bluuebunny/crossref_metadata_2025 huggingface dataset:
Head-to-head comparison of procalcitonin and presepsin for the diagnosis of sepsis in critically ill adult patients: a protocol for a systematic review and meta-analysis
Authors: Hayashida Kei , Kondo Yutaka , Hara Yoshitaka , Aihara Morio , Yamakawa Kazuma
Published: March 2017

Introduction

Early diagnosis and immediate therapeutic intervention, including appropriate antibiotic therapy and goal-directed resuscitation, are necessary to reduce mortality in patients with sepsis. However, a single clinical or biological marker indicative of sepsis has not been adopted unanimously. Although procalcitonin and presepsin are promising biomarkers that can effectively differentiate between sepsis/infection and systemic inflammatory response syndrome of non-infectious origin, little is known about which marker is superior.

Methods and analysis

We will conduct a systematic review and meta-analysis of procalcitonin and presepsin for the diagnosis of sepsis/infection in critically ill adult patients. The primary objective is to evaluate the diagnostic accuracy of these 2 biomarkers to a reference standard of sepsis/infection and to compare the diagnostic accuracy with each other. We will search electronic bibliographic databases such as MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials for retrospective and prospective diagnostic test studies. We will assign 2 reviewers to review all collected titles and associated abstracts, review full articles, and extract study data. We will use the Quality of Diagnostic Accuracy Studies-II tool to report study characteristics and to evaluate methodological quality. If pooling is possible, we will use bivariate random effects and hierarchical summary receiver operating characteristic (ROC) models to calculate parameter estimates to output summary ROCs, pooled sensitivity and specificity data, and 95% CIs around the summary operating point. We will also assess heterogeneity via clinical and methodological subgroup and sensitivity analyses.

Ethics and dissemination

This systematic review will provide guidance on the triage of these tests, help to determine whether existing tests should be revised or replaced, and may also identify knowledge gaps in sepsis diagnosis that could direct further research in the field. Research ethics is not required for this review. The findings will be reported at conferences and in peer-reviewed publications.

Trial registration number

CRD42016035784.
Tourniquet parent artery occlusion after flow diversion
Authors: Srinivasan Visish M , Mokin Maxim , Duckworth Edward A M , Chen Stephen , Puri Ajit , Kan Peter
Published: March 2017

Background

The Pipeline Embolization Device (PED) is increasingly used for both on- and off-label purposes for treatment of intracranial aneurysms. The device gradually slows flow of blood into the aneurysm, but the high metal coverage of PED promotes endothelialization of the device. Occasionally, this leads to in-stent stenosis that is clinically well tolerated. We present a multi-institutional Pipeline series that includes three cases of gradual asymptomatic occlusion within the PED and parent vessel.

Methods

Institutional databases at each participating center were searched for patients treated with the PED. Patients with at least 50% stenosis or occlusion were selected and all relevant clinical and radiographic data were reviewed.

Results

A total of 326 cases performed by five neurointerventionalists across four institutions were reviewed. Among these there were three cases of complete occlusion and two cases of stenosis of more than 50%, for an occlusion rate of 0.9%. All patients were clinically asymptomatic.

Conclusions

A gradual tourniquet-like occlusion can occur following placement of the PED, leading to vessel occlusion. This has been clinically well tolerated by patients in our series due to the formation of pial collaterals as the stenosis progresses, likely due to ischemic preconditioning. Small parent vessel, pre-existing stenosis, fusiform pathology, overlapping devices, and suboptimal antiplatelet therapy seem to be predisposing factors. Further experience and follow-up will allow us to characterize the risk factors and optimize post-procedural therapy for these patients.
Decision-Making in a Real-Time Business Simulation Game: Cultural and Demographic Aspects in Small Group Dynamics
Authors: Bragge Johanna , Kallio Henrik , Seppälä Tomi , Lainema Timo , Malo Pekka
Published: March 2017

Simulated virtual realities offer a promising but currently underutilized source of data in studying cultural and demographic aspects of dynamic decision-making (DDM) in small groups. This study focuses on one simulated reality, a clock-driven business simulation game, which is used to teach operations management. The purpose of our study is to analyze the characteristics of the decision-making groups, such as cultural orientation, education, gender and group size, and their relationship to group performance in a real-time processed simulation game. Our study examines decision-making in small groups of two or three employees from a global manufacturing and service operations company. We aim at shedding new light on how such groups with diverse background profiles perform as decision-making units. Our results reveal that the profile of the decision-making group influences the outcome of decision-making, the final business result of the simulation game. In particular, the cultural and gender diversity, as well as group size seem to have intertwined effects on team performance.
Quantitative analysis of the heterogeneous population of endocytic vesicles
Authors: Kozlov Konstantin , Kosheverova Vera , Kamentseva Rimma , Kharchenko Marianna , Sokolkova Alena , Kornilova Elena , Samsonova Maria
Published: March 2017

