bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further Results in Indices for Diagnostic Screening II
Authors: Bennett B. M. 
Published: August 2019

This article is in continuation of a previous one on properties of diagnostic indices (Bennett, 1976). Results are presented on biases in sample estimates of the sensitivity (ξ) and specificity (η) of a diagnostic test T for a disease, as well as their asymptotic variances.The problem of combining estimates of ξ, η from various clinical centres and obtaining appropriate confidence limits is also discussed. A numerical example is also given. (Tables 1a, b). The log‐linear model for ξ, η is also discussed.
On the Analysis and Synthesis of a Four‐Field‐Table
Authors: Hellmich K. 
Published: August 2019

The real four‐field‐table measure k is calculable as follows: K1 for V(a, b, c, d) with k1 = (arc K1)/100, K11 for V(a, b, 0, 0) with k11 = (arc K11)/100, K12 for V(c, d, 0, 0) with k12 = (arc K12)/100 and K121 for V(0, 0, c, d) with k121 = –k12.The equation k1 = k11 – k12 holds good. It is possible to calculate the probability of error of a four‐field‐table with small frequencies, indirectly from component values. Two examples are given.
Alginate as a support ligand for enhanced colloidal liquid aphron immobilization of proteins and drug delivery
Authors: Ward Keeran , Cortés Juan Guillermo Cediel , Stuckey David 
Published: August 2019

AbstractResearch within the field of colloidal liquid aphrons (CLAs) for enzyme immobilization has often used ionic surfactants for the retention of enzymes. Although these charged interactions allow for enhanced immobilization, they can often lead to denaturation of enzyme activity, and even release of the protein. Sodium alginate has been used in drug delivery applications due to its low toxicity and charged interactions that allow for encapsulation. Hence, alginate systems can be used as an alternative to ionic surfactants in CLA immobilization. This paper presents, for the first time, the use of sodium alginate as potential ligand for enhanced CLA immobilization. The use of five model proteins; lysozyme, bovine serum albumin, ovalbumin, insulin, and α‐chymotrypsin, of various pIs and hydrophobicities, showed the relevance of electrostatic interactions in promoting binding with sodium alginate when the pH < pI, with 100% immobilization attributed to alginate incorporated CLAs over general nonionic formulations. Furthermore, above their pI, >80% protein recovery was observed, with activity and conformation comparable to their native counterparts. Finally, the use of proteolysis showed that as the degree of ionic bonding increased between the protein and sodium alginate, the degree of protease resistance decreased due to conformational changes experienced during binding.
Efficient biosynthesis of antitumor ganoderic acid HLDOA using a dual tunable system for optimizing the expression of CYP5150L8 and a Ganoderma P450 reductase
Authors: Lan Xiaoting , Yuan Wei , Wang Meng , Xiao Han 
Published: August 2019

AbstractGanoderic acid 3‐hydroxy‐lanosta‐8,24‐dien‐26‐oic acid (GA‐HLDOA), an antitumor triterpenoid from the traditional Chinese medicinal higher fungus Ganoderma lucidum, is considered as a key precursor for biosynthesizing other ganoderic acids (GAs) with superior antitumor activities. Our previous study identified CYP5150L8 from G. lucidum as a lanosterol oxidase, and achieved heterologous biosynthesis of GA‐HLDOA in Saccharomyces cerevisiae. However, low production of GA‐HLDOA in either G. lucidum or heterologous host hindered its further investigation and application. In this study, we constructed a dual tunable system for balancing the expression of CYP5150L8 and a Ganoderma P450 reductase iGLCPR, and performed a comprehensive optimization of CYP5150L8 expression, iGLCPR expression, and glycerol usage. Then, we investigated the fermentation behavior of the best strain in optimized condition in flask and achieved 154.45 mg/L GA‐HLDOA production, which was 10.7‐fold higher compared with previous report. This study may facilitate the wide‐spread application of GA‐HLDOA and the discovery of unknown cytochrome P450s in downstream GAs biosynthesis.
Comprehensive comparison of the anti‐inflammatory activity and chemical consistency of traditional Chinese medicine formula granules with Ge‐Gen decoction as a representative sample
Authors: Qin You , Zhou Rongrong , Huang Jianhua , Jin Jian , Zhou Qingyijun , Liu Hao , Xiao Juan , Zhao Yahui , Shu Jun , Zhang Shuihan , Huang Luqi 
Published: August 2019

