bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three‐dimensional coculture of primary hepatocytes and stellate cells in silk scaffold improves hepatic morphology and functionality in vitro
Authors: Wei Guofeng , Wang Jiwen , Lv Qiang , Liu Ming , Xu Hong , Zhang He , Jin Lingling , Yu Jiachuan , Wang Xiuli 
Published: April 2018

AbstractA vigorous in vitro model of liver that could recapitulate hepatic phenotype and functionality in vivo would exclusively improve the efficiency of bioartificial liver, drug discovery, or even transplantation therapy. Owing to the indispensable role of three‐dimensional (3D) microenvironment in supporting viability and function of hepatocytes in vitro, much effort recently has been focused on improving reproducibility and standardization of primary hepatocyte cultures with a paradigm shift to 3D culture system, In the present study, an improved 3D coculture system of hepatocytes was established in which rat primary hepatocytes were cocultured with hepatic stellate cells in silk porous scaffolds. Silk scaffolds with incorporated extracellular matrix provided a suitable microenvironment for maintaining the viability, morphology and gene expression of the primary hepatocyte in vitro. The presence of stromal cells promoted primary hepatocyte to generate cellular aggregates with well‐organized 3D architecture after 3 days of coculture in vitro. These aggregates exhibited proper morphology similar to liver tissue in vivo. Consistent with their phenotypic appearance, well‐maintained functionality of hepatocytes was also observed in the cocultures, where albumin secretion/expression, urea synthesis as well as messenger ribonucleic acid expression of multiple cytochrome Ps (CYPs) enzymes increased significantly compared to either the 3D monocultures or monolayer cultures. Additionally, this 3D multicellular coculture model displayed an improved metabolic activity of CYPs enzymes to the probe drugs treatment. Thus, this culture system would not only contribute to the construction of micro‐organoid tissue of liver but also potentially provide a robust tool for drug metabolism evaluation in vitro. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2171‐2180, 2018.
Designer nuclease‐mediated gene correction via homology‐directed repair in an in vitro model of canine hemophilia B
Authors: Bergmann Thorsten , Ehrke-Schulz Eric , Gao Jian , Schiwon Maren , Schildgen Verena , David Stephan , Schildgen Oliver , Ehrhardt Anja 
Published: April 2018

AbstractBackgroundGene correction at specific target loci provides a powerful strategy for overcoming genetic diseases. In the present study, we aimed to use an in vitro model for canine hemophilia B containing a single point mutation in the catalytic domain of the canine coagulation factor IX (cFIX) gene. To correct the defective gene via homology‐directed repair (HDR), we designed transcription‐activator like effector nucleases and clustered regularly interspaced short palindromic repeats including Cas9 (CRISPR/Cas9) for introduction of double‐strand breaks at the mutation site.MethodsTo generate a stable cell line containing the mutated cFIX locus, a 2‐kb genomic DNA fragment derived from a hemophilia B dog was amplified and integrated utilizing the phiC31 integrase system. Designer nucleases were assembled and cloned into vectors for constitutive and inducible expression. To detect mutations, insertions and deletions, and HDR events after nuclease treatment T7E1 assays, an amplification‐refractory mutation system‐quantitative polymerase chain reaction and pyrosequencing were performed.ResultsTo perform HDR correction experiments, we established a cell line carrying the mutated cFIX locus. In HDR approaches we either explored a wild‐type or an optimized cFIX sequence and we found that our modified HDR cassette showed higher gene correction efficiencies of up to 6.4%. Furthermore, we compared inducible and constitutive designer nuclease expression systems and found that the inducible system resulted in comparable HDR efficiencies.ConclusionsIn conclusion, the present study demonstrates the potential of this strategy for gene therapeutic approaches in vitro and in a canine model for hemophilia B.
An efficient method to isolate Kupffer cells eliminating endothelial cell contamination and selective bias
Authors: Lynch Ruairi W , Hawley Catherine A , Pellicoro Antonella , Bain Calum C , Iredale John P , Jenkins Stephen J 
Published: April 2018

