bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oliceridine, a Novel G Protein–Biased Ligand at the μ‐Opioid Receptor, Demonstrates a Predictable Relationship Between Plasma Concentrations and Pain Relief. II: Simulation of Potential Phase 3 Study Designs Using a Pharmacokinetic/Pharmacodynamic Model
Authors: Fossler Michael J. , Sadler Brian M. , Farrell Colm , Burt David A. , Pitsiu Maria , Skobieranda Franck , Soergel David G. 
Published: February 2018

AbstractOliceridine is a novel G protein–biased ligand at the μ‐opioid receptor that differentially activates G protein coupling while mitigating β‐arrestin recruitment. Unlike morphine, oliceridine has no known active metabolites; therefore, analgesic efficacy is predictably linked to its concentration in the plasma. Oliceridine is primarily hepatically metabolized by CYP3A4 and CYP2D6. Using a pharmacokinetic/pharmacodynamic model relating oliceridine plasma concentrations to its effect on pain intensity as measured by numeric pain‐rating scale (NPRS) scores, we have simulated potential dosing regimens using both fixed‐dose regimens and as‐needed (prn) dosing regimens in which various doses of oliceridine were administered if NPRS scores indicated moderate to severe pain (≥4 on a 0‐10 scale). In addition, regimens in which oliceridine was self‐administered via a patient‐controlled analgesia device were also simulated. The simulated population included 10% CYP2D6 poor metabolizers (PM). The simulation results suggest that oliceridine doses of 1‐3 mg prn should be effective in reducing NPRS scores relative to placebo. The simulations also revealed that a 1‐mg “supplemental dose” given 0.25 hour after the loading dose would decrease NPRS scores further in almost one‐third of patients. In addition, if oliceridine is administered prn, a longer interval between doses is observed in simulated PM patients, consistent with their reduced oliceridine clearance. Because this longer average dosing interval is predicted to decrease oliceridine exposure in PM patients, the need to know the patient's CYP2D6 genotype for dosing is effectively obviated.
Viscosity reduction of pretreated softwood by endoglucanases
Authors: Kadić Adnan , Lidén Gunnar 
Published: February 2018

AbstractBACKGROUNDCost‐effective processing of lignocellulosic biomass into sugar derived products, such as biofuels or biochemicals, needs to be performed at high water insoluble solid (WIS) loading. However, the difficult rheology of such materials presents significant challenges. The aim of this study was to investigate if a Cel5A endoglucanase can be used to reduce the viscosity of two types of pretreated softwood: steam pretreated Scots pine and sulfite pretreated Norway spruce.RESULTSThe viscosity of steam pretreated pine increased (by more than 60%) during the first 20 min of enzymatic hydrolysis, followed by a gradual decrease. A slightly lower viscosity during prolonged hydrolysis could be obtained by replacing 25% of the protein in Cellic CTec3 with the Cel5A endoglucanase. Very different results were obtained with sulfite pretreated spruce. The viscosity of this material was rapidly reduced by either CTec3 or the Cel5A endoglucanase, without a transient initial increase in viscosity. Even very low doses of Cel5A (0.1 mg protein per g glucan) decreased the viscosity of sulfite pretreated spruce 30‐fold within 6 h.CONCLUSIONLow endoglucanase doses can be used to reduce the viscosity of sulfite pretreated softwood, whereas the viscosity of steam pretreated softwood is less affected by endoglucanase activity. © 2018 Society of Chemical Industry
Fostering Diversity in the Creative Arts by Addressing Students' Capacity to Aspire
Authors: Gore Jennifer , Gibson Skye , Fray Leanne , Smith Max , Holmes Kathryn 
Published: February 2018

Research on young people's aspirations and their capacity to aspire to higher education has proliferated in recent decades, however, very little attention has been paid to the creative arts. Diversity in the arts remains a persistent issue in many nations, and repeated attempts to promote diversity in the Australian arts community have had limited impact, suggesting the need for new approaches. Drawing on data from a 4‐year longitudinal study of students from ages 8 to 18 (n = 6,492) in government schools, we examine school students' aspirations for careers in the arts. Arts‐related careers were popular among students, yet we found a distinct lack of diversity among those aspiring to such careers. Using logistic regression analysis we found that being female, high achieving, from an English‐speaking background, possessing high cultural capital, and attending advantaged schools were significant predictors of interest in the arts, suggesting the likely reproduction of existing patterns of participation. We argue that initiatives within schools are essential to disrupting these patterns and building the capacity of a more diverse range of students to aspire to careers in the arts.
Computational evaluation of TKR stability using feedback‐controlled compressive loading
Authors: Sintini Irene , Fitzpatrick Clare K. , Clary Chadd W. , Castelli Vincenzo P. , Rullkoetter Paul J. 
Published: February 2018