The quantitative characterization of endocytic vesicles in images acquired with microscope is critically important for deciphering of endocytosis mechanisms. Image segmentation is the most important step of quantitative image analysis. In spite of availability of many segmentation methods, the accurate segmentation is challenging when the images are heterogeneous with respect to object shapes and signal intensities what is typical for images of endocytic vesicles. We present a Morphological reconstruction and Contrast mapping segmentation method (MrComas) for the segmentation of the endocytic vesicle population that copes with the heterogeneity in their shape and intensity. The method uses morphological opening and closing by reconstruction in the vicinity of local minima and maxima respectively thus creating the strong contrast between their basins of attraction. As a consequence, the intensity is flattened within the objects and their edges are enhanced. The method accurately recovered quantitative characteristics of synthetic images that preserve characteristic features of the endocytic vesicle population. In benchmarks and quantitative comparisons with two other popular segmentation methods, namely manual thresholding and Squash plugin, MrComas shows the best segmentation results on real biological images of EGFR (Epidermal Growth Factor Receptor) endocytosis. As a proof of feasibility, the method was applied to quantify the dynamical behavior of Early Endosomal Autoantigen 1 (EEA1)-positive endosome subpopulations during EGF-stimulated endocytosis.
Electrochemical Performance of Lithium-Ion Capacitors Using Pre-Lithiated Multiwalled Carbon Nanotubes as Anode
Authors: Cai Manyuan , Sun Xiaogang , Nie Yanyan , Chen Wei , Qiu Zhiwen , Chen Long , Liu Zhenhong , Tang Hao
Published: March 2017

Pre-lithiated multiwalled carbon nanotube anode was prepared by internal short circuit approach(ISC) for 5[Formula: see text]min, 30[Formula: see text]min, 60[Formula: see text]min and 120[Formula: see text]min respectively. Lithium ion capacitors (LICs) were assembled by using pre-lithiated multiwalled carbon nanotubes as anodes and activated carbon (AC) as cathodes. The structure of multiwalled carbon nanotubes and electrodes were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The electrochemical performance of pre-lithiated multiwalled carbon nanotube electrodes and pristine carbon nanotube electrodes were tested by galvanostatic charge/discharge and electrochemical impedance. The results indicated that pre-lithiation carbon nanotubes greatly improved the charge/discharge performance of LICs. The energy density was four times than conventional electric double-layer capacitors (EDLCs) at the current density of 100[Formula: see text]mA/g. The LICs achieved a specific capacitance of 59.3[Formula: see text]F/g at the current density of 100[Formula: see text]mA/g with 60[Formula: see text]min pre-lithiatiation process. The maximum energy density and power density was 96[Formula: see text]Wh/kg and 4035[Formula: see text]W/kg, respectively. The energy density still remained about 89.0% after 1000 cycles. The LIC showed excellent supercapacitor performance.
Near infra-red light treatment of Alzheimer’s disease
Authors: Han Mengmeng , Wang Qiyan , Wang Xue , Zeng Yuhui , Huang Yong , Meng Qingqiang , Zhang Jun , Wei Xunbin
Published: March 2017

Alzheimer’s disease (AD) is a chronic neurodegenerative disease. The symptoms include memory and spatial learning difficulties, language disorders, and loss of motivation, which get worse over time, eventually ending in death. No effective treatments are available for AD, currently. Current treatments only attenuate symptoms temporarily and are associated with severe side effects. Near infra-red (NIR) light has been studied for a long time. We investigated the effect of NIR on AD using a transgenic mouse model, which was obtained by co-injecting two vectors carrying AD mutations in amyloid precursor protein (APP) and presenilin-1 (PSEN1) into C57BL/6J mice. The irradiation equipment consisted of an accommodating box and an LED array. The wavelength of NIR light emitted from LED was between 1040[Formula: see text]nm and 1090[Formula: see text]nm. The power density delivered at the level of the mice was approximately 15[Formula: see text]mW/cm2. Firstly, we treated the mice with NIR for 40 days. Then, the irradiation was suspended for 28 days. Finally, another 15 days treatment was brought to mice. We conducted Morris water maze and immunofluorescence analysis to evaluate the effects of treatment. Immunofluorescence analysis was based on measuring the quantity of plaques in mouse brain slices. Our results show that NIR light improves memory and spatial learning ability and reduces plaques moderately. NIR light represents a potential treatment for AD.
Liquid Resins-Based Additive Manufacturing
Authors: Wang Fei , Wang Fuke
Published: March 2017

In this review, additive manufacturing technologies using liquid resins as materials are reviewed from the perspective of printing technologies and materials. Most importantly, recent progress of new printing technologies and printers as well as novel printing materials and their applications are summarized, based on which potential future research directions are discussed at the end of this review.
An Improved Approximation for
k
-Median and Positive Correlation in Budgeted Optimization
Authors: Byrka Jarosław , Pensyl Thomas , Rybicki Bartosz , Srinivasan Aravind , Trinh Khoa
Published: March 2017

Dependent rounding is a useful technique for optimization problems with hard budget constraints. This framework naturally leads to negative correlation properties. However, what if an application naturally calls for dependent rounding on the one hand and desires positive correlation on the other? More generally, we develop algorithms that guarantee the known properties of dependent rounding but also have nearly bestpossible behavior—near-independence, which generalizes positive correlation—on “small” subsets of the variables. The recent breakthrough of Li and Svensson for the classical
k
-median problem has to handle positive correlation in certain dependent rounding settings, and does so implicitly. We improve upon Li-Svensson’s approximation ratio for
k
-median from 2.732 + ϵ to 2.675 + ϵ by developing an algorithm that improves upon various aspects of their work. Our dependent rounding approach helps us improve the dependence of the runtime on the parameter ϵ from Li-Svensson’s
N

O
(1/ϵ
2
)

to
N

O
((1/ϵ)log(1/ϵ))