AbstractTraditional Chinese medicine formula granules (TCMFGs), an advanced dosage form of traditional Chinese medicine, are entering the market on a large scale. However, little attention has been paid to the simultaneous efficacy assessment and quality control of this advanced dosage form. In this study, a comprehensive comparison of the pharmacological activity and chemical consistency of TCMFGs from different manufacturers was performed. Ge‐Gen decoction (GGD) samples were used as the target TCMFG. The in vitro anti‐inflammatory effects among different types of GGDs indicate that all of them showed different abilities to reduce the lipopolysaccharide‐activated production of nitric oxide, interleukin‐1β (IL‐1β), IL‐6 and tumor necrosis factor‐α. The results from a dimethylbenzene‐induced inflammation model in mice indicated that the nine samples in this study showed significant in vivo anti‐inflammatory effects. Qualitative and quantitative analyses were performed by multiwavelength ultra‐high‐performance liquid chromatography with diode array detection and electrospray ionization with quadrupole time‐of‐flight–tandem mass spectrometry. To visually interpret the differences in the chemical materials, a scatter plot analysis was performed. According to the scatter plot analysis, nine compounds were evaluated as important contributors to the differences. This is the first report of TCMFGs on the basis of the spectrum‐effect consistency.
Emotional stability is associated with the MAOA promoter uVNTR polymorphism in women
Authors: Rodríguez‐Ramos Ángel , Moriana Juan Antonio , García‐Torres Francisco , Ruiz‐Rubio Manuel 
Published: August 2019

AbstractBackgroundNeuroticism is associated with low emotional stability, and it is characterized by a tendency to perceive ordinary situations as threatening and difficult to manage. This personality trait has been associated with psychological distress and predicts some mental disorders. Previous studies have shown that women tend to be more neurotic than men and, in general, females have also a higher incidence of anxious and depressive disorders.MethodsWe analyzed in a sample of 99 female university students (from 18 to 26 years old) if emotional stability, measured using the Big Five Questionnaire, was linked to polymorphic variants in candidate genes related to dopaminergic and serotonergic systems, and other personality variables.ResultsWe found that emotional stability and its subdimensions are genetically associated with MAOA‐uVNTR polymorphism. Thus, women carriers of the 3‐repeat allele (lower MAO‐A expression) showed higher levels of emotional stability. No associations were found with other polymorphisms analyzed, including COMT Val158Met, 5‐HTTLPR, and DAT 3′UTR VNTR. Furthermore, our results showed a negative correlation between emotional stability and depression, state anxiety, and trait anxiety. In fact, MAOA‐uVNTR and trait anxiety also explained emotional stability and its subdimensions. We also found that other genetic characteristic, phenylthiocarbamide tasting, explained impulsivity, specifically tasters controlled impulses better than nontasters.ConclusionOur results indicate that neuroticism might be regulated by MAOA and could be a common factor between different phenotypes, such as aggressive behaviors or personality disorders, observed in women with higher activity genotype who had been exposed to negative environments during childhood. This study could lead to a better understanding of the basis of emotional stability and could lead to future projects for this purpose.
Phase II trial of ponatinib in patients with bevacizumab‐refractory glioblastoma
Authors: Lee Eudocia Q. , Muzikansky Alona , Duda Dan G. , Gaffey Sarah , Dietrich Jorg , Nayak Lakshmi , Chukwueke Ugonma N. , Beroukhim Rameen , Doherty Lisa , Laub Caroline Kane , LaFrankie Debra , Fontana Brittney , Stefanik Jennifer , Ruland Sandra , Caruso Victoria , Bruno Jennifer , Ligon Keith , Reardon David A. , Wen Patrick Y. 
Published: August 2019