ABSTRACTPre‐clinical assessment of stability in total knee replacement is crucial for developing preferred implant performance. Current total knee replacement patients often experience joint instability that the human body addresses with compensatory strategies. Specifically, an increased quadriceps‐hamstrings co‐contraction serves to increase joint stability through an increased compressive force across the tibiofemoral joint. The aim of this study is to introduce a novel method to evaluate total knee replacement by determining the compressive loading required to achieve natural knee stability. Four current total knee replacement geometries in both their cruciate‐retaining and posterior‐stabilized forms are modeled in a finite‐element framework. The finite‐element model is initially validated experimentally using traditional knee laxity testing with a constant compressive load and anterior‐posterior displacement or internal‐external rotation. Model predictions of constraint are in reasonable agreement with experimental results (average root mean square errors: 0.46 Nm, 62.5 N). The finite‐element model is subsequently interfaced with a feedback controller to vary the compressive force that the implant requires in order to match experimental natural knee internal‐external and anterior‐posterior stability at different flexion angles. Results show that the lower constraint total knee replacement designs require on average 66.7% more compressive load than the higher constraint designs to achieve natural knee constraint. As expected, total knee replacement stability and compressive load requirements to replicate natural kinematics vary with inclusion of tibiofemoral ligaments. The current study represents a novel approach to evaluate stability in existing total knee replacement geometries and to design implants that better restore natural knee mechanics. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1901–1909, 2018.
Characteristics and Responses of Human Vocal Fold Cells in a Vibrational Culture Model
Authors: Kim Dongjoo , Lee Songyi , Lim Jae‐Yol , Kwon Soonjo 
Published: February 2018

Objectives/HypothesisThis study was conducted to provide a vibrational culture model to investigate the effects of mechanical environments on cellular functions, and elucidate physiological characteristics of two different types of cells in vocal folds under static and vibrational conditions.Study DesignIn vitro study of human vocal fold fibroblasts (hVFFs) and human macula flava stellate cells (hMF‐SCs).MethodshVFFs and hMF‐SCs were exposed to a 2‐second‐on/2‐second‐off, 205 Hz vibration regime for 4 hours by using a vibrational culture model. We compared cell morphology, cell viability, and gene expression in extracellular matrix–related components, growth factors, and differentiation markers under static and vibratory conditions.ResultshVFFs and hMF‐SCs differed in their morphologies and gene expression levels under static condition. The applied vibration did not induce changes in morphology and viability of either cell type. However, gene expression levels changed in both cell types in response to vibration; in particular, hMF‐SCs exhibited a more sensitive response to vibration than that shown by hVFFs.ConclusionsThe vibrational culture model developed in this study enabled us to investigate the effects of the applied vibration on two types of vocal fold resident cells. As a result, we could demonstrate that hVFFs and hMF‐SCs exhibited distinctively different characteristics under vibrational conditions.Level of EvidenceNA. Laryngoscope, 128:E258–E264, 2018
Hospital Diet Enriched With Rapeseed or Sunflower Oils Is Associated With a Decrease in Plasma 16:1n‐7 and Some Metabolic Disorders in the Elderly
Authors: Combe Nicole , Henry Olivier , Lopez Carlos , Vaysse Carole , Fonseca Isabelle , Ribaud Danièle , Driss Fathi , Simon Noëmie , Le Guillou Céline , Mendy François 
Published: February 2018

