bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cost implication of primary prevention in the HOPE 3 trial
Authors: Lamy Andre , Lonn Eva , Tong Wesley , Swaminathan Balakumar , Jung Hyejung , Gafni Amiram , Bosch Jackie , Yusuf Salim 
Published: January 2019

AbstractAimsThe Heart Outcomes Prevention Evaluation-3 (HOPE-3) found that rosuvastatin alone or with candesartan and hydrochlorothiazide (HCT) (in a subgroup with hypertension) significantly lowered cardiovascular events compared with placebo in 12 705 individuals from 21 countries at intermediate risk and without cardiovascular disease. We assessed the costs implications of implementation in primary prevention in countries at different economic levels.Methods and resultsHospitalizations, procedures, study and non-study medications were documented. We applied country-specific costs to the healthcare resources consumed for each patient. We calculated the average cost per patient in US dollars for the duration of the study (5.6 years). Sensitivity analyses were also performed with cheapest equivalent substitutes. The combination of rosuvastatin with candesartan/HCT reduced total costs and was a cost-saving strategy in United States, Canada, Europe, and Australia. In contrast, the treatments were more expensive in developing countries even when cheapest equivalent substitutes were used. After adjustment for gross domestic product (GDP), the costs of cheapest equivalent substitutes in proportion to the health care costs were higher in developing countries in comparison to developed countries.ConclusionRosuvastatin and candesartan/HCT in primary prevention is a cost-saving approach in developed countries, but not in developing countries as both drugs and their cheapest equivalent substitutes are relatively more expensive despite adjustment by GDP. Reductions in costs of these drugs in developing countries are essential to make statins and blood pressure lowering drugs affordable and ensure their use.Clinical trial registrationHOPE-3 ClinicalTrials.gov number, NCT00468923.
Searching for Thomas Nashe in Dido, Queen of Carthage
Authors: Freebury-Jones Darren , Dahl Marcus 
Published: January 2019

Abstract
The title page of the 1594 Quarto text of Dido, Queen of Carthage assigns the play to two authors: Christopher Marlowe and Thomas Nashe. Some scholars, such as J. P. Collier, F. G. Fleay, Alexander Grosart, Tucker Brooke, and Thomas Merriam, have argued that Marlowe and Nashe co-authored the play, or that Nashe added significant material to Marlowe’s text. This article assesses the internal evidence for Nashe’s hand in the play by examining its prosody, vocabulary, phraseology, rhyming habits, and stage directions in comparison to works ascribed to Nashe and Marlowe. The article also explores different modes of collaboration, such as the possibility that Nashe helped to plot, revise, or edit the play.
Longitudinal Analysis of Associations Between Reasons for Electronic Cigarette Use and Change in Smoking Status Among Adults in the Population Assessment of Tobacco and Health Study
Authors: Soule Eric K , Plunk Andrew D , Harrell Paul T , Hayes Rashelle B , Edwards Kathryn C 
Published: January 2019

Abstract

Introduction
Electronic cigarette (ECIG) use and changes in cigarette smoking status may be influenced by self-reported reasons for using ECIGs.

Methods
We analyzed adult current and former cigarette smokers who were also current or former ECIG users at wave 1 (n = 3044) using wave 1 and wave 2 Population Assessment of Tobacco and Health Study data (2013–2015). Prevalence of reporting 13 reasons for ECIG use at wave 1 was examined and weighted logistic regressions were conducted predicting smoking status changes from wave 1 to wave 2.

Results
Reasons for ECIG use ranged from 18.1% (people in the media or public figures use them) to 82.5% (they might be less harmful to people around me than cigarettes). From wave 1 to wave 2, 27.2% of former smokers (n = 249) became current smokers and 11.6% of current smokers (n = 246) became former smokers. Among wave 1 former smokers, using ECIGs because of the availability of flavors (AOR = 0.57, 95% CI = 0.39–0.85) or because they don’t smell (AOR = 0.64, 95% CI = 0.42–0.97) was associated with lower odds of relapse to smoking, but using ECIGs because using them helps people quit smoking (AOR = 1.55, 95% CI = 1.01–2.38) was associated with greater odds of relapse. Among wave 1 current smokers, using ECIGs because they can be used where smoking is not allowed (AOR = 0.56, 95% CI = 0.38–0.85) was associated with reduced odds of quitting cigarettes.