Abstract
Multicolor flow cytometry and cell sorting are powerful immunologic tools for the study of hepatic mϕ, yet there is no consensus on the optimal method to prepare liver homogenates for these analyses. Using a combination of mϕ and endothelial cell reporter mice, flow cytometry, and confocal imaging, we have shown that conventional flow-cytometric strategies for identification of Kupffer cells (KCs) leads to inclusion of a significant proportion of CD31hi endothelial cells. These cells were present regardless of the method used to prepare cells for flow cytometry and represented endothelium tightly adhered to remnants of KC membrane. Antibodies to endothelial markers, such as CD31, were vital for their exclusion. This result brings into focus recently published microarray datasets that identify high expression of endothelial cell-associated genes by KCs compared with other tissue-resident mϕ. Our studies also revealed significant and specific loss of KCs among leukocytes with commonly used isolation methods that led to enrichment of proliferating and monocyte-derived mϕ. Hence, we present an optimal method to generate high yields of liver myeloid cells without bias for cell type or contamination with endothelial cells.
Protocol to remove endothelial cell contamination and selection bias inherent in conventional methods for isolating and analyzing liver Kupffer cells.
DP1 receptor signaling prevents the onset of intrinsic apoptosis in eosinophils and functions as a transcriptional modulator
Authors: Peinhaupt Miriam , Roula David , Theiler Anna , Sedej Miriam , Schicho Rudolf , Marsche Gunther , Sturm Eva M , Sabroe Ian , Rothenberg Marc E , Heinemann Akos 
Published: April 2018

Abstract
Prostaglandin (PG) D2 is the ligand for the G-protein coupled receptors DP1 (D-type prostanoid receptor 1) and DP2 (also known as chemoattractant receptor homologous molecule, expressed on Th2 cells; CRTH2). Both, DP1 and DP2 are expressed on the cellular surface of eosinophils; although it has become quite clear that PGD2 induces eosinophil migration mainly via DP2 receptors, the role of DP1 in eosinophil responses has remained elusive. In this study, we addressed how DP1 receptor signaling complements the pro-inflammatory effects of DP2. We found that PGD2 prolongs the survival of eosinophils via a DP1 receptor-mediated mechanism that inhibits the onset of the intrinsic apoptotic cascade. The DP1 agonist BW245c prevented the activation of effector caspases in eosinophils and protected mitochondrial membranes from depolarization which—as a consequence—sustained viability of eosinophils. DP1 activation in eosinophils enhanced the expression of the anti-apoptotic gene BCL-XL, but also induced pro-inflammatory genes, such as VLA-4 and CCR3. In HEK293 cells that overexpress recombinant DP1 and/or DP2 receptors, activation of DP1, but not DP2, delayed cell death and stimulated proliferation, along with induction of serum response element (SRE), a regulator of anti-apoptotic, early-response genes. We conclude that DP1 receptors promote the survival via SRE induction and induction of pro-inflammatory genes. Therefore, targeting DP1 receptors, along with DP2, may contribute to anti-inflammatory therapy in eosinophilic diseases.
The PGD2-DP1 axis impedes caspase activity, protects mitochondrial function and consequently sustains eosinophil survival by controlling SRE induction and upregulation of pro-inflammatory and anti-apoptotic genes.
Shear strain rate from phase contrast velocity encoded MRI: Application to study effects of aging in the medial gastrocnemius muscle
Authors: Sinha Usha , Malis Vadim , Csapo Robert , Narici Marco , Sinha Shantanu 
Published: April 2018

BackgroundStrain rate (SR) is a measure of the rate of regional deformation that can be computed by analyzing velocity‐encoded phase‐contrast 2D images. Recent studies have explored the changes in normal components of the strain tensor in aging muscle, while shear strain may also provide valuable information.PurposeTo compute the shear SR from velocity‐encoded MRI of the lower leg and to study the correlation of SR parameters measured in the medial gastrocnemius (MG) to muscle force in a cohort of young and senior subjects.Study TypeProspective cohort study.SubjectsSix young (26.1 ± 2.3 years) and six senior (76.7 ± 8.3 years) healthy females; two other subjects were scanned on three separate occasions for repeatability studies.Field Strength/Sequence1.5T using a single oblique sagittal slice with velocity‐encoding in three directions (velocity‐encoded phase contrast gradient echo sequence).AssessmentAge‐related and regional differences in the SR eigenvalues (SRfiber, SRin‐plane), normal SRs (SRff, SRcc), and shear SRs (SRfc, SRfc_max) were statistically analyzed.Statistical TestsDifference between young and senior cohorts were assessed using two‐way analysis of variance (ANOVAs). The coefficient of variation and repeatability coefficient were calculated from repeat studies. Univariate and stepwise multivariable linear regression was performed to identify predictors of force.ResultsDuring isometric plantarflexion contraction, SRs in the principal basis (SRfiber, SRin‐plane) and maximum shear SR (SRfc_max) was significantly lower in the senior cohort (P < 0.05). On multiple variable regression, maximum shear SR (SRfc_max) and normal SR in the fiber cross‐section (SRcc) were significantly associated with force (R = 0.681, F = 14.034, P < 0.001).Data ConclusionThis study establishes that computation of shear strain is feasible and is a significant predictor of force variability with age.Level of Evidence: 2Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018;47:1351–1357.
Discrimination of nitrogen fertilizer levels of tea plant (Camellia sinensis) based on hyperspectral imaging
Authors: Wang Yujie , Hu Xin , Hou Zhiwei , Ning Jingming , Zhang Zhengzhu 
Published: April 2018