.
Evaluating the Combined Effect of Memory Capacity and Concurrency for Many-Core Chip Design
Authors: Liu Yu-Hang , Sun Xian-He
Published: March 2017

Modern memory systems are structured under hierarchy and concurrency. The combined impact of hierarchy and concurrency, however, is application dependent and difficult to describe. In this article, we introduce
C
2
-Bound, a data-driven analytical model that serves the purpose of optimizing many-core design.
C
2
-Bound considers both memory capacity and data access concurrency. It utilizes the combined power of the newly proposed latency model, concurrent average memory access time, and the well-known memory-bounded speedup model (Sun-Ni’s law) to facilitate computing tasks. Compared to traditional chip designs that lack the notion of memory capacity and concurrency, the
C
2
-Bound model finds that memory bound factors significantly impact the optimal number of cores as well as their optimal silicon area allocations, especially for data-intensive applications with a non-parallelizable sequential portion. Therefore, our model is valuable to the design of next-generation many-core architectures that target big data processing, where working sets are usually larger than the conventional scientific computing. These findings are evidenced by our detailed simulations, which show, with
C
2
-Bound, the design space of chip design can be narrowed down significantly up to four orders of magnitude.
C
2
-Bound analytic results can be either used in reconfigurable hardware environments or, by software designers, applied to scheduling, partitioning, and allocating resources among diverse applications.
A Temporal Order Modeling Approach to Human Action Recognition from Multimodal Sensor Data
Authors: Ye Jun , Hu Hao , Qi Guo-Jun , Hua Kien A.
Published: March 2017

From wearable devices to depth cameras, researchers have exploited various multimodal data to recognize human actions for applications, such as video gaming, education, and healthcare. Although there many successful techniques have been presented in the literature, most current approaches have focused on statistical or local spatiotemporal features and do not explicitly explore the temporal dynamics of the sensor data. However, human action data contain rich temporal structure information that can characterize the unique underlying patterns of different action categories. From this perspective, we propose a novel temporal order modeling approach to human action recognition. Specifically, we explore subspace projections to extract the latent temporal patterns from different human action sequences. The temporal order between these patterns are compared, and the index of the pattern that appears first is used to encode the entire sequence. This process is repeated multiple times and produces a compact feature vector representing the temporal dynamics of the sequence. Human action recognition can then be efficiently solved by the nearest neighbor search based on the Hamming distance between these compact feature vectors. We further introduce a sequential optimization algorithm to learn the optimized projections that preserve the pairwise label similarity of the action sequences. Experimental results on two public human action datasets demonstrate the superior performance of the proposed technique in both accuracy and efficiency.
Algorithmic and Enumerative Aspects of the Moser-Tardos Distribution
Authors: Harris David G. , Srinivasan Aravind
Published: March 2017

Moser and Tardos have developed a powerful algorithmic approach (henceforth MT) to the Lovász Local Lemma (LLL); the basic operation done in MT and its variants is a search for “bad” events in a current configuration. In the initial stage of MT, the variables are set independently. We examine the distributions on these variables that arise during intermediate stages of MT. We show that these configurations have a more or less “random” form, building further on the MT-distribution concept of Haeupler et al. in understanding the (intermediate and) output distribution of MT. This has a variety of algorithmic applications; the most important is that bad events can be found relatively quickly, improving on MT across the complexity spectrum. It makes some polynomial-time algorithms sublinear (e.g., for Latin transversals, which are of basic combinatorial interest), gives lower-degree polynomial runtimes in some settings, transforms certain superpolynomial-time algorithms into polynomial-time algorithms, and leads to Las Vegas algorithms for some coloring problems for which only Monte Carlo algorithms were known.

We show that, in certain conditions when the LLL condition is violated, a variant of the MT algorithm can still produce a distribution that avoids most of the bad events. We show in some cases that this MT variant can run faster than the original MT algorithm itself and develop the first-known criterion for the case of the asymmetric LLL. This can be used to find partial Latin transversals—improving on earlier bounds of Stein (1975)—among other applications. We furthermore give applications in enumeration, showing that most applications (for which we aim for all or most of the bad events to be avoided) have large solution sets. We do this by showing that the MT distribution has large Rényi entropy.
Menin and PRMT5 suppress GLP1 receptor transcript and PKA-mediated phosphorylation of FOXO1 and CREB
Authors: Muhammad Abdul Bari , Xing Bowen , Liu Chengyang , Naji Ali , Ma Xiaosong , Simmons Rebecca A. , Hua Xianxin
Published: March 2017