AbstractWe recently demonstrated that the prevalence of dysglycemia was high among hospitalized elderly people who were fed a low fat diet (27.7% of energy) and was positively associated with plasma 16:1n‐7, an indicator of de novo lipogenesis (DNL). Fatty acids in the DNL pathway have been shown to be associated with a higher risk of metabolic syndrome (MetS). The purpose of this study was to investigate the potential beneficial effects of fat enrichment (up to 34.1%en) of the hospital diet in 111 patients (30 men and 81 women, 84 ± 7 years) during 6 weeks. Based on gender, they were randomly given a diet supplemented either with rapeseed oil (RO) or with sunflower oil (SO). Fatty acids of cholesteryl esters and erythrocyte phospholipids and markers of metabolic disorders were evaluated before and after dietary intervention. Both enriched diets significantly, and to a similar extent, decreased (1) the overall prevalence of dysglycemia (by 25–33%) and MetS (by 31–43%) and (2) plasma 16:1n‐7 mol% in men and women. Dysglycemia prevalence adjusted by the diets was reduced in men versus baseline; no change was found in women. Enrichment of the diet with RO or SO resulted in a difference in fatty acid compositions, that is, EPA (mol%) and the omega‐3 index increased with RO, while proportions of 18:1n‐7, 18:1n‐9, and EPA decreased with SO. These findings highlight the need for adequate fat intake in the elderly. For supplementation of the hospital diet, RO, which led to a higher proportion of circulating n‐3 polyunsaturated fatty acids (PUFA) and is known to be beneficial, may be preferred to SO.
Diffusion kurtosis imaging with free water elimination: A bayesian estimation approach
Authors: Collier Quinten , Veraart Jelle , Jeurissen Ben , Vanhevel Floris , Pullens Pim , Parizel Paul M. , den Dekker Arnold J. , Sijbers Jan 
Published: February 2018

PurposeDiffusion kurtosis imaging (DKI) is an advanced magnetic resonance imaging modality that is known to be sensitive to changes in the underlying microstructure of the brain. Image voxels in diffusion weighted images, however, are typically relatively large making them susceptible to partial volume effects, especially when part of the voxel contains cerebrospinal fluid. In this work, we introduce the “Diffusion Kurtosis Imaging with Free Water Elimination” (DKI‐FWE) model that separates the signal contributions of free water and tissue, where the latter is modeled using DKI.Theory and MethodsA theoretical study of the DKI‐FWE model, including an optimal experiment design and an evaluation of the relative goodness of fit, is carried out. To stabilize the ill‐conditioned estimation process, a Bayesian approach with a shrinkage prior (BSP) is proposed. In subsequent steps, the DKI‐FWE model and the BSP estimation approach are evaluated in terms of estimation error, both in simulation and real data experiments.ResultsAlthough it is shown that the DKI‐FWE model parameter estimation problem is ill‐conditioned, DKI‐FWE was found to describe the data significantly better compared to the standard DKI model for a large range of free water fractions. The acquisition protocol was optimized in terms of the maximally attainable precision of the DKI‐FWE model parameters. The BSP estimator is shown to provide reliable DKI‐FWE model parameter estimates.ConclusionThe combination of the DKI‐FWE model with BSP is shown to be a feasible approach to estimate DKI parameters, while simultaneously eliminating free water partial volume effects. Magn Reson Med 80:802–813, 2018. © 2018 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Influence of natural ageing on the flame retardancy and thermal properties of intumescent flame retardant long glass fibre reinforced polypropylene composites
Authors: He Weidi , Li Lingtong , Zhou Dengfeng , Chen Xiaolang , Guo Jianbing 
Published: February 2018

In this work, the composites based on long glass fiber reinforced polypropylene/intumescent flame retardant (LGFPP/IFR) were prepared by melt blending. This article presented an experimental research on the influence of combined environment elements in natural condition on the properties of LGFPP/IFR composites with 0–12 months ageing. The flammability and thermal properties of the composites were investigated by limiting oxygen index (LOI), UL–94 test, cone calorimeter test (CCT), thermal gravimetric analysis (TGA), mechanical properties test and energy dispersive X‐ray analysis (EDAX). The LOI values increased from 27.5 to 28.3 in 0–6 months ageing, and then decreased back, however, the TGA curves shift to the lower temperature. The thermal degradation kinetics were analyzed and the apparent active energy (E) of aged and unaged samples were calculated by Flynn‐Wall‐Ozawa method. The results indicated that much lower E values were obtained after 3–12 months ageing. EDAX data proved that the IFR particles gathered on the surface of samples in natural exposing, by which had some effect on the thermal stability and flame retardancy of the composites. The mechanical properties showed a global decrease in the whole ageing period by matrix degradation and interface debonding under the influence of combined environment elements. POLYM. ENG. SCI., 58:2098–2105, 2018. © 2018 Society of Plastics Engineers
Structure of DSM‐5 and ICD‐11 personality domains in Iranian community sample
Authors: Lotfi Mozhgan , Bach Bo , Amini Mahdi , Simonsen Erik 
Published: February 2018