AbstractBACKGROUNDNitrogen (N) fertilizer plays an important role in tea plantation management, with significant impacts on the photosynthetic capacity, productivity and nutrition status of tea plants. The present study aimed to establish a method for the discrimination of N fertilizer levels using hyperspectral imaging technique.RESULTSSpectral data were extracted from the region of interest, followed by the first derivative to reduce background noise. Five optimal wavelengths were selected by principal component analysis. Texture features were extracted from the images at optimal wavelengths by gray‐level gradient co‐occurrence matrix. Support vector machine (SVM) and extreme learning machine were used to build classification models based on spectral data, optimal wavelengths, texture features and data fusion, respectively. The SVM model using fused data gave the best performance with highest correct classification rate of 100% for prediction set.CONCLUSIONThe overall results indicated that visible and near‐infrared hyperspectral imaging combined with SVM were effective in discriminating N fertilizer levels of tea plants. © 2018 Society of Chemical Industry
The effect of natural rainfall on salt leaching under watertable management
Authors: Li Shan , Luo Wan , Jia Zhonghua , Tang Shuangcheng , Chen Cheng 
Published: April 2018

AbstractNatural rainfall may produce effective leaching in some salt‐impacted irrigation areas; but the variable nature of rainfall often makes it difficult to assess the actual leaching effect of rainfall under different irrigation and drainage management. With a proposed analytical model that considers watertable management and crop use of shallow groundwater, this paper presents a case study that examined salt leaching effect of the natural rainfall in a semiarid irrigation area; the salt balance calculation was based on the daily watertable depth predicted by the DRAINMOD model using 55‐year weather data. The results showed that salt leaching effect of the natural rainfall depended on the control depth of field watertable through drainage system, crop use of shallow groundwater, and supplemental irrigation. For the salt tolerant crop—cotton, with the field watertable depth controlled at 1.5 m and the annual supplemental irrigation as 80 mm, the predicted average root zone salinity did not exceed the cotton tolerance level (4.92 g/L) in the simulation period. When the watertable depth was controlled at 1.2 m, due to increased shallow groundwater use, the predicted average root zone salinity was below the cotton tolerance level in 80% years with annual irrigation of 100 mm; and the predicted root zone salinity was below the cotton tolerance level in 96.4% years with annual irrigation of 150 mm. To achieve higher water use efficiency in semiarid irrigation area with saline shallow groundwater, proper watertable management is necessary to make use of the natural rainfall for salt leaching and shallow groundwater for temporary drought relief.
Physical therapy needs for patients with physical function injuries post‐earthquake disasters: A systematic review of Chinese and Western literature
Authors: Li Hao , Nyland John , Kuban Katrina , Givens Justin 
Published: April 2018