Menin is a scaffold protein that interacts with several epigenetic mediators to regulate gene transcription, and suppresses pancreatic β-cell proliferation. Tamoxifen-inducible deletion of multiple endocrine neoplasia type 1 ( MEN1) gene, which encodes the protein menin, increases β-cell mass in multiple murine models of diabetes and ameliorates diabetes. Glucagon-like-peptide-1 (GLP1) is another key physiological modulator of β-cell mass and glucose homeostasis. However, it is not clearly understood whether menin crosstalks with GLP1 signaling. Here, we show that menin and protein arginine methyltransferase 5 (PRMT5) suppress GLP1 receptor (GLP1R) transcript levels. Notably, a GLP1R agonist induces phosphorylation of forkhead box protein O1 (FOXO1) at S253, and the phosphorylation is mediated by PKA. Interestingly, menin suppresses GLP1-induced and PKA-mediated phosphorylation of both FOXO1 and cAMP response element binding protein (CREB), likely through a protein arginine methyltransferase. Menin-mediated suppression of FOXO1 and CREB phosphorylation increases FOXO1 levels and suppresses CREB target genes, respectively. A small-molecule menin inhibitor reverses menin-mediated suppression of both FOXO1 and CREB phosphorylation. In addition, ex vivo treatment of both mouse and human pancreatic islets with a menin inhibitor increases levels of proliferation marker Ki67. In conclusion, our results suggest that menin and PRMT5 suppress GLP1R transcript levels and PKA-mediated phosphorylation of FOXO1 and CREB, and a menin inhibitor may reverse this suppression to induce β-cell proliferation.
A four-compartment compartmental model to assess net whole body protein breakdown using a pulse of phenylalanine and tyrosine stable isotopes in humans
Authors: Mason Alvise , Engelen Mariëlle P. K. J. , Ivanov Ivan , Toffolo Gianna M. , Deutz Nicolaas E. P.
Published: March 2017

The stable isotopes of phenylalanine (Phe) and tyrosine (Tyr) are often used to study whole body protein metabolism in humans. Noncompartmental approaches give limited physiological insight in the compartmental characteristics. We therefore developed a compartmental mathematical model of Phe/Tyr metabolism to describe protein fluxes by using stable tracer dynamic data in plasma following intravenous bolus of l-[ring-13C6]Phe and l-[ ring-2H4]Tyr in healthy subjects. The model consists of four compartments describing Phe/Tyr kinetics. Because the model is a priori nonidentifiable, it is quantified in terms of two uniquely identifiable submodels representing two limit case scenarios, based on known physiology. The two submodels, identified by using the software SAAM II, fit well the experimental data of all individuals and provide an unbiased overview of the metabolic pathway in terms of intervals of validity of the non-uniquely identifiable variables. The model provides estimates of the flux from Phe to Tyr [4.1 ± 1.0 µmol·kg fat-free mass (FFM)−1·h−1 (mean ± SE)] and intervals of validity of the flux and pool estimates. Our preferred submodel yielded protein breakdown flux (50.5 ± 5.2 µmol·kg FFM−1·h−1), net protein breakdown (4.1 ± 1.0 µmol·kg FFM−1·h−1), Tyr from Phe hydroxylation (~12%), hydroxylated Phe (~8%), and flux ratio of Tyr to Phe arising from protein catabolism (0.68), consistent with available literature. The other submodel suggest that the assumptions made by noncompartmental analysis are consistently underestimated. Our accurate and detailed model for estimating Phe/Tyr metabolic pathways in humans might be essential to applications in a variety of scenarios describing whole body protein synthesis and breakdown in health and disease.
Optimizing Production Scheduling of Steel Plate Hot Rolling for Economic Load Dispatch under Time‐of‐Use Electricity Pricing
Authors: Tan Mao , Yang Hua-li , Duan Bin , Su Yong-xin , He Feng
Published: March 2017

Time‐of‐Use (TOU) electricity pricing provides an opportunity for industrial users to cut electricity costs. Although many methods for Economic Load Dispatch (ELD) under TOU pricing in continuous industrial processing have been proposed, there are still difficulties in batch‐type processing, since power load units are not directly adjustable and nonlinearly depend on production planning and scheduling. In this paper, for hot rolling, a typical batch‐type and energy intensive process in steel industry, a production scheduling optimization model for ELD is proposed under TOU pricing, in which the objective is to minimize electricity costs while considering penalties caused by jumps between adjacent slabs. A NSGA‐II based multiobjective production scheduling algorithm is developed to obtain Pareto optimal solutions, and then TOPSIS based multicriteria decision‐making is performed to recommend an optimal solution to facilitate field operation. Experimental results and analyses show that the proposed method cuts electricity costs in production, especially in case of allowance for penalty score increase in a certain range. Further analyses show that the proposed method has effect on peak load regulation of power grid.
Nonlinear Unknown Input Observer Based on Singular Value Decomposition Aided Reduced Dimension Cubature Kalman Filter
Authors: Zhao Wei , Li Huiguang , Zou Liying , Huang Wenjuan
Published: March 2017

The paper presents a nonlinear unknown input observer (NUIO) based on singular value decomposition aided reduced dimension Cubature Kalman filter (SVDRDCKF) for a special class of nonlinear systems, the nonlinearity of which is only caused by part of its states. Firstly, the algorithm of general NUIO is discussed and the unknown input observer based on singular value decomposition aided Cubature Kalman filter (SVDCKF) given. Then a special nonlinear system model with unknown input is introduced. Based on the proposed model and the corresponding NUIO, the equivalent integral form with partial sampling and all sampling of the state vector in Cubature Kalman filter is analyzed. Finally the nonlinear unknown input observer based on singular value decomposition aided reduced dimension Cubature Kalman filter is obtained. Simulation results show that the proposed algorithm can meet the requirements of the system and is more important to increase the calculating efficiency a lot, although it has a decline in the accuracy of the filter.
Lectins, Interconnecting Proteins with Biotechnological/Pharmacological and Therapeutic Applications
Authors: Coelho Luana Cassandra Breitenbach Barroso , Silva Priscila Marcelino dos Santos , Lima Vera Lúcia de Menezes , Pontual Emmanuel Viana , Paiva Patrícia Maria Guedes , Napoleão Thiago Henrique , Correia Maria Tereza dos Santos
Published: March 2017