Conclusions
Some reasons for ECIG use are associated with changes in self-reported smoking status. Researchers should examine ECIG user characteristics when assessing associations between ECIG use and smoking status transitions.

Implications
Given that certain reasons for ECIG use, such as using ECIGs in locations are where smoking is not allowed, may inhibit smoking reduction, policies may be developed to prevent ECIG use in locations where smoking is banned. In addition, because certain reasons for ECIG use may aid in relapse prevention, such as availability of desired flavors, efforts should be made to identify ECIG device characteristics that are appealing to smokers but not youth or nontobacco users. These results provide support for future research on reasons for ECIG use to inform regulatory policies.
Medieval Optics
Authors: Denery Dallas G. 
Published: January 2019

Medieval optics, also known as perspectivist optics from the mid-13th century on, offered a complete theory of human cognition. Whereas modern optics limits itself to the study of the behavior and properties of light, perspectivist optics sought to explain how human beings perceive and then understand the world around them. The perspectivists contended that vision proceeds through a process of intromission, in other words, we see objects in the world because information from those objects, called “species,” reach and then reproduce themselves within the eye and then throughout the various faculties of human the brain. Prior to the 13th-century popularization of perspectivist optics, most European and Christian thinkers believed vision occurred through a process of extramission, in which vision depended on visual rays extending out from the eyes to the things in the world. Medieval optics derives largely from the work of Alhacen (b. c. 965–d. c. 1040), the 12th-century Arabic thinker. In The Book of Optics, translated into Latin in 1200 as De aspectibus, Alhacen (Ibn al-Haytham) wove together the mathematical and geometrical aspects of Ptolemy’s extramission account of vision, Galen’s physiological account of the eye, and ideas about light from such Arabic thinkers as Alkindi (b. c. 801–d. c. 873), to create a sophisticated intromissionist account of vision. The Franciscan Roger Bacon (b. c. 1219–d. c. 1292), working from the Latin translation, borrowed all of these ideas for his own treatise, Perspectiva, and combined them with Avicenna’s Aristotelian-influenced faculty psychology. If not terribly original, Bacon’s treatise, along with works by his fellow Franciscan John Pecham (b. c. 1230–d. c. 1292), and the Silesian cleric Witelo (b. c. 1230–d. c. 1300), proved tremendously influential. Perspectivist ideas filtered into scholastic debates about natural causation and physics, cognition, epistemology, the Eucharist, and, even, the beatific vision. Various religious and pastoral treatises bear the imprint of perspectivist ideas, as do works by such renowned medieval authors as Jean de Meun (b. c. 1240–d. c. 1305), Dante (b. c. 1265–d. c. 1321), and Chaucer (b. c. 1343–d. c. 1400). Perspectivist ideas may even have played a part in the development of illusionistic painting in Italy, beginning with Giotto’s early-14th-century frescos at the Arena Chapel in Padua and culminating with Alberti’s 1435 treatise, On Painting. It was only in the early 17th century, with the publication of Johannes Kepler’s Emendations to Witelo, that the tradition of medieval optics as a comprehensive account of human cognition came to an end. Kepler (b. 1571–d. 1630) reimagined the eye as a camera obscura with a lens to focus light on the retina, effectively separating the study of optics from the study of cognition. The modern science of optics was born.
Informal Clinical Integration in Medicare Accountable Care Organizations and Mortality Following Coronary Artery Bypass Graft Surgery
Authors: Kim Dennie , Funk Russell J. , Yan Phyllis , Nallamothu Brahmajee K. , Zaheer Aks , Hollingsworth John M. 
Published: January 2019

Background:
Accountable care organizations’ (ACOs’) focus on formal clinical integration to improve outcomes overlooks actual patterns of provider interactions around shared patients.

Objective:
To determine whether such informal clinical integration relates to a health system’s performance in an ACO.

