subtilis
Authors: Liu Dingyu , Huang Can , Guo Jiaxin , Zhang Peiji , Chen Tao , Wang Zhiwen , Zhao Xueming 
Published: September 2019

AbstractBackgroundMetabolic engineering has expanded from a focus on designs requiring a small number of genetic modifications to increasingly complex designs driven by advances in multiplex genome editing technologies. However, simultaneously modulating multiple genes on the chromosome remains challenging inBacillus subtilis. Thus, developing an efficient and convenient method forB. subtilismultiplex genome editing is imperative.ResultsHere, we developed a CRISPR/Cas9n-based multiplex genome editing system for iterative genome editing inB. subtilis. This system enabled us to introduce various types of genomic modifications with more satisfying efficiency than using CRISPR/Cas9, especially in multiplex gene editing. Our system achieved at least 80% efficiency for 1–8 kb gene deletions, at least 90% efficiency for 1–2 kb gene insertions, near 100% efficiency for site-directed mutagenesis, 23.6% efficiency for large DNA fragment deletion and near 50% efficiency for three simultaneous point mutations. The efficiency for multiplex gene editing was further improved by regulating the nick repair mechanism mediated byligDgene, which finally led to roughly 65% efficiency for introducing three point mutations on the chromosome. To demonstrate its potential, we applied our system to simultaneously fine-tune three genes in the riboflavin operon and significantly improved the production of riboflavin in a single cycle.ConclusionsWe present not only the iterative CRISPR/Cas9n system forB. subtilisbut also the highest efficiency for simultaneous modulation of multiple genes on the chromosome inB. subtilisreported to date. We anticipate this CRISPR/Cas9n mediated system to greatly enhance the optimization of diverse biological systems via metabolic engineering and synthetic biology.
Occupational stress and its related demographic factors among Iranian CCU nurses: a cross-sectional study
Authors: Faraji Azam , Karimi Mahtab , Azizi Seyyed Mohsen , Janatolmakan Maryam , Khatony Alireza 
Published: September 2019

Abstract

Objectives
Occupational stress can have an adverse effect on mental and physical health and performance of nurses. The aim of this study was to investigate the occupational stress of Iranian critical care unit (CCU) nurses and its related demographic factors.

Results
In this cross-sectional study, 155 CCU nurses were randomly selected. The Osipow Occupational Stress Questionnaire was used as data collection tool. The mean of nurses’ occupational stress was 210.13 ± 40.87 out of 300, which was at the “moderate-to-high” level. The highest mean of occupational stress was related to the subscale of “Role Overload” (36.30 ± 6.98) and the lowest mean was related to the subscale of “Physical Environment” (33.58 ± 9.76). There was no statistically significant difference between the mean occupational stress and variables of sex, age, academic degree and working experience.
Assessing biases in phylodynamic inferences in the presence of super-spreaders
Authors: Hidano Arata , Gates M. Carolyn 
Published: September 2019

Abstract
Phylodynamic analyses using pathogen genetic data have become popular for making epidemiological inferences. However, many methods assume that the underlying host population follows homogenous mixing patterns. Nevertheless, in real disease outbreaks, a small number of individuals infect a disproportionately large number of others (super-spreaders). Our objective was to quantify the degree of bias in estimating the epidemic starting date in the presence of super-spreaders using different sample selection strategies. We simulated 100 epidemics of a hypothetical pathogen (fast evolving foot and mouth disease virus-like) over a real livestock movement network allowing the genetic mutations in pathogen sequence. Genetic sequences were sampled serially over the epidemic, which were then used to estimate the epidemic starting date using Extended Bayesian Coalescent Skyline plot (EBSP) and Birth–death skyline plot (BDSKY) models. Our results showed that the degree of bias varies over different epidemic situations, with substantial overestimations on the epidemic duration occurring in some occasions. While the accuracy and precision of BDSKY were deteriorated when a super-spreader generated a larger proportion of secondary cases, those of EBSP were deteriorated when epidemics were shorter. The accuracies of the inference were similar irrespective of whether the analysis used all sampled sequences or only a subset of them, although the former required substantially longer computational times. When phylodynamic analyses need to be performed under a time constraint to inform policy makers, we suggest multiple phylodynamics models to be used simultaneously for a subset of data to ascertain the robustness of inferences.