Lectins are proteins extensively used in biomedical applications with property to recognize carbohydrates through carbohydrate‐binding sites, which identify glycans attached to cell surfaces, glycoconjugates, or free sugars, detecting abnormal cells and biomarkers related to diseases. These lectin abilities promoted interesting results in experimental treatments of immunological diseases, wounds, and cancer. Lectins obtained from virus, microorganisms, algae, animals, and plants were reported as modulators and tool markers in vivo and in vitro; these molecules also play a role in the induction of mitosis and immune responses, contributing for resolution of infections and inflammations. Lectins revealed healing effect through induction of reepithelialization and cicatrization of wounds. Some lectins have been efficient agents against virus, fungi, bacteria, and helminths at low concentrations. Lectin‐mediated bioadhesion has been an interesting characteristic for development of drug delivery systems. Lectin histochemistry and lectin‐based biosensors are useful to detect transformed tissues and biomarkers related to disease occurrence; antitumor lectins reported are promising for cancer therapy. Here, we address lectins from distinct sources with some biological effect and biotechnological potential in the diagnosis and therapeutic of diseases, highlighting many advances in this growing field.
Development and Assessment of the Sand Dust Prediction Model by Utilizing Microwave-Based Satellite Soil Moisture and Reanalysis Datasets in East Asian Desert Areas
Authors: Kim Hyunglok , Zohaib Muhammad , Cho Eunsang , Kerr Yann H. , Choi Minha
Published: March 2017

For several decades, satellite-based microwave sensors have provided valuable soil moisture monitoring in various surface conditions. We have first developed a modeled aerosol optical depth (AOD) dataset by utilizing Soil Moisture and Ocean Salinity (SMOS), Advanced Microwave Scanning Radiometer 2 (AMSR2), and the Global Land Data Assimilation System (GLDAS) soil moisture datasets in order to estimate dust outbreaks over desert areas of East Asia. Moderate Resolution Imaging Spectroradiometer- (MODIS-) based AOD products were used as reference datasets to validate the modeled AOD (MA). The SMOS-based MA (SMOS-MA) dataset showed good correspondence with observed AOD (R-value: 0.56) compared to AMSR2- and GLDAS-based MA datasets, and it overestimated AOD compared to observed AOD. The AMSR2-based MA dataset was found to underestimate AOD, and it showed a relatively lowR-value (0.35) with respect to observed AOD. Furthermore, SMOS-MA products were able to simulate the short-term AOD trends, having a highR-value (0.65). The results of this study may allow us to acknowledge the utilization of microwave-based soil moisture datasets for investigation of near-real time dust outbreak predictions and short-term dust outbreak trend analysis.
Protection of Human Umbilical Vein Endothelial Cells against Oxidative Stress by MicroRNA‐210
Authors: Li Tianyi , Song Xianjing , Zhang Jichang , Zhao Lei , Shi Yongfeng , Li Zhibo , Liu Jia , Liu Ning , Yan Youyou , Xiao Yanlong , Tian Xin , Sun Wei , Guan Yinuo , Liu Bin
Published: March 2017

Oxidative stress induces endothelial cell apoptosis and promotes atherosclerosis development. MicroRNA‐210 (miR‐210) is linked with apoptosis in different cell types. This study aimed to investigate the role of miR‐210 in human umbilical vein endothelial cells (HUVECs) under oxidative stress and to determine the underlying mechanism. HUVECs were treated with different concentrations of hydrogen peroxide (H2O2), and cell viability was evaluated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and ATP assay. To evaluate the role of miR‐210 in H2O2‐mediated apoptosis, gain‐and‐loss‐of‐function approaches were used, and the effects on apoptosis and reactive oxygen species (ROS) level were assayed using flow cytometry. Moreover, miR‐210 expression was detected by quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR), and expression of the following apoptosis‐related genes was assessed by qRT‐PCR and Western blot at the RNA and protein level, respectively: caspase‐8‐associated protein 2 (CASP8AP2), caspase‐8, and caspase‐3. The results showed that H2O2 induced apoptosis in HUVECs in a dose‐dependent manner and increased miR‐210 expression. Overexpression of miR‐210 inhibited apoptosis and reduced ROS level in HUVECs treated with H2O2. Furthermore, miR‐210 downregulated CASP8AP2 and related downstream caspases at protein level. Thus, under oxidative stress, miR‐210 has a prosurvival and antiapoptotic effect on HUVECs by reducing ROS generation and downregulating the CASP8AP2 pathway.
Spermidine Oxidation‐Mediated Degeneration of Retinal Pigment Epithelium in Rats
Authors: Ohashi Koji , Kageyama Masaaki , Shinomiya Katsuhiko , Fujita-Koyama Yukie , Hirai Shin-ichiro , Katsuta Osamu , Nakamura Masatsugu
Published: March 2017