Research Design:
We analyzed national Medicare data (2008–2014), identifying beneficiaries who underwent coronary artery bypass grafting (CABG). After determining which physicians delivered care to them, we aggregated across episodes to construct physician networks for each health system. We used network analysis to measure each system’s level of informal clinical integration (defined by cross-specialty ties). We fit regression models to examine the association between a health system’s CABG mortality rate and ACO participation, conditional on informal clinical integration.

Subjects:
Beneficiaries age 66 and older undergoing CABG.

Measures:
Ninety-day CABG mortality.

Results:
Over the study period, 3385 beneficiaries were treated in 161 ACO-participating health systems. The remaining 49,854 were treated in 875 nonparticipating systems or one of the 161 ACO-participating systems before the ACO start date. ACO systems with higher levels of informal clinical integration had lower CABG mortality rates than nonparticipating ones (2.8% versus 5.5%; P<0.01); however, there was no difference based on ACO participation for health systems with lower to relatively moderate informal clinical integration. Regression results corroborate this finding (coefficient for interaction between ACO participation and informal clinical integration level is −0.25; P=0.01).

Conclusions:
Formal clinical integration through ACO participation may be insufficient to improve outcomes. Health systems with higher informal clinical integration may benefit more from ACO participation.
Microtubule bundling by MAP65-1 protects against severing by inhibiting the binding of katanin
Authors: Burkart Graham M , Dixit Ram 
Published: January 2019

ABSTRACTThe microtubule-severing enzyme katanin regulates the organization and turnover of microtubule arrays by the localized breakdown of microtubule polymers. In land plants, katanin (KTN1) activity is essential for the formation of linearly organized cortical microtubule arrays which determine the axis of cell expansion. Cell biological studies have shown that even though KTN1 binds to the sidewalls of single and bundled microtubules, severing activity is restricted to microtubule crossover and nucleation sites, indicating that cells contain protective mechanisms to prevent indiscriminate microtubule severing. Here, we show that the microtubule bundling protein MAP65-1 inhibits KTN1-mediated microtubule severingin vitro. Severing is inhibited at bundled microtubule segments and the severing rate of non-bundled microtubules is reduced by MAP65-1 in a concentration-dependent manner. Using various MAP65-1 mutant proteins, we demonstrate that efficient crosslinking of microtubules is crucial for this protective effect and that microtubule binding alone is not sufficient. Reduced severing due to microtubule bundling by MAP65-1 correlated to decreased binding of KTN1 to these microtubules. Taken together, our work reveals that crosslinking of microtubules by MAP65-1 confers resistance to severing by inhibiting the binding of katanin and identifies the structural features of MAP65-1 that are important for this activity.Highlight SummaryCortical microtubule bundles resist severingin vivo. Here, we show that crosslinking of microtubules by MAP65-1 inhibits severing in a dose-dependent manner by preventing katanin from binding to these microtubules.
Metabolic Modeling of Cystic Fibrosis Airway Communities Predicts Mechanisms of Pathogen Dominance
Authors: Henson Michael A. , Orazi Giulia , Phalak Poonam , O’Toole George A. 
Published: January 2019