AbstractAimPersonality disorders (PD) have been deemed the most problematic diagnostic grouping in terms of validity and utility, which particularly applies to non‐Western societies. The current study evaluated the structural validity of PD trait domains in the Diagnostic and Statistical Manual of Mental Disorders‐5 (DSM‐5) Section III and the proposed International Classification of Diseases‐11 (ICD‐11) in the Iranian population.MethodsCommunity‐dwelling adults (n = 285; 66% women) were administered the Personality Inventory for DSM‐5, whereas the proposed ICD‐11 trait domains were delineated using an algorithm for Personality Inventory for DSM‐5 trait facets. The five‐factor organization and higher‐order hierarchical structure of both models were examined using exploratory structural equation modelling analyses.ResultsThe five‐factor exploratory structural equation modelling loadings overall resembled international findings on DSM‐5 Section III traits (including Psychoticism), whereas the ICD‐11 five‐factor structure aligned with the proposed ICD‐11 domain features (including Anankastia). Additionally, we identified a hierarchical structure from one to five factors for both models that conceptually aligned with established models of personality and psychopathology.ConclusionsThis study provided initial support for the structural validity of DSM‐5 and ICD‐11 PD trait models in Iranian culture. Future research warrants replication in larger samples and clinical populations. Copyright © 2018 John Wiley & Sons, Ltd.
The Peptide Repertoire of HLA‐B27 may include Ligands with Lysine at P2 Anchor Position
Authors: Yair‐Sabag Shira , Tedeschi Valentina , Vitulano Carolina , Barnea Eilon , Glaser Fabian , Melamed Kadosh Dganit , Taurog Joel D. , Fiorillo Maria Teresa , Sorrentino Rosa , Admon Arie 
Published: February 2018

AbstractThe HLA‐B*27 peptidome has drawn significant attention due to the genetic association between some of the HLA‐B*27 alleles and the inflammatory rheumatic disease ankylosing spondylitis (AS), for which a comprehensive biological explanation is still lacking. This study aims to expand the known limits of the HLA‐B*27 peptidome to facilitate selection and testing of new peptides, possibly involved in the disease. The HLA peptidomes of HeLa and C1R cell lines stably transfected with the AS‐associated HLA‐B*27:05 allele, the nonassociated HLA‐B*27:09 allele, or their cysteine 67 to serine mutants (C67S), are analyzed on a very large scale. In addition, the peptidomes of HLA‐B*27:05 and HLA‐B*27:05‐C67S are analyzed from the spleens of rats transgenic for these alleles. The results indicate that C67S mutation increases the percentage of peptides with glutamine or lysine at their P2 position (P2‐Lys), in both HLA‐B*27:05 and HLA‐B*27:09. Furthermore, a small fraction of HLA‐B*27 peptides contains lysine at their second position (P2), in addition to the more commonly found peptides with arginine (P2‐Arg) or the less common glutamine (P2‐Gln) located at this anchor position. Overall these data indicate that peptides with P2‐Lys should be considered as real ligands of HLA‐B*27 molecules and taken into account while looking for putative peptides implicated in the AS.
Growth trajectories and oxygen use in neuroendocrine cell hyperplasia of infancy
Authors: Nevel Rebekah J. , Garnett Errine T. , Schaudies Deneen A. , Young Lisa R. 
Published: February 2018