AbstractBackgroundResponses to bevacizumab in glioblastoma (GBM) are not durable. Plasma levels of basic fibroblast growth factor (bFGF) increase at the time of tumor progression. By targeting vascular endothelial growth factor receptor (VEGFR), platelet‐derived growth factor receptor, Src, and FGF receptor pathways, ponatinib may potentially help to overcome some of the putative mechanisms of adaptive resistance.MethodsWe performed a phase II trial of ponatinib in patients with bevacizumab‐refractory GBM and variants. Adult patients with Karnofsky performance score (KPS) ≥60, measurable disease, and normal organ and marrow function received 45 mg ponatinib daily. No limit on the number of prior therapies but only one prior bevacizumab‐containing regimen was allowed. Primary endpoint was 3‐month progression‐free survival. Plasma biomarkers of angiogenesis and inflammation were evaluated before and after treatment.ResultsThe study closed after the first stage. Fifteen patients enrolled: median age 61 [27‐74]; median KPS 80 [70‐90]; median number of prior relapses 2 [2‐4]. Three‐month progression‐free survival rate was 0, median overall survival was 98 days [95% CI 56, 257], and median PFS was 28 days [95% CI 27, 30]. No responses were seen. The most common grade ≥3 adverse events included fatigue (n = 3), hypertension (2), and lipase elevation (2). Ponatinib treatment significantly increased plasma VEGF, soluble (s)VEGFR1, sVEGFR2, sTIE2, interferon gamma (IFNγ), tumor necrosis factor alpha (TNF‐α), interleukin (IL)‐6, IL‐8, and IL‐10 and decreased sVEGFR2.ConclusionsPonatinib was associated with minimal activity in bevacizumab‐refractory GBM patients. Circulating biomarker data confirmed pharmacodynamic changes and suggested that resistance to ponatinib may be related to an increase in inflammatory cytokines.
Ubiquitin C‐Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine‐Based Inhibitor
Authors: Krabill Aaron D. , Chen Hao , Hussain Sajjad , Feng Chao , Abdullah Ammara , Das Chittaranjan , Aryal Uma K. , Post Carol Beth , Wendt Michael K. , Galardy Paul J. , Flaherty Daniel P. 
Published: August 2019

AbstractThe deubiquitinase (DUB) ubiquitin C‐terminal hydrolase L1 (UCHL1) is expressed primarily in the central nervous system under normal physiological conditions. However, UCHL1 is overexpressed in various aggressive forms of cancer with strong evidence supporting UCHL1 as an oncogene in lung, glioma, and blood cancers. In particular, the level of UCHL1 expression in these cancers correlates with increased invasiveness and metastatic behavior, as well as poor patient prognosis. Although UCHL1 is considered an oncogene with potential as a therapeutic target, there remains a significant lack of useful small‐molecule probes to pharmacologically validate in vivo targeting of the enzyme. Herein, we describe the characterization of a new covalent cyanopyrrolidine‐based UCHL1 inhibitory scaffold in biochemical and cellular studies to better understand the utility of this inhibitor in elucidating the role of UCHL1 in cancer biology.
Late‐term safety and effectiveness of everolimus‐eluting stents in chronic total coronary occlusion revascularization: Final 4‐year results from the evaluation of the XIENCE coronary stent, Performance, and Technique in Chronic Total Occlusions (EXPERT CTO) multicenter trial
Authors: Kandzari David E. , Karmpaliotis Dimitri , Kini Annapoorna S. , Moses Jeffrey W. , Tummala Pradyumna E. , Grantham J. Aaron , Orr Charles , Lombardi William , Nicholson William J. , Lembo Nicholas J. , Popma Jeffrey J. , Wang Jin , Zhao Weiying , McGreevy Robert 
Published: August 2019

AbstractBackgroundLimited study has detailed the late‐term safety and efficacy of chronic total coronary occlusion (CTO) revascularization among multiple centers applying modern techniques and with newer‐generation drug‐eluting stents.MethodsAmong 20 centers, 222 patients enrolled in the XIENCE coronary stent, performance, and technique (EXPERT) CTO trial underwent CTO percutaneous coronary intervention (PCI) with everolimus‐eluting stents (EES). Through planned 4‐year follow‐up, the primary composite endpoint of major adverse cardiac events (MACE; death, myocardial infarction [MI] and target lesion revascularization) and rates of individual component endpoints and stent thrombosis were determined.ResultsDemographic, lesion, and procedural characteristics included prior bypass surgery, 9.9%; diabetes, 40.1%; lesion length, 36.1 ± 18.5 mm; and stent length, 51.7 ± 27.2 mm. By 4 years, MACE rates were 31.6 and 22.4% by the pre‐specified ARC and per‐protocol definitions, respectively. Clinically‐indicated target lesion revascularization at 4 years was 11.3%. In landmark analyses of events beyond the first year of revascularization, the annualized rates of target vessel‐related MI and clinically‐indicated target lesion revascularization were 0.53 and 1.3%, respectively. Through 4 years, the cumulative definite/probable stent thrombosis rate was 1.7% with no events occurring beyond the initial year of index revascularization.ConclusionsIn a multicenter registration trial representing contemporary technique and EES, these results demonstrate sustained long‐term safety and effectiveness of EES in CTO percutaneous revascularization and can be used to inform shared decision making with patients being considered for CTO PCI relative to late safety and vessel patency.
Impact of Cellulose and Surfactants on Mass Transfer of Bubble Columns
Authors: Ahmia Aida C. , Idouhar Madjid , Wongwailikit Kritchart , Dietrich Nicolas , Hébrard Gilles 
Published: August 2019