AbstractCystic fibrosis (CF) is a fatal genetic disease characterized by chronic lung infections due to aberrant mucus production and the inability to clear invading pathogens. The traditional view that CF infections are caused by a single pathogen has been replaced by the realization that the CF lung usually is colonized by a complex community of bacteria, fungi and viruses. To help unravel the complex interplay between the CF lung environment and the infecting microbial community, we developed a community metabolic model comprised of the 17 most abundant bacterial taxa, which account for >95% of reads across samples, from three published studies in which 75 sputum samples from 46 adult CF patients were analyzed by 16S rRNA gene sequencing. The community model was able to correctly predict high abundances of the “rare” pathogens Enterobacteriaceae, Burkholderia and Achromobacter in three patients whose polymicrobial infections were dominated by these pathogens. With these three pathogens were removed, the model correctly predicted that the remaining 43 patients would be dominated by Pseudomonas and/or Streptococcus. This dominance was predicted to be driven by relatively high monoculture growth rates of Pseudomonas and Streptococcus as well as their ability to efficiently consume amino acids, organic acids and alcohols secreted by other community members. Sample-by-sample heterogeneity of community composition could be qualitatively captured through random variation of the simulated metabolic environment, suggesting that experimental studies directly linking CF lung metabolomics and 16S sequencing could provide important insights into disease progression and treatment efficacy.ImportanceCystic fibrosis (CF) is a genetic disease in which chronic airway infections and lung inflammation result in respiratory failure. CF airway infections are usually caused by bacterial communities that are difficult to eradicate with available antibiotics. Using species abundance data for clinically stable adult CF patients assimilated from three published studies, we developed a metabolic model of CF airway communities to better understand the interactions between bacterial species and between the bacterial community and the lung environment. Our model predicted that clinically-observed CF pathogens could establish dominance over other community members across a range of lung nutrient conditions. Heterogeneity of species abundances across 75 patient samples could be predicted by assuming that sample-to-sample heterogeneity was attributable to random variations in the CF nutrient environment. Our model predictions provide new insights into the metabolic determinants of pathogen dominance in the CF lung and could facilitate the development of improved treatment strategies.
Locating a transgene integration site by nanopore sequencing
Authors: Nicholls Peter K. , Bellott Daniel W. , Cho Ting-Jan , Pyntikova Tatyana , Page David C. 
Published: January 2019

AbstractThe introduction of foreign DNA into cells and organisms has facilitated much of modern biological research, and it promises to become equally important in clinical practice. Locating sites of foreign DNA incorporation in mammalian genomes has proven burdensome, so the genomic location of most transgenes remains unknown. To address this challenge, we applied nanopore sequencing in search of the site of integration ofTg(Pou5f1-EGFP)2Mnm(also known asOct4:EGFP), a widely used fluorescent reporter in mouse germ line research. Using this nanopore-based approach, we identified the site ofOct4:EGFPtransgene integration near the telomere of Chromosome 9. This methodology simultaneously yielded an estimate of transgene copy number, provided direct evidence of transgene inversions, revealed contaminatingE. coligenomic DNA within the transgene array, validated the integrity of neighboring genes, and enabled definitive genotyping. We suggest that such an approach provides a rapid, cost-effective method for identifying and analyzing transgene integration sites.
Mechanism of microtubule plus-end tracking by the plant-specific SPR1 protein and its development as a versatile plus-end marker
Authors: Balkunde Rachappa , Foroughi Layla , Ewan Eric , Emenecker Ryan , Cavalli Valeria , Dixit Ram 
Published: January 2019

ABSTRACTThe dynamics and functions of microtubule plus-ends are governed by microtubule plus-end tracking proteins (+TIPs). Here, we report that the diminutiveArabidopsis thalianaSPIRAL1 (SPR1) protein, which regulates directional cell expansion, is an autonomous +TIP. Usingin vitroreconstitution experiments and total internal reflection fluorescence microscopy, we demonstrate that the conserved N-terminal domain of SPR1 and its GGG motif are necessary for +TIP activity, whereas the conserved C-terminal domain and its PGGG motif are not. In addition, we show that the N-and C-terminal domains, either separated or in tandem, are sufficient for +TIP activity and do not significantly perturb microtubule plus-end dynamics compared to full-length SPR1. We also found that exogenously expressed SPR1-GFP and NC-GFP label microtubule plus-ends in animal cells. These data establish SPR1 as a new type of intrinsic +TIP and demonstrate its utility as a universal microtubule plus-end marker.
HDAC and MAPK/ERK Inhibitors Cooperate to Reduce Viability and Stemness in Medulloblastoma
Authors: da Cunha Jaeger Mariane , Ghisleni Eduarda Chiesa , Cardoso Paula Schoproni , Siniglaglia Marialva , Falcon Tiago , Brunetto André T. , Brunetto Algemir L. , de Farias Caroline Brunetto , Taylor Michael D. , Nör Carolina , Ramaswamy Vijay , Roesler Rafael 
Published: January 2019