AbstractBackground and purposeOver the last 500 years, the most earthquakes with 10,000 or more fatalities and the most overall fatalities have occurred in China. Physical therapists must develop a better understanding of the patient and injury types that they are likely to treat post‐earthquake disasters. This systematic review of Chinese and Western literature identified the primary patients treated by physical therapists post‐earthquake disasters for injuries that negatively impacted physical function, activity, and participation.MethodsComparisons were made between reports of earthquakes in China and reports from the rest of the world combined.ResultsSixty‐seven studies of 71,986 patients (51.8% male) at 40.6 ± 15 years of age were included. Studies were mostly prospective (n = 48, 71.6%). Reports of earthquakes in China represented more recently occurring disasters (p = .003) and more prospective research designs (p = .003). Reports from China also had a higher median fracture number (p = .004). Studies from China used manual muscle testing (p = .02), visual analogue pain scales (p = .008), Barthel index or modified Barthel index (p < .0001), and joint motion assessment (p = .007) with greater frequencies.DiscussionPhysical therapists from China are more likely to treat patients with a fracture; however, physical therapists from both regions are likely to treat patients with general injuries representing poly‐trauma to multiple body regions, traumatic brain‐closed head injuries, spinal cord injuries, peripheral nerve injuries, and soft tissue injuries.Implications on physiotherapy practiceThese data can help improve earthquake disaster planning, infrastructure development, and resource needs assessment effectiveness. More prospective research study designs and more recent earthquake disasters in China are likely associated with greater explicit use of valid and reliable outcome measurements such as joint motion assessment, manual muscle testing, visual analogue pain scale, and the Barthel index or modified Barthel index.
Adaptive multivariate double sampling and variable sampling interval Hotelling's T2 charts
Authors: Khatun Mahfuza , Khoo Michael B.C. , Yeong W.C. , Teoh W.L. , Chong Z.L. 
Published: April 2018

AbstractIn this article, two adaptive multivariate charts, which combine the double sampling (DS) and variable sampling interval (VSI) features, called the adaptive multivariate double sampling variable sampling interval T2 (AMDSVSI T2) and the adaptive multivariate double sampling variable sampling interval combined T2 (AMDSVSIC T2) charts, are proposed. The real purpose of using the proposed charts is to provide flexibility by enabling the sampling interval length of the DS T2 chart to be varied so that the chart's sensitivity can be enhanced. The fundamental difference between the two proposed charts is that when a second sample is taken, the AMDSVSI T2 chart uses the information of the combined sample mean vectors while the AMDSVSIC T2 chart uses the information of the combined T2 statistics, in deciding about the process status. This research is motivated by existing combined DS
and VSI
charts in the literature, which show convincing performance improvement over the standard DS
chart. Consequently, it is believed that adopting this existing approach in the multivariate case will enable superior multivariate DS charts to be proposed. Numerical results show that the proposed charts outperform the existing standard T2 and other adaptive multivariate charts, in detecting shifts in the mean vector, for the zero‐state and steady‐state cases. The performances of both charts when the shift sizes in the mean vector are unknown are also measured. The application of the AMDSVSI T2 chart is illustrated with an example.
Neurodevelopmental outcome of fetal isolated ventricular asymmetry without dilation: a cohort study
Authors: Meyer R. , Bar‐Yosef O. , Barzilay E. , Hoffman D. , Toussia‐Cohen S. , Zvi E. , Achiron R. , Katorza E. 
Published: April 2018

ABSTRACTObjectiveFetal isolated ventricular asymmetry (IVA) is a relatively common finding in pregnancy, but data regarding its effect on neurodevelopmental outcome are scarce and founded principally on ultrasound‐based studies. The purpose of this study was to assess the neurodevelopmental outcome of IVA cases in a magnetic resonance imaging (MRI)‐based study.MethodsCases referred for fetal brain MRI as part of the assessment of IVA without ventriculomegaly (lateral ventricular atrial diameter ≤ 10 mm), identified during routine ultrasound examination, were assessed for possible inclusion. Asymmetry was defined as a difference in width of ≥ 2 mm between the two lateral ventricles. Forty‐three cases were included in the study group and compared with a control group of 94 normal cases without IVA. Children were assessed at ages 13–74 months using the Vineland‐II Adaptive Behavior Scales (VABS‐II).ResultsVABS‐II scores were within normal range. There was no significant difference in composite VABS‐II score between the study and control groups (106.5 vs 108.0; P = 0.454). VABS‐II scores did not differ between the groups when matched for gender and age at VABS‐II interview (109.6 in study group vs 107.8 in control group; P = 0.690).ConclusionIn cases of IVA without ventriculomegaly on MRI, neurodevelopmental test scores were normal and did not differ from cases without IVA. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Integrated free‐form method for aerostructural optimization of wind turbine blades
Authors: Barrett R. , Ning A. 
Published: April 2018