AbstractThe effects of cellulose, surfactants, and their combination on the hydrodynamic behavior and the liquid‐side mass transfer coefficient of a bubble column were evaluated. For that purpose, different aqueous solutions containing surfactants (sodium dodecyl sulfate) and cellulose (microcrystalline cellulose, MCC) were investigated. The interfacial areas were calculated from the bubble diameters, the bubble frequencies, and the terminal bubble rising velocities. The liquid‐side mass transfer coefficients were determined from the volumetric mass transfer coefficients measured by the dynamic method. In the concentration range under test, the experimental results proved that the addition of MCC to the studied liquid phases did not affect the mass transfer coefficient.
Molecular Dynamics Simulation of Methane Hydrate Decomposition in the Presence of Alcohol Additives
Authors: Sun Xiaoliang , Zhou Guanggang , Zhu Jianwei , Wu Haicheng , Lu Guiwu , Bai Dongsheng 
Published: August 2019

AbstractThe decomposition process of methane hydrate in pure water and methanol aqueous solution was studied by molecular dynamics simulation. The effects of temperature and pressure on hydrate structure and decomposition rate are discussed. The results show that decreasing pressure and increasing temperature can significantly enhance the decomposition rate of hydrate. After adding a small amount of methanol molecules, bubbles with a diameter of about 2 nm are formed, and the methanol molecules are mainly distributed at the gas‐liquid interface, which greatly accelerates the decomposition rate and gas‐liquid separation efficiency. The radial distribution function and sequence parameter analysis show that the water molecules of the undecomposed hydrate with ordered ice‐like configuration at a temperature of 275 K evolve gradually into a long‐range disordered liquid structure in the dynamic relaxation process. It was found that at temperatures above 280 K and pressures between 10 atm and 100 atm, the pressure has no significant effect on hydrate decomposition rate, but when the pressure is reduced to 1 atm, the decomposition rate increases sharply. These findings provided a theoretical insight for the industrial exploitation of hydrates.
Chronic radiation exposure at Chernobyl shows no effect on genetic diversity in the freshwater crustacean, Asellus aquaticus thirty years on
Authors: Fuller Neil , Ford Alex T. , Lerebours Adélaïde , Gudkov Dmitri I. , Nagorskaya Liubov L. , Smith Jim T. 
Published: August 2019

AbstractAnalysis of genetic diversity represents a fundamental component of ecological risk assessments in contaminated environments. Many studies have assessed the genetic implications of chronic radiation exposure at Chernobyl, generally recording an elevated genetic diversity and mutation rate in rodents, plants, and birds inhabiting contaminated areas. Only limited studies have considered genetic diversity in aquatic biota at Chernobyl, despite the large number of freshwater systems where elevated dose rates will persist for many years. Consequently, the present study aimed to assess the effects of chronic radiation exposure on genetic diversity in the freshwater crustacean, Asellus aquaticus, using a genome‐wide SNP approach (Genotyping‐by‐sequencing). It was hypothesized that genetic diversity in A. aquaticus would be positively correlated with dose rate. A. aquaticus was collected from six lakes in Belarus and the Ukraine ranging in dose rate from 0.064 to 27.1 µGy/hr. Genotyping‐by‐sequencing analysis was performed on 74 individuals. A significant relationship between geographical distance and genetic differentiation confirmed the Isolation‐by‐Distance model. Conversely, no significant relationship between dose rate and genetic differentiation suggested no effect of the contamination gradient on genetic differentiation between populations. No significant relationship between five measures of genetic diversity and dose rate was recorded, suggesting that radiation exposure has not significantly influenced genetic diversity in A. aquaticus at Chernobyl. This is the first study to adopt a genome‐wide SNP approach to assess the impacts of environmental radiation exposure on biota. These findings are fundamental to understanding the long‐term success of aquatic populations in contaminated environments at Chernobyl and Fukushima.
The effects of graphic metaphor, gesture interaction, and form factor on e‐book performances and preferences
Authors: Park Kyeongjin , Seok Hyesung , Kim Kyungdoh 
Published: August 2019