AbstractRationaleNeuroendocrine cell hyperplasia of infancy (NEHI) typically presents in infancy with tachypnea, retractions, and hypoxemia. Some infants have failure to thrive, yet the frequency of this and other non‐respiratory phenotypic features have not been delineated. While gradual improvement occurs, the clinical course is variable and the duration of supplemental oxygen requirement has not been defined.ObjectivesOur objective was to identify factors in NEHI that may drive differences in clinical course. We hypothesized that failure to thrive would be associated with greater duration of supplemental oxygen use.MethodsChildren with NEHI were identified as a nested retrospective cohort within an ongoing observational prospective study. An electronic questionnaire evaluating health status was distributed to the parents/guardians. Clinical data were obtained via chart review and parent interview.ResultsOf 42 children, 74% had a diagnosis of failure to thrive during their clinical course. Time to event analysis demonstrated that 50% discontinued daytime and nighttime oxygen at 32 and 87.5 months after initiation, respectively. Diagnosis of failure to thrive was associated with longer continuous oxygen supplementation, P = 0.03. Additional parental concerns identified through the electronic questionnaire included developmental delays, multiple hospitalizations, and delays in diagnosis.ConclusionsNEHI is associated with substantial respiratory and extra‐pulmonary morbidity. Failure to thrive may be associated with greater respiratory morbidity, though further studies are required to define this interaction. Determining the association of these comorbidities and respiratory course in NEHI may enable development of strategies to improve these modifiable factors and potentially pulmonary outcomes.
The transformed gamma process for degradation phenomena in presence of unexplained forms of unit‐to‐unit variability
Authors: Giorgio Massimiliano , Guida Maurizio , Pulcini Gianpaolo 
Published: February 2018

AbstractThe transformed gamma process is a suitable model for degradation phenomena where damages accumulate gradually over time in a sequence of tiny increments. Attractiveness of the transformed gamma process mainly lies in the fact that it provides a relatively easy way for dealing with phenomena in which the degradation increments over disjoint time intervals are not independent. The transformed gamma process is also a very flexible model. In fact, it is indexed by 2 functions, the “age function” and the “state function,” whose mathematical form can be chosen ad hoc for modeling the dependence of the future degradation increment of a unit on its current age and state, respectively. In this paper, the transformed gamma process is adopted to describe the degradation paths of degrading units in the presence of an unexplained form of unit‐to‐unit variability. The degradation path of each unit is described via a transformed gamma process. Heterogeneity among paths of different units is accounted for by assuming that the scale parameters of the age and state functions vary randomly from unit to unit. Under these assumptions, a quite mathematically tractable model is obtained. The main properties of the proposed model are discussed, and inferential procedures based on the maximum likelihood criterion are implemented. A simple test is presented to check the goodness of fit of the proposed model. Three applicative examples, based on real degradation data, are developed.
Ex Vivo Expansion of CD34+CD90+CD49f+ Hematopoietic Stem and Progenitor Cells from Non-Enriched Umbilical Cord Blood with Azole Compounds
Authors: Bari Sudipto , Zhong Qixing , Fan Xiubo , Poon Zhiyong , Lim Alvin Soon Tiong , Lim Tse Hui , Dighe Niraja , Li Shang , Chiu Gigi Ngar Chee , Chai Christina Li Lin , Hwang William Ying Khee 
Published: February 2018

Abstract
Umbilical cord blood (UCB) transplants in adults have slower hematopoietic recovery compared to bone marrow (BM) or peripheral blood (PB) stem cells mainly due to low number of total nucleated cells and hematopoietic stem and progenitor cells (HSPC). As such in this study, we aimed to perform ex vivo expansion of UCB HSPC from non-enriched mononucleated cells (MNC) using novel azole-based small molecules. Freshly-thawed UCB–MNC were cultured in expansion medium supplemented with small molecules and basal cytokine cocktail. The effects of the expansion protocol were measured based on in vitro and in vivo assays. The proprietary library of &gt;50 small molecules were developed using structure-activity-relationship studies of SB203580, a known p38-MAPK inhibitor. A particular analog, C7, resulted in 1,554.1 ± 27.8-fold increase of absolute viable CD45+CD34+CD38–CD45RA– progenitors which was at least 3.7-fold higher than control cultures (p &lt; .001). In depth phenotypic analysis revealed &gt;600-fold expansion of CD34+/CD90+/CD49f+ rare HSPCs coupled with significant (p &lt; .01) increase of functional colonies from C7 treated cells. Transplantation of C7 expanded UCB grafts to immunodeficient mice resulted in significantly (p &lt; .001) higher engraftment of human CD45+ and CD45+CD34+ cells in the PB and BM by day 21 compared to non-expanded and cytokine expanded grafts. The C7 expanded grafts maintained long-term human multilineage chimerism in the BM of primary recipients with sustained human CD45 cell engraftment in secondary recipients. In conclusion, a small molecule, C7, could allow for clinical development of expanded UCB grafts without pre-culture stem cell enrichment that maintains in vitro and in vivo functionality.