Retinal pigment epithelium (RPE) degeneration is a crucial event in dry age‐related macular degeneration and gyrate atrophy. The polyamine spermidine has been shown to induce RPE cell death in vitro. The present study aimed to establish a novel in vivo model of spermidine‐induced RPE degeneration and to determine whether spermidine‐induced RPE cell death involves oxidative mechanisms. In this study, spermidine caused ARPE‐19 cell death in a concentration‐dependent manner. This effect was prevented by removal of serum from the culture medium or treatment with amine oxidase inhibitors, N‐acetylcysteine (NAC), or aldehyde dehydrogenase (ALDH). Intravitreal injection of spermidine into rats significantly increased the permeability of the blood‐retinal barrier and decreased the amplitudes of scotopic electroretinogram a‐ and b‐waves. Histological analysis revealed that spermidine induced vacuolation, atrophy, and dropout of RPE cells, leading to the disruption of photoreceptor outer segments. Simultaneous intravitreal administration of NAC and ALDH with spermidine prominently inhibited the functional and morphological changes induced by spermidine. In conclusion, this study demonstrated that the intravitreal administration of spermidine induced RPE cell dysfunction and death followed by photoreceptor degeneration in rats. These effects of spermidine are thought to be mediated by oxidative stress and a toxic aldehyde generated during spermidine oxidation.
The Psychometric Properties of the Arabic Preschool Activity Card Sort
Authors: Malkawi Somaya H. , Abu-Dahab Sana M. N. , Amro Ahmad F. , Almasri Nihad A.
Published: March 2017

Background. The Preschool Activity Card Sort (PACS) is an interview-based assessment tool to measure participation of preschool children with age range from 3 to 6 years. Objective of Study. The purpose of this study was to establish the psychometric properties of the recently translated Arabic PACS (A-PACS). Methods. One hundred fifty-one Jordanian parents participated in the study representing different geographical areas. Children were almost equally distributed between males and females and into three age groups. Construct and concurrent validity were examined as well as the internal consistency of the scale and the test-retest reliability. Findings. The A-PACS was able to differentiate between the participation level of young and old children in the domains of education, community mobility, and low demand leisure of the A-PACS giving evidence to its construct validity and it significantly correlated with some aspects of the Vineland Adaptive Behavior Scale (VABS) giving evidence to its concurrent validity. The A-PACS showed excellent overall internal consistency (α=.859) for all domains and good test-retest reliability (r=.976, p<.001). Conclusion. The A-PACS can be considered as a valid and reliable tool to measure participation of preschool children with normal development from Arabic cultures. Future studies should focus on the validity of the A-PACS for use with children with disabilities.
Capsular Polysaccharide of Mycoplasma ovipneumoniae Induces Sheep Airway Epithelial Cell Apoptosis via ROS‐Dependent JNK/P38 MAPK Pathways
Authors: Jiang Zhongjia , Song Fuyang , Li Yanan , Xue Di , Zhao Ning , Zhang Jiamei , Deng Guangcun , Li Min , Liu Xiaoming , Wang Yujiong
Published: March 2017

In an attempt to better understand the pathogen‐host interaction between invading Mycoplasma ovipneumoniae (M. ovipneumoniae) and sheep airway epithelial cells, biological effects and possible molecular mechanism of capsular polysaccharide of M. ovipneumoniae (CPS) in the induction of cell apoptosis were explored using sheep bronchial epithelial cells cultured in air‐liquid interface (ALI). The CPS of M. ovipneumoniae was first isolated and purified. Results showed that CPS had a cytotoxic effect by disrupting the integrity of mitochondrial membrane, accompanied with an increase of reactive oxygen species and decrease of mitochondrial membrane potential (ΔΨm). Of importance, the CPS exhibited an ability to induce caspase‐dependent cell apoptosis via both intrinsic and extrinsic apoptotic pathways. Mechanistically, the CPS induced extrinsic cell apoptosis by upregulating FAS/FASL signaling proteins and cleaved‐caspase‐8 and promoted a ROS‐dependent intrinsic cell apoptosis by activating a JNK and p38 signaling but not ERK1/2 signaling of mitogen‐activated protein kinases (MAPK) pathways. These findings provide the first evidence that CPS of M. ovipneumoniae induces a caspase‐dependent apoptosis via both intrinsic and extrinsic apoptotic pathways in sheep bronchial epithelial cells, which may be mainly attributed by a ROS‐dependent JNK and p38 MAPK signaling pathways.
High Precise Scattering Centers Models for Cone-Shaped Targets Based on Induced Currents
Authors: Li Qi-Feng , Guo Kun-Yi , Sheng Xin-Qing , Liu Tian-Shu
Published: March 2017

Based on induced currents of cone-shaped targets, the high precise scattering center model is derived in this paper. The distribution characteristics of the induced currents and their relationships with the attributes of scattering centers are investigated in detail; the high precise scattering center model is obtained. In order to validate the scattering center model, numerical simulations of two cone-shaped targets are presented, and the accuracies of the models are validated through comparing the range profiles simulated by the models with those by a full-wave numerical method. The validation results demonstrate that this model is superior to the existing model in precisely characterizing the scattering centers induced by creeping waves.
Experimental Study and Numerical Simulation of Seismic Behavior for RC Columns Subjected to Freeze-Thaw Cycles
Authors: Qin Qing , Zheng Shansuo , Li Lei , Dong Liguo , Zhang Yixin , Ding Sha
Published: March 2017