AbstractReading e‐books on touch‐based mobile devices such as smartphones and tablet personal computer (PCs) are increasing. We conducted a comparative study on the usability of e‐books provided on smartphones and tablet PCs, which are typical touch‐based mobile devices. An experiment was carried out to see the effects of graphic metaphor and gesture interaction. This study evaluated reading speed, readability, similarity, and satisfaction for 16 combinations of e‐book interfaces (two Metaphor levels × four Display size and Screen modes × two Gesture levels). Overall, performance and subjective ratings showed better results on tablet PCs with larger fonts on a larger screen than on smartphones with smaller fonts on smaller screens. In the smartphone‐landscape mode, the effect of turning a page is a factor that hinders the speed of user reading. In contrast, the users’ readability, similarity, and satisfaction were higher when the page‐turning effect was provided. It showed faster reading speeds when a flicking interaction is provided on tablet PCs. From the standpoint of readability, the portrait mode was better on smartphones. Also, the tablet PC‐portrait mode was the most satisfactory.
A Short Sequence for the Iterative Synthesis of Fused Polyethers
Authors: Elustondo Frédéric , Chintalapudi Venkaiah , Clark J. Stephen 
Published: August 2019

AbstractA simple and efficient four‐step sequence for the synthesis of fused polyether arrays has been developed. Cyclic ethers are installed by sequential alkynyl ether formation, carbocupration, ring‐closing metathesis and hydroboration with acidic workup. Crucially, the alkene required for the subsequent ring formation by ring‐closing metathesis is present in the substrate but is masked in the form of a vinylic silane, which prevents competitive metathesis of the side chain. Generation of the reactive alkene from the unreactive vinylic silane is accomplished by hydroboration and subsequent acid‐mediated Peterson elimination of the intermediate hydroxysilane.
Hall current and ion‐slip effects on free convection flow in a vertical microchannel with an induced magnetic field
Authors: Jha Basant K. , Malgwi Peter B. 
Published: August 2019

AbstractThe steady fully developed hydromagnetic flow of a viscous incompressible and electrically conducting fluid in a vertical microchannel has been studied taking into account the influence of Hall current, ion‐slip effects and an induced magnetic field. Exact solutions for the governing equations responsible for the flow formation are obtained by the method of the undetermined coefficient and presented graphically. It is found that in the presence of the ion‐slip effect, both primary and secondary components of fluid velocity increase with the Hall parameter for symmetric as well as asymmetric heating of the microchannel surfaces. Also, the magnetic field supports flow along the secondary flow direction while the reverse impact is observed along the primary flow direction.
Unfolded protein response‐mediated modulation of mesenchymal stem cells
Authors: Tavasolian Fataneh , Hosseini Ahmad Z. , Mirzaei Ali , Abdollahi Elham , Jandaghi Pouria , Soudi Sara , Naderi Mahmood , Saburi Ehsan , Momtazi‐Borojeni Amir Abbas , Johnston Thomas P. , Sahebkar Amirhossein 
Published: August 2019

AbstractThe endoplasmic reticulum (ER) receives unfolded proteins predestined for the secretory pathway or to be incorporated as transmembrane proteins. The ER has to accommodate the proper folding and glycosylation of these proteins and also to properly incorporate transmembrane proteins. However, under various circumstances, the proteins shuttling through the ER can be misfolded and undergo aggregation, which causes activation of the unfolded protein response (UPR). The UPR is mediated through three primary pathways: activating transcription factor‐6, inositol‐requiring enzyme‐1 (IRE1), and PKR‐like endoplasmic reticulum kinase, which up‐regulate ER folding chaperones and temporarily suppress protein translation. The UPR can be both cytoprotective and/or cytotoxic depending on the duration of UPR activation and the type of host cell. Proteostasis controls stem cell function, while stress responses affect stem cell identity and differentiation. The present review aimed to explore and discuss the effects of the UPR pathways on mesenchymal stem cells.