AbstractA typical approach to optimize wind turbine blades separates the airfoil shape design from the blade planform design. This approach is sequential, where the airfoils along the blade span are preselected or optimized and then held constant during the blade planform optimization. In contrast, integrated blade design optimizes the airfoils and the blade planform concurrently and thereby has the potential to reduce cost of energy (COE) more than sequential design. Nevertheless, sequential design is commonly performed because of the ease of precomputation, or the ability to compute the airfoil analyses prior to the blade optimization. This research compares 2 integrated blade design approaches. The precomputational method combines precomputation with the ability to change the airfoil shapes in limited ways during the optimization. The free‐form method allows for a complete range of airfoil shapes, but without precomputation. The airfoils are analyzed with a panel method (XFOIL) and a Reynolds‐averaged Navier‐Stokes computational fluid dynamics method (RANS CFD). Optimizing the NREL 5‐MW reference turbine showed COE reductions of 2.0%, 4.2%, and 4.7% when using XFOIL and 2.7%, 6.0%, and 6.7% when using RANS CFD for the sequential, precomputational, and free‐form methods, respectively. The precomputational method captures most of the benefits of integrated design for minimal additional computational cost and complexity, but the free‐form method provides modest additional benefits if the extra effort is made in computational cost and development time.
C.elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death
Authors: Li Yang , Zhang Yu , Gan Qiwen , Xu Meng , Ding Xiao , Tang Guihua , Liang Jingjing , Liu Kai , Liu Xuezhao , Wang Xin , Guo Lingli , Gao Zhiyang , Hao Xiaojiang , Yang Chonglin 
Published: April 2018

AbstractLysosomes are degradation and signaling centers within the cell, and their dysfunction impairs a wide variety of cellular processes. To understand the cellular effect of lysosome damage, we screened natural small-molecule compounds that induce lysosomal abnormality using Caenorhabditis elegans (C. elegans) as a model system. A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A–D) were identified that caused lysosome enlargement in C. elegans macrophage-like cells. Intriguingly, these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway. In mammalian cells, ervachinines A–D induced lysosomal enlargement and damage, leading to leakage of cathepsin proteases, inhibition of autophagosome degradation and necrotic cell death. Further analysis revealed that this ervachinine-induced lysosome damage and lysosomal cell death depended on STAT3 signaling, but not RIP1 or RIP3 signaling. These findings suggest that lysosome-damaging compounds are promising reagents for dissecting signaling mechanisms underlying lysosome homeostasis and lysosome-related human disorders.
Correlation of Hand Hygiene Compliance Measured by Direct Observation with Estimates Obtained from Product Usage
Authors: Branch-Elliman Westyn , Snyder Graham M. , King Aleah D. , Baldini Linda M. , Dooley Kaitlyn M. , Yassa David S. , Wright Sharon B. 
Published: April 2018

Improving compliance with hand hygiene is a cornerstone of infection prevention. However, data regarding practical methods for monitoring compliance are limited. We found that product use metrics have a moderate correlation with direct observation in ward settings and limited correlation in intensive care units.Infect Control Hosp Epidemiol 2018;39:746–749
THE NEW GENEALOGY OF RELIGIOUS FREEDOM
Authors: Decosimo David 
Published: April 2018

AbstractThis article pursues an immanent critique of a scholarly movement and mood that I call “the new genealogy of religious freedom” and sketches an alternative proposal. The new genealogy of religious freedom claims that religious freedom is incoherent, systemically biased, oppressive, ideological—and necessarily so. Its critique deploys a methodology inherited from Nietzsche and targets a vision of religious freedom associated with “foundationalists” like Kant and Rawls. This article calls both the methodology and the vision into question. The version of genealogy that this movement promotes proves self-destructive and incoherent, veering toward nihilism and unable to account for its own status ascritique. Its attack on foundationalist religious freedom is effective, but it presupposes—and targets—conceptions of freedom, neutrality, and power that we need not endorse. For foundationalists and genealogists alike, these assumptions define religious freedom. This article rejects those assumptions and that vision of religious freedom. It sketches a pragmatist, dialectical vision of religious freedom rooted in alternate conceptions of power, freedom, and neutrality and a corresponding strategy for legally defining “religion,” inheriting the strengths of genealogy and foundationalism while avoiding their weaknesses.