Freeze-thaw of concrete is significantly responsible for serious damage to RC buildings, which may result in premature failure with little warning. Therefore, it is necessary to consider the effects of freeze-thaw environment when assessing seismic performance for RC structures. In this study, pseudo-static experiments of four RC columns were conducted in terms of different number of freeze-thaw cycles (FTCs). The results showed that the FTCs had an influence on the bearing capacity, ductility, strength, and stiffness of RC columns. What is more, the simulation results were commonly smaller than the experimental ones when simply assuming that the degrees of freeze-thaw damage for RC components were uniform. Thus, a numerical model considering uneven distribution of freeze-thaw damage was proposed by utilizing the results of Petersen’s test for relative dynamic modulus of elasticity (RDME) for different depths of concrete sample and based on Berto’s method which was proved to be effective to convert the numbers of FTCs under different freeze-thaw conditions. On the basis of the existing constitutive relations for concrete, four RC columns subjected to different numbers of FTCs were simulated by OpenSees. As a result, the simulation hysteretic curves were in good agreement with the experimental ones.
FOLFOX Induced Takotsubo Cardiomyopathy Treated with Impella Assist Device
Authors: Sundaravel Swethika , Alrifai Abdulah , Kabach Mohamad , Ghumman Waqas
Published: March 2017

Chemotherapy induced cardiotoxicity is becoming increasingly prevalent with several new agents being used recently. The incidence of Takotsubo cardiomyopathy due to 5-fluorouracil based chemotherapeutic regimens like FOLFOX is not uncommon. It is also seen with platinum based chemotherapy. Most of these patients have reversible cardiotoxicity and the cardiac function recovers within a short period with supportive treatment. Here we have a patient who presented with cardiogenic shock after 5 days of receiving FOLFOX regimen for colorectal adenocarcinoma. She was treated with a percutaneous left ventricular assist device, Impella CP, for hemodynamic support with excellent outcome.
Women’s Joint Decision on Contraceptive Use in Gedeo Zone, Southern Ethiopia: A Community Based Comparative Cross-Sectional Study
Authors: Eshete Akine , Adissu Yohannes
Published: March 2017

A community based comparative cross-sectional study design was employed to assess the mutual consent of women about family planning use in urban and rural villages of Gedeo zone. Two-thirds (67.4%) of women made joint decision on contraceptive use, varying between urban (70.9%) and rural (63.4%) settings. This difference was statistically significant where women in urban setup had a 41% (AOR, 1.41; 95% CI (1.15, 2.01) added chance of making joint decision than the rural counterpart. In both settings, attitude towards contraceptive method was an independent predictor of joint contraceptive decision (AOR = 2.85) in urban and (AOR = 2.81) rural women. Contrarily, different factors were found to be associated with joint contraceptive decision in either setup. In urban, having better knowledge about contraceptive methods (AOR = 2.9) and having lower age difference (AOR = 2.2) were found to be strong predictors of joint decision on contraceptive use, while having too many children (AOR = 2.2) and paternal support (AOR = 7.1) in rural setups. Lower level of joint decision making on contraceptive use was reported in both setups. Factors associated with joint decision varied between the two setups, except for attitude towards contraceptive methods. Future family planning program should address sociocultural, knowledge and attitude factors.
A Prospective Cohort Study of Cigarette Prices and Smoking Cessation in Older Smokers
Authors: Stevens Victoria L. , Diver W. Ryan , Stoklosa Michal , Flanders W. Dana , Westmaas J. Lee , Jemal Ahmedin , Drope Jeffrey M. , Gapstur Susan M. , Jacobs Eric J.
Published: March 2017

Background: Cigarette price increases effectively prevent smoking initiation and reduce cigarette consumption among young smokers. However, the impact of cigarette prices on smoking cessation among older smokers is less clear, particularly for those aged 65 years and older, a group that is at highest risk of smoking-related disease and will almost double in the United States between 2012 and 2050.

Methods: Biennial questionnaires administered between 1997 and 2013 assessed smoking status for 9,446 Cancer Prevention Study-II Nutrition Cohort participants who were ≥50 years old and lived in Washington, DC, and 48 states. For each interval between biennial questionnaires, change in price per pack and average price level per pack were calculated. The separate associations between these price variables and smoking cessation during the same time interval were determined.

Results: In multivariable-adjusted models, each $1.00 price increase was associated with a 9% higher rate of quitting [rate ratio (RR) = 1.09; 95% confidence interval (CI), 1.04–1.14). Each $1.00 increase in average price was associated with a 6% higher rate of quitting (RR = 1.06; 95% CI, 1.02–1.10). The association with average price was strongest among smokers aged 65 years and older (RR = 1.07; 95% CI, 1.04–1.11) and, for price change, for smokers with no major prevalent disease (RR = 1.13; 95% CI, 1.07–1.19).

Conclusions: These results suggest that increasing cigarette prices will promote quitting even among smokers aged 65 years and older.

Impact: Increasing cigarette prices through higher taxes could reduce smoking rates among older adults and decrease risk of smoking-related cancers and diseases in this high-risk group. Cancer Epidemiol Biomarkers Prev; 26(7); 1071–7. ©2017 AACR.
Genetically Predicted Telomere Length is not Associated with Pancreatic Cancer Risk
Authors: Antwi Samuel O. , Bamlet William R. , Broderick Brendan T. , Chaffee Kari G. , Oberg Ann , Jatoi Aminah , Boardman Lisa A. , Petersen Gloria M.
Published: March 2017

Background: Epidemiologic associations of leukocyte telomere length (LTL) and pancreatic ductal adenocarcinoma (PDAC) have been inconsistent owing, in part, to variation in telomere length (TL) assessment across studies. To overcome this limitation and address concerns of potential reverse causation, we used carriage of telomere-related alleles to genetically predict TL and examined its association with PDAC.