AbstractMedulloblastoma (MB), which originates from embryonic neural stem cells (NSCs) or neural precursors in the developing cerebellum, is the most common malignant brain tumor of childhood. Recurrent and metastatic disease is the principal cause of death and may be related to resistance within cancer stem cells (CSCs). Chromatin state is involved in maintaining signaling pathways related to stemness, and inhibition of histone deacetylase enzymes (HDAC) has emerged as an experimental therapeutic strategy to target this cell population. Here, we observed antitumor actions and changes in stemness induced by HDAC inhibition in MB. Analyses of tumor samples from patients with MB showed that the stemness markersBMI1andCD133are expressed in all molecular subgroups of MB. The HDAC inhibitor (HDACi) NaB reduced cell viability and expression ofBMI1andCD133and increased acetylation in human MB cells. Enrichment analysis of genes associated withCD133orBMI1expression showed mitogen-activated protein kinase (MAPK)/ERK signaling as the most enriched processes in MB tumors. MAPK/ERK inhibition reduced expression of the stemness markers, hindered MB neurosphere formation, and its antiproliferative effect was enhanced by combination with NaB. These results suggest that combining HDAC and MAPK/ERK inhibitors may be a novel and more effective approach in reducing MB proliferation when compared to single-drug treatments, through modulation of the stemness phenotype of MB cells.
Involvement of birth weight and body composition on autonomic recovery following aerobic exercise in children: A prospective, observational and analytical study
Authors: Spada Juliana Edwiges Martinez , Oliveira Fernando R. , Garner David M. , Valenti Vitor E. 
Published: January 2019

ABSTRACTBirth weight (BW) can be used to assess the health status of the newborn. However, its impacts on later in life regarding heart rate (HR) variability (HRV) is not totally clear. We aimed to analyze the involvement of BW and body composition on HRV recovery following aerobic exercise in children. The study was conducted in healthy children 9 to 11 years of age (40 females and 27 males) divided into two groups: G1 (BW < 3400 grams, N = 33) and G2 (BW > 3400 grams, N = 34). The volunteers completed an experimental protocol of submaximal aerobic exercise on a treadmill and remained seated for 30 minutes after exercise. Systolic (SAP) and diastolic arterial pressure (DAP), respiratory rate (f) and HRV were analyzed before and during recovery from exercise. SAP and f were significantly decreased 30 minutes after exercise compared to 1 minute after exercise in G1 and G2. Mean HR, high frequency band of spectral analysis (HF), root mean square of successive interbeat intervals difference, SD1 index and mean lenght were diminished 0 to 5 minutes after exercise compared to rest in G2 while maximum lenght increased 0 to 5 minutes after exercise compared to resting in G2. Linear regression revealed association of fat percentage and BW with nonlinear HRV recovery. In conclusion, autonomic recovery after exercise was somewhat delayed in children with high BW. BW and fat percentage slightly influence HRV recovery.
Corrosion behaviors of X70 steel under direct current interference
Authors: Wang Jun , Li Zili , Cui Gan , Liu JianGuo , Kong Chuanping , Wang Long , Gao Ge , Guo Jian 
Published: January 2019

PurposeThe purpose of this paper is to study the corrosion behaviors of X70 steel under direct current (DC) interference at 0-1,200 A/m2in simulated soil solution.Design/methodology/approachThe Tafel polarization curves of X70 steel under DC interference were tested using electrochemical method, the corrosion rate was calculated using weight-loss method and the change in steel surface was analyzed by optical microscopy.FindingsThe results showed that E-I polarization curves under 200-1,200 A/m2interference were linear; with an increase in the DC density, the corrosion potential of X70 steel shifted positively, solution pH after the weight-loss tests increased and corrosion rate increased linearly. A mathematical relationship between polarization resistance Rp and current density was established. Corrosion morphology indicated that pitting corrosion and crevice corrosion occurred on the X70 steel under DC interference in simulated soil solution.Originality/valueAll tests were conducted at a relative higher DC density (200-1,200 A/m2). The linear fitting method is proposed to fit data of Tafel polarization curves under DC interference. This study provides guidelines for safe operation of X70 steel pipelines.