Methods: A case–control study of 1,500 PDAC cases and 1,500 controls, frequency-matched on age and sex was performed. Eight of nine polymorphisms previously associated with variation in LTL were analyzed. Genetic risk scores (GRS) consisting of the TL-related polymorphisms were computed as the number of long TL alleles carried by an individual scaled to published kilobase pairs of TL associated with each allele. Participants were further categorized on the basis of the number of short TL alleles they carry across all eight SNPs. Associations were examined in additive and dominant models using logistic regression to calculate ORs and 95% confidence intervals (CI).

Results: In age- and sex-adjusted models, one short TL allele (rs10936599, T) was associated with reduced risk, whereas another short TL allele (rs2736100, A) was associated with increased risk, with per-allele ORs of 0.89 (95% CI, 0.79–0.99) and 1.13 (95% CI, 1.01–1.24), respectively. No association was observed with GRS or short TL allele counts, and no associations were observed in the dominant models.

Conclusions: Findings suggest that genetically predicted short TL is not associated with PDAC risk.

Impact: Common genetic determinants of short TL do not appear to influence PDAC risk. Cancer Epidemiol Biomarkers Prev; 26(6); 971–4. ©2017 AACR.
A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors
Authors: Kristeleit Rebecca , Shapiro Geoffrey I. , Burris Howard A. , Oza Amit M. , LoRusso Patricia , Patel Manish R. , Domchek Susan M. , Balmaña Judith , Drew Yvette , Chen Lee-may , Safra Tamar , Montes Ana , Giordano Heidi , Maloney Lara , Goble Sandra , Isaacson Jeff , Xiao Jim , Borrow Jen , Rolfe Lindsey , Shapira-Frommer Ronnie
Published: March 2017

Purpose: Rucaparib is a potent, oral, small-molecule PARP inhibitor. This phase I–II study was the first to evaluate single-agent oral rucaparib at multiple doses.

Experimental Design: Part 1 (phase I) sought to determine the MTD, recommended phase II dose (RP2D), and pharmacokinetics of oral rucaparib administered in 21-day continuous cycles in patients with advanced solid tumors. Part 2A (phase II) enrolled patients with platinum-sensitive, high-grade ovarian carcinoma (HGOC) associated with a germline BRCA1/2 mutation who received two to four prior regimens and had a progression-free interval of 6 months or more following their most recent platinum therapy. The primary endpoint was investigator-assessed objective response rate (ORR) by RECIST version 1.1.

Results: In part 1, 56 patients received oral rucaparib (40 to 500 mg once daily and 240 to 840 mg twice daily). No MTD was identified per protocol-defined criteria; 600 mg twice daily was selected as the RP2D based on manageable toxicity and clinical activity. Pharmacokinetics were approximately dose-proportional across all dose levels. In part 2A, 42 patients with germline BRCA1/2–mutated HGOC received rucaparib 600 mg twice daily. Investigator-assessed ORR was 59.5%. The most common treatment-emergent adverse events (all grades) were asthenia/fatigue (85.7%; 36/42), nausea (83.3%; 35/42), anemia (71.4%; 30/42), alanine transaminase and/or aspartate transaminase elevations (57.1%; 24/42), and vomiting (54.8%; 23/42). Among 98 patients, 5 (5.1%) discontinued because of an adverse event (excluding disease progression).

Conclusions: Rucaparib was tolerable and had activity in patients with platinum-sensitive germline BRCA1/2–mutated HGOC. Clin Cancer Res; 23(15); 4095–106. ©2017 AACR.
Preclinical Mammalian Safety Studies of EPHARNA (DOPC Nanoliposomal EphA2-Targeted siRNA)
Authors: Wagner Michael J. , Mitra Rahul , McArthur Mark J. , Baze Wallace , Barnhart Kirstin , Wu Sherry Y. , Rodriguez-Aguayo Cristian , Zhang Xinna , Coleman Robert L. , Lopez-Berestein Gabriel , Sood Anil K.
Published: March 2017

To address the need for efficient and biocompatible delivery systems for systemic siRNA delivery, we developed 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine (DOPC) nanoliposomal EphA2-targeted therapeutic (EPHARNA). Here, we performed safety studies of EPHARNA in murine and primate models. Single dosing of EPHARNA was tested at 5 concentrations in mice (N = 15 per group) and groups were sacrificed on days 1, 14, and 28 for evaluation of clinical pathology and organ toxicity. Multiple dosing of EPHARNA was tested in mice and Rhesus macaques twice weekly at two dose levels in each model. Possible effects on hematologic parameters, serum chemistry, coagulation, and organ toxicity were assessed. Following single-dose EPHARNA administration to mice, no gross pathologic or dose-related microscopic findings were observed in either the acute (24 hours) or recovery (14 and 28 days) phases. The no-observed-adverse-effect level (NOAEL) for EPHARNA is considered >225 μg/kg when administered as a single injection intravenously in CD-1 mice. With twice weekly injection, EPHARNA appeared to stimulate a mild to moderate inflammatory response in a dose-related fashion. There appeared to be a mild hemolytic reaction in the female mice. In Rhesus macaques, minimal to moderate infiltration of mononuclear cells was found in some organs including the gastrointestinal tract, heart, and kidney. No differences attributed to EPHARNA were observed. These results demonstrate that EPHARNA is well tolerated at all doses tested. These data, combined with previously published in vivo validation studies, have led to an ongoing first-in-human phase I clinical trial (NCT01591356). Mol Cancer Ther; 16(6); 1114–23. ©2017 AACR.